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1
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Das P, Acharyya BC, Mukhopadhyay M. Short Term Biologicals in Pediatric IBD. Indian J Pediatr 2025; 92:91. [PMID: 39546121 DOI: 10.1007/s12098-024-05323-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 10/30/2024] [Indexed: 11/17/2024]
Affiliation(s)
- Pritha Das
- Department of Pediatric Gastroenterology, Institute of Child Health (ICH), 11, Dr Biresh Guha Street, Kolkata, 700017, India
| | - Bhaswati C Acharyya
- Department of Pediatric Gastroenterology, Institute of Child Health (ICH), 11, Dr Biresh Guha Street, Kolkata, 700017, India.
| | - Meghdeep Mukhopadhyay
- Department of Pediatric Gastroenterology, Institute of Child Health (ICH), 11, Dr Biresh Guha Street, Kolkata, 700017, India
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2
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Srinivasan AR. Treat to target in Crohn's disease: A practical guide for clinicians. World J Gastroenterol 2024; 30:50-69. [PMID: 38293329 PMCID: PMC10823901 DOI: 10.3748/wjg.v30.i1.50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/23/2023] [Accepted: 12/21/2023] [Indexed: 01/06/2024] Open
Abstract
A treat-to-target (T2T) approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)-II guidelines specify short, intermediate, and long-term treatment goals, documenting specific treatment targets to be achieved at each of these timepoints. Scheduled appraisal of Crohn's disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified. Consensus treatment targets in Crohn's disease comprise combination clinical and patient-reported outcome remission, in conjunction with biomarker normalisation and endoscopic healing. Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing, clinicians must consider that this may not always be appropriate, acceptable, or achievable in all patients. This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets. The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques, particularly intestinal ultrasound, holds great promise; as do emerging treatment targets such as transmural healing. Two randomised clinical trials, namely, CALM and STARDUST, have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn's disease. Findings from these studies reflect that patient subgroups and Crohn's disease characteristics likely to benefit most from a T2T approach, remain to be clarified. Moreover, outside of clinical trials, data pertaining to the real-world effectiveness of a T2T approach remains scare, highlighting the need for pragmatic real-world studies. Despite the obvious promise of a T2T approach, a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake. This highlights the need to describe strategies, processes, and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice. Hence, this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn's disease.
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Affiliation(s)
- Ashish R Srinivasan
- Department of Gastroenterology, Austin Health, Victoria, Melbourne 3083, Australia
- Department of Gastroenterology, Eastern Health, Victoria, Melbourne 3128, Australia
- Department of Medicine, University of Melbourne, Victoria, Melbourne 3052, Australia
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3
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Bashir NS, Hughes A, Ungar WJ. Infliximab Pricing in International Economic Evaluations in Inflammatory Bowel Disease to Inform Biologic and Biosimilar Access Policies: A Systematic Review. MDM Policy Pract 2023; 8:23814683231156433. [PMID: 36860664 PMCID: PMC9969457 DOI: 10.1177/23814683231156433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 01/17/2023] [Indexed: 03/03/2023] Open
Abstract
Background. Policies mandating the use of lower cost biosimilars in patients with inflammatory bowel disease (IBD) have created concerns for patients who prefer their original biologic. Purpose. To inform the cost-effectiveness of biosimilar infliximab treatment in IBD by systematically reviewing the effect of infliximab price variation on cost-effectiveness for jurisdictional decision making. Data Sources. MEDLINE, Embase, Healthstar, Allied and Complementary Medicine, Joanna Briggs Institute EBP Database, International Pharmaceutical Abstracts, Health and Psychosocial Instruments, Mental Measurements Yearbook citation databases, PEDE, CEA registry, HTA agencies. Study Selection. Economic evaluations of infliximab for adult or pediatric Crohn's disease and/or ulcerative colitis published from 1998 through 2019 in which drug price was varied in sensitivity analysis were included. Data Extraction. Study characteristics, main findings, and results of drug price sensitivity analyses were extracted. Studies were critically appraised. The cost-effective price of infliximab was determined based on the stated willingness-to-pay (WTP) thresholds for each jurisdiction. Data Synthesis. Infliximab price was examined in sensitivity analysis in 31 studies. Infliximab showed favorable cost-effectiveness at a price ranging from CAD $66 to $1,260 per vial, depending on jurisdiction. A total of 18 studies (58%) demonstrated cost-effectiveness ratios above the jurisdictional WTP threshold. Limitations. Drug prices were not always reported separately, WTP thresholds varied, and funding sources were not consistently reported. Conclusion. Despite the high cost of infliximab, few economic evaluations examined price variation, limiting the ability to infer the effects of biosimilar introduction. Alternative pricing strategies and access to treatment could be considered to enable IBD patients to maintain access to their current medications. Highlights In an effort to reduce public drug expenditures, Canadian and other jurisdictional drug plans have mandated the use of lower cost, but similarly effective, biosimilars in patients with newly diagnosed inflammatory bowel disease or require a nonmedical switch for established patients. This switch has created concerns for patients and clinicians who want to maintain the ability to make treatment decisions and remain with the original biologic.It is customary for economic evaluations to assess the robustness of results to variations in high-cost items such as medications. In the absence of economic evaluations of biosimilars, examining biologic drug price in sensitivity analysis provides insight into the cost-effectiveness of biosimilar alternatives. A total of 31 economic evaluations of infliximab for the treatment of inflammatory bowel disease varied the infliximab price in sensitivity analysis.The infliximab price deemed to be cost-effective within each study ranged from CAD $66 to CAD $1,260 per 100-mg vial. A total of 18 studies (58%) demonstrated an incremental cost-effectiveness ratio above the jurisdictional willingness-to-pay threshold. If policy decisions are based on price, then originator manufacturers could consider reducing the price or negotiating alternative pricing models to enable patients with inflammatory bowel disease to remain on their current medications.
