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Larson C, Berinstein JA, Tedesco N, Seidelin JB, Ovesen PD, Uzzan M, Amiot A, Nuzzo A, Laharie D, Constant BD, Albenberg L, El-Hussuna A, Bishu S, Cohen-Mekelburg S, Higgins PDR, Steenholdt C. Postoperative Outcomes in Tofacitinib-Treated Patients With Acute Severe Ulcerative Colitis Undergoing Colectomy. Clin Gastroenterol Hepatol 2025:S1542-3565(25)00287-3. [PMID: 40239733 DOI: 10.1016/j.cgh.2025.01.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 12/26/2024] [Accepted: 01/22/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND AND AIMS Up to 30% of patients with acute severe ulcerative colitis (ASUC) will require urgent colectomy despite initiation of intravenous corticosteroids and rescue therapies. Janus kinase inhibitors, such as tofacitinib, have emerged as an effective agent for ASUC; however, there are currently limited data evaluating the risk of postoperative complications among patients who received tofacitinib treatment for an episode of ASUC compared with infliximab. METHODS We conducted a multicenter, retrospective, case-control study of patients hospitalized with ASUC who underwent colectomy, comparing patients treated with tofacitinib prior to colectomy with infliximab-treated controls. The primary outcome was rate of serious postoperative complications within 30 days of colectomy. Outcomes were compared between the tofacitinib-treated cases and infliximab-treated controls using multivariable regression adjusted for open surgery and cumulative corticosteroid exposure. RESULTS Forty-one tofacitinib-treated patients were compared with 68 infliximab-treated patients with ASUC. Compared with tofacitinib-treated patients, infliximab-treated patients had higher overall rates of overall (44 [64.7%] vs 13 [31.7%]; P = .002) and serious (19 [27.9%] vs 3 [12%]; P = .019) postoperative complications. No significant different risk for developing serious postoperative complications (odds ratio, 0.28; 95% confidence interval, 0.06-0.96; P = .061) was observed in multivariable analysis; however, a significantly lower rate of overall postoperative complications (odds ratio, 0.38; 95% confidence interval, 0.16-0.87; P = .023) was observed in tofacitinib-treated patients compared with infliximab-treated patients. CONCLUSIONS We observed a significantly lower rate of overall postoperative complications in ASUC patients treated with tofacitinib compared with infliximab; however, no difference was observed in the risk for serious postoperative complications. Larger prospective trials are needed to confirm these findings.
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Affiliation(s)
- Charlotte Larson
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan
| | - Jeffrey A Berinstein
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan; Department of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
| | - Nicholas Tedesco
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan; Department of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | | | - Pernille D Ovesen
- Department of Gastroenterology and Hepatology, Herlev Hospital, Herlev, Denmark
| | - Mathieu Uzzan
- TRUE (InnovaTive theRapy for immUne disordErs), Gastroenterology Department, Henri Mondor Hospital, Fédération Hospitalo-Universitaire, Assistance Publique-Hôpitaux de Paris, Paris Est-Créteil University, Créteil, France
| | - Aurélien Amiot
- EC2M3-EA7375, Department of Gastroenterology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est-Creteil University, Creteil, France
| | - Alexandre Nuzzo
- Department of Gastroenterology, IBD, and Nutritional Support, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - David Laharie
- Gastroenterology Department, CHU de Bordeaux, Centre Medico-Chirurgical Magellan, Hôpital Haut-Lévêque, Université de Bordeaux, Bordeaux, France; INSERM CIC 1401, Gastroenterology Department, Université de Bordeaux, Bordeaux, France
| | - Brad D Constant
- Digestive Health Institute, Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Philadelphia
| | - Lindsey Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Philadelphia
| | | | - Shrinivas Bishu
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan; Department of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Shirley Cohen-Mekelburg
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan; Department of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Peter D R Higgins
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan; Department of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Casper Steenholdt
- Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark
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Cornet N, Aboubakr A, Ahmed W, Battat R. Combined Advanced Targeted Therapy in Inflammatory Bowel Diseases: An Extensive Update. Inflamm Bowel Dis 2025; 31:1138-1144. [PMID: 39207309 DOI: 10.1093/ibd/izae189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Indexed: 09/04/2024]
Abstract
Lay Summary
This article discusses the rationale for and the current data on the efficacy and safety of combined advanced targeted therapy (CATT) for the treatment of moderate-to-severe inflammatory bowel disease.
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Affiliation(s)
- Nicole Cornet
- Department of Medicine, NewYork Presbyterian-Weill Cornell Medicine, New York, NY, USA
| | - Aiya Aboubakr
- Division of Gastroenterology, NewYork Presbyterian-Weill Cornell Medicine, New York, NY, USA
| | - Waseem Ahmed
- Department of Gastroenterology, University of Colorado Crohn's and Colitis Center, Aurora, CO, USA
| | - Robert Battat
- Department of Gastroenterology and Hepatology, Center Hospitalier de l' Université de Montreal, Montreal, QC, Canada
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Abdelmeguid A, El Banna AA, Elsheikh W, Ellakany AI, Sebastian S. Evaluation of Acute Severe Ulcerative Colitis Predictors for Steroid Therapy Refractoriness. Dig Dis Sci 2025:10.1007/s10620-025-08982-4. [PMID: 40188169 DOI: 10.1007/s10620-025-08982-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 03/10/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND One-third of patients presenting with acute severe ulcerative colitis (ASUC) are steroid-refractory and require either colectomy or rescue therapy. Timely identification of risk factors predictive of steroid non-response in ASUC patients is crucial for initiating early rescue therapy. AIM To identify factors predicting steroid failure or colectomy in ASUC. METHODS Records of ASUC admissions over a six-year period in a tertiary inflammatory bowel disease center were included. Clinical variables, laboratory markers, and endoscopic scores at admission were obtained. The primary outcome was non-response to intravenous (IV) steroids. Univariate and multivariate regression analyses were performed to identify factors associated with steroid non-response. Day-one and day-three composite indices were calculated. Their predictive value was assessed against the outcomes of steroid failure and requiring colectomy. RESULTS One hundred and three ASUC patients were included, of which 51 were steroid non-responders. Among non-responders, 48 received rescue therapy, and 6 underwent colectomy at index admission (3 after rescue therapy and 3 without). Day-one albumin (OR 0.906, P = 0.043) and being on oral steroids at entry (OR 3.009, P = 0.014) predicted non-response to steroids in both univariate and multivariate analyses. Admission hemoglobin level predicted steroid non-response only in univariate (OR 0.982, P = 0.047). Although an old score, Travis criteria predicted both steroid non-response (OR 8.4, P = 0.001) and requiring colectomy (OR 22.19, P = 0.006). CONCLUSION Lower albumin levels and being on oral steroids at admission for ASUC can predict IV steroid failure, and we suggest the possibility of early initiation of advanced therapy in this subgroup.
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Affiliation(s)
- Alaa Abdelmeguid
- Faculty of Medicine, Alexandria University, Alexandria, Egypt.
- IBD Unit, Hull University Teaching Hospitals, Hull, UK.
| | | | - Wafaa Elsheikh
- Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Naganuma M, Shiga H, Shimoda M, Matsuura M, Takenaka K, Fujii T, Yamamoto S, Matsubayashi M, Kobayashi T, Aoyama N, Saito D, Yokoyama K, Moriya K, Tsuchiya K, Shibui S, Kawamoto A, Shimizu H, Okamoto R, Sakamoto K, Yaguchi K, Kunisaki R, Akiyama S, Hayashi R, Hasui K, Kanmura S, Bamba S, Mishima Y, Kakimoto K, Sugimoto S, Nakazawa A, Abe T, Ogata H, Hisamatsu T. First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study. J Gastroenterol 2025; 60:430-441. [PMID: 39883201 DOI: 10.1007/s00535-025-02216-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 01/11/2025] [Indexed: 01/31/2025]
Abstract
BACKGROUND Despite the availability of several biologics for ulcerative colitis (UC), there remains a critical need to identify first-line treatment biologics. The superiority of infliximab (IFX) over vedolizumab (VED) and ustekinumab (UST) was evaluated as initial UC treatments in patients with biologic-naïve UC. METHODS This multicenter, randomized control trial was conducted across 20 Japanese medical institutions. An independent center randomly allocated patients with UC (Mayo score ≥ 6) who had not previously used biologics to three treatment groups (IFX, VED, UST). The primary endpoint was the clinical remission (CR) rate at week 12, with other endpoints including the treatment continuation rate at week 26 and adverse events (AEs). RESULTS From May 2021 to June 2023, 107 cases were registered, including 104 for safety and 97 for efficacy evaluation. CR rate at week 12 was 36.4% (95%CI:20.4-54.9), 32.4% (95%CI:17.4-50.5) and 43.3% (95%CI:25.5-62.6) in IFX, VED, and UST group, respectively. Continuation rates at week 26 were 50.0%(IFX), 58.3% (VED), and 82.4% (UST). AEs related to study medication were 14.7% (IFX), 16.7% (VED), and 5.9% (UST). Predictors for CR at week 12 were thiopurine use in IFX (p = 0.04), lower baseline Mayo score (p = 0.007), and lower Patient report outcome 2 (p = 0.003) at week 2 in VED. CONCLUSION Due to small sample size, it is challenging to make conclusions for main endpoints from this study while our study suggested that use of thiopurines in IFX group and lower activity at enrollment in VED group may enhance treatment efficacy. (jRCT1031200329; available at https://jrct.niph.go.jp/ ).
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Affiliation(s)
- Makoto Naganuma
- Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
| | - Hisashi Shiga
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Masayuki Shimoda
- Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
| | - Kento Takenaka
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Shojiro Yamamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Mao Matsubayashi
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Nobuo Aoyama
- Gastrointestinal Endoscopy and Inflammatory Bowel Disease Center, Aoyama Medical Clinic, Hyogo, Japan
| | - Daisuke Saito
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
| | - Kaoru Yokoyama
- Department of Gastroenterology, Kitasato University School of Medicine Sagamihara, Tokyo, Japan
| | - Kei Moriya
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Shunsuke Shibui
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Ami Kawamoto
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Hiromichi Shimizu
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Ryuichi Okamoto
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Kazuki Sakamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Katsuki Yaguchi
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Shintaro Akiyama
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Ryohei Hayashi
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Keisuke Hasui
- Department of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Shuji Kanmura
- Department of Gastroenterology and Hepatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shigeki Bamba
- Division of Digestive Endoscopy, Shiga University of Medical Science, Otsu, Japan
| | - Yoshiyuki Mishima
- Department of Internal Medicine II, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kazuki Kakimoto
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Shinya Sugimoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Atsushi Nakazawa
- Department of Gastroenterology, Saiseikai Central Hospital, Tokyo, Japan
| | - Takayuki Abe
- Faculty of Data Science, Kyoto Women's University, Kyoto, Japan
| | | | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
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Rabinowitz LG, Gade A, Feuerstein JD. Medical management of acute severe ulcerative colitis in the hospitalized patient. Expert Rev Gastroenterol Hepatol 2025; 19:467-480. [PMID: 40187895 DOI: 10.1080/17474124.2025.2488884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 04/01/2025] [Indexed: 04/07/2025]
Abstract
INTRODUCTION Approximately one in every four patients with ulcerative colitis will develop acute severe ulcerative colitis (ASUC). Historically, this was managed with intravenous steroids and surgery when steroids failed. The use of rescue therapy. AREAS COVERED This review summarizes the latest research in the management of hospitalized patients with ASUC. Covering the historical data and success of rescue therapy with cyclosporine and then with infliximab changed outcomes and reduced the risk of colectomy during the hospitalization and at 1 year. More recently, more biologics and small molecules have been approved and more patients present to the hospital with ASUC already failing anti-tumor necrosis factor antagonists. More recent studies have shown some efficacy of rescue therapy with other classes of biologics (e.g. interleukins and anti-integrins). The more recently approved small molecules (i.e. tofacitinib and Upadacitinib) have shown a rapid onset in therapeutic efficacy in as little as 1 day with sustained response at 1 year in reducing the risk of colectomy following ASUC. EXPERT OPINION In the expert opinion, we discuss the challenges in the treatment of patients with ASUC. We summarize the data of current biologics and new small molecules and their emerging roles in the management of ASUC.
