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Chaemsupaphan T, Pudipeddi A, Lin H, Paramsothy S, Kariyawasam V, Kermeen M, Leong RW. Development and Validation of a Scoring System to Predict 2-Year Clinical Remission in Ulcerative Colitis Patients on Vedolizumab. CROHN'S & COLITIS 360 2025; 7:otae068. [PMID: 39760127 PMCID: PMC11700619 DOI: 10.1093/crocol/otae068] [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: 10/03/2024] [Indexed: 01/07/2025] Open
Abstract
Background and Aims Vedolizumab is s gut-selective advanced therapy that is safe and efficacious for the treatment of ulcerative colitis (UC). Once patients achieve successful induction, there is a risk of loss of response leading to eventual flare. We aimed to identify these predictive factors and develop a practical scoring system to determine the ongoing efficacy of vedolizumab. Methods We performed logistic regression on prospectively recruited UC subjects from the Vedolizumab Immunomodulator Enforced Withdrawal Study (VIEWS). All patients were in corticosteroid-free clinical remission and endoscopic improvement at baseline and continued vedolizumab. Predictive factors of 2-year corticosteroid-free clinical remission were determined and modeled into the VIEWS score, then validated in a real-world UC cohort. Results Of 62 patients in the derivation cohort, 48 (77.4%) maintained clinical remission over two years. The predictive factors of remission were female (odds ratio [OR] 6.0, 95% confidence interval [CI], 1.2-29.7), antitumor necrosis factor naive (OR 3.8, 95% CI,1.0-14.0), baseline histological remission (OR 10.8, 95% CI, 2.4-48.4), thiopurine combination (OR 3.6, 95% CI, 0.7-18.0), and fecal calprotectin level ≤250 µg/g (OR 6.3, 95% CI, 0.9-42.2). These factors were incorporated into VIEWS score, yielding an area under the receiver-operating characteristic (AUROC) curve of 0.89 (95% CI, 0.81-0.98) in the prediction of 2-year clinical remission. Of 64 UC patients in the validation cohort, 40 (62.5%) remained in clinical remission at 2 years with AUROC of 0.77 (95% CI, 0.60-0.94). At the cut-off threshold of 4, the VIEWS score identified 2-year clinical remission with a sensitivity of 88.4% and specificity of 63.6%. Conclusions Our study determined predictive factors and proposed a scoring system of ongoing clinical remission in UC patients on maintenance vedolizumab. In patients at high risk of relapse, combination therapy with thiopurine may be beneficial.
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Affiliation(s)
- Thanaboon Chaemsupaphan
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
- Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Aviv Pudipeddi
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Huiyu Lin
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
- Department of Gastroenterology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Sudarshan Paramsothy
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Viraj Kariyawasam
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
- Department of Gastroenterology and Hepatology, Blacktown and Mount Druitt Hospital, Sydney, New South Wales, Australia
- Blacktown Clinical School, Western Sydney University, Sydney, New South Wales, Australia
| | - Melissa Kermeen
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Rupert W Leong
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
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Carbery I, Selinger CP, Todd O, Sebastian S. Considerations on Multimorbidity and Frailty in Inflammatory Bowel Diseases. J Crohns Colitis 2024; 18:ii46-ii54. [PMID: 39475079 PMCID: PMC11523040 DOI: 10.1093/ecco-jcc/jjae067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/27/2024] [Accepted: 05/03/2024] [Indexed: 11/02/2024]
Abstract
There are growing numbers of older people with inflammatory bowel diseases [IBD]. These older patients are more likely to have other comorbidities and polypharmacy, which can make recognizing and treating IBD complex. Frailty is a newer concept in the IBD field, and we are beginning to recognize the importance of this as a marker of biological age and its association with risk of adverse IBD-related outcomes. In this review article we aim to provide practical insight into the specific challenges facing older patients and their clinicians at each stage of the patient journey. We also discuss the latest understanding of the impact of frailty for these patients with IBD and highlight areas for future research.
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Affiliation(s)
- Isabel Carbery
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Christian P Selinger
- Academic Unit for Ageing and Stroke Research, University of Leeds, Bradford Institute for Health Research, Bradford, UK
| | - Oliver Todd
- Academic Unit for Ageing and Stroke Research, University of Leeds, Bradford Institute for Health Research, Bradford, UK
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Chen W, Liu Y, Zhang Y, Zhang H, Chen C, Zhu S, Zhou Y, Zhao H, Zong Y. Risk of Clostridioides difficile infection in inflammatory bowel disease patients undergoing vedolizumab treatment: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:377. [PMID: 39448963 PMCID: PMC11515399 DOI: 10.1186/s12876-024-03460-z] [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: 01/09/2024] [Accepted: 10/14/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing condition wherein biologics have improved disease prognosis but introduced elevated infection susceptibility. Vedolizumab (VDZ) demonstrates unique safety advantages; however, a comprehensive systematic comparison regarding the risk of Clostridioides difficile infection (CDI) between vedolizumab and alternative medications remains absent. METHOD Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of CDI proportion, incidence, pooled risk ratio between ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab and other medications were calculated. Data synthesis was completed in R using the package "meta". RESULTS Of the 338 studies initially identified, 30 met the inclusion/exclusion criteria. For CDI risk, the pooled proportion was 0.013 (95% CI 0.010-0.017), as well as the pooled proportion of serious CDI was 0.004 (95% CI 0.002-0.008). The comparative pooled risk ratios revealed: UC versus CD at 2.25 (95% CI 1.73-2.92), vedolizumab versus anti-TNF agents at 0.15 (95% CI 0.04-0.63) for UC and 1.29 (95% CI 0.41-4.04) for CD. CONCLUSION The overall CDI risk in IBD patients exposed to vedolizumab was estimated to be 0.013. An increased risk of CDI was noted in UC patients receiving vedolizumab compared to those with CD. Vedolizumab potentially offers an advantage over anti-TNF agents for UC regarding CDI risk, but not for CD. TRIAL REGISTRATION The study was registered on the PROSPERO registry (CRD42023465986).
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Affiliation(s)
- Wei Chen
- Department of Gastroenterology, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Capital Medical University, 95 Yong-an Road, Xi- cheng District, Beijing, China
| | - Yuhang Liu
- Department of Gastroenterology, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Capital Medical University, 95 Yong-an Road, Xi- cheng District, Beijing, China
| | - Yuelun Zhang
- Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhang
- Wenzhou Integrated Traditional Chinese and Western Medicine Hospital Pharmacy Department, Wenzhou, Zhejiang Province, China
| | - Chuyan Chen
- Department of Gastroenterology, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Capital Medical University, 95 Yong-an Road, Xi- cheng District, Beijing, China
| | - Siying Zhu
- Department of Gastroenterology, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Capital Medical University, 95 Yong-an Road, Xi- cheng District, Beijing, China
| | - Yanhua Zhou
- Department of Gastroenterology, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Capital Medical University, 95 Yong-an Road, Xi- cheng District, Beijing, China
| | - Haiying Zhao
- Department of Gastroenterology, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Capital Medical University, 95 Yong-an Road, Xi- cheng District, Beijing, China
| | - Ye Zong
- Department of Gastroenterology, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Capital Medical University, 95 Yong-an Road, Xi- cheng District, Beijing, China.
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Gros B, Ross H, Nwabueze M, Constantine-Cooke N, Derikx LAAP, Lyons M, O’Hare C, Noble C, Arnott ID, Jones GR, Lees CW, Plevris N. Long-term outcomes and predictors of vedolizumab persistence in ulcerative colitis. Therap Adv Gastroenterol 2024; 17:17562848241258372. [PMID: 39086990 PMCID: PMC11289824 DOI: 10.1177/17562848241258372] [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: 10/04/2023] [Accepted: 05/13/2024] [Indexed: 08/02/2024] Open
Abstract
Background Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed. Objectives We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years. Design We performed a retrospective, observational, cohort study. Methods All adult inflammatory bowel disease (IBD) patients who had received VDZ induction for ulcerative colitis (UC)/IBD-unclassified (IBDU) were included. Baseline phenotype and follow-up data were collected via a review of electronic medical records. Results We included 290 patients [UC n = 271 (93.4%), IBDU n = 19 (6.6%)] with a median time on VDZ of 27.6 months (interquartile range: 14.4-43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. The median time to discontinuation was 14.1 months (7.0-23.3). Previous exposure to ⩾1 advanced therapy, steroid use at baseline and disease extension (E3 and E2 versus E1) were independent predictors for worse VDZ persistence. Clinical remission (partial Mayo < 2) was 75.7% (171/226), 72.4% (157/217) and 70.2% (127/181) at years 1, 3 and 5, respectively. Steroid use during maintenance VDZ therapy occurred in 31.7% (92/290), hospitalization in 15.5% (45/290) and surgery in 3.4% (10/291). The rate of serious adverse events was 1.2 per 100 patient-years of follow-up. Conclusion VDZ effectiveness appears enduring with favourable long-term safety profile. VDZ persistence was influenced by previous exposure to biologics/small molecules, disease distribution and steroid use at baseline in our study.