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Affiliation(s)
- Naazish S. Bashir
- Program of Child Health Evaluative Sciences,
The Hospital for Sick Children Research Institute, Toronto, ON, Canada
| | - Avery Hughes
- Institute of Health Policy, Management and
Evaluation, the University of Toronto, Toronto, ON, Canada
| | - Wendy J. Ungar
- Wendy J. Ungar, Program of Child Health
Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for
Research and Learning, 686 Bay Street, 11th Floor, Toronto, ON M5G 0A4, USA;
()
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Yao J, Fekadu G, Jiang X, You JHS. Telemonitoring for patients with inflammatory bowel disease amid the COVID-19 pandemic—A cost-effectiveness analysis. PLoS One 2022; 17:e0266464. [PMID: 35390064 PMCID: PMC8989217 DOI: 10.1371/journal.pone.0266464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 03/21/2022] [Indexed: 11/18/2022] Open
Abstract
Background and aim
COVID-19 pandemic burdens the healthcare systems, causes healthcare avoidance, and might worsen the outcomes of inflammatory bowel disease (IBD) management. We aimed to estimate the impact of pandemic-related avoidance on outpatient IBD management, and the cost-effectiveness of adding telemonitoring during pandemic from the perspective of Hong Kong public healthcare provider.
Methods
The study was performed by a decision-analytic model to estimate the quality-adjusted life-years (QALYs) and cost of care for IBD patients before and during the pandemic, and to compare the cost and QALYs of adding telemonitoring to standard care (SC-TM) versus standard care alone (SC) for IBD patients during the pandemic. The sources of model inputs included publications (retrieved from literature search) and public data. Sensitivity analyses were conducted to examine the robustness of base-case results.
Results
Standard care with pandemic-related avoidance (versus without avoidance) lost 0.0026 QALYs at higher cost (by USD43). The 10,000 Monte Carlo simulations found standard care with pandemic-related avoidance lost QALYs and incurred higher cost in 100% and 96.82% of the time, respectively. Compared with the SC group, the SC-TM group saved 0.0248 QALYs and reduced cost by USD799. Monte Carlo simulations showed the SC-TM group gained higher QALYs at lower cost in 100% of 10,000 simulations.
Conclusions
Standard care for IBD patients during pandemic with healthcare avoidance appears to worsen treatment outcomes at higher cost and lowered QALYs. The addition of telemonitoring to standard care seems to gain higher QALYs and reduce cost, and is therefore a potential cost-effective strategy for IBD management during the pandemic.
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Affiliation(s)
- Jiaqi Yao
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ginenus Fekadu
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Xinchan Jiang
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Joyce H. S. You
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- * E-mail:
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5
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Clinical Practice Survey of Repeat Endoscopy in Pediatric Inflammatory Bowel Disease in North America. J Pediatr Gastroenterol Nutr 2021; 73:61-66. [PMID: 33633082 DOI: 10.1097/mpg.0000000000003100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Endoscopic remission has become a standard treatment target in inflammatory bowel disease (IBD). It is unclear how widely this practice has been adopted amongst pediatric gastroenterology providers. This study determines the frequency of repeat endoscopy in pediatric IBD and evaluates for predictive baseline characteristics of providers. METHODS We developed a cross-sectional survey, which was distributed via 3 national email listservs to pediatric gastroenterology providers. We obtained baseline characteristics of respondents and assessed motivations and barriers for the practice of repeat endoscopy compared with none. RESULTS Two hundred and thirty-eight unique respondents completed the online survey. Response rate was 11% (238 of 2300 possible participants). The majority practice in an academic setting (77%) and reported participation in ImproveCareNow (63%). Overall, 65% of respondents perform repeat endoscopy to assess for endoscopic remission in pediatric IBD as part of routine clinical practice. Fifty-six percent reported repeat endoscopy as individuals in the absence of a departmental protocol. "Symptoms are not sufficient to follow IBD patients" was reported by 82% of those who repeat endoscopy; conversely, "I perform endoscopy based on clinical, biomarker, and/or imaging trends" was reported by 81% of those who do not repeat endoscopy. The establishment of a pediatric-specific guideline was most commonly reported to change current practice, based on rank-order scoring. CONCLUSIONS A majority of representative providers repeat endoscopy to assess for endoscopic remission in pediatric IBD. Fewer years in practice favored repeating endoscopy. The need for North American pediatric guidelines with pediatric-specific evidence to support the long-term benefits of endoscopic remission are highlighted in this study.