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Affiliation(s)
- Loren G Rabinowitz
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Ajay Gade
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Etchegaray A, Tambakis G, Kumar R, Croft A, Radford-Smith G, Walker GJ. Sequential rescue therapy with JAK inhibitors in corticosteroid and infliximab-refractory acute severe ulcerative colitis: a case series. Therap Adv Gastroenterol 2025; 18:17562848251323511. [PMID: 40166591 PMCID: PMC11956511 DOI: 10.1177/17562848251323511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 02/10/2025] [Indexed: 04/02/2025] Open
Abstract
Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency affecting over 20% of patients with ulcerative colitis (UC). Up to 40% of patients are refractory to intravenous corticosteroids (IVCS) and require rescue medical therapy or immediate colectomy. The potent Janus kinase (JAK) inhibitors, upadacitinib and tofacitinib, have proven efficacy in a randomised control trial setting for moderate-to-severe UC, but not ASUC. We describe a case series of sequential rescue therapy with JAK inhibitors following the failure of dose-intensified infliximab in corticosteroid-refractory ASUC. Six adult (>16 years old) patients received sequential rescue therapy with a JAK inhibitor (upadacitinib n = 5, tofacitinib n = 1) following failure of IVCS and dose-intensified infliximab at the Royal Brisbane and Women's Hospital (QLD, Australia) between October 2023 and April 2024. All patients met the Truelove and Witts criteria for ASUC on admission. Data were captured during admission and at 90-days post-discharge. Co-primary outcomes were 90-day colectomy-free survival and inpatient clinical response (<4 non-bloody stools per day) 72 h after JAK-inhibitor initiation. Secondary outcomes included 90-day clinical (PRO-2 score < 1) and biochemical (faecal calprotectin (FCP) < 150 µg/g and C-reactive protein (CRP) < 5 mg/L) corticosteroid-free remission and adverse events. Median CRP on admission was 100 mg/L (interquartile range (IQR) 58-105), median FCP 3400 µg/g (IQR 910-4950) and median Mayo Endoscopic Score 3. Four out of six patients had a clinical response within 72 h of sequential JAK-inhibitor rescue therapy. Two patients underwent emergent inpatient colectomy for refractory disease - one of whom developed post-operative sepsis. Among the four JAK-responders at 90 days, all achieved corticosteroid-free clinical remission and three achieved biochemical remission. No other adverse events were recorded. There is a promising role for JAK inhibitors as sequential rescue therapy following the failure of dose-intensified infliximab in select patients with corticosteroid-refractory ASUC.
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Affiliation(s)
| | - George Tambakis
- Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
- University of Queensland, Brisbane, QLD, Australia
| | - Rina Kumar
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Anthony Croft
- Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
- University of Queensland, Brisbane, QLD, Australia
| | - Graham Radford-Smith
- Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
- University of Queensland, Brisbane, QLD, Australia
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Gareth J. Walker
- Clinical Lead for IBD and Research, Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Herston, Brisbane QLD, 4029, Australia
- UQ Centre for Clinical Research (UQCCR), Faculty of Health, Medicine, and Behavioural Sciences, University of Queensland, Brisbane, QLD, 4006, Australia
- Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia
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Bergemalm D, Baban B, Ljungqvist O, Halfvarson J. Insulin sensitivity in moderately severe to acute severe ulcerative colitis. Scand J Gastroenterol 2025; 60:243-247. [PMID: 39882844 DOI: 10.1080/00365521.2025.2459870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 01/01/2025] [Accepted: 01/22/2025] [Indexed: 01/31/2025]
Abstract
BACKGROUND Patients hospitalized with moderately severe or acute severe ulcerative colitis (UC) may experience metabolic disturbances, including alterations in insulin resistance due to inflammation and the administration of glucocorticoids (GCs). This pilot study aimed to evaluate insulin sensitivity in patients hospitalized for moderately severe to severe UC. METHOD Patients hospitalized for moderately-severely active UC at Örebro University Hospital, Sweden, were eligible for inclusion. Quantification of insulin sensitivity was performed using the hyperinsulinemic euglycemic clamp (HEC) methodology. Assessment of insulin sensitivity was performed during both the index flare and while patients were in steroid-free clinical, biochemical and endoscopic remission during follow-up. Additionally, healthy controls were evaluated using HEC for comparison. RESULTS Five patients with moderately-severely active UC, treated with intravenous GCs for ≥2 days, were included and underwent HEC assessment. During the index flare, four patients received second-line treatment with infliximab due to non-response to GC, and one patient was subsequently referred for acute subtotal colectomy. At inclusion, all five patients exhibited significantly reduced insulin sensitivity, and levels appeared similar regardless of the outcome of the index flare. At remission during follow-up, the insulin sensitivity was restored to levels comparable to healthy controls (n = 5). CONCLUSION The study demonstrates that patients with moderately severe to severe UC experience significant insulin resistance, irrespective of the outcome of the flare. The reduced insulin sensitivity is likely driven by a combination of active inflammation and GC treatment, as insulin sensitivity returned to normal levels when patients achieved remission during follow-up.
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Affiliation(s)
- Daniel Bergemalm
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Bayar Baban
- Department of Surgery, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Olle Ljungqvist
- Department of Surgery, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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Meng MJ, Kuo CJ, Lai MW, Chiu CT, Su MY, Chang ML, Le PH. Advanced Combination Therapy with Biologics and Upadacitinib in Refractory Inflammatory Bowel Disease: A Retrospective Study from Taiwan. J Inflamm Res 2025; 18:2733-2742. [PMID: 40026313 PMCID: PMC11872097 DOI: 10.2147/jir.s511309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 02/15/2025] [Indexed: 03/05/2025] Open
Abstract
Background Refractory inflammatory bowel disease (IBD) remains challenging despite the availability of various biologics. Advanced combination therapy (ACT) with biologics and Upadacitinib (UPA), a rapid-onset oral selective Janus kinase inhibitor, has shown promise in managing refractory IBD. However, its use in Asia has not been explored. This study aims to fill that gap by providing data from Taiwan. Materials and Methods This retrospective study included refractory IBD patients who received ACT with biologics and UPA, followed up at the Chang Gung Inflammatory Bowel Disease Center from July 2020 to August 2024. Patients were assessed for clinical response and remission at weeks 4, 12, and 24. Safety profiles were monitored throughout the follow-up period to evaluate the risk of adverse events. Results Sixteen refractory IBD patients were enrolled. The median disease duration was 4.5 years [IQR 2.25-9.50]. The most common regimen was Ustekinumab plus UPA (63%). Clinical response rates at weeks 4, 12, and 24 were 88%, 83%, and 100%, respectively, while remission rates were 31%, 50%, and 80%. One patient (6.25%) experienced a minor adverse event (acne), with no major events like herpes zoster reactivation or major cardiac complications. Conclusion This is the first study in Asia to demonstrate that UPA-based ACT is both effective and safe in treating refractory IBD. However, the limitations of this retrospective, single-center study with a relatively small sample size highlight the need for future larger-scale, multi-center prospective studies to confirm these findings, identify predictors of treatment response, and evaluate long-term outcomes.
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Affiliation(s)
- Ming-Jung Meng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chia-Jung Kuo
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Taoyuan, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Wei Lai
- Chang Gung Inflammatory Bowel Disease Center, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Taoyuan, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Paediatric Gastroenterology, Chang Gung Children's Hospital, Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Taoyuan, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Yao Su
- Chang Gung Inflammatory Bowel Disease Center, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Taoyuan, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan
| | - Ming-Ling Chang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Taoyuan, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
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Pellegrino R, Imperio G, De Costanzo I, Izzo M, Landa F, Tambaro A, Gravina AG, Federico A. Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence. Pharmaceuticals (Basel) 2025; 18:308. [PMID: 40143087 PMCID: PMC11944803 DOI: 10.3390/ph18030308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/14/2025] [Accepted: 02/20/2025] [Indexed: 03/28/2025] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease in which one-quarter of patients are at risk of developing a severe form of the disease known as acute severe UC (ASUC). This condition exposes patients to serious complications, including toxic megacolon, surgical intervention, and even death. The current therapeutic strategy relies on time-dependent, multi-step algorithms that integrate systemic corticosteroids, calcineurin inhibitors, and biologic agents (specifically infliximab) as medical therapy aimed at avoiding colectomy. Despite this approach, a significant proportion of patients fail to respond to either corticosteroids or infliximab and may require alternative therapeutic options if there is no urgent surgical necessity. These alternatives include other biologics or emerging small molecules, although the evidence supporting these treatments remains extremely low, even considering their well-documented and promising efficacy and safety in moderate-to-severe UC. Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators.
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Affiliation(s)
- Raffaele Pellegrino
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, Italy
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Bourgonje AR, Posner H, Carbonnel F, Colombel JF, Kayal M. Prior Anti-TNF Exposure Is Associated with an Increased Risk of Short- and Long-Term Colectomy in Acute Severe Ulcerative Colitis. Dig Dis Sci 2025; 70:738-745. [PMID: 39746889 DOI: 10.1007/s10620-024-08809-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 12/17/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC. METHODS A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed. RESULTS We included 158 patients; 34 (21.5%) underwent colectomy during hospital admission and 41 (25.9%) within a year. On multivariable analysis, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P = 0.005), and biologic use at admission (OR 3.31, 95%CI 1.14-9.63, P = 0.028) were associated with an increased risk of 1-year colectomy. Conversely, mesalamine use at admission decreased this risk (OR 0.31, 95%CI 0.13-0.72, P = 0.006). Other risk factors included recent UC-related hospitalization (< 1 year of admission), higher bowel movement frequency after 3 days of treatment, low hemoglobin and albumin levels, and elevated CRP. Infliximab treatment was associated with decreased risk of urgent (OR 0.30, 95%CI 0.13-0.73, P = 0.007) and 1-year colectomy (OR 0.31, 95%CI 0.14-0.73, P = 0.007). CONCLUSION In patients with ASUC, prior anti-TNF exposure is linked to a higher risk of both short- and long-term colectomy, while recycling infliximab may reduce colectomy risk.
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Affiliation(s)
- Arno R Bourgonje
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
| | - Hannah Posner
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Franck Carbonnel
- Department of Gastroenterology, University Hospital of Bicêtre, Assistance Publique-Hôpitaux de Paris and Université Paris-Saclay, Le Kremlin Bicêtre, France
| | - Jean-Frédéric Colombel
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Maia Kayal
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
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Chaemsupaphan T, Arzivian A, Leong RW. Comprehensive care of ulcerative colitis: new treatment strategies. Expert Rev Gastroenterol Hepatol 2025. [PMID: 39865726 DOI: 10.1080/17474124.2025.2457451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 01/16/2025] [Accepted: 01/20/2025] [Indexed: 01/28/2025]
Abstract
INTRODUCTION Ulcerative colitis is a chronic inflammatory condition of the colon driven by aberrant immune activation. Although advanced medical therapies form the cornerstone of ulcerative colitis management, unmet needs include failure to induce and sustain remission in a substantial proportion of patients and in managing acute severe ulcerative colitis. We review new treatment strategies that might improve patient outcomes in the management of moderate-to-severe ulcerative colitis. AREAS COVERED A literature search was conducted using the PubMed database, including studies published from inception to October 2024, selected for their relevance. Recognizing current limitations, this article reviews strategies to improve treatment outcomes in ulcerative colitis using advanced therapies. These approaches include early treatment initiation, dose optimization, positioning newer agents as first-line therapies, combination therapy, targeting novel therapeutic endpoints, and the management of acute severe ulcerative colitis. EXPERT OPINION The strategies discussed may contribute to establishing new standards of care aimed at achieving long-term remission and enhancing patient outcomes. Personalized therapy, which tailors treatment based on individual disease characteristics and risk factors, is anticipated to become a critical aspect of delivering more effective care in the future.