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Affiliation(s)
- Beatriz Gros
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
- Department of Gastroenterology; Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), Madrid, Spain and Hepatology, Reina Sofía University Hospital, Córdoba, Spain
| | - Hannah Ross
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Maureen Nwabueze
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Nathan Constantine-Cooke
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
- Centre for Genomics and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
| | - Lauranne A. A. P. Derikx
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Mathew Lyons
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Claire O’Hare
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
- Edinburgh Pharmacy Unit, Western General Hospital, Edinburgh, UK
| | - Colin Noble
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Ian D. Arnott
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Gareth-Rhys Jones
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
- Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, Scotland, UK
| | - Charlie W. Lees
- Edinburgh IBD Unit, Western General Hospital, NHS Lothian, Crewe Road, Edinburgh EH4 2XU, UK
- Centre for Genomics and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
| | - Nikolas Plevris
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
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Yan J, Ding X, Wu J, Liu A, Fang L, Xu Y. Real-life effectiveness and safety of vedolizumab in moderate-to-severe ulcerative colitis: A single-center experience in Northern China. Medicine (Baltimore) 2024; 103:e38759. [PMID: 38968537 PMCID: PMC11224876 DOI: 10.1097/md.0000000000038759] [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: 11/21/2023] [Accepted: 06/07/2024] [Indexed: 07/07/2024] Open
Abstract
Vedolizumab (VDZ), a monoclonal antibody to α4β7 integrin, is available for patients with moderate-to-severe ulcerative colitis (UC). This study planned to assess the real-world effectiveness and safety of VDZ for UC patients in Northern China. We enrolled patients with moderate-to-severe UC who underwent VDZ induction therapy from March 2021 to November 2022 at the Affiliated Hospital of Qingdao University. The primary outcome was clinical remission at weeks 14 and 52 after the initial VDZ therapy. Overall adverse events and risk factors associated with loss of response (LOR) were also evaluated. Seventy-three UC patients receiving VDZ therapy were included in this study. The rates of clinical response, clinical remission, and steroid-free clinical remission were 69.9%, 39.7%, and 34.2% at week 14 and 90.5%, 66.7%, and 64.4% at week 52, respectively. The mucosal remission rates were 37.5% (18/48) at week 14 ± 8 and 27.3% (9/33) at week 52 ± 16, while only 2 and 3 patients achieved mucosal healing at weeks 14 ± 8 and 52 ± 16, respectively. Of the UC patients, 23.3% experienced adverse events associated with VDZ, most of which were mild and self-limiting. Until the last follow-up, 37 of 73 UC patients experienced LOR during the maintenance period. Patients with a higher ulcerative colitis endoscopic severity index (UCEIS), partial Mayo scores (PMS), or hemoglobin below 120 g/L at baseline were more likely to experience LOR after VDZ induction therapy. VDZ is an effective and safe agent for patients with moderate-to-severe UC in Northern China. A high baseline UCEIS, PMS, or hemoglobin < 120 g/L may be an independent risk factor for LOR during the maintenance period.
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Affiliation(s)
- Jing Yan
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Xueli Ding
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Jun Wu
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Ailing Liu
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Liang Fang
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Yonghong Xu
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
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Talar-Wojnarowska R, Caban M, Jastrzębska M, Woźniak M, Strigáč A, Małecka-Wojciesko E. Inflammatory Bowel Diseases in the Elderly: A Focus on Disease Characteristics and Biological Therapy Patterns. J Clin Med 2024; 13:2767. [PMID: 38792308 PMCID: PMC11122211 DOI: 10.3390/jcm13102767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 04/30/2024] [Accepted: 05/05/2024] [Indexed: 05/26/2024] Open
Abstract
Background: The incidence of inflammatory bowel diseases (IBDs) in elderly patients is constantly increasing. It results from the combination of an aging population with compounding prevalence of IBD, as well as the growing burden of elderly-onset IBD. The clinical characteristics of elderly patients differ from young subjects with IBD due to the multimorbidity or polypharmacy, affecting the choice of adequate therapeutic options. The aim of this study was to determine the clinical aspects and biological therapy safety in elderly Polish IBD patients. Methods: We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD patients treated with a biological therapy in two referral centers within the National Drug Program in Poland. Results: Out of the entire group of 366 studied patients, 51 (13.9%) were aged over 60-32 with ulcerative colitis (UC) and 19 with Crohn's disease (CD). The disease location was predominantly ileocolonic (57.89%) in patients with CD and pancolitis for patients with UC (56.25%). Most of the elderly IBD subjects were characterized by significant comorbidities, with Charlson Comorbidity Index (CCI) ≥ 1 in 66.67% patients. The probability of stopping biological therapy due to adverse events had the tendency to be higher in the CCI ≥ 1 group (20.58% vs. 5.88% in CCI = 0; p = 0.087). The main reasons for the therapy discontinuation included hypersensitivity reactions and liver enzyme abnormalities. Conclusions: In conclusion, our results underline the importance of assessing the comorbidity status instead of the age prior to initiating biological therapy, analyzing additional safety risks, and close monitoring in IBD patients with multiple comorbidities.
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Affiliation(s)
- Renata Talar-Wojnarowska
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (R.T.-W.); (M.W.); (A.S.); (E.M.-W.)
| | - Miłosz Caban
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (R.T.-W.); (M.W.); (A.S.); (E.M.-W.)
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland
| | - Marta Jastrzębska
- Department of Gastroenterology, Health Care Center, 26-200 Konskie, Poland;
| | - Małgorzata Woźniak
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (R.T.-W.); (M.W.); (A.S.); (E.M.-W.)
| | - Aleksandra Strigáč
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (R.T.-W.); (M.W.); (A.S.); (E.M.-W.)
| | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (R.T.-W.); (M.W.); (A.S.); (E.M.-W.)
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Resál T, Bacsur P, Keresztes C, Bálint A, Bor R, Fábián A, Farkas B, Katsanos K, Michalopoylos G, Ribaldone DG, Attauabi M, Zhao M, Barak HA, Yanai H, Bezzio C, Rispo A, Castiglione F, Bar-Gil Shitrit A, Pugliese D, Armuzzi A, Savarino EV, Kolar M, Lukáš M, Chashkova E, Filip R, Rozieres A, Nancey S, Krznarić Ž, Schäfer E, Szamosi T, Sarlós P, Franko M, Drobne D, Knyazev OV, Kagramanova AV, Limdi J, Wetwittayakhlang P, Lakatos PL, Maharshak N, Bannon L, Nyári T, Szepes Z, Farkas K, Molnár T. Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study. Inflamm Bowel Dis 2024; 30:768-779. [PMID: 37542737 PMCID: PMC11063556 DOI: 10.1093/ibd/izad135] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Indexed: 08/07/2023]
Abstract
BACKGROUND AND AIMS Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.
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Affiliation(s)
- Tamás Resál
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Péter Bacsur
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Csilla Keresztes
- Department for Medical Communication and Translation Studies, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Anita Bálint
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Renáta Bor
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Anna Fábián
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Bernadett Farkas
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Kostas Katsanos
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - George Michalopoylos
- Gastroenterology Department, General Hospital of Athens G. Gennimatas, Athens, Greece
| | | | - Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Mirabella Zhao
- Gastrounit, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | - Hadar Amir Barak
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Cristina Bezzio
- IBD Unit/Gastroenterology Unit, Rho Hospital, ASST Rhodense, Rho, Italy
| | - Antonio Rispo
- IBD Unit Department, Clinical Medicine and Surgery, Azienda Ospedaliera Universitaria Federico II of Naples, Naples, Italy
| | - Fabiana Castiglione
- IBD Unit Department, Clinical Medicine and Surgery, Azienda Ospedaliera Universitaria Federico II of Naples, Naples, Italy
| | - Ariella Bar-Gil Shitrit
- Digestive Diseases Institute, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Daniela Pugliese
- IBD Center, Centro Malattie Apparato Digerente, Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Martin Kolar
- IVth Medical Department, Charles University in Prague, Prague, Czech Republic
| | - Milan Lukáš
- IVth Medical Department, Charles University in Prague, Prague, Czech Republic
| | - Elena Chashkova
- Irkutsk Scientific Center of Surgery and Traumatology, Irkutsk, Russia
| | - Rafał Filip
- Department of Gastroenterology with IBD, Unit of Clinical Hospital No. 2 im. Sw. Jadwigi Królowej, Rzeszow, Poland
| | - Aurore Rozieres
- Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France
- Centre International de Recherche et Infectologie, INSERM U1111, Lyon, France
| | - Stéphane Nancey
- Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France
- Centre International de Recherche et Infectologie, INSERM U1111, Lyon, France
| | - Željko Krznarić
- Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb, Croatia
- Department of Nutrition, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Eszter Schäfer
- Department of Gastroenterology, Military Hospital Medical Centre, State Health Centre, Budapest, Hungary
| | - Tamás Szamosi
- Department of Gastroenterology, Military Hospital Medical Centre, State Health Centre, Budapest, Hungary
| | - Patrícia Sarlós
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Matej Franko
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - David Drobne
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of Gastroenterology, University Medical Centre Ljubljana, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Oleg V Knyazev
- Moscow Clinical Scientific Center named after A. S. Loginov, Moscow, Russia
- National Medical Research Center of Coloproctology named after A. N. Ryzhykh, Moscow, Russia
| | - Anna V Kagramanova
- Moscow Clinical Scientific Center named after A. S. Loginov, Moscow, Russia
- Research Institute of Health Organization and Medical Management, Moscow, Russia
| | - Jimmy Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester, United Kingdom
| | - Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Peter L Lakatos
- Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
- Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Nitsan Maharshak
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lian Bannon
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Tibor Nyári
- Department of Medical Physics and Informatics, Albert Szent-Györgyi Medical School University of Szeged, Szeged, Hungary
| | - Zoltán Szepes
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Klaudia Farkas
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Tamás Molnár
- Division of Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
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8
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Abstract
INTRODUCTION Appropriate treatment is critical in elderly inflammatory bowel disease (IBD) subjects since they are at higher risk of complications such as infections, malignancies and mortality. EVIDENCE ACQUISITION We conducted an extensive PubMed search for guidelines, systematic reviews and primary studies to perform a critical analysis of the existing literature on the efficacy and safety of conventional and biological therapies for elderly IBD patients. EVIDENCE SYNTHESIS Due to the exclusion of elderly population from clinical trials, most evidences comes from real-life studies. While aminosalicylates remain a cornerstone treatment of elderly patients with ulcerative colitis (UC), for their effectiveness and safety, their use in Crohn's disease (CD) should not be further supported. Corticosteroid use should be limited for the induction of remission, while as maintenance treatment it should be avoided, due to the low safety profile. Although as efficacious as in the younger population, immunosuppressant use has been associated with higher risk of infective/malignant issues and further use should be carefully evaluated. Biologics have demonstrated high effectiveness in the elderly. However, due to increased morbidity and mortality described in elderly subjects treated with anti-TNF alpha agents, vedolizumab and ustekinumab should be favoured over anti-TNF alpha agents. CONCLUSIONS Treatment of elderly IBD patients remains challenging, since comorbidities and the risk of adverse events can complicate the effectiveness and safety of therapy. Close monitoring of such patients in a multidisciplinary team is advocated to reduce the risk of infections and optimize the treatment, choosing a suitable agent.