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6
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Dal Buono A, Roda G, Argollo M, Paridaens K, Peyrin-Biroulet L, Danese S. 'Treat to Target' in Mild to Moderate Ulcerative Colitis: Evidence to Support this Strategy. Curr Drug Targets 2020; 22:117-125. [PMID: 32718289 DOI: 10.2174/1389450121666200727120305] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/27/2020] [Accepted: 06/12/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND The management of chronic conditions, above all rheumatic disease and diabetes, now incorporates a "treat to target" strategy where treatment aims to achieve objective outcomes. This is applicable in ulcerative colitis (UC) as well. Targets are demonstrated to prevent endorgan dysfunction, specifically bowel damage and its complications, and lastly colorectal cancer. Recently, the scientific community has tried to define further targets beyond those currently recommended, namely mucosal healing and clinical remission. Studies that prospectively investigated this approach in UC are scanty and a treat-to-target (T2T) algorithm is not routinely used in daily clinical practice. OBJECTIVE We aim to review current evidence on T2T in UC and discuss its adoption in routine clinical practice as well as in clinical trials. METHODS A PubMed search was conducted in February 2020 to identify published papers investigating targets' achievement rates in UC. RESULTS Different targets can be achieved through approved drugs for mild to moderate UC; histological remission is emerging as a robust target with respect to long-term outcomes. CONCLUSION Further studies to compare a T2T strategy with the traditional care are needed, particularly in the mild to moderate spectrum of disease.
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Affiliation(s)
- Arianna Dal Buono
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | - Giulia Roda
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | - Marjorie Argollo
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University of Lorraine, 54500 Vandoeuvre-les- Nancy, France
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
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7
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Abstract
Mucosal healing (MH) is the goal of the “treat to target” strategy in Crohn's disease (CD), which seeks to prevent disability. However, evidence is limited regarding whether achieving MH can reduce disability in CD. We aimed to estimate the probability of disabling disease and to investigate the association between MH and disabling disease in CD.
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8
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Chen P, Zhou G, Lin J, Li L, Zeng Z, Chen M, Zhang S. Serum Biomarkers for Inflammatory Bowel Disease. Front Med (Lausanne) 2020; 7:123. [PMID: 32391365 PMCID: PMC7188783 DOI: 10.3389/fmed.2020.00123] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/20/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids. Aims: To review the available data on serological biomarkers for IBD. Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD. Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management. Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.
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Affiliation(s)
- Peng Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Gaoshi Zhou
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingxia Lin
- Division of Blood Transfusion, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Li Li
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhirong Zeng
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shenghong Zhang
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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9
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Limdi JK, Picco M, Farraye FA. A review of endoscopic scoring systems and their importance in a treat-to-target approach in inflammatory bowel disease (with videos). Gastrointest Endosc 2020; 91:733-745. [PMID: 31786161 DOI: 10.1016/j.gie.2019.11.032] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 11/19/2019] [Indexed: 02/08/2023]
Abstract
Endoscopic assessment is currently the criterion standard for the diagnosis and assessment of mucosal disease activity, prognosis and monitoring for dysplasia, and assessment of response to therapy. Wider appreciation of the potential disconnect between symptoms and objective measures of disease activity and evidence that uncontrolled inflammation may lead to progressive intestinal injury and irreversible bowel damage with adverse events has led to the concept of treating to target. Treating to target is defined as treating patients with high risk for disease progression early to prevent or limit intestinal injury or disability. Endoscopic remission (mucosal healing) has emerged as a key goal of therapy. Although there are no currently validated definitions of endoscopic mucosal remission, the use of endoscopic scoring systems add uniformity and objectivity and aid standardization with reporting of mucosal appearance, augmenting clinical decision making. A plethora of scoring systems exist to define activity, response, and remission in both Crohn's disease and ulcerative colitis. In this review, we discuss the most commonly used endoscopic scoring systems and proposed definitions of response and remission, and how they can be integrated into a treat-to-target approach to optimize patient outcomes.