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Affiliation(s)
- Thanaboon Chaemsupaphan
- Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Thailand
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Arteen Arzivian
- Department of Gastroenterology and Hepatology, St Vincent's Hospital, Sydney, Australia
| | - Rupert W Leong
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
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Narula N, Pray C, Hamam H, Peerani F, Hansen T, Bessissow T, Bressler B, Arun A, Schmit M, Castelli J, Marshall JK. Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management (The TRIUMPH Study). CROHN'S & COLITIS 360 2025; 7:otaf013. [PMID: 40092634 PMCID: PMC11906967 DOI: 10.1093/crocol/otaf013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Indexed: 03/19/2025] Open
Abstract
Background Tofacitinib is a rapidly acting Janus kinase (JAK) inhibitor with increasing evidence of effectiveness in patients with acute severe ulcerative colitis (ASUC). However, there are scarce prospective data analyzing the efficacy and rapidity of action in hospitalized ASUC. Methods The TRIUMPH study is a prospective open-label interventional trial of tofacitinib in hospitalized patients with ASUC conducted in 5 hospitals across Canada (Clinicaltrials.gov: NCT04925973). Eligible participants included biologic-naïve and experienced patients with ASUC refractory to 3 days of intravenous (IV) corticosteroids (Modified Truelove-Witts Severity Index [MTWSI] > 10 despite steroids). Participants were treated with tofacitinib 10 mg twice daily and assessed daily while in hospital. The primary outcome was day 7 clinical response (MTWSI reduction of > 3 from baseline and ≤ 10). Results Among 24 subjects, 33.3% (8/24) had previous anti-TNF failure. Day 7 clinical response was achieved in 58.3% (14/24). The mean number of days to achieve clinical response was 2.4 (SD 1.3). Marked reduction in C-reactive protein was observed in responders within the first two days after tofacitinib initiation compared to nonresponders. Colectomy occurred in 25% (6/24) by 6 months, with no additional colectomy beyond this time point. Five participants reported a total of 13 adverse events. Conclusions Tofacitinib is an effective rescue therapy in hospitalized patients with steroid-refractory ASUC. Randomized controlled trials are warranted to compare JAK inhibitors with other rescue therapies, including infliximab in steroid-refractory ASUC (Clinicaltrials.gov: NCT04925973).
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Affiliation(s)
- Neeraj Narula
- Department of Medicine, Division of Gastroenterology, McMaster University Medical Centre, Hamilton, ON, Canada
| | - Cara Pray
- Department of Medicine, Division of Gastroenterology, McMaster University Medical Centre, Hamilton, ON, Canada
| | - Hasan Hamam
- Department of Medicine, Division of Gastroenterology, McMaster University Medical Centre, Hamilton, ON, Canada
| | - Farhad Peerani
- Division of Gastroenterology, University of Alberta Hospital, Edmonton, AB, Canada
| | - Tawnya Hansen
- Department of Medicine, Division of Gastroenterology, Health Sciences Centre/University of Manitoba, Winnipeg, MB, Canada
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Center, Montreal, QC, Canada
| | - Brian Bressler
- Department of Medicine, Division of Gastroenterology, St. Paul’s Hospital/University of British Colombia, Vancouver, BC, Canada
| | - Arathi Arun
- Department of Medicine, Division of Gastroenterology, McMaster University Medical Centre, Hamilton, ON, Canada
| | - Maria Schmit
- Department of Medicine, Division of Gastroenterology, St. Paul’s Hospital/University of British Colombia, Vancouver, BC, Canada
| | - Jane Castelli
- Department of Medicine, Division of Gastroenterology, McMaster University Medical Centre, Hamilton, ON, Canada
| | - John K Marshall
- Department of Medicine, Division of Gastroenterology, McMaster University Medical Centre, Hamilton, ON, Canada
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Mishra S, Sekar A, Jena A, Prasad KK, Sachan A, Singh AK, Shah J, Mandavdhare HS, Singh H, Dutta U, Sharma V. Histological scores are poor predictors of short term outcomes in acute severe ulcerative colitis: An observational study. Dig Liver Dis 2025; 57:303-307. [PMID: 39389857 DOI: 10.1016/j.dld.2024.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 09/17/2024] [Accepted: 09/18/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND The role of various histologic scores in predicting outcomes in acute severe ulcerative colitis (ASUC) is unexplored. METHODS Consecutive patients of ASUC undergoing sigmoidoscopy and histological assessment by two independent pathologists for Simplified Geboes score (SGS), Robarts Histopathology Index (RHI) and Nancy histological index (NHI)] were included. Primary outcome was the role of histology in predicting need for second-line therapy or colectomy. RESULTS Of 82 patients with ASUC (mean age: 36 years, males 47.5 %), non-response to steroids was observed in 27 (32.9 %) of cases. Sixteen patients required second-line drug therapy and 8 required colectomy. There was no significant association between the need for second-line therapy or colectomy and the baseline histological scores [NHI (p = 0.61), SGS (p = 0.116) and RHI (p = 0.109)]. All three scores performed poorly to predict the need for second-line treatment or colectomy within 28 days. There was no significant association between histological scores and steroid response (NHI (p = 0.796), SGS (p = 0.57) and RHI (p = 0.941)]. All three scores had a strong positive correlation observed between each other but not with endoscopic Mayo score. CONCLUSION The three histologic scores (SGS, RHI and NHI) performed poorly in prediction of need for second-line treatment or colectomy in ASUC. Future studies should study the impact of histologic assessment on long term outcomes in ASUC.
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Affiliation(s)
- Shubhra Mishra
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Aravind Sekar
- Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Anuraag Jena
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Kaushal K Prasad
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Anurag Sachan
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Anupam Kumar Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Jimil Shah
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Harshal S Mandavdhare
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Harjeet Singh
- GI Surgery, HPB and Liver Transplantation, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Kotze PG, Honap S, Savio MC, Araújo RMM, Quaresma AB, Peyrin-Biroulet L. Acute severe ulcerative colitis: defining the precise moment for colectomy. Expert Rev Gastroenterol Hepatol 2025; 19:5-14. [PMID: 39753508 DOI: 10.1080/17474124.2024.2448451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 12/27/2024] [Indexed: 02/05/2025]
Abstract
INTRODUCTION Acute severe ulcerative colitis (ASUC) is a critical manifestation of ulcerative colitis (UC), often necessitating colectomy when medical management fails. Despite advancements in therapeutic interventions such as corticosteroids, biologics, and JAK inhibitors, a significant proportion of patients require surgery, with colectomy rates ranging from 10% to 15%. AREAS COVERED This paper reviews the factors influencing the timing and necessity of colectomy in ASUC management, emphasizing the importance of multidisciplinary decision-making involving gastroenterologists and surgeons. EXPERT OPINION Key surgical indications include failure of medical therapy, toxic megacolon, perforation, uncontrolled bleeding, and systemic deterioration. Delays in surgery can result in higher morbidity and mortality rates, making timely intervention essential. This review highlights surgical techniques, including total colectomy and end ileostomy, and discusses potential complications, urging a balanced approach to optimize patient outcomes.
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Affiliation(s)
- Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil
- IBD outpatient clinics, Cajuru University Hospital, Curitiba, Brazil
| | - Sailish Honap
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King's College London, London, UK
| | | | | | - Abel Botelho Quaresma
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil
- Department of Colorectal Surgery, Universidade do Oeste Catarinense (UNOESC), Joaçaba, Brazil
| | - Laurent Peyrin-Biroulet
- INFINY Institute, Department of Gastroenterology, CHRU Nancy, INSERM NGERE, Université de Lorraine, Vandœuvre-lès-Nancy, France
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15
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Pillay L, Selvarajah J, Andrew B, Christensen B, Macrae F, Segal JP. Future of Acute Severe Ulcerative Colitis-A Narrative Review. J Clin Med 2024; 13:7723. [PMID: 39768646 PMCID: PMC11678293 DOI: 10.3390/jcm13247723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 12/13/2024] [Accepted: 12/14/2024] [Indexed: 01/11/2025] Open
Abstract
While corticosteroids have led to significant reduction in ASUC mortality over the last few decades, they are associated with significant side effects and up to 30% of patients have steroid refractory ASUC, which means we require safer and better therapies for patients with ASUC. Several salvage therapies have been proposed in guidelines; however, we lack high quality head-to-head randomised controlled trials to assess effectiveness and safety of these agents. Furthermore, the role of newer novel agents in ASUC management is unclear. We aim to present an up to date review and envisage future treatment of ASUC without steroids based on current trials and data. In summary, we conclude that ASUC treatment still heavily relies on corticosteroids despite the side effect profile. While infliximab and cyclosporine have extensive data, there are no prospective studies comparing them with corticosteroids as initial therapy. Novel therapies open up the possibility of oral options but require prospective data before any conclusion can be made.
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Affiliation(s)
- Leshni Pillay
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne 3052, Australia
| | - Janakan Selvarajah
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne 3052, Australia
| | - Bridgette Andrew
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne 3052, Australia
| | - Britt Christensen
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville, Melbourne 3010, Australia
| | - Finlay Macrae
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville, Melbourne 3010, Australia
| | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville, Melbourne 3010, Australia
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Honap S, Jairath V, Sands BE, Dulai PS, Higgins PDR, De Cruz P, Gutiérrez A, Kotze PG, Ye BD, Kobayashi T, Gearry RB, Olivera PA, Amiot A, Mosli MH, Al Awadhi S, Halfvarson J, Patel KV, Sebastian S, Danese S, Peyrin-Biroulet L. Acute Severe Ulcerative Colitis: An International Delphi Consensus on Clinical Trial Design and Endpoints. Clin Gastroenterol Hepatol 2024:S1542-3565(24)01082-6. [PMID: 39681225 DOI: 10.1016/j.cgh.2024.10.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 10/09/2024] [Accepted: 10/10/2024] [Indexed: 12/18/2024]
Abstract
BACKGROUND & AIMS Interventional clinical trials in acute severe ulcerative colitis (ASUC) are characterized by substantial heterogeneity due to a lack of consensus in several key areas of trial design-this impedes clinical research efforts to identify novel therapies. The objective of this initiative was to achieve the first consensus and provide clear position statements on ASUC trial design. METHODS A modified Delphi consensus approach was employed with a panel of 20 clinicians with international representation and expertise in ASUC trial design and delivery. Agreement was defined as at least 75% of participants voting as "agree" with each statement. RESULTS In total, 30 statements achieved consensus and were approved. Statements centred on proposing suitable eligibility criteria (disease extent, disease severity, prior therapy exposure), optimizing trial design (randomization, stratification, corticosteroid handling, timing of assessments), and recommending primary and secondary endpoints alongside defining key efficacy outcomes (clinical and endoscopic response and remission, treatment failure, quality of life). CONCLUSIONS The expansion of drugs to treat moderate-severe ulcerative colitis over the past decade, particularly the rapidly acting Janus kinase inhibitors, is promising and has reignited the interest in identifying suitable therapeutic candidates for ASUC. Clinical trials in this high-risk population are challenging to conduct and this consensus provides a framework for future trials to advance drug development.
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Affiliation(s)
- Sailish Honap
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, Nancy, France; Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom; School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada; Lawson Health Research Institute, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Chicago, Illinois
| | - Peter D R Higgins
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health, Melbourne, Victoria, Australia; Department of Medicine (Austin Health), University of Melbourne, Melbourne, Victoria, Australia
| | - Ana Gutiérrez
- Department of Gastroenterology, Hospital General Universitario Dr Balmis de Alicante, Alicante, Spain; Instituto de Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Paulo G Kotze
- Colorectal Surgery Unit, Pontificia Universidade Católica do Paraná, Curitiba, Brazil
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand; Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Pablo A Olivera
- IBD Unit, Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigación Clínica, Buenos Aires, Argentina; Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
| | - Aurélien Amiot
- Department of Gastroenterology, Hôpitaux Universitaires Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris Saclay, Le Kremlin Bicêtre, France; Centre for Epidemiology and Population Health, INSERM, Université Paris Saclay, Villejuif, France
| | - Mahmoud H Mosli
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sameer Al Awadhi
- Digestive Diseases Unit, Rashid Hospital, Dubai, United Arab Emirates
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Kamal V Patel
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom
| | - Shaji Sebastian
- IBD Unit, Department of Gastroenterology, Hull University Teaching Hospitals, Hull, United Kingdom
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, INSERM NGERE, University of Lorraine, Nancy, France
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Fanizzi F, Allocca M, Fiorino G, Zilli A, Furfaro F, Parigi TL, Peyrin-Biroulet L, Danese S, D’Amico F. Raising the bar in ulcerative colitis management. Therap Adv Gastroenterol 2024; 17:17562848241273066. [PMID: 39600566 PMCID: PMC11589388 DOI: 10.1177/17562848241273066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 07/17/2024] [Indexed: 11/29/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by growing incidence and prevalence around the world in the last few decades. The range of available existing treatment and strategies for its management is being implemented. Given the introduction of newly developed molecules and the lack of specific guidelines, drug positioning may represent a tough clinical challenge. UC management is mostly medical, and it has been shifting toward a more personalized approach with the aim to create a tailored strategy depending on the patient's profile. A treat-to target strategy seems to be the best approach to reach disease control as it allows to carry out therapeutic choices based on objective and specific parameters: histological, ultrasonographic, and molecular targets may add to the already used clinical, endoscopic, and biochemical targets. In addition, dual-targeted therapy has emerged as an attractive therapeutic strategy for patients not achieving remission. This review aims to provide an overview of the available strategies to raise the bar in UC.