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Affiliation(s)
- Fabiana Castiglione
- Unit of Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Nicola Imperatore
- Unit of Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology, and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Renata D'Incà
- Department of Surgery, Oncology, and Gastroenterology, University Hospital of Padua, Padua, Italy -
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9
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Tursi A, Mocci G, Del Gaudio A, Papa A. Clinical use of biologics for Crohn's disease in adults: lessons learned from real-world studies. Expert Opin Biol Ther 2024:1-19. [PMID: 38321868 DOI: 10.1080/14712598.2024.2316180] [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: 11/01/2023] [Accepted: 02/05/2024] [Indexed: 02/08/2024]
Abstract
INTRODUCTION The therapeutic armamentarium for managing Crohn's disease (CD) has expanded significantly in recent decades. Several biologics with three different mechanisms of action [anti-tumor necrosis factor (TNF)-α, anti-integrin α4β7, and anti-IL 12/23] are currently available to manage CD. AREA COVERED This narrative review aims to summarize the most significant efficacy and safety data on the use of infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ) and ustekinumab (UST) for the treatment of CD obtained from studies conducted in the real world (RW), compared to the results of randomized clinical trials (RCTs). EXPERT OPINION RW studies reported that biologic agents included in this analysis have higher remission rates and lower adverse event rates than findings from RCTs for treating patients with CD. All biological agents have proven effective and safe in RW studies, even when using biosimilars or switching to subcutaneous administration of the molecules for which they are available. Finally, anti-TNF-α agents, particularly IFX, have a higher rate of adverse events (AEs) than VDZ and UST. Therefore, patients at higher risk of AEs may benefit from other biologics than anti-TNF-α. However, further long-term RW studies are needed to confirm these findings.
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Affiliation(s)
- Antonio Tursi
- Territorial Gastroenterology Service, ASL BAT, Andria, Italy
- Department of Medical and Surgical Sciences, Catholic University, School of Medicine, Rome, Italy
| | - Giammarco Mocci
- Division of Gastroenterology, "Brotzu" Hospital, Cagliari, Italy
| | - Angelo Del Gaudio
- Division of Internal Medicine and Gastroenterology, Policlinico Universitario "A. Gemelli" IRCCS Foundation, Rome, Italy
| | - Alfredo Papa
- Department of Medical and Surgical Sciences, Catholic University, School of Medicine, Rome, Italy
- Division of Internal Medicine and Gastroenterology, Policlinico Universitario "A. Gemelli" IRCCS Foundation, Rome, Italy
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10
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García MJ, Rivero M, Fernández-Clotet A, de Francisco R, Sicilia B, Mesonero F, de Castro ML, Casanova MJ, Bertoletti F, García-Alonso FJ, López-García A, Vicente R, Calvet X, Barreiro-de Acosta M, Ferrer Rosique J, Varela Trastoy P, Nuñez A, Ricart E, Riestra S, Arias García L, Rodríguez M, Arranz L, Pajares R, Mena R, Calafat M, Camo P, Bermejo F, Ponferrada Á, Madrigal RE, Llaó J, Sesé E, Sánchez E, Pineda Mariño JR, González Muñoza C, Carbajo López AY, Julián AB, Villoria Ferrer A, Baston-Rey I, Jara L, Almela P, Codesido L, de la Maza S, Leal C, Caballol B, Pérez-Martínez I, Vinuesa Campo R, Crespo J, Domènech E, Chaparro M, Gisbert JP. Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry. J Crohns Colitis 2024; 18:65-74. [PMID: 37522878 DOI: 10.1093/ecco-jcc/jjad124] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Indexed: 08/01/2023]
Abstract
BACKGROUND Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.
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Affiliation(s)
- María José García
- Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain
| | - Montserrat Rivero
- Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain
| | - Agnès Fernández-Clotet
- Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Ruth de Francisco
- Gastroenterology Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Beatriz Sicilia
- IBD Unit, Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - Francisco Mesonero
- Gastroenterology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | - María José Casanova
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Federico Bertoletti
- Gastroenterology Department, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
| | | | | | - Raquel Vicente
- Gastroenterology Department, Hospital Universitario Miguel Servet, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain
| | - Xavier Calvet
- Gastroenterology Department, Consorci Corporació Sanitària Parc Taulí, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Sabadell, Spain
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Universitario Clínico de Santiago, Santiago de Compostela, Spain
| | - Juan Ferrer Rosique
- Gastroenterology Department, Hospital Universitario Fundación de Alcorcón, Alcorcón, Spain
| | | | - Alejandro Nuñez
- Gastroenterology Department, Hospital Universitario de Salamanca, Salamanca, Spain
| | - Elena Ricart
- Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Sabino Riestra
- Gastroenterology Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Lara Arias García
- IBD Unit, Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - María Rodríguez
- Gastroenterology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | - Laura Arranz
- Gastroenterology Department, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain
| | - Ramón Pajares
- Gastroenterology Department, Hospital Universitario Infanta Sofía, Madrid, Spain
| | - Raquel Mena
- Gastroenterology Department, Consorci Sanitari de Terrasa, Barcelona, Spain
| | - Margalida Calafat
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
| | - Patricia Camo
- Gastroenterology Department, Hospital General San Jorge, Huesca, Spain
| | - Fernando Bermejo
- Gastroenterology Department, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - Ángel Ponferrada
- Gastroenterology Department, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Rosa Eva Madrigal
- Gastroenterology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Jordina Llaó
- Gastroenterology Department, Althaia Xarxa Assistencial Universitària de Manresa, Manresa, Spain
| | - Eva Sesé
- Gastroenterology Department, Hospital Universitario Arnau de Vilanova de Lleida, Lleida, Spain
| | - Eugenia Sánchez
- Gastroenterology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | | | - Ana Belén Julián
- Gastroenterology Department, Hospital Universitario Miguel Servet, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain
| | - Albert Villoria Ferrer
- Gastroenterology Department, Consorci Corporació Sanitària Parc Taulí, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Sabadell, Spain
| | - Iria Baston-Rey
- Gastroenterology Department, Hospital Universitario Clínico de Santiago, Santiago de Compostela, Spain
| | - Lorena Jara
- Gastroenterology Department, Hospital Universitario Fundación de Alcorcón, Alcorcón, Spain
| | - Pedro Almela
- Gastroenterology Department, Hospital General Universitario de Castellón, Castellón, Spain
| | - Laura Codesido
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain
| | - Saioa de la Maza
- Gastroenterology Department, Hospital Universitario de Basurto, Bilbao, Spain
| | - Carles Leal
- Gastroenterology Department, Consorci Hospitalari de Vic, Vic, Spain
| | - Berta Caballol
- Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Isabel Pérez-Martínez
- Gastroenterology Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Raquel Vinuesa Campo
- IBD Unit, Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - Javier Crespo
- Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain
| | - Eugeni Domènech
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
| | - María Chaparro
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Javier P Gisbert
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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11
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González-Lama Y, Ricart E, Carpio D, Bastida G, Ceballos D, Ginard D, Marin-Jimenez I, Menchen L, Muñoz F. Controversies in the management of anti-TNF therapy in patients with Crohn's disease: a Delphi consensus. BMJ Open Gastroenterol 2024; 11:e001246. [PMID: 38267072 PMCID: PMC10870792 DOI: 10.1136/bmjgast-2023-001246] [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: 09/04/2023] [Accepted: 10/24/2023] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Despite research, there are still controversial areas in the management of Crohn's disease (CD). OBJECTIVE To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD. METHODS Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process. RESULTS Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator. CONCLUSION This document sought to pull together the best evidence, experts' opinions, and treating physicians' attitudes when using anti-TNF therapies in patients with CD.
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Affiliation(s)
- Yago González-Lama
- Gastroenterology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | - Elena Ricart
- Gastroenterology Department, CIBEREHD, Madrid, Spain
| | - Daniel Carpio
- Gastroenterology Department, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | | | - Daniel Ceballos
- Gastroenterology Department, Hospital Universitario Doctor Negrin, Las Palmas de Gran Canaria, Spain
| | - Daniel Ginard
- Gastroenterology Department, Hospital Universitario Son Espases, Palma, Spain
| | | | - Luis Menchen
- Gastroenterology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Fernando Muñoz
- Gastroenterology Department, Hospital Universitario de Salamanca, Salamanca, Spain
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12
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Garg R, Aggarwal M, Mohammed A, Achkar JP, Lashner B, Philpott J, Cohen B, Qazi T, Rieder F, Regueiro M, Click B. Real-world effectiveness and safety of ustekinumab and vedolizumab in elderly patients with Crohn's disease. Indian J Gastroenterol 2023; 42:718-723. [PMID: 37523059 PMCID: PMC10993992 DOI: 10.1007/s12664-023-01391-3] [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: 03/31/2022] [Accepted: 05/09/2023] [Indexed: 08/01/2023]
Abstract
Studies report favorable efficacy and safety profiles of ustekinumab (UST) and vedolizumab (VDZ) in Crohn's disease (CD), but effectiveness and safety data in elderly patients with CD is lacking. We retrospectively analyzed 78 elderly patients (39 each UST and VDZ) and found that patients on UST and VDZ experienced similar rates of clinical response, remission and mucosal healing despite high proportion of prior biologic exposure. Both UST and VDZ appear to be effective and safe in this at-risk CD population. Further large studies are needed to validate our findings.
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Affiliation(s)
- Rajat Garg
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
| | - Manik Aggarwal
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Abdul Mohammed
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Jean Paul Achkar
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Bret Lashner
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jessica Philpott
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Benjamin Cohen
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Taha Qazi
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Florian Rieder
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Miguel Regueiro
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Benjamin Click
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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13
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Shaffer SR, Kuenzig ME, Windsor JW, Bitton A, Jones JL, Lee K, Murthy SK, Targownik LE, Peña-Sánchez JN, Rohatinsky N, Ghandeharian S, Tandon P, St-Pierre J, Natt N, Davis T, Weinstein J, Im JHB, Benchimol EI, Kaplan GG, Goddard Q, Gorospe J, Bergevin M, Silver K, Bowles D, Stewart M, Pearlstein M, Dawson EH, Bernstein CN. The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-IBD in Seniors. J Can Assoc Gastroenterol 2023; 6:S45-S54. [PMID: 37674503 PMCID: PMC10478801 DOI: 10.1093/jcag/gwad013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/08/2023] Open
Abstract
Approximately one out of every 88 seniors has inflammatory bowel disease (IBD), and this is expected to increase in the future. They are more likely to have left-sided disease in ulcerative colitis, and isolated colonic disease in Crohn's disease; perianal disease is less common. Other common diagnoses in the elderly must also be considered when they initially present to a healthcare provider. Treatment of the elderly is similar to younger persons with IBD, though considerations of the increased risk of infections and malignancy must be considered when using immune modulating drugs. Whether anti-TNF therapies increase the risk of infections is not definitive, though newer biologics, including vedolizumab and ustekinumab, are thought to be safer with lower risk of adverse events. Polypharmacy and frailty are other considerations in the elderly when choosing a treatment, as frailty is associated with worse outcomes. Costs for IBD-related hospitalizations are higher in the elderly compared with younger persons. When elderly persons with IBD are cared for by a gastroenterologist, their outcomes tend to be better. However, as elderly persons with IBD continue to age, they may not have access to the same care as younger people with IBD due to deficiencies in their ability to use or access technology.