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Affiliation(s)
- Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, Manchester, United Kingdom
| | - Michael Picco
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center, Mayo Clinic, Jacksonville, Florida, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center, Mayo Clinic, Jacksonville, Florida, USA
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10
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Colombel JF, D’haens G, Lee WJ, Petersson J, Panaccione R. Outcomes and Strategies to Support a Treat-to-target Approach in Inflammatory Bowel Disease: A Systematic Review. J Crohns Colitis 2020; 14:254-266. [PMID: 31403666 PMCID: PMC7008150 DOI: 10.1093/ecco-jcc/jjz131] [Citation(s) in RCA: 184] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Management of Crohn's disease and ulcerative colitis has typically relied upon treatment intensification driven by symptoms alone. However, a 'treat-to-target' management approach may help to address underlying inflammation, minimise disease activity at early stages of inflammatory bowel disease, limit progression, and improve long-term outcomes. METHODS A systematic literature review was conducted to identify data relevant to a treat-to-target approach in inflammatory bowel disease, published between January 1, 2007 and May 15, 2017. RESULTS Consistent with recommendations of the Selecting Therapeutic Targets in Inflammatory Bowel Disease [STRIDE] working group, studies have investigated factors influencing the achievement of both endoscopic and histological mucosal healing and patient-level outcomes in inflammatory bowel disease [IBD]. Histological healing and biomarker levels have also been shown to be modifiable outcomes. Although there is a lack of prospectively derived evidence validating mucosal healing as a treatment target, data are emerging to suggest that targeting mucosal healing or inflammation rather than symptoms may be cost-effective in some settings. The review highlighted several strategies that may support the implementation of a treat-to-target approach in IBD. The prospective randomised CALM study demonstrated how tight control [whereby treatment decisions are based on close monitoring of inflammatory biomarkers] leads to improvements in endoscopic and clinical outcomes. The review also considered the influence of coordinated care from a multidisciplinary team and patient engagement with improved adherence, as well as the role of therapeutic drug monitoring in inflammatory bowel disease management. CONCLUSIONS A treat-to-target strategy may impact on disease progression and improve outcomes in inflammatory bowel disease. Prospective studies including long-term data are required to ensure that the most appropriate targets and strategies are identified.
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Affiliation(s)
- Jean-Frédéric Colombel
- Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Geert D’haens
- Amsterdam University Medical Centers – Inflammatory Bowel Disease Unit, University of Amsterdam, Amsterdam, The Netherlands
| | - Wan-Ju Lee
- Global Gastroenterology, AbbVie, North Chicago, IL, USA
| | | | - Remo Panaccione
- Inflammatory Bowel Disease Clinic, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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11
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Gonczi L, Bessissow T, Lakatos PL. Disease monitoring strategies in inflammatory bowel diseases: What do we mean by "tight control"? World J Gastroenterol 2019; 25:6172-6189. [PMID: 31749591 PMCID: PMC6848014 DOI: 10.3748/wjg.v25.i41.6172] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Revised: 09/26/2019] [Accepted: 10/30/2019] [Indexed: 02/06/2023] Open
Abstract
In recent years, there has been a critical change in treatment paradigms in inflammatory bowel diseases (IBD) triggered by the arrival of new effective treatments aiming to prevent disease progression, bowel damage and disability. The insufficiency of symptomatic disease control and the well-known discordance between symptoms and objective measures of disease activity lead to the need of reviewing conventional treatment algorithms and developing new concepts of optimal therapeutic strategy. The treat-to-target strategies, defined by the selecting therapeutic targets in inflammatory bowel disease consensus recommendation, move away from only symptomatic disease control and support targeting composite therapeutic endpoints (clinical and endoscopical remission) and timely assessment. Emerging data suggest that early therapy using a treat-to-target approach and an algorithmic therapy escalation using regular disease monitoring by clinical and biochemical markers (fecal calprotectin and C-reactive protein) leads to improved outcomes. This review aims to present the emerging strategies and supporting evidence in the current therapeutic paradigm of IBD including the concepts of "early intervention", "treat-to-target" and "tight control" strategies. We also discuss the real-word experience and applicability of these new strategies and give an overview on the future perspectives and areas in need of further research and potential improvement regarding treatment targets and ("tight") disease monitoring strategies.
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Affiliation(s)
- Lorant Gonczi
- First Department of Medicine, Semmelweis University, Budapest H-1083, Hungary
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Centre, Montreal H3G 1A4, Quebec, Canada
| | - Peter Laszlo Lakatos
- First Department of Medicine, Semmelweis University, Budapest H-1083, Hungary
- Division of Gastroenterology, McGill University Health Centre, Montreal H3G 1A4, Quebec, Canada
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12
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Jerger L, Hyams JS. Special considerations for biologic medications in pediatric ulcerative colitis. Expert Opin Biol Ther 2019; 20:429-435. [PMID: 31652087 DOI: 10.1080/14712598.2020.1685492] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Introduction: More extensive disease, high rates of corticosteroid refractory and dependent disease, and the potential impact of disease on growth and development differentiate inflammatory bowel disease in children from adults. This is particularly evident in ulcerative colitis where pancolitis predominates, success of mesalamine alone in achieving remission is less than 50%, and there is a high need for immunomodulator or biologic therapies.Areas Covered: This review describes the use of infliximab, adalimumab, golimumab, and vedolizumab in the treatment of children with ulcerative colitis but is limited in scope due to the paucity of controlled clinical trials. A search of existing literature with keywords of these specific biological therapies as well as 'pediatric', 'ulcerative colitis,' and 'inflammatory bowel disease' was used to complete this review.Expert Opinion: Therapeutic drug monitoring has become standard of care when assessing dosing and changes in therapy and will play a role in future treatment planning.