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Affiliation(s)
- Fabrizio Fanizzi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Mariangela Allocca
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Gionata Fiorino
- Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, Rome, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Furfaro
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré—Hartmann, Paris IBD Center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Via Olgettina 60, Milan 20132, Italy
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Liu X, Xue X, Zhu X, Liu J, Shi Y, Chen M. Corticosteroids combined with infliximab vs. corticosteroids sequential infliximab for acute severe ulcerative colitis with mucosal deficiency: a retrospective study. Front Med (Lausanne) 2024; 11:1442519. [PMID: 39635590 PMCID: PMC11614599 DOI: 10.3389/fmed.2024.1442519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 11/04/2024] [Indexed: 12/07/2024] Open
Abstract
Introduction Mucosal deficiency is one of the most challenging conditions in patients with acute severe ulcerative colitis (ASUC). Intravenous corticosteroids (CS) are the first-line treatment, with infliximab (IFX) used as a rescue therapy. However, the efficacy remains unsatisfactory. We investigated whether CS combined with IFX as first-line therapy would improve outcomes in patients with ASUC with mucosal deficiency. Methods A retrospective study was performed at a tertiary inflammatory bowel disease center. The primary outcomes included clinical remission, endoscopic improvement, and endoscopic remission at week 14. The secondary outcomes included the colectomy rate within 90 days and durable clinical remission. Results A total of 43 patients with ASUC with mucosal deficiency were included in the analysis (25 in the CS combined with the IFX group and 18 in the CS sequential IFX group). At week 14, endoscopic improvement was observed in 21 of 25 patients (84.0%) receiving the CS combined with the IFX regimen, compared to 9 of 18 (50.0%) patients receiving the CS sequential IFX regimen (p = 0.017). Durable clinical remission rates were significantly higher in the combined group than in the sequential group (85.7% vs. 35.7%, p = 0.004). There was no statistically significant difference between the two groups in terms of clinical and endoscopic remission at week 14 or colectomy rate within 90 days. Multivariate analysis confirmed that the CS combined with the IFX regimen was an independent predictive factor for a higher endoscopic improvement rate at week 14 (odds ratio (OR) 8.428, 95%confidence interval (CI) 1.539-46.153, p = 0.014) and a higher durable clinical remission rate (OR 10.800, 95%CI 2.095-55.666, p = 0.004). Conclusion CS combined with IFX as first-line therapy may be an effective induction strategy in patients with ASUC with mucosal deficiency. Further large-scale, multicenter prospective studies are needed.
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Affiliation(s)
- Xiaolei Liu
- Department of Medical Insurance, Xijing Hospital, Air Force Military Medical University, Xi’an, China
| | - Xianmin Xue
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, China
| | - Xiaojing Zhu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, China
| | - Jun Liu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, China
| | - Yongquan Shi
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, China
| | - Min Chen
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, China
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19
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Zheng J, Fan Z, Li C, Wang D, Zhang S, Chen R. Predictors for colectomy in patients with acute severe ulcerative colitis: a systematic review and meta-analysis. BMJ Open Gastroenterol 2024; 11:e001587. [PMID: 39542522 PMCID: PMC11575343 DOI: 10.1136/bmjgast-2024-001587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 10/15/2024] [Indexed: 11/17/2024] Open
Abstract
OBJECTIVES Acute severe ulcerative colitis (ASUC) poses challenges to patient management owing to its high surgical rate. This study aimed to identify predictors of colectomy in patients with ASUC. DESIGN This is a systematic review and meta-analysis. DATA SOURCES PubMed and Web of Science were searched up to April 2024. ELIGIBILITY CRITERIA Studies on the predictors of colectomy in adult patients with ASUC were eligible. DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted the data using a prespecified data collection sheet. A qualitative synthesis was performed in tabular form. Random-effect meta-analyses were conducted using OR and 95% CI. RESULTS Forty-two studies were included in the systematic review. The reported variables can be categorised into biomarkers, auxiliary examination findings, demographic and clinical characteristics, and drug factors. Through meta-analysis, albumin (OR 0.39 (95% CI 0.26 to 0.59) per 1 g/dL increment, I2=0.0%), high C reactive protein level (2.63 (1.53 to 4.52), I2=29.6%), high erythrocyte sedimentation rate level (2.92 (1.39 to 6.14), I2=0.0%), low haemoglobin level (2.08 (1.07 to 4.07), I2=56.4%), fulfilling the Oxford criteria (4.42 (2.85 to 6.84), I2=0.0%), extensive colitis (1.85 (1.24 to 2.78), I2=47.5%), previous steroids (1.75 (1.23 to 2.50), I2=17.7%) or azathioprine (2.25 (1.28 to 3.96), I2=0.0%) use, and sarcopenia (1.90 (1.04 to 3.45), I2=0.0%) were identified as valuable predictors for colectomy within 1 year. The ulcerative colitis endoscopic index of severity (OR 2.41 (95% CI 1.72 to 3.39), I2=1.5%) was the only predictor found to predict colectomy over 1 year. CONCLUSION Identification of these predictors may facilitate risk stratification of patients with ASUC, drive personalised treatment and reduce the need for colectomy.
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Affiliation(s)
- Jieqi Zheng
- Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zinan Fan
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Chao Li
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Daiyue Wang
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Shenghong Zhang
- Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Gastroenterology, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Nanning, China
| | - Rirong Chen
- Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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20
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Mundhra SK, Madan D, Golla R, Sahu P, Vuyyuru SK, Kante B, Kumar P, Mathew Thomas D, Prasad S, Vaishnav M, Verma M, Virmani S, Bajaj A, Markandey M, Ranjan MK, Arora U, Singh MK, Makharia GK, Ahuja V, Kedia S. Intravenous Albumin Infusion Does not Augment the Response Rate to a Combination of Exclusive Enteral Nutrition and Intravenous Steroids in Acute Severe Ulcerative Colitis: A Randomised Controlled Trial. J Crohns Colitis 2024; 18:1870-1878. [PMID: 38881153 DOI: 10.1093/ecco-jcc/jjae094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 05/31/2024] [Accepted: 06/15/2024] [Indexed: 06/18/2024]
Abstract
INTRODUCTION Overall, 30-40% patients with acute severe ulcerative colitis [ASUC] fail intravenous [IV] steroids, requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition [EEN] has been shown to improve steroid response and albumin levels. Albumin infusion, due to its anti-inflammatory and antioxidant properties, might further improve steroid response in ASUC, which was evaluated in the present study. METHODS In this open-label, randomised, controlled trial, patients with ASUC were randomised in 1:1 ratio to either albumin + standard of care [SOC] + EEN [Albumin arm] or SOC + EEN [SOC arm], over January 2021-February 2023. Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in the Albumin arm were administered 5 days of 20% weight/volume [w/v] intravenous albumin [100 ml]. Primary outcome was first, steroid failure [need for rescue medical therapy or colectomy] and second, proportion of patients with adverse events. RESULTS In all, 61 patients [albumin: 30, SOC: 31][mean age 31.6 ± 0.4 years, male 57.4%], were included. Baseline characteristics were comparable. There was no difference in steroid failure between Albumin and SOC arms (10/30 [33.33%] vs 13/31[41.94%], p = 0.49). No adverse events were reported with albumin infusions. Colectomy rate [10% vs 9.68%, p = 1], response to salvage medical therapy [88.89% vs 76.92%, p = 0.62] and median [interquartile range] duration of hospitalisation [10.5 [7-16] vs 10 [7-20], p = 0.43] were also comparable. The long-term composite outcome of colectomy and re-admission rates was numerically higher in the Albumin than the SOC arm [37.04% vs 17.86%, p > 0.05], although this did not reach statistical significance. CONCLUSION There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.
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Affiliation(s)
- Sandeep K Mundhra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Divya Madan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Rithvik Golla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - David Mathew Thomas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Shubham Prasad
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Manas Vaishnav
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mahak Verma
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Shubi Virmani
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Aditya Bajaj
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Manasvani Markandey
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Umang Arora
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh Kumar Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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21
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Abstract
Severe colitis is a well-defined condition encompassing several etiologies but is most often caused by severe ulcerative colitis or Clostridioides difficile infection. Severe colitis can evolve into toxic colitis, or toxic megacolon when associated with bowel dilation and systemic manifestations, resulting in a life-threatening scenario where multidisciplinary management is often required. Medical management continues to play an important role in the initial treatment of toxic megacolon. However, timely surgical intervention can be lifesaving.
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Affiliation(s)
- Marjorie R. Liggett
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Hasan B. Alam
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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22
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Choy MC, Li Wai Suen CFD, Con D, Boyd K, Pena R, Burrell K, Rosella O, Proud D, Brouwer R, Gorelik A, Liew D, Connell WR, Wright EK, Taylor KM, Pudipeddi A, Sawers M, Christensen B, Ng W, Begun J, Radford-Smith G, Garg M, Martin N, van Langenberg DR, Ding NS, Beswick L, Leong RW, Sparrow MP, De Cruz P. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9:981-996. [PMID: 39236736 DOI: 10.1016/s2468-1253(24)00200-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/18/2024] [Accepted: 06/18/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC. METHODS In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed. FINDINGS Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study. INTERPRETATION Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3. FUNDING Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag.
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Affiliation(s)
- Matthew C Choy
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia; Department of Medicine (Austin Health), University of Melbourne, Melbourne, VIC, Australia
| | - Christopher F D Li Wai Suen
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia; Department of Medicine (Austin Health), University of Melbourne, Melbourne, VIC, Australia
| | - Danny Con
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia; Department of Medicine (Austin Health), University of Melbourne, Melbourne, VIC, Australia
| | - Kristy Boyd
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
| | - Raquel Pena
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
| | - Kathryn Burrell
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
| | - Ourania Rosella
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
| | - David Proud
- Department of Colorectal Surgery, Austin Health, Melbourne, VIC, Australia
| | - Richard Brouwer
- Department of Colorectal Surgery, Austin Health, Melbourne, VIC, Australia
| | - Alexandra Gorelik
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Danny Liew
- Department of Medicine, University of Adelaide, Adelaide, SA, Australia
| | - William R Connell
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia
| | - Kirstin M Taylor
- Department of Gastroenterology, Alfred Health and Monash University, Melbourne, VIC, Australia
| | - Aviv Pudipeddi
- Department of Gastroenterology Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Michelle Sawers
- Department of Gastroenterology, Barwon Health, Geelong, VIC, Australia
| | - Britt Christensen
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, VIC, Australia
| | - Watson Ng
- Department of Gastroenterology, Liverpool Hospital, Sydney, NSW, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital, Brisbane, QLD, Australia
| | - Graham Radford-Smith
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Mayur Garg
- Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Gastroenterology, Northern Health, Melbourne, VIC, Australia
| | - Neal Martin
- Department of Gastroenterology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | | | - Nik S Ding
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia
| | - Lauren Beswick
- Department of Gastroenterology, Barwon Health, Geelong, VIC, Australia
| | - Rupert W Leong
- Department of Gastroenterology Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Miles P Sparrow
- Department of Gastroenterology, Alfred Health and Monash University, Melbourne, VIC, Australia
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia; Department of Medicine (Austin Health), University of Melbourne, Melbourne, VIC, Australia.