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Affiliation(s)
- Seth R Shaffer
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - M Ellen Kuenzig
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Joseph W Windsor
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Alain Bitton
- Division of Gastroenterology and Hepatology, McGill University Health Centre IBD Centre, McGill University, Montréal, Quebec, Canada
| | - Jennifer L Jones
- Departments of Medicine, Clinical Health, and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Kate Lee
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | - Sanjay K Murthy
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada
| | - Laura E Targownik
- Division of Gastroenterology and Hepatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Juan-Nicolás Peña-Sánchez
- Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Noelle Rohatinsky
- College of Nursing, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | | | - Parul Tandon
- Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Joëlle St-Pierre
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Navneet Natt
- Northern Ontario School of Medicine University, Sudbury, Ontario, Canada
| | - Tal Davis
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Jake Weinstein
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - James H B Im
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Eric I Benchimol
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
- Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Gilaad G Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Quinn Goddard
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Julia Gorospe
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Maxime Bergevin
- École de kinésiologie et des sciences de l’activité physique, Faculté de médecine, Université́ de Montréal, Montreal, Quebec, Canada
- Centre de recherche de l’Institut universitaire de gériatrie de Montréal, Montreal, Quebec, Canada
| | - Ken Silver
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | - Dawna Bowles
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | | | | | | | - Charles N Bernstein
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
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14
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Macaluso FS, Ventimiglia M, Orlando A. Effectiveness and Safety of Vedolizumab in Inflammatory Bowel Disease: A Comprehensive Meta-analysis of Observational Studies. J Crohns Colitis 2023; 17:1217-1227. [PMID: 36913311 DOI: 10.1093/ecco-jcc/jjad043] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Indexed: 03/14/2023]
Abstract
BACKGROUND AND AIMS Many observational studies on the use of vedolizumab [VDZ] in patients with Crohn's disease [CD] and ulcerative colitis [UC] have been published in the past few years. We aimed to comprehensively summarise its effectiveness and safety by pooling data only from observational studies. METHODS PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalisation, loss of response, VDZ dose escalation, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes. RESULTS In all, 88 studies comprising 25 678 patients [13 663 with CD and 12 015 with UC] met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC. CONCLUSIONS Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.
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Affiliation(s)
| | - Marco Ventimiglia
- Directorate General of Medical Device and Pharmaceutical Service, Italian Ministry of Health, Rome, Italy
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15
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Honap S, Netter P, Danese S, Peyrin-Biroulet L. An update on the safety of long-term vedolizumab use in inflammatory bowel disease. Expert Opin Drug Saf 2023; 22:767-776. [PMID: 37610086 DOI: 10.1080/14740338.2023.2247976] [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: 05/11/2023] [Accepted: 08/10/2023] [Indexed: 08/24/2023]
Abstract
INTRODUCTION Vedolizumab (Entyvio) is a humanized monoclonal antibody that disrupts the interaction between α4β7 integrin on circulating T-lymphocytes and MAdCAM-1 on the vascular endothelium to prevent their egress to sites of gut inflammation. It has proven therapeutic efficacy for the treatment of moderate-to-severe Crohn's disease, ulcerative colitis, and pouchitis. AREAS COVERED This narrative review assesses the safety profile of vedolizumab from the registration trial programs, open-label extension studies, observational real-world data, and pooled safety analyses. This includes an evaluation of the long-term overall safety in special populations typically underrepresented in clinical trials. EXPERT OPINION Vedolizumab is an effective therapy for inflammatory bowel disease with a well-established safety profile. No unexpected long-term safety signals have been identified. Safety data in pregnancy, in pediatric and elderly populations, in patients undergoing surgery, and in patients with a prior history of cancer are reassuring. Due to its safety merits, we propose that vedolizumab is an excellent candidate for advanced combination treatment with an anti-cytokine approach using another biologic or novel small molecule inhibitor. This is important in patients with medically refractory IBD, in patients at high risk of developing disease-related complications, or in patients with concomitant uncontrolled immune-mediated inflammatory diseases.
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Affiliation(s)
- 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
| | - Patrick Netter
- Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, Faculté de Médecine, University of Lorraine and University Hospital of Nancy, Nancy, France
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INFINY Institute, 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, Quebec, Canada
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16
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Sharip MT, Subramanian S. IBD in the elderly - beware of pitfalls! Saudi J Gastroenterol 2023; 29:201-203. [PMID: 37470664 PMCID: PMC10445498 DOI: 10.4103/sjg.sjg_185_23] [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: 06/15/2023] Open
Affiliation(s)
- Mohmmed T. Sharip
- Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
| | - Sreedhar Subramanian
- Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
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17
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Fries W, Basile G, Bellone F, Costantino G, Viola A. Efficacy and Safety of Biological Therapies and JAK Inhibitors in Older Patients with Inflammatory Bowel Disease. Cells 2023; 12:1722. [PMID: 37443755 PMCID: PMC10340637 DOI: 10.3390/cells12131722] [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: 06/02/2023] [Revised: 06/20/2023] [Accepted: 06/24/2023] [Indexed: 07/15/2023] Open
Abstract
With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years-old is steadily increasing, and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g., infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients, and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.
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Affiliation(s)
- Walter Fries
- Gastroenterology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.C.); (A.V.)
| | - Giorgio Basile
- Unit of Geriatrics, Department of Biomedical and Dental Science and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy;
| | - Federica Bellone
- Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy;
| | - Giuseppe Costantino
- Gastroenterology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.C.); (A.V.)
| | - Anna Viola
- Gastroenterology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.C.); (A.V.)
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18
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Huang K, Liu J, Xia W, Tian C, Yao L, Cao Q, Chen H. Effectiveness and safety of vedolizumab for ulcerative colitis: a single-center retrospective real-world study in China. Front Pharmacol 2023; 14:1188751. [PMID: 37214457 PMCID: PMC10192573 DOI: 10.3389/fphar.2023.1188751] [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: 03/17/2023] [Accepted: 04/24/2023] [Indexed: 05/24/2023] Open
Abstract
Introduction: The effectiveness and safety of vedolizumab (VDZ) against ulcerative colitis (UC) have been validated in several randomized controlled trials and real-world studies in Western countries. However, there are few studies on VDZ in Asia, and the follow-up period for these studies is generally short. Therefore, this study evaluates the long-term effectiveness and safety of VDZ in Chinese patients with UC. Methods: This retrospective study included patients with moderate to severe UC treated with VDZ between September 2019 and April 2022 at Sir Run Run Shaw Hospital, College of Medicine Zhejiang University. Clinical response and remission were assessed using the patient reported outcomes and the partial Mayo Score, and mucosal remission and healing were assessed using the Mayo Endoscopy Score. The primary endpoint was defined as clinical remission at week 14, and secondary endpoints included clinical response and steroid-free clinical remission at week 14, clinical response, clinical remission, and steroid-free clinical remission at week 52, and mucosal remission and healing at weeks 14 ± 8 and 52 ± 8. Results: Overall, 64 patients with moderate to severe UC were enrolled. The clinical response, clinical remission, and steroid-free clinical remission rates at week 14 were 73.4% (47/64), 65.6% (42/64), and 54.7% (35/64), respectively. Mucosal remission and healing rates at week 14 ± 8 were 64.7% (22/34) and 38.2% (13/34), respectively. A total of 48 patients were treated with VDZ for 52 weeks. Based on intention-to-treat analysis, the clinical response, clinical remission, and steroid-free clinical remission rates at week 52 were 68.8% (44/64), 64.1% (41/64), and 64.1% (41/64), respectively. Mucosal remission and healing rates at week 52 ± 8 were 70.6% (12/17) and 35.3% (6/17), respectively. During the follow-up period, the most common adverse event was skin rash (6/64). No cases of acute infusion reactions, delayed allergic reactions, new hepatitis B infections, active tuberculosis, or malignant tumors were reported. Conclusion: In this single-center retrospective real-world study, the effectiveness of long-term use of VDZ for Chinese patients with UC was similar to the outcomes previously reported in other geographical regions and populations; no new safety signals were found compared with other registered studies.
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Affiliation(s)
- Kaituo Huang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center of Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
| | - Jing Liu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center of Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
| | - Wenhao Xia
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center of Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
| | - Chuwen Tian
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center of Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
| | - Lingya Yao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center of Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
| | - Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center of Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
| | - Haotian Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center of Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China
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19
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Lin J, Zhang M, Zhi M. Clinical characteristics of elderly-onset inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2023; 31:98-104. [DOI: 10.11569/wcjd.v31.i3.98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a group of chronic non-specific intestinal inflammatory diseases whose etiology has not been elucidated. The prevalence of elderly-onset IBD is increasing; however, its disease phenotype, pathophysiology, and clinical characteristics are different from those of adult-onset IBD. In order to better manage elderly IBD patients, it is becoming increasingly important to accurately describe the unique characteristics of elderly-onset IBD. Therefore, this article, based on the domestic and foreign literature reports from 2017 to now, describes the characteristics of elderly-onset IBD with regard to pathogenesis, epidemiological characteristics, clinical features, and treatment.
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Affiliation(s)
- Jue Lin
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Min Zhang
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Min Zhi
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
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20
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Casas-Deza D, Lamuela-Calvo LJ, Gomollón F, Arbonés-Mainar JM, Caballol B, Gisbert JP, Rivero M, Sánchez-Rodríguez E, Arias García L, Gutiérrez Casbas A, Merino O, Márquez L, Laredo V, Martín-Arranz MD, López Serrano P, Riestra Menéndez S, González-Muñoza C, de Castro Parga L, Calvo Moya M, Fuentes-Valenzuela E, Esteve M, Iborra M, Dura Gil M, Barreiro-De Acosta M, Lorente-Poyatos RH, Manceñido N, Calafat M, Rodríguez-Lago I, Guardiola Capo J, Payeras MA, Morales Alvarado VJ, Tardillo C, Bujanda L, Muñoz-Nuñez JF, Ber Nieto Y, Bermejo F, Almela P, Navarro-Llavat M, Martínez Montiel P, Rodríguez Gutiérrez C, Van Domselaar M, Sesé E, Martínez Pérez T, Ricart E, Chaparro M, García MJ, López-Sanromán A, Sicilia B, Orts B, López-García A, Martín-Arranz E, Pérez-Calle JL, de Francisco R, García-Planella E, Domènech E, García-López YS. Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry. J Crohns Colitis 2023; 17:83-91. [PMID: 35913456 DOI: 10.1093/ecco-jcc/jjac108] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIMS Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.