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Affiliation(s)
- Logan Jerger
- Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford, USA
| | - Jeffrey S Hyams
- Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford, USA
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13
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Vasudevan A, Gibson PR, Van Langenberg DR. Systematic Review: Cost-effective Strategies of Optimizing Anti-tumor Necrosis and Immunomodulators in Inflammatory Bowel Disease. Inflamm Bowel Dis 2019; 25:1462-1473. [PMID: 30689858 DOI: 10.1093/ibd/izy399] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 12/02/2018] [Accepted: 12/20/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Medication costs in inflammatory bowel disease (IBD) are now the principal driver of health care costs. Cost-effective strategies to optimize and rationalize treatment are therefore necessary. METHODS A systematic review until April 30, 2018, was performed to identify economic evaluations of strategies to optimize infliximab, adalimumab, and immunomodulators for the treatment of IBD in adults. A qualitative synthesis of the identified studies was performed. RESULTS Seventy articles were identified that met the inclusion criteria. Adalimumab seems cost-effective compared with infliximab as maintenance therapy for moderate to severe Crohn's disease (CD). Infusion costs are a significant additional treatment cost with infliximab. However, other studies found biosimilar infliximab more cost-effective than alternative biologics in fistulizing and moderate-severe luminal CD-although the latter did not reach a willingness-to-pay threshold of <$50,000. In moderate-severe ulcerative colitis, infliximab seems more cost-effective than adalimumab. Multiple tailored approaches to treatment based on objective markers of disease activity or efficacy have been shown to be cost-effective in CD, including following secondary loss of response to anti-TNF therapy for postoperative recurrence and in escalating treatment. For immunomodulator treatment, both thiopurine methyltransferase (TPMT) testing before commencing thiopurines and thiopurine metabolite testing for dose optimization seem cost-effective. CONCLUSION In a win-win for patients and payers, several potential avenues to achieve cost-effectiveness-but also therapeutic optimization of anti-TNF therapies-were elucidated in this review with comparatively sparse data for immunomodulators. Optimizing immunomodulator and anti-tumor necrosis factor alpha therapy to achieve objective disease control seems to be cost-effective at conventional willingness-to-pay thresholds in a number of clinical settings.
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Affiliation(s)
- Abhinav Vasudevan
- Department of Gastroenterology and Hepatology, Eastern Health, Monash University, Eastern Health Clinical School, Box Hill, Victoria, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Health and Monash University, Victoria, Australia
| | - Daniel R Van Langenberg
- Department of Gastroenterology and Hepatology, Eastern Health, Monash University, Eastern Health Clinical School, Box Hill, Victoria, Australia
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14
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Agrawal M, Colombel JF. Treat-to-Target in Inflammatory Bowel Diseases, What Is the Target and How Do We Treat? Gastrointest Endosc Clin N Am 2019; 29:421-436. [PMID: 31078245 DOI: 10.1016/j.giec.2019.02.004] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Inflammatory bowel diseases, including Crohn disease (CD) and ulcerative colitis (UC), are chronic, progressive, immune-mediated inflammatory diseases of the gastrointestinal tract. Early therapy using a treat-to-target (T2T) approach, which implies identification of a pre-defined target, followed by optimization of therapy and regular monitoring until the goal is achieved is critical in preventing adverse long-term outcomes. In this review, the authors discuss the T2T guidance developed by the Selecting Therapeutic Targets in Inflammatory Bowel Disease committee, new evidence published on the role of various targets in CD and UC, as well as the real-world applicability of T2T."
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Affiliation(s)
- Manasi Agrawal
- Division of Gastroenterology, Lenox Hill Hospital, Northwell Health, 100 East 77th Street, New York, NY 10075, USA.