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23
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Chaaban L, Cohen B, Cross RK, Kayal M, Long M, Ananthakrishnan A, Melia J. Predicting Outcomes in Hospitalized Patients With Acute Severe Ulcerative Colitis in a Prospective Multicenter Cohort. Inflamm Bowel Dis 2024:izae193. [PMID: 39418122 DOI: 10.1093/ibd/izae193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND AND AIMS Acute severe ulcerative colitis (UC) (ASUC) requiring hospitalization affects up to 1 in 4 patients with UC. There is a paucity of prospective and multicenter clinical cohorts to study treatment trends and predictors of disease outcomes. Here, we conduct a US-based multicenter prospective clinical cohort of ASUC to study predictors of the need for medical rescue therapy and colectomy. METHODS A total of 94 patients hospitalized for ASUC were included across 5 academic centers from December 2018 to December 2021. Demographic, clinical, and laboratory data were collected throughout the hospitalization. Patients were followed up to 1-year post-hospitalization to identify predictors of the need for rescue therapy and colectomy. RESULTS A total of 21 (22.3%) patients required colectomy within 1 year of admission with 11 (12%) requiring colectomy during the index admission. On multivariate analyses, a BMI < 21.5 kg/m2 (OR = 6.16, P = .02), a simple clinical colitis activity index (SCCAI) greater than 8 (OR = 14.44, P = .01) and an albumin level at admission lower than 2.4 g/dL (OR = 10.61, P = .04) were significant predictors of inpatient colectomy after adjusting for sex, age, and duration of disease. CONCLUSIONS In a prospective, multicenter cohort of patients hospitalized with ASUC, BMI, SCCAI, and albumin at admission were important determinants of colectomy risk during the index hospitalization and within 1 year of admission. Colectomy rates remain high-22.3% in this cohort across 5 academic, tertiary care centers-underscoring the need to identify the highest-risk patients, establish novel treatment and care paradigms, and examine opportunities to standardize care.
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Affiliation(s)
- Lara Chaaban
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Benjamin Cohen
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Gastroenterology, Hepatology, & Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Raymond K Cross
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Maia Kayal
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Millie Long
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Ashwin Ananthakrishnan
- Crohn's and Colitis Center, Division of Gastroenterology and Hepatology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Joanna Melia
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Curci D, Lucafò M, Decorti G, Stocco G. Monoclonal antibodies against pediatric ulcerative colitis: a review of clinical progress. Expert Opin Biol Ther 2024; 24:1133-1144. [PMID: 39285823 DOI: 10.1080/14712598.2024.2404076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 09/10/2024] [Indexed: 09/21/2024]
Abstract
INTRODUCTION In children, ulcerative colitis (UC) is often more severe and extensive than in adults and hospitalization for acute exacerbations occurs in around a quarter of subjects. There is a need for effective drugs, which could avoid or reduce the use of corticosteroids which, especially in children, are burdened by a number of severe side effects. The introduction in therapy of monoclonal antibodies has completely changed the therapeutic scenario and the prognosis of the disease. AREAS COVERED In this review, the use of the monoclonal antibodies directed against tumor necrosis factor (TNF)α or other inflammatory targets for the treatment of pediatric UC will be discussed. A search of the literature was done using the keywords 'pediatric,' 'ulcerative colitis,' 'inflammatory bowel disease,' 'monoclonal antibodies;' 'infliximab,' 'adalimumab,' 'golimumab,' vedolizumab," 'ustekinumab' and 'risankizumab.' EXPERT OPINION The use of monoclonal antibodies has greatly increased in recent years in pediatric UC, both in patients who did not respond to conventional therapies, and, more often, as initial therapy. Thanks to therapeutic drug monitoring and to the availability of biologics with different targets, therapy has become more targeted and personalized, with a significant improvement in response, in quality of life, and with a good safety profile.
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Affiliation(s)
- Debora Curci
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy
| | - Marianna Lucafò
- Department of Life Sciences, University of Trieste, Trieste, Italy
| | - Giuliana Decorti
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
| | - Gabriele Stocco
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy
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Revés J, Bravo AC, Nascimento CN, Morão B, Frias-Gomes C, Roque Ramos L, Glória L, Torres J, Palmela C. Steroid-Refractory Acute Severe Ulcerative Colitis in Infliximab-Experienced Patients. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:314-324. [PMID: 39360172 PMCID: PMC11444699 DOI: 10.1159/000537693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 01/31/2024] [Indexed: 10/04/2024]
Abstract
Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis (UC) that can lead to significant morbidity and mortality, with a substantial number of patients needing colectomy. Infliximab (IFX) has been increasingly used as a rescue therapy for patients who have failed intravenous steroids and has been more frequently used as an induction and maintenance therapy in moderate-to-severe UC. Therefore, the number of patients admitted with ASUC previously exposed to IFX has been increasing, raising additional challenges in the medical management of these patients to avoid emergent colectomy. This narrative review intends to summarise the most recent evidence in the medical management of steroid-refractory ASUC patients previously exposed to IFX and to propose a treatment algorithm for approaching this difficult-to-treat group of patients.
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Affiliation(s)
- Joana Revés
- Gastroenterology Department, Hospital Beatriz Ângelo, Loures, Portugal
| | | | | | - Bárbara Morão
- Gastroenterology Department, Hospital Beatriz Ângelo, Loures, Portugal
| | | | - Lídia Roque Ramos
- Gastroenterology Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Luísa Glória
- Gastroenterology Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Joana Torres
- Gastroenterology Department, Hospital Beatriz Ângelo, Loures, Portugal
- Faculty of Medicine, University of Lisbon, Lisbon, Portugal
| | - Carolina Palmela
- Gastroenterology Department, Hospital Beatriz Ângelo, Loures, Portugal
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Suen CFDLW, Choy MC, Cruz PD. What to do when traditional rescue therapies fail in acute severe ulcerative colitis. Intest Res 2024; 22:397-413. [PMID: 38749658 PMCID: PMC11534448 DOI: 10.5217/ir.2024.00003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 03/15/2024] [Accepted: 03/22/2024] [Indexed: 06/12/2024] Open
Abstract
Acute severe ulcerative colitis (ASUC) is a medical emergency that affects approximately 25% of patients with ulcerative colitis at some point in time in their lives. Outcomes of ASUC are highly variable. Approximately 30% of patients do not respond to corticosteroids and up to 50% of patients do not respond to rescue therapy (infliximab or cyclosporin) and require emergency colectomy. Data are emerging on infliximab dosing strategies, use of cyclosporin as a bridge to slower acting biologic agents and Janus kinase inhibition as primary and sequential therapy. In this review, we outline contemporary approaches to clinical management of ASUC in the setting of failure to respond to traditional rescue therapies.
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Affiliation(s)
- Christopher F. D. Li Wai Suen
- Department of Gastroenterology, Austin Health, Melbourne, Australia
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Australia
| | - Matthew C. Choy
- Department of Gastroenterology, Austin Health, Melbourne, Australia
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Australia
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health, Melbourne, Australia
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Australia
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Kuriakose Kuzhiyanjal AJ, Limdi JK. Management of acute severe ulcerative colitis-an update for generalist and specialist clinicians. Br Med Bull 2024; 151:3-15. [PMID: 38823040 DOI: 10.1093/bmb/ldae006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 04/15/2024] [Accepted: 05/20/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND Acute severe ulcerative colitis (ASUC) is a potentially life-threatening medical emergency that occurs in up to 25% of patients with ulcerative colitis. Although intravenous corticosteroids remain the cornerstone of therapy, 30-40% of patients will not respond and need timely consideration of rescue therapy with (currently) either infliximab or ciclosporin or indeed colectomy, underscoring the importance of multidisciplinary care to ensure favourable outcomes for patients. We discuss the current evidence and present an approach to the management of ASUC for general and specialist clinicians caring for patients with ASUC. SOURCES OF DATA The information in this review is derived from data published in peer- reviewed academic journals and registered clinical trials. AREAS OF AGREEMENT Management of acute severe colitis requires a multidisciplinary approach with early initiation with steroids and timely escalation of treatment to either medical rescue therapy or surgery. AREAS OF CONTROVERSY Balancing the risks of delayed surgery vs. optimizing medical therapy, including accelerated dosing schedules for biologics, remains ambiguous. GROWING POINTS The position on newer molecules like Janus Kinase inhibitors, such as tofacitinib, is a growing area with early real-world data showing promise for steroid refractory ASUC. AREAS TIMELY FOR DEVELOPING RESEARCH Developing predictive biomarkers and clinical risk scores for personalized rescue therapy selection is an evolving area of research.
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Affiliation(s)
| | - Jimmy K Limdi
- Division of Gastroenterology-Section of IBD, Northern Care Alliance NHS Foundation Trust, Rochdale Old Rd, Bury, Manchester BL97TD, UK
- Manchester Academic Health Sciences, University of Manchester, Oxford Rd, Manchester M139PL, UK
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Honap S, Jairath V, Sands BE, Dulai PS, Danese S, Peyrin-Biroulet L. Acute severe ulcerative colitis trials: the past, the present and the future. Gut 2024; 73:1763-1773. [PMID: 38834296 PMCID: PMC11610420 DOI: 10.1136/gutjnl-2024-332489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 05/13/2024] [Indexed: 06/06/2024]
Abstract
Acute severe ulcerative colitis (ASUC), characterised by bloody diarrhoea and systemic inflammation, is associated with a significant risk of colectomy and a small risk of mortality. The landmark trial of cortisone in 1955 was pivotal for two reasons: first, for establishing the efficacy of a drug that remains a first-line therapy today and, second, for producing the first set of disease severity criteria and clinical trial endpoints that shaped the subsequent ASUC trial landscape. Trials in the 1990s and at the turn of the millennium established the efficacy of infliximab and ciclosporin, but since then, there has been little progress in drug development for this high-risk population. This systematic review evaluates all interventional randomised controlled trials (RCTs) conducted in patients hospitalised with severe UC. It provides an overview of the efficacy of treatments from past to present and assesses the evolution of trial characteristics with respect to study populations, eligibility criteria and study designs over time. This review details ongoing RCTs in this field and provides a perspective on the challenges for future clinical trial programmes and how these can be overcome to help deliver novel ASUC therapies.
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Affiliation(s)
- Sailish Honap
- King's College London, School of Immunology & Microbial Sciences, London, UK
- INFINY Institute, Nancy University Hospital Center, Vandœuvre-lès-Nancy, France
| | - Vipul Jairath
- Departments of Gastroenterology and Medicine, Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
- Departments of Epidemiology and Biostatistics, Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Evanston, Illinois, USA
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, San Raffaele Hospital, Milan, Italy
| | - Laurent Peyrin-Biroulet
- INFINY Institute, Nancy University Hospital Center, Vandœuvre-lès-Nancy, France
- Inserm NGERE U1256, University of Lorraine, Nancy, Vandœuvre-lès-Nancy, France
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Deputy M, Worley G, Burns EM, Bottle A, Aylin P, Hart A, Faiz O. Incidence of rectal cancer after colectomy for inflammatory bowel disease: nationwide study. BJS Open 2024; 8:zrae074. [PMID: 39404038 PMCID: PMC11474238 DOI: 10.1093/bjsopen/zrae074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 06/01/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease increases the risk of colorectal neoplasia. A particular problem arises in patients who have undergone subtotal colectomy leaving a rectal remnant. The risk of future rectal cancer must be accurately estimated and weighed against the risks of further surgery or surveillance. The aim of this study was to estimate the 10-year cumulative incidence of rectal cancer in such patients. METHODS A nationwide study using England's hospital administrative data was performed. A cohort of patients undergoing subtotal colectomy between April 2002 and March 2014 was identified. A competing risks survival analysis was performed to calculate the cumulative incidence of rectal cancer. The effect of the COVID-19 pandemic on endoscopic surveillance was investigated using time-trend analysis. RESULTS A total of 8120 patients were included and 61 patients (0.8%) were diagnosed with cancer. The cumulative incidence of rectal cancer was 0.26% (95% c.i. 0.17% to 0.39%), 0.49% (95% c.i. 0.36% to 0.68%), and 0.77% (95% c.i. 0.57% to 1.02%) at 5, 10, and 15 years respectively. A previous diagnosis of colonic dysplasia (HR 3.34, 95% c.i. 1.01 to 10.97; P = 0.047), primary sclerosing cholangitis (HR 5.42, 95% c.i. 1.34 to 21.85; P = 0.018), and elective colectomy (HR 1.83, 95% c.i. 1.11 to 3.02; P = 0.018) was associated with an increased incidence of rectal cancer. Regarding endoscopic surveillance, there was a 43% decline in endoscopic procedures performed in 2020 (333 procedures) compared with 2019 (585 procedures). CONCLUSION The incidence of rectal cancer after subtotal colectomy is low. Asymptomatic patients without evidence of rectal dysplasia should be carefully counselled on the possible benefits and risks of prophylactic proctectomy.