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Affiliation(s)
- Diego Casas-Deza
- Gastroenterology Department, University Hospital Miguel Servet, Zaragoza, Spain.,Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain
| | - Luis Javier Lamuela-Calvo
- Gastroenterology Department, University Hospital Miguel Servet, Zaragoza, Spain.,Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain
| | - Fernando Gomollón
- Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain.,Gastroenterology Department, University Hospital Lozano Blesa, Zaragoza, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - José Miguel Arbonés-Mainar
- Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain.,Instituto Aragonés de Ciencias de la Salud (IACS), Instituto de Investigación Sanitaria (IIS) de Aragón, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain
| | - Berta Caballol
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital Clínic, Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Montserrat Rivero
- Gastroenterology Department, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación IDIVAL Santander, Spain
| | | | - Lara Arias García
- Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - Ana Gutiérrez Casbas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital General de Alicante, Alicante, Spain
| | - Olga Merino
- Gastroenterology Department, Hospital Universitario de Cruces, Baracaldo, Spain
| | - Lucía Márquez
- Gastroenterology Department, Hospital del Mar, Barcelona, Spain
| | - Viviana Laredo
- Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain.,Gastroenterology Department, University Hospital Lozano Blesa, Zaragoza, Spain
| | - María Dolores Martín-Arranz
- Department of Gastroenterology of La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, Hospital La Paz Institute for Health Research, La Paz Hospital, Madrid, Spain
| | - Pilar López Serrano
- Gastroenterology Department, Hospital Universitario Fundación de Alcorcón, Alcorcón, Spain
| | - Sabino Riestra Menéndez
- Gastroenterology Department, University Hospital Central de Asturias, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, España
| | | | - Luisa de Castro Parga
- Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Marta Calvo Moya
- Gastroenterology Department, Hospital Universitario Puerto de Hierro, Madrid, Spain
| | | | - Maria Esteve
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital Mútua de Terrasa, Terrasa, Spain
| | - Marisa Iborra
- Gastroenterology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Miguel Dura Gil
- Gastroenterology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | | | | | - Noemí Manceñido
- Gastroenterology Department, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Spain
| | - Margalida Calafat
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital Universitario Germans Trias i Pujol, Badalona, Spain
| | | | - Jordi Guardiola Capo
- Gastroenterology Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain
| | | | | | - Carlos Tardillo
- Gastroenterology department, Hospital Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain
| | - Luis Bujanda
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | | | | | - Fernando Bermejo
- Gastroenterology Department, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
| | - Pedro Almela
- Gastroenterology Department, Hospital General de Castelló, Castellón, Spain
| | | | | | | | | | - Eva Sesé
- Gastroenterology Department, Hospital Universitario Arnau de Vilanova, Lleida, Spain
| | | | - Elena Ricart
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital Clínic, Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - María Chaparro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - María José García
- Gastroenterology Department, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación IDIVAL Santander, Spain
| | | | - Beatriz Sicilia
- Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - Beatriz Orts
- Clinical Pharmacology, ISABIAL, Hospital General Universitario de Alicante, Spain
| | | | - Eduardo Martín-Arranz
- Department of Gastroenterology of La Paz University Hospital. Hospital La Paz Institute for Health Research, La Paz Hospital, Madrid, Spain
| | | | - Ruth de Francisco
- Gastroenterology Department, University Hospital Central de Asturias, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, España
| | | | - Eugeni Domènech
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.,Gastroenterology Department, Hospital Universitario Germans Trias i Pujol, Badalona, Spain
| | - Y Santiago García-López
- Gastroenterology Department, University Hospital Miguel Servet, Zaragoza, Spain.,Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain
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Hu Q, Tang XZ, Liu F, Liu DW, Cao B. Vedolizumab subcutaneous formulation maintenance therapy for patients with IBD: a systematic review and meta-analysis. Therap Adv Gastroenterol 2023; 16:17562848231166227. [PMID: 37124368 PMCID: PMC10141260 DOI: 10.1177/17562848231166227] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 03/07/2023] [Indexed: 05/02/2023] Open
Abstract
Background The application of vedolizumab (VDZ) subcutaneous (SC) formulation has brought more convenience and hope to patients with moderate-to-severe inflammatory bowel diseases (IBDs) in the coronavirus disease 2019 context. Objective This study aimed to systematically evaluate all previous studies that used VDZ SC formulation for maintenance therapy in patients with IBD. Design Systematic review and meta-analysis. Data Sources and Methods The search was conducted using the subject and free terms related to 'Vedolizumab', 'Subcutaneous', and 'IBD', in Embase, PubMed, Web of Science, Cochrane, and at ClinicalTrials.gov databases between 2008 and 2022. The methodological quality of randomized controlled trials (RCTs) and cohort studies was assessed using the Cochrane Handbook of Systematic Reviews and the Newcastle-Ottawa Scale, respectively. The endpoints included efficacy, safety, and immunogenicity. Results A total of 60 studies and 2 completed clinical registry trials were retrieved, of which 3 RCTs with high methodological quality, and 3 cohort studies with large heterogeneity were included in the meta-analysis. In the RCT study design, patients with ulcerative colitis (UC) under different conditions after treated with VDZ SC were significantly distinct than those for placebo (PBO) in clinical remission, endoscopic remission, and biochemical remission. In Crohn's disease (CD), the aforementioned parameters were slightly higher than those for PBO, but there was not statistically significant in endoscopic remission and the efficacy of anti-tumor necrosis factor-naive patients. The clinical remission, endoscopic remission, and biochemical remission in patients with UC after VDZ SC treatment were similar to those after intravenous (IV) treatment. The risk ratios in patients experiencing adverse events (AEs) and serious AEs after VDZ SC and PBO treatments were 86% and 89% in UC, and 96% and 80% in CD, respectively. Compared with IV, safety was not statistically different. The risk of developing anti-VDZ antibody after VDZ SC treatment was only 20% of that after PBO in patients with UC, but it was 9.38 times in CD. Conclusion VDZ SC treatment maintained the clinical efficacy of IV induction in patients with IBD without increasing the safety risk, and the efficacy was more pronounced in patients with UC. Immunogenicity might be a potential factor for the decrease in efficacy rate in patients with IBD. Registration INPLASY 2022120115.
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Affiliation(s)
| | | | - Fang Liu
- AnoRectal Surgery, Sixth affiliated hospital of
Sun Yat-sen University, Guangdong, Guangzhou, China
| | - De-wu Liu
- AnoRectal Surgery, Second Affiliated Hospital
of Guizhou University of Traditional Chinese Medicine, Guizhou, Guiyang,
China
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22
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Chen SL, Faye AS, Chang S. Ileal Pouch-Anal Anastomosis in the Older Adult: a Review of Postoperative Outcomes and Pouchitis Treatment. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2022; 20:564-581. [PMID: 36844648 PMCID: PMC9957085 DOI: 10.1007/s11938-022-00405-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/12/2022] [Indexed: 06/18/2023]
Abstract
PURPOSE OF REVIEW Ileal pouch-anal anastomosis (IPAA) has become the preferred surgical treatment for patients with medically refractive ulcerative colitis (UC). Previous studies have suggested that outcomes of this procedure may be worse in older patients; however, more recent reports have suggested that IPAA in select patients is safe, feasible, and results in good quality of life. In this review, we discuss the recent literature surrounding clinical considerations and treatment management of IPAA in older adults. RECENT FINDINGS IPAA complication rates and adverse events are similar in the older adult population, as compared to the younger adult patient population. Although fecal urgency and incontinence may be more common among older adults, chronological age alone is not a contraindication for IPAA surgery, as good quality of life can still be achieved. In this review, we will also discuss the development of pouchitis after IPAA, particularly among older adults, as the emergence of newer biologic drugs has shifted the treatment landscape. SUMMARY IPAA can be a safe and effective treatment modality for older adults with UC, with high self-reported patient satisfaction. Patient optimization and careful case selection are vital to achieving these outcomes, and specialized preoperative assessments and counseling can help facilitate the proper treatment.
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Affiliation(s)
- Sabrina L. Chen
- Department of Gastroenterology, New York University Grossman School of Medicine, 305 East 33rd Street, NY 10016 New York, USA
| | - Adam S. Faye
- Department of Gastroenterology, New York University Grossman School of Medicine, 305 East 33rd Street, NY 10016 New York, USA
| | - Shannon Chang
- Department of Gastroenterology, New York University Grossman School of Medicine, 305 East 33rd Street, NY 10016 New York, USA
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Ustekinumab and Vedolizumab Are Equally Safe and Effective in Elderly Crohn's Disease Patients. Dig Dis Sci 2022; 68:1983-1994. [PMID: 36436155 PMCID: PMC9702964 DOI: 10.1007/s10620-022-07770-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/14/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Anti-tumour necrosis factor (anti-TNF) agents are associated with increased infection risk among elderly inflammatory bowel disease (IBD) patients, and thus, alternative biologics may be preferable. However, little comparative data exist on the safety and efficacy of vedolizumab and ustekinumab in elderly IBD patients. AIMS To compare the safety and effectiveness of ustekinumab and vedolizumab in elderly Crohn's disease patients. METHODS Patients ≥ 60 years old who commenced ustekinumab or vedolizumab for Crohn's disease (CD) were included. Primary outcome was serious infections, defined as requiring hospitalisation. Efficacy was assessed by treatment persistence and clinical response rates. We appropriately adjusted for confounders using propensity score-matched analysis weighted by the inverse predicted probability of treatment weighing and performed a logistic regression analysis to assess factors associated with serious infections and treatment persistence. RESULTS Eighty-three patients commencing ustekinumab and 42 commencing vedolizumab therapy were included. In a propensity adjusted cohort, the rate of serious infection and treatment persistence were comparable between ustekinumab and vedolizumab. There was a significant reduction in HBI at 6 and 12 months compared to baseline in both groups. Male gender was positively associated with serious infection risk at 12 months, and penetrating disease behaviour was positively associated with 12-month treatment persistence. Baseline HBI score was negatively associated with 12-month treatment persistence. Cox regression analysis showed no overall difference in treatment discontinuation-free and serious infection-free survival by 12 months. CONCLUSIONS We observed comparable safety and effectiveness for ustekinumab and vedolizumab in treating elderly CD patients.