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1428 Madison Avenue, New York, NY 10029, USA
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Mucosal healing in inflammatory bowel disease: Expanding horizon. Indian J Gastroenterol 2019; 38:98-109. [PMID: 31037509 DOI: 10.1007/s12664-019-00950-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 02/27/2019] [Indexed: 02/06/2023]
Abstract
Management of inflammatory bowel diseases has witnessed paradigm shift from 5-aminosalicylic acid and glucocorticoids to various immunosuppressant and biological agents. Targets of therapy have also been changed drastically from symptomatic improvement to mucosal, histological healing, and recently transmural healing. Mucosal healing is associated with reduced need of steroid therapy, hospitalization, and surgery. However, whether mucosal healing alters the natural history of disease remains to be proven. Though assessment of mucosal healing is traditionally done by endoscopic examination, newer tests like fecal calprotectin, capsule endoscopy, and magnetic resonance enterography have also shown promising results. Various immunosuppressants and biologicals are the main therapy being used to achieve mucosal healing. This review focuses on the need for achieving mucosal healing, its long-term benefits, various methods and algorithm for diagnosis, and achievement of mucosal healing.
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Deepak P, Fletcher JG, Fidler JL, Barlow JM, Sheedy SP, Kolbe AB, Harmsen WS, Therneau T, Hansel SL, Becker BD, Loftus EV, Bruining DH. Predictors of Durability of Radiological Response in Patients With Small Bowel Crohn's Disease. Inflamm Bowel Dis 2018; 24:1815-1825. [PMID: 29668921 PMCID: PMC6391864 DOI: 10.1093/ibd/izy074] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The long-term significance of radiological transmural response (TR) as a treatment goal at the first follow-up scan in small bowel Crohn's disease (CD) has been previously shown. We examined the durability of a long-term strategy of treating to a target of radiological TR and the influence of baseline predictors on the maintenance of TR. METHODS Small bowel CD patients between January 1, 2002, and December 31, 2014, were identified with serial computed tomography enterography (CTE)/magnetic resonance enterography (MRE) before and after initiation of therapy or on maintenance therapy. Overall TR (inflammatory lesions with/without strictures) w1as characterized by abdominal radiologists in up to 5 small bowel lesions per patient at each serial scan until last follow-up or small bowel resection, as response, partial response, or nonresponse. The rate of conversion between TR states and transition to surgery, including the effect of baseline patient/disease characteristics, was examined using a multistate model (mstate R-package). RESULTS CD patients (n = 150, 705 CTE/MRE) with a median of 4 CTE/MRE during 4.6 years of follow-up, 49% with ileal-only distribution, had 260 examined bowel segments. Conversion from response to partial response/nonresponse was 37.4% per year of follow-up with no transitions seen directly from response to surgery. Current smoking status (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.1-4.3) and internal penetrating disease at baseline scan (HR, 2.2; 95% CI, 1.2-4.1) were associated with a 2-fold increased risk of transition from partial response/nonresponse to surgery. CONCLUSIONS Achievement and maintenance of radiological response is associated with avoidance of small bowel surgery. Continued follow-up with CTE/MRE is recommended to identify loss of response, especially in current smokers and patients with internal penetrating disease at baseline CTE/MRE.
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Affiliation(s)
- Parakkal Deepak
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota,Department of Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri
| | - Joel G Fletcher
- Division of Abdominal Imaging, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Jeff L Fidler
- Division of Abdominal Imaging, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - John M Barlow
- Division of Abdominal Imaging, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Shannon P Sheedy
- Division of Abdominal Imaging, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Amy B Kolbe
- Division of Abdominal Imaging, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - William S Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Terry Therneau
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Stephanie L Hansel
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Brenda D Becker
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota,Address correspondence to: David H. Bruining, MD, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905 ()
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Economic Evaluations of Treatments for Inflammatory Bowel Diseases: A Literature Review. Can J Gastroenterol Hepatol 2018; 2018:7439730. [PMID: 30009158 PMCID: PMC6020513 DOI: 10.1155/2018/7439730] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 01/17/2018] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The objective of this literature review was to evaluate the existing evidence regarding the cost-effectiveness of treatment options in IBD. METHODS A systematic review of the literature was conducted to identify economic evaluations of IBD therapy. The literature search was performed using electronic databases MEDLINE and EMBASE. Searches were limited to full economic evaluations published in English or French between 2004 and 2016. RESULTS A total of 5,403 potentially relevant studies were identified. After screening titles and abstracts, 48 studies were included, according to the eligibility criteria. A total of 56% and 42% of the studies were assessing treatments of UC or CD, respectively. Treatment options under evaluation included biological agents, mesalamine, immunosuppressants, and surgery. The majority of studies evaluated the cost-effectiveness of biological treatments. Biological therapies were dominant in 23% of the analyses and were cost-effective according to a $CAD50,000/QALY and $CAD100,000/QALY threshold in 41% and 62% of the analyses, respectively. CONCLUSION This literature review provided a comprehensive overview of the economic evaluations for the different treatment options for IBD over the past 12 years and represents a helpful reference for future economic evaluations.