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Affiliation(s)
- Mohammed Deputy
- Surgical Epidemiology, Trials and Outcome Centre, St Mark’s Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Guy Worley
- Surgical Epidemiology, Trials and Outcome Centre, St Mark’s Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Elaine M Burns
- Surgical Epidemiology, Trials and Outcome Centre, St Mark’s Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Alex Bottle
- School of Public Health, Imperial College London, London, UK
| | - Paul Aylin
- School of Public Health, Imperial College London, London, UK
| | - Ailsa Hart
- Department of Surgery and Cancer, Imperial College London, London, UK
- Department of Gastroenterology, St Mark’s Hospital and Academic Institute, Harrow, UK
| | - Omar Faiz
- Surgical Epidemiology, Trials and Outcome Centre, St Mark’s Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
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Li Wai Suen CFD, Seah D, Choy MC, De Cruz P. Factors Associated With Response to Rescue Therapy in Acute Severe Ulcerative Colitis. Inflamm Bowel Dis 2024; 30:1389-1405. [PMID: 37725044 DOI: 10.1093/ibd/izad183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND Acute severe ulcerative colitis (ASUC) is a medical emergency for which colectomy is required in patients who do not respond to rescue therapy. While previous studies have predominantly focused on predicting outcome to first-line corticosteroid therapy, there is a need to understand the factors associated with response to rescue therapies in order to improve clinical outcomes. We reviewed the evidence regarding factors associated with response to rescue therapy in adults with ASUC and identified future directions for research. METHODS A systematic search of the literature was conducted, and 2 reviewers independently assessed studies for inclusion. RESULTS Of 3509 records screened, 101 completed studies were eligible for inclusion. We identified 42 clinical, hematological, biochemical, endoscopic, or pharmacological factors associated with response to rescue therapy. Older age (≥50 years), thiopurine experience, and cytomegalovirus or Clostridioides difficile infection were associated with a higher risk of nonresponse to rescue therapy. Biochemical factors associated with poorer response included an elevated C-reactive protein (CRP) ≥30mg/L on admission, hypoalbuminemia and an elevated ratio of CRP to albumin. Severe endoscopic findings, including a Mayo endoscopic score of 3 or Ulcerative Colitis Endoscopic Index of Severity ≥5, portended poorer outcomes. The role of fecal calprotectin and therapeutic value of measuring infliximab drug levels in ASUC remain to be defined. CONCLUSIONS Response to rescue therapy can be predicted by several specific factors, which would aid clinical decision-making. Existing and emerging factors should be integrated within predictive and prognostic models to help improve clinical outcomes.
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Affiliation(s)
- Christopher F D Li Wai Suen
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, VIC, Australia
| | - Dean Seah
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
| | - Matthew C Choy
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, VIC, Australia
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health, Melbourne, VIC, Australia
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, VIC, Australia
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Vuyyuru SK, Nardone OM, Jairath V. Predicting Outcome after Acute Severe Ulcerative Colitis: A Contemporary Review and Areas for Future Research. J Clin Med 2024; 13:4509. [PMID: 39124775 PMCID: PMC11312513 DOI: 10.3390/jcm13154509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/25/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
Acute Severe Ulcerative Colitis (ASUC) is a severe form of ulcerative colitis relapse which requires hospitalization and intensive medical intervention to avoid colectomy. The timely recognition of patients at risk of corticosteroid failure and the early initiation of medical rescue therapy are paramount in the management of ASUC. The choice of medical rescue therapy is influenced by multiple factors, especially patient's prior treatment history. This decision should involve the patient and ideally a multidisciplinary team of healthcare professionals, including gastroenterologists, radiologists, surgeons and enterostomal therapists. Although several predictive models have been developed to predict corticosteroid failure in ASUC, there is no single validated tool that is universally utilized. At present, infliximab and cyclosporine are the only agents systematically evaluated and recommended for medical rescue therapy, with recent reports of off-label utilization of tofacitinib and upadacitinib in small case series. The available evidence regarding the efficacy and safety of these oral small molecules for ASUC is insufficient to provide definitive recommendations. Early decision-making to assess the response to medical rescue therapy is essential, and the decision to pursue surgery in the case of treatment failure should not be delayed.
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Affiliation(s)
- Sudheer Kumar Vuyyuru
- Departments of Medicine, Division of Gastroenterology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada
| | - Olga Maria Nardone
- Gastroenterology, Department of Public Health, University Federico II of Naples, 80131 Naples, Italy
| | - Vipul Jairath
- Departments of Medicine, Division of Gastroenterology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada
- Division of Epidemiology and Biostatistics, Western University, London, ON N6A 5C1, Canada
- Lawson Health Research Institute, London, ON N6A 3K7, Canada
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Romaniuk F, Franus A, Sobolewska-Włodarczyk A, Gąsiorowska A. Clinical Utility of Disease Activity Indices in Predicting Short-Term Response to Biologics in Patients with Ulcerative Colitis. J Clin Med 2024; 13:3455. [PMID: 38929982 PMCID: PMC11204427 DOI: 10.3390/jcm13123455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 06/04/2024] [Accepted: 06/08/2024] [Indexed: 06/28/2024] Open
Abstract
Background: The Mayo Score [MS], endoscopic Mayo Score [eMS] and the Ulcerative Colitis Index of Severity [UCEIS] are employed in the assessment of ulcerative colitis [UC] severity. This study compared the aforementioned indices in terms of predictory value for response to remission induction treatment with anti-TNF and anti-integrin biologics. Methods: A total of 38 patients were retrospectively evaluated in the study, 23 male and 15 female, aged 18-74 years old who had undergone a total of 53 biological therapy courses with either infliximab [IFX] or vedolizumab [VDZ] at the Department of Gastroenterology of the Medical University of Łódź. The clinical and endoscopic activity of UC was assessed at the outset of biological therapy and the 14th week remission induction assessment juncture. Results: The study analyzed 19 IFX and 34 VDZ treatment courses. The response rate of patients receiving IFX reached 73.67% and the response rate was 58.82% for VDZ. The mean MS, eMS and UCEIS improved among all patient groups: 8.316 ± 1.974 to 4.158 ± 2.218 (p < 0.05), 2.632 ± 0.597 to 1.790 ± 0.713 (p < 0.05) and 4.790 ± 1.745 to 3.000 ± 1.453 (p < 0.05) for IFX, 7.088 ± 2.234 to 3.618 ± 2.412 (p < 0.05), 2.706 ± 0.524 to 1.677 ± 1.065 (p < 0.05) and 4.235 ± 1.350 to 2.735 ± 1.880 (p < 0.05) for VDZ. Conclusions: The outcome assessment in induction treatment of UC includes clinical data and endoscopic evaluation. Severity of inflammatory lesion activity according to the eMS and UCEIS indices correlates with the overall disease presentation as evaluated with MS. The UCEIS provides an overall better predictor for biological induction treatment when compared with the eMS in both patient groups, particularly in those receiving VDZ. It provides a promising alternative to the eMS and can be employed for both initial disease severity assessment as well as for treatment response monitoring.
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Parra-Izquierdo V, Frías-Ordoñez JS, Juliao-Baños F, Cuadros C, Romero Sanchez C, Flórez-Sarmiento C. Colombian experience with the use of tofacitinib in severe acute ulcerative colitis: A case series study. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:582-590. [PMID: 37806342 DOI: 10.1016/j.gastrohep.2023.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 10/01/2023] [Accepted: 10/02/2023] [Indexed: 10/10/2023]
Abstract
INTRODUCTION Tofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. MATERIALS AND METHODS Descriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. RESULTS Six patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. CONCLUSIONS Tofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.
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Affiliation(s)
- Viviana Parra-Izquierdo
- Gastroenterología y Reumatología, Hospital Internacional de Colombia, Bucaramanga, Colombia; Grupo de Inmunología Celular y Molecular (INMUBO), Universidad El Bosque, Bogotá, Colombia; Gastroadvanced IPS, Bogotá, Colombia
| | | | - Fabián Juliao-Baños
- Gastroenterología y Endoscopia Digestiva, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Carlos Cuadros
- Gastroenterología Pediátrica, Hospital Internacional de Colombia, Bucaramanga, Colombia
| | | | - Cristian Flórez-Sarmiento
- Grupo de Inmunología Celular y Molecular (INMUBO), Universidad El Bosque, Bogotá, Colombia; Gastroadvanced IPS, Bogotá, Colombia; Gastroenterología y Endoscopia Digestiva, Hospital Internacional de Colombia, Bucaramanga, Colombia
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Lelièvre O, Benoist S, Brouquet A. Indications, modalities, and outcomes of surgery for ulcerative colitis in 2024. J Visc Surg 2024; 161:182-193. [PMID: 38897710 DOI: 10.1016/j.jviscsurg.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
Treatment of ulcerative colitis (UC) has been revolutionized by the arrival of biotherapies and technical progress in interventional endoscopy and surgery. (Sub)total emergency colectomy is required in the event of complicated severe acute colitis: colectasis, perforation, hemorrhage, organ failure. Corticosteroid therapy is the reference treatment for uncomplicated severe acute colitis, while infliximab and ciclosporin are 2nd-line treatments. At each step, before and after each line of treatment failure, surgery should be considered as an option. In cases refractory to medical treatment, the choice between surgery and change in medication must weigh the chronic symptoms associated with the disease against the risks of postoperative complications and functional sequelae inherent to surgery. Detection of dysplastic lesions necessitates chromoendoscopic imaging with multiple biopsies and anatomopathological verification. Endoscopic treatment of these lesions remains reserved for selected patients. These different indications call for multidisciplinary medical-surgical discussion. Total coloproctectomy with ileo-anal anastomosis (TCP-IAA) is the standard surgery, and it holds out hope for healing. Modalities depend on patient characteristics, previous emergency colectomy, and presence of dysplasia. It may be carried out in one, in two modified, or in three phases. The main complications are anastomotic fistula, short-term pouch-related fistula, ileo-anal pouch syndrome, pouchitis and long-term digestive and sexual disorders. For selected cases, an alternative can consist in total colectomy with ileo-rectal anastomosis or permanent terminal ileostomy. The objective of this update is to clarify the indications, modalities, and results of surgical treatment of ulcerative colitis in accordance with the most recent data in the literature.
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Affiliation(s)
- Océane Lelièvre
- Department of oncologic and digestive surgery, Bicêtre Hospital, Assistance publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Paris-Saclay University, Paris, France
| | - Stéphane Benoist
- Department of oncologic and digestive surgery, Bicêtre Hospital, Assistance publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Paris-Saclay University, Paris, France
| | - Antoine Brouquet
- Department of oncologic and digestive surgery, Bicêtre Hospital, Assistance publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Paris-Saclay University, Paris, France.
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Ovesen PD, Attauabi M, Ilvemark JFKF, Wewer MD, Warren DJ, Burisch J, Klaasen RA, Bolstad N, Steenholdt C, Seidelin JB. Effects of prednisolone tapering on effectiveness of infliximab in patients with ulcerative colitis: data from a retrospective cohort. BMJ Open Gastroenterol 2024; 11:e001343. [PMID: 38719549 PMCID: PMC11085681 DOI: 10.1136/bmjgast-2024-001343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 04/17/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND AND OBJECTIVE The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. RESULTS There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. CONCLUSION In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy.