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Mosli MH, Almudaiheem HY, AlAmeel T, Bakkari SA, Alharbi OR, Alenzi KA, Khardaly AM, AlMolaiki MA, Al-Omari BA, Albarakati RG, Al-Jedai AH, Saadah OI, Almadi MA, Al-Bawardy B. Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease. Saudi J Gastroenterol 2022; 29:361671. [PMID: 36412460 PMCID: PMC10540981 DOI: 10.4103/sjg.sjg_277_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/23/2022] [Accepted: 09/05/2022] [Indexed: 02/10/2023] Open
Abstract
Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment.
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Affiliation(s)
- Mahmoud H. Mosli
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | | | - Turki AlAmeel
- Department of Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Shakir A. Bakkari
- Division of Gastroenterology, King Saud Medical City, Riyadh, Saudi Arabia
| | - Othman R. Alharbi
- Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Khalidah A. Alenzi
- Regional Drug Information and Pharmacovigilance Center, Ministry of Health, Tabuk, Saudi Arabia
| | | | - Maha A. AlMolaiki
- Department of Pharmaceutical Care, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Bedor A. Al-Omari
- Pharmaceutical Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Rayan G. Albarakati
- Department of Obstetrics and Gynecology, Majmaah University, Riyadh, Saudi Arabia
| | - Ahmed H. Al-Jedai
- Deputyship of Therapeutic Affairs, Ministry of Health, Riyadh, Saudi Arabia
| | - Omar I. Saadah
- Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Majid A. Almadi
- Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Badr Al-Bawardy
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
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25
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Fiske J, Liu E, Limdi JK, Conley TE, Townsend T, Davies M, Brockwell R, Baig D, Abdelbadiee S, Uney A, Liaros A, Gaba W, Smith PJ, Flanagan PK, Subramanian S. Safety and effectiveness of ustekinumab in elderly Crohn's disease patients. Eur J Gastroenterol Hepatol 2022; 34:1132-1139. [PMID: 36170682 DOI: 10.1097/meg.0000000000002436] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Anti-tumour necrosis factor (TNF) agents are associated with increased infection risk among elderly IBD patients, but little is known about non anti-TNF biologics in this cohort. We examined the safety and effectiveness of ustekinumab in elderly Crohn's patients. METHODS This retrospective multi-centre cohort study included Crohn's patients ≥60-years old who commenced ustekinumab. We recorded Harvey-Bradshaw index (HBI), concomitant steroid therapy, treatment persistence and new infections or malignancies. Primary outcome was serious infections requiring hospitalisation. RESULTS Seventy patients were included, with median age of 68 years. 43 (61.4%) had prior anti-TNF exposure, and 15 (21.4%) vedolizumab. Median treatment duration was 12 months, totalling 84 patient-years. Nine serious infections were reported, incidence 106.7/1000 patient-years. Systemic steroids were associated with increased risk of serious infections [odds ratio (OR) 7.83, 95% confidence interval (CI): 1.44-44.32, P = 0.02]. There were 27 "non-serious" infections; 321.4/1000 patient-years. Charlson co-morbidity index (OR 1.49, 95% CI: 1.05-2.12, P = 0.03) and steroid exposure (OR 44.10, 95% CI: 1.75-1112.10, P = 0.02) increased non-serious infection risk (P < 0.05). Mean HBI improved from 8.13 to 4.64 at 6 months and 4.10 at last follow up (P < 0.0001). 12-month treatment persistence was 55.7% (N = 39); 34 (48.6%) were steroid-free. CONCLUSION Ustekinumab was safe and effective in a cohort of elderly Crohn's disease patients. Infections were mostly mild, not resulting in therapy discontinuation. Serious infection risk was comparable to previously reported rates with anti-TNF agents. Steroid exposure was associated with an increased serious infection risk.
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Affiliation(s)
- Joseph Fiske
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Eleanor Liu
- Department of Gastroenterology, Pennine Acute Hospital NHS Trust
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospital NHS Trust
- Manchester Academic Health Sciences; Faculty of Medicine, Biology &Health, University of Manchester, Manchester
| | - Thomas E Conley
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Tristan Townsend
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Mike Davies
- Department of Gastroenterology, Arrowe Park Hospital, Wirral
| | | | - Daniyal Baig
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Sherif Abdelbadiee
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Anastasia Uney
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Angela Liaros
- Department of Gastroenterology, Whiston Hospital, Whiston
| | - Waqas Gaba
- Department of Gastroenterology, Warrington Hospital, Warrington
| | - Philip J Smith
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Paul K Flanagan
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Sreedhar Subramanian
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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Hahn GD, LeBlanc JF, Golovics PA, Wetwittayakhlang P, Qatomah A, Wang A, Boodaghians L, Liu Chen Kiow J, Al Ali M, Wild G, Afif W, Bitton A, Lakatos PL, Bessissow T. Effectiveness, safety, and drug sustainability of biologics in elderly patients with inflammatory bowel disease: A retrospective study. World J Gastroenterol 2022; 28:4823-4833. [PMID: 36156919 PMCID: PMC9476849 DOI: 10.3748/wjg.v28.i33.4823] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/17/2022] [Accepted: 08/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease (IBD) however data on the efficacy and side effects of these therapies in the elderly is scant.
AIM To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population.
METHODS Consecutive elderly (≥ 60 years old) IBD patients, treated with biologics [infliximab (IFX), adalimumab (ADAL), vedolizumab (VDZ), ustekinumab (UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020. Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events (AEs) or serious AE were collected during and within three months of stopping of the biologic therapy.
RESULTS We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn’s disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX (28.5%), ADAL (38.7%), VDZ (15.6%), UST (17%). The mean duration of biologic treatment was 157.5 (SD = 148) wk. Parallel steroid therapy was given in 34% at baseline, 19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (P = 0.195), time to adverse event (P = 0.158) or infection rates (P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection.
CONCLUSION Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.
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Affiliation(s)
- Gustavo Drügg Hahn
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
- School of Medicine, Graduate Course Sciences in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90000-000, Brazil
| | - Jean-Frédéric LeBlanc
- Division of Gastroenterology, McGill University Health Centre, Montreal H3G 1A4, Quebec, Canada
| | - Petra Anna Golovics
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
- Department of Gastroenterology, Hungarian Defense Forces, Medical Centre, Budapest 1134, Hungary
| | - Panu Wetwittayakhlang
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
- Unit of Gastroenterology and Hepatology, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Abdulrahman Qatomah
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Anna Wang
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Levon Boodaghians
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Jeremy Liu Chen Kiow
- Department of Gastroenterology, Centre Hospitalier de l’Université de Montréal, Montreal H2X 3E4, Quebec, Canada
| | - Maryam Al Ali
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Gary Wild
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Waqqas Afif
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Alain Bitton
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
| | - Talat Bessissow
- Division of Gastroenterology, IBD Center, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
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Attauabi M, Madsen GR, Bendtsen F, Seidelin JB, Burisch J. Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. Dig Liver Dis 2022; 54:1168-1178. [PMID: 34903497 DOI: 10.1016/j.dld.2021.11.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/06/2021] [Accepted: 11/15/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The efficacy and safety of vedolizumab in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD) remain unknown. AIMS To perform a meta-analysis regarding vedolizumab as first line of biological therapy for UC or CD. METHODS A systematic review of Medline, EMBASE, and Cochrane databases per December 2020 was undertaken. Meta-analysis was conducted using random-effects models. RESULTS This systematic review identified 79 eligible studies with 4,520 and 3,494 bio-naïve patients with UC and CD, respectively, and 8,105 and 11,140 bio-exposed patients. Among bio-naïve patients with UC, a total of 40.0% (95%CI 27.0-54.0, I2=86%) and 63.9% (95%CI 47.0-79.2, I2=36%) achieved clinical remission at weeks 14 and 52, respectively. The corresponding rates in CD were 54.0% (95%CI 42.0-66.0, I2=23%), and 61.7% (95%CI 55.2-68.1, I2=0%). Bio-naïvety was associated with a higher probability of clinical remission at week 52 in UC (relative risk (RR)=1.32 (95%CI 1.14-1.53)), while this was only apparent until week 26 in CD (RR=1.60 (95%CI 1.30-1.95)). Finally, bio-naïve UC patients had a lower risk of serious adverse events (RR=0.29 (95%CI 0.09-0.95)). CONCLUSION Vedolizumab was found to have a favorable efficacy and safety profile in bio-naïve patients with UC and CD. The findings have implications in the management of IBD.
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Affiliation(s)
- Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730 Denmark; Gastrounit, Medical Section, Hvidovre University Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark.
| | - Gorm Roager Madsen
- Gastrounit, Medical Section, Hvidovre University Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Section, Hvidovre University Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark
| | - Jakob Benedict Seidelin
- Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730 Denmark
| | - Johan Burisch
- Gastrounit, Medical Section, Hvidovre University Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Hvidovre, Kettegaard Alle 30, 2650 Denmark
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Hahn GD, Golovics PA, Wetwittayakhlang P, Santa Maria DM, Britto U, Wild GE, Afif W, Bitton A, Bessissow T, Lakatos PL. Safety of Biological Therapies in Elderly Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. J Clin Med 2022; 11:4422. [PMID: 35956040 PMCID: PMC9369299 DOI: 10.3390/jcm11154422] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/17/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Background and Aim: Newer biologics appeared safer in landmark clinical trials, but their safety is understudied in vulnerable populations. The aim of the present study was to perform a systematic review and meta-analysis to assess the safety of available biologicals in the elderly IBD population. Methods: We systematically searched PubMed/Medline and conference proceedings between 1 April 1969 and 1 June 2021 to identify eligible studies that examined the safety of biologics in elderly patients with IBD. Of the 2885 articles and 12 congress abstracts identified, 12 peer reviewed papers and 3 abstracts were included after independent evaluation by two reviewers. The identified studies collected safety data on anti-TNF, vedolizumab (VDZ) and ustekinumab (UST). Results: Rates of AE and infections were not different among the biologics (AE mean rate: 11.3 (CI 95% 9.9-12.7)/100 pts-years; p = 0.11, infection mean rate: 9.5 (CI 95% 8.4-10.6)/100 pts-years; p = 0.56) in elderly IBD patients on anti-TNF, VDZ or UST. Infusion/injection reaction rates were more common on anti-TNFs (mean rate: 2.51 (CI 95% 1.7-3.4/100 pts-years; p = 0.02). and malignancy rates were higher on VDZ/UST (mean rate: 2.14 (CI 95% 1.6-2.8)/100 pts-years; p = 0.01). Conclusions: Rates of AEs and infections were not different among biologicals. Infusion/injection reactions were more common on anti-TNFs. Current data are insufficient to suggest the sequencing of biologicals in elderly patients based on safety.