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Abstract
BACKGROUND Mucosal healing (MH) is associated with improved clinical outcomes in patients with Crohn's disease (CD) and ulcerative colitis (UC). MH as a target for treatment has been suggested, although there is little pediatric data. The goal of this study was to evaluate MH in clinical practice in pediatric patients with inflammatory bowel disease in clinical remission. METHODS A retrospective review of electronic health record data was performed on all patients with CD or UC who underwent at least 2 colonoscopies from 2010 through 2016. Only patients in clinical remission undergoing a scope for MH were included in our study. The incidence of MH and histologic healing (HH) was analyzed, along with cumulative rates of MH in each group. MH was defined by both physician assessment of MH and an endoscopic score of zero for CD and UC. RESULTS A total of 76 patients with CD and 28 patients with UC underwent at least one MH scope while in clinical remission. Of the 76 patients with CD, 51 patients (67%) demonstrated MH by physician assessment, 34 patients (45%) demonstrated MH by a simple endoscopic score for CD of zero, and 35 patients (46%) demonstrated HH. Of the 28 patients with UC, 20 patients (71%) demonstrated MH by physician assessment, 10 patients (36%) demonstrated MH by a Mayo score of zero, and 10 patients (36%) demonstrated HH. Nineteen patients underwent a second MH scope and 11 (58%) demonstrated MH by physician assessment, 7 patients (37%) demonstrated MH by simple endoscopic score for CD or Mayo scores of zero, and 5 patients (26%) demonstrated HH. Of those patients with active disease, 21 of 25 patients with CD underwent escalation of therapy, whereas 8 of 8 patients with UC underwent escalation of therapy. Cumulative rates of MH when defined by physician assessment were 79% (60 of 76 patients) in CD and 79% (22 of 28 patients) in UC. CONCLUSIONS MH is feasible in pediatric CD and UC, and rates of cumulative MH in pediatric patients are similar to previously published adult data. In children with inflammatory bowel disease in clinical remission, approximately one-third demonstrate active disease at endoscopy.
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Mao R, Qiu Y, Chen BL, Zhang SH, Feng R, He Y, Zeng ZR, Ben-Horin S, Chen MH. Factors associated with the achievement of mucosal healing in Crohn's disease: the benefit of endoscopic monitoring in treating to target. Therap Adv Gastroenterol 2017; 10:453-463. [PMID: 28567115 PMCID: PMC5424871 DOI: 10.1177/1756283x17698089] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2016] [Accepted: 01/30/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Mucosal healing (MH), the proposed treat to target in Crohn's disease (CD), is associated with improved disease outcomes. There are still scant data on factors associated with achieving MH in clinical practice. We evaluated the probability of achieving MH and identified factors predictive of subsequent MH in patients with CD. METHODS This was a retrospective, observational cohort study. A total of 272 patients with CD with serial endoscopy assessment and subsequent therapeutic management were reviewed. The primary outcome was MH. The cumulative incidence of MH and endoscopic improvement was estimated using the Kaplan-Meier method. Factors independently associated with MH were identified using the Cox proportional hazards model. RESULTS Of the 272 patients, 126 (46.32%) achieved MH after a median follow-up period of 33 months (interquartile range: 27-38 months). Factors independently associated with MH by multivariate analysis were time between endoscopic procedures within 26 weeks (hazard ratio [HR]: 1.56; 95% confidence interval [CI]: 1.05-3.39), adjustment of medical therapy when MH was not achieved (HR: 2.07; 95% CI: 1.26-2.33), prior enteric fistula (HR: 0.22; 95% CI: 0.06-0.91), perianal disease at CD diagnosis (HR: 0.58; 95% CI: 0.35-0.95), and C-reactive protein normalization within 12 weeks (HR: 3.23; 95% CI: 1.82-5.88). Similar factors have also been identified for endoscopic improvement. CONCLUSIONS Performing serial endoscopic procedures at a 26-week interval and subsequent adjustment in medical treatment are helpful in achieving MH. Endoscopic monitoring plays an important role in the treating to target of CD.
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Affiliation(s)
| | | | - Bai-Li Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Sheng-Hong Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Rui Feng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Yao He
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Zhi- Rong Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Shomron Ben-Horin
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China, and IBD Service, Department of Gastroenterology, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Tel HaShomer, Israel
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20
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Cholapranee A, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials. Aliment Pharmacol Ther 2017; 45:1291-1302. [PMID: 28326566 PMCID: PMC5395316 DOI: 10.1111/apt.14030] [Citation(s) in RCA: 241] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/30/2017] [Accepted: 02/16/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. AIM To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. METHODS We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. RESULTS A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. CONCLUSIONS Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.