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Affiliation(s)
- Pernille Dige Ovesen
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital-Herlev and Gentofte, Herlev Hospital, Copenhagen, Denmark
| | - Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital-Herlev and Gentofte, Herlev Hospital, Copenhagen, Denmark
| | - Johan F K F Ilvemark
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital-Herlev and Gentofte, Herlev Hospital, Copenhagen, Denmark
| | | | - David J Warren
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | - Johan Burisch
- Gastrounit, Hvidovre Hospital Gastro Unit, Hvidovre, Denmark
| | - Rolf A Klaasen
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | - Nils Bolstad
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | - Casper Steenholdt
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital-Herlev and Gentofte, Herlev Hospital, Copenhagen, Denmark
| | - Jakob Benedict Seidelin
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital-Herlev and Gentofte, Herlev Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Kobenhavn, Denmark
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Stephens IJB, Murphy B, Burns L, McCawley N, McNamara DA, Burke JP. Contemporary perioperative outcomes after total abdominal colectomy for ulcerative colitis in a tertiary referral centre. Eur J Gastroenterol Hepatol 2024; 36:578-583. [PMID: 38489595 DOI: 10.1097/meg.0000000000002755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/17/2024]
Abstract
OBJECTIVE Colectomy for ulcerative colitis (UC) is common despite therapeutic advances. Post-operative morbidity and mortality demonstrate an association between hospital volumes and outcomes. This single-centre retrospective study examines outcomes after emergency colectomy for UC. METHODS Patient demographics, perioperative variables and outcomes were collected in Beaumont Hospital between 2010 and 2023. Univariant analysis was used to assess relationships between perioperative variables and morbidity and length of stay (LOS). RESULTS A total of 115 patients underwent total abdominal colectomy with end ileostomy for UC, 8.7 (±3.8) per annum. Indications were refractory acute severe colitis (88.7%), toxic megacolon (6.1%), perforation (4.3%), or obstruction (0.9%). Over 80% of cases were performed laparoscopically. Pre-operative steroid (93%) and biologic (77.4%) use was common. Median post-operative LOS was 8 days (interquartile range 6-12). There were no 30-day mortalities, and 30-day post-operative morbidity was 38.3%. There was no association between time to colectomy ( P = 0.85) or biologic use ( P = 0.24) and morbidity. Increasing age was associated with prolonged LOS ( P = 0.01). Laparoscopic approach (7 vs. 12 days P =0.01, 36.8% vs. 45% P = 0.66) was associated with reduced LOS and morbidity. CONCLUSION This study highlights contemporary outcomes after emergency colectomy for UC at a specialist high-volume, tertiary referral centre, and superior outcomes after laparoscopic surgery in the biologic era.
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Affiliation(s)
- Ian J B Stephens
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
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Bajaj A, Markandey M, Singh M, Sahu P, Vuyyuru SK, Kante B, Kumar P, Verma M, Makharia G, Kedia S, Travis SPL, Ahuja V. Exclusive Enteral Nutrition Mediates Beneficial Gut Microbiome Enrichment in Acute Severe Colitis. Inflamm Bowel Dis 2024; 30:641-650. [PMID: 37950921 DOI: 10.1093/ibd/izad232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Indexed: 11/13/2023]
Abstract
BACKGROUND Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters. METHODS Stool samples from patients with ASUC (n = 44) who received either EEN-supplemented SOC (EEN group; n = 20) or SOC alone (SOC group; n = 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages. RESULTS Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool. CONCLUSIONS Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC.
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Affiliation(s)
- Aditya Bajaj
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Manasvini Markandey
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh Singh
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Peeyush Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Mahak Verma
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Simon P L Travis
- Translational Gastroenterology Unit, University of Oxford and Oxford Biomedical Research Centre, Oxford, United Kingdom
- Kennedy Institute of Rheumatology, University of Oxford and Oxford Biomedical Research Centre, Oxford, United Kingdom
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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Miyatani Y, Micic D. Revisiting the Risk of Hospital Readmission in Severe Ulcerative Colitis. Inflamm Bowel Dis 2024; 30:688-689. [PMID: 37682866 DOI: 10.1093/ibd/izad212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Indexed: 09/10/2023]
Affiliation(s)
- Yusuke Miyatani
- Inflammatory Bowel Disease Center, Section of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Chicago Medicine, University of Chicago, Chicago, IL, USA
| | - Dejan Micic
- Inflammatory Bowel Disease Center, Section of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Chicago Medicine, University of Chicago, Chicago, IL, USA
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39
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Ochoa B, McMahon L. Surgery for ulcerative colitis. Semin Pediatr Surg 2024; 33:151404. [PMID: 38615424 DOI: 10.1016/j.sempedsurg.2024.151404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
Ulcerative colitis (UC) has a more severe presentation and rapid progression in pediatric patients, resulting in a greater need for surgical intervention compared to adults. Though medical management of UC has advanced with new biologic therapies, surgery continues to play an important role when disease progresses in the form of worsened or persistent symptoms, hemodynamic instability, or sepsis. The goals of surgical management are to restore intestinal continuity with a functional pouch when possible. While the literature has been growing regarding studies of pediatric patients with UC, high level of evidence studies are limited and most recommendations are based on adult studies. Similar to adults, pediatric patients who have ileal pouches created require surveillance for recurrent disease and cancer surveillance. Unique issues for pediatric patients include monitoring of growth and appropriate transition to adult care after adolescence. This review includes indications for surgical management, overview of staged surgical approaches, and the technical details of the three-stage approach.
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Affiliation(s)
- Brielle Ochoa
- Division of Pediatric Surgery, Department of Surgery, Phoenix Children's, Phoenix, Arizona, USA
| | - Lisa McMahon
- Division of Pediatric Surgery, Department of Surgery, Phoenix Children's, Phoenix, Arizona, USA.
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Alomari M, Chadalavada P, Afraz S, AlGhadir-AlKhalaileh M, Suarez ZK, Swartz A, Rashid M, Khazaaleh S, Cohen BL, Ur Rahman A, Alomari M. Post-hospitalization Short Versus Long Steroid Taper Strategies in Patients With Acute Severe Ulcerative Colitis: A Comparison of Clinical Outcomes. CROHN'S & COLITIS 360 2024; 6:otae025. [PMID: 38711857 PMCID: PMC11071514 DOI: 10.1093/crocol/otae025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Indexed: 05/08/2024] Open
Abstract
Background Ulcerative colitis (UC) is a chronic inflammatory colon disease characterized by relapsing flares and remission episodes. However, the optimal steroid tapering strategy in patients hospitalized for acute severe UC (ASUC) remains relatively unknown. We aim to examine the clinical outcomes in patients hospitalized for ASUC regarding variable prednisone taper regimens upon discharge. Methods We retrospectively reviewed all adult patients admitted to our facility with ASUC between 2000 and 2022. Patients were divided into 2 groups based on the duration of steroid taper on discharge (< 6 and > 6 weeks). Patients who had colectomy at index admission were excluded from the analysis. The primary outcome was rehospitalization for ASUC within 6 months of index admission. Secondary outcomes included the need for colectomy, worsening endoscopic disease extent and/or severity during the follow-up period (6 months), and a composite outcome as a surrogate of worsening disease (defined as a combination of all products above). Two-sample t-tests and Pearson's chi-square tests were used to compare the means of continuous and categorical variables, respectively. Multivariate logistic regression analysis was performed to identify independent predictors for rehospitalization with ASUC. Results A total of 215 patients (short steroid taper = 91 and long steroid taper = 124) were analyzed. A higher number of patients in the long steroid taper group had a longer disease duration since diagnosis and moderate-severe endoscopic disease activity (63.8 vs. 25.6 months, p < 0.0001, 46.8% vs. 23.1%, P = ≤ .05, respectively). Both groups had similar disease extent, prior biologic therapy, and the need for inpatient rescue therapy. At the 6-month follow-up, rates of rehospitalization with a flare of UC were comparable between the 2 groups (68.3% vs. 68.5%, P = .723). On univariate and multivariate logistic regression, escalation of steroid dose within four weeks of discharge (aOR 6.09, 95% CI: 1.82-20.3, P = .003) was noted to be the only independent predictor for rehospitalization with ASUC. Conclusions This is the first study comparing clinical outcomes between post-discharge steroid tapering regimens in hospitalized patients for ASUC. Both examined steroid taper regimens upon discharge showed comparable clinical results. Hence, we suggest a short steroid taper as a standard post-hospitalization strategy in patients following ASUC encounters. It is likely to enhance patient tolerability and reduce steroid-related adverse effects without adversely affecting outcomes.
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Affiliation(s)
- Mohammad Alomari
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Pravallika Chadalavada
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
| | - Sadaf Afraz
- Internal Medicine Department, Cleveland Clinic Florida, Weston, FL, USA
| | | | - Zoilo K Suarez
- Internal Medicine Department, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, USA
| | - Alec Swartz
- Internal Medicine Department, Cleveland Clinic Florida, Weston, FL, USA
| | - Mamoon Rashid
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
| | - Shrouq Khazaaleh
- Internal Medicine Department, Cleveland Clinic Fairview Hospital, Cleveland, OH, USA
| | - Benjamin L Cohen
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Asad Ur Rahman
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
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Rivière P, Li Wai Suen C, Chaparro M, De Cruz P, Spinelli A, Laharie D. Acute severe ulcerative colitis management: unanswered questions and latest insights. Lancet Gastroenterol Hepatol 2024; 9:251-262. [PMID: 38340753 DOI: 10.1016/s2468-1253(23)00313-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 08/30/2023] [Accepted: 09/05/2023] [Indexed: 02/12/2024]
Abstract
Acute severe ulcerative colitis (ASUC) is a distinctive ulcerative colitis flare presentation characterised by the presence of systemic inflammation as well as bloody diarrhoea, and occurs at least once in 25% of patients with ulcerative colitis during their disease course. Each episode carries a risk of complications, need for colectomy, and mortality. Little is known about ASUC pathogenesis, although impaired host-microbiota crosstalk involving pathobionts is suspected. In this Review, we discuss unanswered questions and results from the latest research on the medical-first-line, second-line, and potential third-line therapies-and surgical management of ASUC. We detail promising options for management, such as the use of enteral nutrition in combination with intravenous steroids, the ability to predict early failure of first-line or second-line therapies, and the emerging role of JAK inhibitors. An optimal framework to personalise therapy on the basis of multiomics tools is yet to be developed.
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Affiliation(s)
- Pauline Rivière
- CHU de Bordeaux, Centre Medico-Chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Christopher Li Wai Suen
- Department of Gastroenterology, Austin Health and Department of Medicine, Austin Academic Centre, The University of Melbourne, Melbourne, VIC, Australia
| | - María Chaparro
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain; Universidad Autonoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health and Department of Medicine, Austin Academic Centre, The University of Melbourne, Melbourne, VIC, Australia
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Milan Italy; Colon and Rectal Surgery Division, IRCCS Humanitas Research Hospital, Milan, Italy
| | - David Laharie
- CHU de Bordeaux, Centre Medico-Chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France.
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42
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Vuyyuru SK, Jairath V. Unresolved challenges in acute severe ulcerative colitis. Indian J Gastroenterol 2024; 43:9-14. [PMID: 38189896 DOI: 10.1007/s12664-023-01503-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Affiliation(s)
| | - Vipul Jairath
- Departments of Medicine, Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON, N6A 3K7, Canada.
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AbdelMeguid AMA, Whitehead E, Sebastian S. Modern practical management of acute severe colitis. Indian J Gastroenterol 2024; 43:78-92. [PMID: 38407787 DOI: 10.1007/s12664-024-01522-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 12/28/2023] [Indexed: 02/27/2024]
Abstract
Acute severe ulcerative colitis (ASUC) is one of life-threatening complications that occur in one-fifth of ulcerative colitis (UC) patients with significant morbidity and an estimated mortality rate up to 1%. There are no validated clinical scoring systems for ASUC. Intravenous corticosteroids remain the cornerstone for the management of ASUC patients However, one-third of patients are steroid refractory and require colectomy in the pre-biologic era or salvage therapy in the post-biologic era. The currently available predictors of non-response to steroids and salvages therapy are sub-optimal. Furthermore, there is a need for the development of clear outcome measures for ASUC patients. Although infliximab and cyclosporin are both effective as salvage therapy, they still carry a rate of treatment failure. Hence, there is an unmet need to explore alternative therapeutic options before colectomy particularly in prior infliximab-exposed patients. This may include the introduction of small molecules with rapid onset of action as a salvage or sequential therapy and the use of slow-onset other biological therapy after "bridging" with cyclosporine. In this article, we explore the current best evidence-based practice and detail the gaps in knowledge in the management of ASUC.
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Affiliation(s)
| | - Emma Whitehead
- IBD Unit, Hull University Teaching Hospitals, Hull, HU3 2JZ, UK
| | - Shaji Sebastian
- IBD Unit, Hull University Teaching Hospitals, Hull, HU3 2JZ, UK.