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Affiliation(s)
- Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
- School of Medicine, Graduate Course Sciences in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil; (D.M.S.M.); (U.B.)
| | - Petra Anna Golovics
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
- Department of Gastroenterology, Hungarian Defense Forces, Medical Centre, 1062 Budapest, Hungary
| | - Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
- Unit of Gastroenterology and Hepatology, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Dirlene Melo Santa Maria
- School of Medicine, Graduate Course Sciences in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil; (D.M.S.M.); (U.B.)
| | - Usiara Britto
- School of Medicine, Graduate Course Sciences in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil; (D.M.S.M.); (U.B.)
| | - Gary Edward Wild
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
| | - Waqqas Afif
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
| | - Alain Bitton
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (G.D.H.); (P.A.G.); (P.W.); (G.E.W.); (W.A.); (A.B.); (T.B.)
- 1st Department of Medicine, Semmelweis University, 1085 Budapest, Hungary
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Pugliese D, Privitera G, Crispino F, Mezzina N, Castiglione F, Fiorino G, Laterza L, Viola A, Bertani L, Caprioli F, Cappello M, Barberio B, Ricci C, Balestrieri P, Daperno M, Pluchino D, Rizzello F, Scribano ML, Sablich R, Pastorelli L, Manguso F, Variola A, Di Sario A, Grossi L, Armuzzi A, Biscaglia G, Buda A, Mocci G, Viscido A, Di Paolo MC, Onali S, Rodino S, Coletta M, Principi M, Miranda A, Amato A, Bezzio C, Petruzzellis C, Mazzuoli S, Festa S, Sartini A, Checchin D, Fanigliulo L, Gallina S, Cesarini M, Bodini G, Stradella D, Spagnuolo R, Guidi L, Savarino E, Scrivo B, Soru P, Costa F, Fries W, Scaldaferri F, Allocca M, Pellegrini L, Massari A, Orlando A. Effectiveness and safety of vedolizumab in a matched cohort of elderly and nonelderly patients with inflammatory bowel disease: the IG-IBD LIVE study. Aliment Pharmacol Ther 2022; 56:95-109. [PMID: 35876062 PMCID: PMC9324100 DOI: 10.1111/apt.16923] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/13/2022] [Accepted: 03/25/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Vedolizumab registration trials were the first to include elderly patients with moderate-to-severe ulcerative colitis (UC) or Crohn's disease (CD), but few real-life data have been reported in this population. AIMS We investigated the effectiveness and safety of vedolizumab in matched cohorts of elderly and nonelderly UC and CD patients. METHODS The Long-term Italian Vedolizumab Effectiveness (LIVE) study is a retrospective-prospective study including UC and CD patients who started vedolizumab from April 2016 to June 2017. Elderly patients (≥65 years) were matched clinically 1:2 to nonelderly patients (18-64 years); the 2 groups were followed until drug discontinuation or June 2019. RESULTS The study included 198 elderly (108 UC, 90 CD) and 396 matched nonelderly patients (205 UC, 191 CD). Nonelderly UC patients had a significantly higher persistence on vedolizumab compared to elderly patients (67.6% vs. 51.4%, p = 0.02). No significant difference in effectiveness was observed between elderly and nonelderly CD patients (59.4% vs. 52.4%, p = 0.32). Age ≥65 years was associated with lower persistence in UC; for CD, previous exposure to anti-TNF-α agents, Charlson comorbidity index >2 and moderate-to-severe clinical activity at baseline were associated with lower persistence. There were recorded 130 adverse events, with comparable rates between the two groups. A Charlson comorbidity index >2 was associated with an increased risk of adverse events. CONCLUSION Vedolizumab can be considered a safe option in elderly IBD patients. Its effectiveness in elderly UC patients may be reduced, while no age-dependent effect on effectiveness was observed in CD.
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Affiliation(s)
- Daniela Pugliese
- CEMAD – IBD UNIT, Unità Operativa Complessa di Medicina Interna e GastroenterologiaDipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCSRomeItaly
| | - Giuseppe Privitera
- Dipartimento Universitario di Medicina e Chirurgia TraslazionaleUniversità Cattolica del Sacro CuoreRomeItaly
| | - Federica Crispino
- Riuniti Villa Sofia–Cervello Hospital, Internal Medicine e 2IBD Unit PalermoPalermoItaly
| | - Nicolò Mezzina
- Department of Biochemical and Clinical Science “L. Sacco” ASST Fatebenefratelli Sacco–University of MilanMilanItaly
| | | | - Gionata Fiorino
- IBD Center, Gastroenterology, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy¸ Department of Biomedical SciencesHumanitas UniversityMilanItaly
| | - Lucrezia Laterza
- CEMAD – IBD UNIT, Unità Operativa Complessa di Medicina Interna e GastroenterologiaDipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCSRomeItaly
| | - Anna Viola
- UOSD Malattie Intestinali Croniche, Dip. di Medicina Clinica e SperimentalePoliclinico MessinaSicilyItaly
| | - Lorenzo Bertani
- Gastroenterology and Digestive Endoscopy Department of Medical Specialties Apuane HospitalTuscany North‐West ASLMassaItaly
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, La Fondazione IRCCS Ca’ Granda Ospedale Maggiore di Milano Policlinico, Department of Pathophysiology and TransplantationUniversity of MilanMilanLombardiaItaly
| | - Maria Cappello
- Head IBD Clinic, Gastroenterology Section, PromiseUniversity of PalermoSicilyItaly
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and GastroenterologyUniversity of PaduaPaduaItaly
| | - Chiara Ricci
- Gastroenterology Unit, Spedali Civili Hospital, Department of Experimental and Clinical SciencesUniversity of BresciaBresciaItaly
| | - Paola Balestrieri
- Unit of Digestive Disease of Campus Bio Medico University of RomeItaly
| | - Marco Daperno
- Gastroenterology UnitAzienda Ospedaliera Ordine Mauriziano di TorinoTorinoPiemonteItaly
| | - Dario Pluchino
- Gastroenterology UnitA.O.U. Policlinico "Vittorio Emanuele"CataniaItaly
| | - Fernando Rizzello
- Department of Internal Medicine and GastroenterologyPoliclinico Sant’Orsola MalpighiBolognaItaly
| | | | - Renato Sablich
- Gastroenterology UnitSanta Maria degli Angeli HospitalPordenoneItaly
| | - Luca Pastorelli
- Gastroenterology UnitIRCCS Policlinico San Donato Research HospitalMilanItaly
| | - Francesco Manguso
- Gastoenterology UnitAO A. CardarelliVia A. Cardarelli, 5Naples80131Italy
| | - Angela Variola
- IBD Unit, IRCCS Sacro Cuore Don CalabriaNegrar di ValpolicellaVeronaItaly
| | - Antonio Di Sario
- Clinica di GastroenterologiaUniversità Politecnica delle MarcheAnconaItaly,IBD‐UNIT, and Dipartimento Gastroenterologico e dei TrapiantiPolo Ospedaliero‐Universitario "Umberto I‐G.M. Lancisi‐ G. Salesi"AnconaItaly
| | - Laurino Grossi
- G. D’Annunzio University‐Digestive Physiopathology Ospedale Spirito Santo PescaraPescaraItaly
| | - Alessandro Armuzzi
- IBD CenterIRCCS Humanitas Research HospitalMilanItaly,Department of Biomedical Sciences, Humanitas UniversityPieve EmanueleMilanItaly
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Ulcerative Colitis in Adulthood and in Older Patients: Same Disease, Same Outcome, Same Risks? Drugs Aging 2022; 39:441-452. [PMID: 35641753 PMCID: PMC9155981 DOI: 10.1007/s40266-022-00943-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2022] [Indexed: 02/07/2023]
Abstract
The number of patients with inflammatory bowel disease (IBD) approaching an older age, together with the number of over-60-year-old patients newly diagnosed with IBD, is steadily increasing, reaching 25% of all patients. The present review focuses on late-onset ulcerative colitis (UC) and its initial disease course in comparison with that observed in younger adults in terms of extension at onset and the risk of proximal disease progression, medical treatment, surgery and hospitalization in the first years after diagnosis. We summarize the clues pointing to a milder disease course in a population which frequently presents major frailty due to comorbidities. With increasing age and thus increasing comorbidities, medical and surgical therapies frequently represent a challenge for treating physicians. The response, persistence, and risks of adverse events of conventional therapies indicated for late onset/older UC patients are examined, emphasizing the risks in this particular population, who are still being treated with prolonged corticosteroid therapy. Finally, we concentrate on data on biotechnological agents for which older patients were mostly excluded from pivotal trials. Real-life data from newer agents such as vedolizumab and ustekinumab show encouraging efficacy and safety profiles in the population of older UC patients.
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Hong SJ, Galati J, Katz S. Crohn's Disease of the Elderly: Unique Biology and Therapeutic Efficacy and Safety. Gastroenterol Clin North Am 2022; 51:425-440. [PMID: 35595423 DOI: 10.1016/j.gtc.2021.12.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
The incidence and prevalence of inflammatory bowel disease (IBD) is increasing in the elderly population. Compared with patients with onset during younger years, patients with elderly-onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas aging-related biological changes, such as immunosenescence and dysbiosis, are associated with elderly-onset IBD. Frailty is an increasingly recognized predictor of adverse outcomes. As an increasingly wider array of biologic and small molecule therapeutic options becomes available, data regarding efficacy and safety of these agents in patients are paramount given the unique characteristics of this population.
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Affiliation(s)
- Simon J Hong
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center at New York University Langone Health, 305 East 33rd St, New York, NY 10016, USA.
| | - Jonathan Galati
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center at New York University Langone Health, 305 East 33rd St, New York, NY 10016, USA
| | - Seymour Katz
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center at New York University Langone Health, 305 East 33rd St, New York, NY 10016, USA
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Attauabi M, Höglund C, Fassov J, Pedersen KB, Hansen HB, Wildt S, Jensen MD, Neumann A, Lind C, Jacobsen HA, Popa AM, Kjeldsen J, Pedersen N, Molazahi A, Haderslev K, Aalykke C, Knudsen T, Cebula W, Munkholm P, Bendtsen F, Seidelin JB, Burisch J. Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases. Scand J Gastroenterol 2021; 56:1040-1048. [PMID: 34224299 DOI: 10.1080/00365521.2021.1946588] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Data from real-life populations about vedolizumab as first-line biological therapy for ulcerative colitis (UC) and Crohn's disease (CD) are emerging. OBJECTIVE To investigate the efficacy and safety of vedolizumab in bio-naïve patients with UC and CD. METHODS A Danish nationwide cohort study was conducted between November 2014 and November 2019. Primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission from weeks 14 through 52. RESULTS The study included 56 patients (UC:31, CD:25) who initiated treatment with vedolizumab mainly because of contraindications to anti-TNFs, of whom 54.8 and 24.0%, respectively received systemic steroids at the initiation. Rates of clinical remission at weeks 6, 14, and 52 were 32.0, 48.0, and 40.0%, respectively, in UC, and 36.8, 36.8, and 47.4% in CD. Steroid-free clinical remission at week 52 was achieved among 36.0 and 47.4% of UC and CD patients, while sustained clinical remission was achieved in 32.0 and 36.8%. Lack of remission was associated with being female (68.8 vs. 11.1%, p = .01) in UC and non-structuring, non-penetrating behavior in CD (90.0 vs. 44.4%, p = .03); however, this was not confirmed in multivariate analysis. Discontinuation due to primary non-response occurred in 20.0 and 5.3% of UC and CD patients, respectively, while rates of secondary loss of response were 12.0 and 5.3% after 52 weeks of follow-up. Vedolizumab was well-tolerated as only one UC patient experienced a serious adverse event. CONCLUSION Vedolizumab is effective in the achievement of short-term, long-term, and steroid-free clinical remission in bio-naïve UC and CD patients.
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Affiliation(s)
- Mohamed Attauabi
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark.,Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
| | - Camilla Höglund
- Department of Medicine, Section of Gastroenterology, OUH Svendborg Hospital, Odense, Denmark
| | - Janne Fassov
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Kenneth Bo Pedersen
- Department of Medical Gastroenterology, Hospital of South West Denmark, Esbjerg, Denmark
| | - Heidi Bansholm Hansen
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Signe Wildt
- Department of Medicine, Division of Gastroenterology, Zealand University Hospital, Koege, Denmark
| | - Michael Dam Jensen
- Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital, Vejle, Denmark
| | - Anders Neumann
- Department of Internal Medicine, Regional Hospital Viborg, Viborg, Denmark
| | - Cecilie Lind
- Department of Internal Medicine, Regional Hospital Viborg, Viborg, Denmark
| | - Henrik Albaek Jacobsen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Ana-Maria Popa
- Department of Medicine, Nykoebing Falster Hospital, Nykoebing Falster, Denmark
| | - Jens Kjeldsen
- Department of Medical Gastroenterology, OUH Odense University Hospital, Odense, Denmark
| | - Natalia Pedersen
- Department of Gastroenterology, Slagelse Hospital, Slagelse, Denmark
| | - Akbar Molazahi
- Department of Internal Medicine, Holbaek Hospital, Holbaek, Denmark
| | - Kent Haderslev
- Department of Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Claus Aalykke
- Department of Medicine, Section of Gastroenterology, OUH Svendborg Hospital, Odense, Denmark
| | - Torben Knudsen
- Department of Medical Gastroenterology, Hospital of South West Denmark, Esbjerg, Denmark
| | - Wojciech Cebula
- Department of Medicine, Nykoebing Falster Hospital, Nykoebing Falster, Denmark
| | - Pia Munkholm
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark
| | - Jakob Benedict Seidelin
- Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark
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Gagnon AL, Beauchesne W, Tessier L, David C, Berbiche D, Lavoie A, Michaud-Herbst A, Tremblay K. Adalimumab, Infliximab, and Vedolizumab in Treatment of Ulcerative Colitis: A Long-Term Retrospective Study in a Tertiary Referral Center. CROHN'S & COLITIS 360 2021; 3:otab049. [PMID: 36777273 PMCID: PMC9802068 DOI: 10.1093/crocol/otab049] [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: 04/14/2021] [Indexed: 11/12/2022] Open
Abstract
Background Biological therapies have changed the landscape of pharmacological management of ulcerative colitis (UC). However, a large proportion of patients do not respond to biologics, lose their response over time, or present adverse drug events. This study aims to assess therapeutic response and treatment persistence to adalimumab, infliximab, and vedolizumab, 3 agents widely used in a tertiary referral center of Saguenay-Lac-Saint-Jean (Quebec, Canada). Methods We conducted a retrospective population-based study with a thorough review of patients' medical charts. Adults at UC diagnosis, with current or past use of adalimumab, infliximab, or vedolizumab, were included in the study. Clinical data were collected in order to assess response phenotypes and persistence to treatment. Kaplan-Meier curves were performed to assess treatment persistence, and predictors for discontinuation were assessed using Cox regression analyses. Results A total of 134 patients were included in this study. For the cases exposed to adalimumab, infliximab, and vedolizumab, 56.9%, 62.5%, and 47.5% were responders, respectively. Mean persistence rates (95% CI) were 5.5 (4.3-6.6), 10.1 (8.7-11.5), and 3.6 (2.9-4.2) years for adalimumab, infliximab, and vedolizumab, respectively. Increased persistence rates were observed in biologic-naïve patients treated with infliximab in comparison to those with the previous exposition to 2 biologics, but no such effect was observed for adalimumab or vedolizumab. Overall, 61.9% of cases had adverse drug events and of these, 6 led to treatment discontinuation. Conclusion This study presents long-term treatment persistence data with adalimumab, infliximab, and vedolizumab, showing that more than half of cases treated with these biologics remained on treatment at least 24 months after initiation.
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Affiliation(s)
- Ann-Lorie Gagnon
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada
| | - William Beauchesne
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada,Parmacology–Physiology Department, Université de Sherbrooke, Saguenay, Quebec, Canada
| | - Laurence Tessier
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada
| | - Charles David
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada
| | - Djamal Berbiche
- Centre de Recherche Charles-Le Moyne-Saguenay–Lac-Saint-Jean Sur Les Innovations en Santé (CR-CSIS), Université de Sherbrooke, Longueuil, Quebec, Canada
| | - Alexandre Lavoie
- Pharmacy Department, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Saguenay, Quebec, Canada
| | - Alban Michaud-Herbst
- Gastroenterology Department, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Saguenay, Quebec, Canada
| | - Karine Tremblay
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada,Parmacology–Physiology Department, Université de Sherbrooke, Saguenay, Quebec, Canada,Address correspondence to: Karine Tremblay, PhD, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean, 225, St-Vallier Street, Pavillon des Augustines, Saguenay, QC G7H 7P2, Canada ()
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Hong SJ, Katz S. The elderly IBD patient in the modern era: changing paradigms in risk stratification and therapeutic management. Therap Adv Gastroenterol 2021; 14:17562848211023399. [PMID: 34276809 PMCID: PMC8255562 DOI: 10.1177/17562848211023399] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 05/20/2021] [Indexed: 02/04/2023] Open
Abstract
The incidence and prevalence of inflammatory bowel disease (IBD) is rising in the elderly population. Compared with patients with onset during their younger years, patients with elderly onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas biological changes associated with aging including immunosenescence, dysbiosis, and frailty have a greater impact on disease outcomes. With the advent of an increasingly wider array of biologic and small-molecule therapeutic options, data regarding efficacy and safety of these agents in elderly IBD patients specifically are paramount, given the unique characteristics of this population.
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Affiliation(s)
- Simon J. Hong
- Inflammatory Bowel Disease Center at New York University Langone Health, Division of Gastroenterology and Hepatology, 305 East 33rd Street, New York, NY 10016-4576, USA
| | - Seymour Katz
- Inflammatory Bowel Disease Center at New York University Langone Health, Division of Gastroenterology and Hepatology, New York, NY, USA
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Effectiveness of Third-Class Biologic Treatment in Crohn's Disease: A Multi-Center Retrospective Cohort Study. J Clin Med 2021; 10:jcm10132914. [PMID: 34209880 PMCID: PMC8268494 DOI: 10.3390/jcm10132914] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. AIMS AND METHODS In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. RESULTS Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). CONCLUSION Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.
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Calafat M, Mañosa M, Cañete F, Domènech E. Clinical Considerations Regarding the Use of Thiopurines in Older Patients with Inflammatory Bowel Disease. Drugs Aging 2021; 38:193-203. [PMID: 33438138 DOI: 10.1007/s40266-020-00832-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2020] [Indexed: 12/19/2022]
Abstract
The number of older patients with inflammatory bowel disease (IBD) is increasing due to both improvements in the life expectancy of patients with long-lasting IBD and later onset of the disease. In spite of a less aggressive IBD phenotype, disease management in older patients is hampered by comorbidities and polypharmacy (which increase the risk of drug-related adverse events and errors in medication intake) and also by an increased risk of the infections and malignancies associated with the immunosuppressive drugs that are frequently used to treat IBD. Thiopurines are the most frequently used immunosuppressive drugs in IBD, though they are often discontinued due to adverse events. However, when tolerated, thiopurines are efficient in the maintenance of remission in ulcerative colitis and Crohn's disease. In fact, thiopurines still have a role to play in the treatment algorithm of older patients with IBD because anti-tumor necrosis factor agents do not provide clear advantages for this population in terms of their safety profile, while data on the new biological drugs are still scarce. In this article, we review the optimal use of thiopurines in older patients with IBD.
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Affiliation(s)
- Margalida Calafat
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916, Badalona, Catalonia, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Hepaticas y Digestivas, Madrid, Spain
| | - Míriam Mañosa
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916, Badalona, Catalonia, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Hepaticas y Digestivas, Madrid, Spain
| | - Fiorella Cañete
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916, Badalona, Catalonia, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Hepaticas y Digestivas, Madrid, Spain
| | - Eugeni Domènech
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916, Badalona, Catalonia, Spain.
- Centro de Investigaciones Biomédicas en Red de Enfermedades Hepaticas y Digestivas, Madrid, Spain.
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
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