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44
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Kayal M, Colombel JF. Letter: 'No first among equals'-Authors' reply. Aliment Pharmacol Ther 2024; 59:145. [PMID: 37933427 DOI: 10.1111/apt.17806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2023]
Abstract
LINKED CONTENTThis article is linked to Kayal et al papers. To view these articles, visit https://doi.org/10.1111/apt.17731 and https://doi.org/10.1111/apt.17792
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Affiliation(s)
- Maia Kayal
- The Henry D. Janowitz Division of Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jean Frederic Colombel
- The Henry D. Janowitz Division of Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Vitali F, Rath T, Klenske E, Vögele AL, Ganzleben I, Zundler S, Strobel D, Geppert C, Hartmann A, Neurath MF, Atreya R. Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis. Therap Adv Gastroenterol 2023; 17:17562848231218555. [PMID: 38164363 PMCID: PMC10757791 DOI: 10.1177/17562848231218555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 11/14/2023] [Indexed: 01/03/2024] Open
Abstract
BACKGROUND Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin induction therapy. OBJECTIVES We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC. DESIGN Monocentric, prospective study. METHODS We included patients with steroid refractory ASUC with multiple failed prior advanced therapies, who were treated with cyclosporin and ustekinumab combination therapy. RESULTS Among the 11 included patients, 10 had prior failure to infliximab and 8 failed at least three previous biological therapies. The mean baseline Mayo and Lichtiger scores were 10.9 (9-12) and 13.3 (11-14), respectively. Ustekinumab was initiated 3.2 weeks (1-8) after initiation of cyclosporin treatment and combination therapy was continued for a mean of 11.5 (4-20) weeks. Clinical response was achieved in six patients at week 16 and clinical steroid-free clinical remission in five patients at week 48. Endoscopic remission was achieved in five patients at week 16 and together with histological remission in five patients at week 52. Intestinal ultrasound demonstrated mean bowel wall thickening in the sigmoid colon of 5.5 mm at baseline and 3.5 mm at week 52, respectively. Two patients had to undergo colectomy (mean 4.5 months, range 3-6) and three stopped ustekinumab therapy due to ineffectiveness. Overall, combination therapy was well tolerated. CONCLUSION Combination of cyclosporin and ustekinumab therapy allowed nearly half of ASUC patients to reach clinical and endoscopic remission after 52 weeks, warranting further studies. TRIAL REGISTRATION Not applicable.
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Affiliation(s)
- Francesco Vitali
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Timo Rath
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Entcho Klenske
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Anna-Lena Vögele
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Ingo Ganzleben
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Sebastian Zundler
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Deike Strobel
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Carol Geppert
- Institute of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Arndt Hartmann
- Institute of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Markus F. Neurath
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Ulmenweg 18, Erlangen 91054, Germany
- Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
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Gilmore R, Tan WL, Fernandes R, An YK, Begun J. Upadacitinib Salvage Therapy for Infliximab-Experienced Patients with Acute Severe Ulcerative Colitis. J Crohns Colitis 2023; 17:2033-2036. [PMID: 37422724 PMCID: PMC10798861 DOI: 10.1093/ecco-jcc/jjad115] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Indexed: 07/10/2023]
Abstract
BACKGROUND AND AIMS Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab. METHODS Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes. RESULTS All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified. CONCLUSIONS Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.
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Affiliation(s)
- Robert Gilmore
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Department of Medicine, University of Queensland, Brisbane, Australia
- Mater Research Institute, Brisbane, Australia
| | - Wei Lian Tan
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
| | - Richard Fernandes
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Department of Medicine, University of Queensland, Brisbane, Australia
- Mater Research Institute, Brisbane, Australia
| | - Yoon-Kyo An
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Department of Medicine, University of Queensland, Brisbane, Australia
- Mater Research Institute, Brisbane, Australia
- Mater Private Hospital, Brisbane, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Department of Medicine, University of Queensland, Brisbane, Australia
- Mater Research Institute, Brisbane, Australia
- Mater Private Hospital, Brisbane, Australia
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Barchi A, Dal Buono A, D’Amico F, Furfaro F, Zilli A, Fiorino G, Parigi TL, Peyrin-Biroulet L, Danese S, Allocca M. Leaving behind the Mucosa: Advances and Future Directions of Intestinal Ultrasound in Ulcerative Colitis. J Clin Med 2023; 12:7569. [PMID: 38137644 PMCID: PMC10744120 DOI: 10.3390/jcm12247569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/27/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
Inflammatory Bowel Diseases (IBD), mainly Ulcerative Colitis (UC) and Crohn's Disease (CD), are disorders characterized by chronic inflammation with severe morbidity and long-term disabling quality of life outcomes. UC mainly affects the mucosal and sub-mucosal layers of the colon, without embracing the peri-intestinal structures. Considering the predominant mucosal location of UC inflammation, the implementation of transmural evaluation by cross-sectional imaging techniques, mainly Intestinal Ultrasound (IUS), has been left behind for ages, especially if compared to CD. Nevertheless, studies analyzing intestinal ultrasound parameters accuracy in disease activity detection reported a good-to-optimal correlation of IUS markers with colonic inflammation, suggesting comparable feasibility of IUS monitoring in UC as in CD. The easy-to-use, costless and point-of-care available status of IUS is therefore crucial in order to improve the diagnostic process and, according to the recent literature, to monitor the response to treatment leading to speeding up decision making and therapy adjustments. Recent studies have demonstrated the correlation between transmural healing in UC with favorable outcomes even in the long term. An evidence gap still exists in the assessment of the rectum, with trans-perineal ultrasound (TPUS) a potential answer to reach a more precise evaluation of rectal inflammation. Eventually, IUS is also increasingly showing promises in emergent or post-surgical UC settings, considering various efforts put in line to demonstrate its feasibility in predicting response to salvage therapy for surgery avoidance and in studying inflammation relapse after procto-colectomy with ileo-pouch-anal anastomosis (IPAA) creation.
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Affiliation(s)
- Alberto Barchi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
| | - Arianna Dal Buono
- IBD Center, Humanitas Research Hospital-IRCCS, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Federica Furfaro
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
| | - Gionata Fiorino
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, 54500 Vandoeuvre-lès-Nancy, France;
- Department of Gastroenterology, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- INFINY Institute, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- Federation Hospitalo-Univeristaire-CURE, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré-Hartmann, Paris IBD Center, 92200 Neuilly-sur-Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
| | - Mariangela Allocca
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.B.); (F.D.); (F.F.); (A.Z.); (G.F.); (S.D.)
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Naganuma M, Kobayashi T, Kunisaki R, Matsuoka K, Yamamoto S, Kawamoto A, Saito D, Nanki K, Narimatsu K, Shiga H, Esaki M, Yoshioka S, Kato S, Saruta M, Tanaka S, Yasutomi E, Yokoyama K, Moriya K, Tsuzuki Y, Ooi M, Fujiya M, Nakazawa A, Abe T, Hisamatsu T. Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis. J Gastroenterol 2023; 58:1198-1210. [PMID: 37831183 DOI: 10.1007/s00535-023-02048-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 09/25/2023] [Indexed: 10/14/2023]
Abstract
BACKGROUND This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). METHODS In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. RESULTS Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. CONCLUSION Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.
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Affiliation(s)
- Makoto Naganuma
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan
| | - Shojiro Yamamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Ami Kawamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Daisuke Saito
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
| | - Kosaku Nanki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kazuyuki Narimatsu
- Department of Internal Medicine, National Defence Medical University, Tokorozawa, Japan
| | - Hisashi Shiga
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Shinichiro Yoshioka
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Shingo Kato
- Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Shinji Tanaka
- Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Eriko Yasutomi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Kaoru Yokoyama
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Kei Moriya
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Yoshikazu Tsuzuki
- Department of Gastroenterology, Saitama Medical University, Saitama, Japan
| | - Makoto Ooi
- Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| | - Atsushi Nakazawa
- Department of Gastroenterology, Saiseikai General Hospital, Tokyo, Japan
| | - Takayuki Abe
- School of Data Science, Yokohama City University, Yokohama, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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Angkeow J, Rothman A, Chaaban L, Paul N, Melia J. Systematic Review: Outcome Prediction in Acute Severe Ulcerative Colitis. GASTRO HEP ADVANCES 2023; 3:260-270. [PMID: 39129959 PMCID: PMC11307437 DOI: 10.1016/j.gastha.2023.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 11/06/2023] [Indexed: 08/13/2024]
Abstract
Background and Aims Approximately 1 in 4 patients with ulcerative colitis experiences a severe exacerbation of disease requiring hospitalization, termed acute severe ulcerative colitis (ASUC). These episodes pose a major burden on patients with ulcerative colitis and early prediction of their outcomes based on clinical data is crucial to optimize therapy. Methods A systematic review was performed using Embase and Medline for articles between 2000 and 2023. Studies obtained from the databases were uploaded on Covidence for screening by 2 independent reviewers. Quality appraisal for each study was done using the Critical Appraisals Skills Program depending on study design. Results A total of 48 eligible studies were included in the review. The key predictors of ASUC identified in this review included clinical, endoscopic, and radiographic biomarkers, which were summarized. The main outcomes assessed in the studies were intravenous corticosteroid failure, need for rescue therapy, and need for colectomy. Score-based predictions and some novel markers were also included in the results. Conclusion Utilization of evidence-based predictors of outcome in ASUC could serve as a powerful tool in customizing therapeutic measures and a step forward toward personalized patient care. Despite promising candidates, there remains a significant opportunity to identify and test additional clinical and laboratory-based predictors, especially early in the hospitalization and as the clinical practice and medical therapies evolve.
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Affiliation(s)
- Julia Angkeow
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Alissa Rothman
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Lara Chaaban
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nicole Paul
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joanna Melia
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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50
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Croft NM, Korczowski B, Kierkuś J, Caballero B, Thakur MK. Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind study. EClinicalMedicine 2023; 65:102232. [PMID: 37855022 PMCID: PMC10579284 DOI: 10.1016/j.eclinm.2023.102232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 09/06/2023] [Accepted: 09/07/2023] [Indexed: 10/20/2023] Open
Abstract
Background Previous studies have demonstrated the tolerability and efficacy of multimatrix mesalamine in inducing and maintaining remission in adults with mild-to-moderate ulcerative colitis (UC). We evaluated the safety and efficacy of low-dose and high-dose once-daily multimatrix mesalamine in children and adolescents with mild-to-moderate UC or those in remission. Methods This prospective, randomised, parallel-group, phase 3 study (8-week double-blind acute [DBA] phase; 26-week double-blind maintenance [DBM] phase; and an additional 8-week, open-label acute [OLA] phase) was conducted in 33 sites across North America, Europe, and the Middle East between December 12, 2014, and November 28, 2018. Eligible patients aged 5-17 years and weighing 18-90 kg were randomised 1:1 to either low (900-2400 mg) or high (1800-4800 mg) oral doses of multimatrix mesalamine once daily, stratified by body weight. Interactive response technology was used for randomisation. The primary efficacy outcome was to estimate the clinical response of multimatrix mesalamine (two doses) in different weight groups. Efficacy and safety analyses were conducted in the safety analysis set (Clinicaltrials.gov: NCT02093663; Study completed). Findings Overall, 107 patients were randomised into the DBA (n = 54) or DBM phase (n = 88; directly or after completing the double-blind or OLA phases); the overall safety analysis set included 105 patients. In the DBA phase, the high-dose group (n = 17; 65.4%) achieved a higher clinical response rate than the low-dose (n = 10; 37.0%) group; difference 28.3% (95% CI: 2.5-54.2; p = 0.039), odds ratio (OR) 3.21 (95% CI: 1.04-9.88). In the DBM phase at Week 26, similar proportions of patients maintained clinical response in the low-dose (n = 23; 54.8%) and high-dose (n = 24; 53.3%) groups: OR 0.99 (0.42-2.34); p = 0.981. Overall, 246 treatment-emergent adverse events (TEAEs) were reported in 73 patients (69.5%); 23 TEAEs in 14 patients (13.3%) were considered related to the study drug. No treatment-related deaths were reported. Interpretation Our findings suggested that the benefit-risk ratio of once-daily multimatrix mesalamine in paediatric patients was favourable and comparable with that reported in adults with mild-to-moderate UC. Funding Shire Development LLC, a Takeda company.
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Affiliation(s)
- Nicholas Michael Croft
- Faculty of Medicine, Blizard Institute, Queen Mary University of London, London, UK
- Paediatric Gastroenterology, Royal London Children’s Hospital, Barts Health NHS Trust, London, UK
| | - Bartosz Korczowski
- Department of Pediatrics and Pediatric Gastroenterology, College of Medical Sciences, University of Rzeszów, Rzeszów, Poland
| | - Jarosław Kierkuś
- Department of Gastroenterology, Hepatology and Feeding Disorders, Children’s Memorial Health Institute, Warsaw, Poland
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