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Affiliation(s)
- Aurada Cholapranee
- Department of Internal Medicine, Montefiore Medical Center, New York, New York, USA
| | - Glen S Hazlewood
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada,McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada
| | - Gilaad G. Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Laurent Peyrin-Biroulet
- Inserm U954 and Department of Gastroenterology, Nancy University Hospital, and Université de Lorraine, Vandoeuvre, France
| | - Ashwin N Ananthakrishnan
- Gastroenterology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA
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Hu H, Xiang C, Qiu C, Chen Z, Huang S, Liang L, Wang X. Discontinuation of Scheduled Infliximab in Crohn's Patients With Clinical Remission: A Retrospective Single-Center Study. Gastroenterology Res 2017; 10:92-99. [PMID: 28496529 PMCID: PMC5412541 DOI: 10.14740/gr800w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/03/2017] [Indexed: 12/18/2022] Open
Abstract
Background It is crucial to determine whether infliximab (IFX) therapy could be safely interrupted in Crohn’s disease (CD) patients with clinical remission. The outcome and risk predictors of relapse after IFX therapy stopped are controversial. The aim was to assess the relapse and predictive factors after IFX discontinuation in CD patients with clinical remission. Methods A retrospective cohort of CD patients with clinical remission who discontinued scheduled IFX therapy at Nanfang Hospital were included. The primary outcome was relapse. All patients were followed up for more than 3 months. Demographic, clinical, and laboratory parameters were evaluated for their predictive value of relapse. Results After a median follow-up period of 12.2(4.8 - 21.2) months, 55.7% (59/106) patients experienced a relapse. The cumulative relapse rate was 39%, 48% and 61% at 6 months, 1 year and 2 years, respectively. Based on multivariable analysis, CD-related surgery before infusion (P = 0.013, hazard ratio (HR): 2.671, 95% confidential interval (CI): 1.230 - 5.798), step-up therapeutic regimen (P = 0.035, HR: 2.073, 95%CI: 1.054 - 4.080), low albumin (Alb) level at week 0 (P = 0.022, HR: 3.431, 95%CI: 1.196 - 9.846) and high C-reactive protein (CRP) level at week 30 (P = 0.007, HR: 2.643, 95%CI: 1.310 - 5.332) were associated with clinical relapse. Conclusions After cessation of scheduled IFX therapy in CD patients with clinical remission, nearly half of the patients experienced a relapse within 1 year. In the event of the presence of certain predictive factors, IFX scheduled therapy should probably be continued.
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Affiliation(s)
- Huiqin Hu
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,These authors contributed equally to this work
| | - Cheng Xiang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,These authors contributed equally to this work
| | - Chen Qiu
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhao Chen
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Silin Huang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Li Liang
- Departmemt of Pathology, Southern Medical University, Guangzhou, China
| | - Xinying Wang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Sofia MA, Rubin DT. The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions. Dig Dis Sci 2017; 62:833-842. [PMID: 28197743 DOI: 10.1007/s10620-017-4479-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.
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Affiliation(s)
- M Anthony Sofia
- Inflammatory Bowel Disease Center, University of Chicago Medicine, 5841 South Maryland Avenue, MC 4076, Chicago, IL, 60637, USA.
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, 5841 South Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
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Are Anti-Tumor Necrosis Factor Trough Levels Predictive of Mucosal Healing in Patients With Inflammatory Bowel Disease?: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2016; 50:733-41. [PMID: 26535480 DOI: 10.1097/mcg.0000000000000441] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
GOALS Our primary goal was to evaluate whether anti-tumor necrosis factor (TNF)-α trough levels above author-determined thresholds are associated with increased rates of mucosal healing among patients with Crohn's disease and ulcerative colitis. BACKGROUND The introduction of anti-TNF agents has considerably advanced the approach to the management of patients with inflammatory bowel disease (IBD). As use of anti-TNF therapy has increased, there has been new interest in algorithms focused on the monitoring of pharmacodynamics and pharmacokinetics to improve outcomes. In addition, there has been an increased focus on mucosal healing as marker of treatment success. STUDY We performed a systematic review and meta-analysis. The studies examined were restricted to randomized controlled trials and cohort studies with a high Jadad or Newcastle-Ottawa score. RESULTS All pooled analyses were based on a random-effects model. Data from 2 randomized controlled trials and 5 observational studies (n=652) were included in the meta-analysis. Among patients with IBD, anti-TNF trough levels above prespecified values were associated with increased rates of mucosal healing (OR=5.57; 95% CI, 3.80-8.15). There was no heterogeneity detected (I=0, Q=5.88, df=6; P=0.436) and there was minimal evidence of publication bias present. CONCLUSIONS There is a strong relationship between anti-TNF trough levels and increased rates of mucosal healing among patients with IBD. Given the increased emphasis on mucosal healing as an outcome in practice and clinical trials, continued focus on the proactive use of pharmacokinetic testing appears warranted.
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Zenlea T, Yee EU, Rosenberg L, Boyle M, Nanda KS, Wolf JL, Falchuk KR, Cheifetz AS, Goldsmith JD, Moss AC. Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission: A Prospective Study. Am J Gastroenterol 2016; 111:685-90. [PMID: 26977756 DOI: 10.1038/ajg.2016.50] [Citation(s) in RCA: 133] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Accepted: 01/15/2016] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Objective evidence of inflammation has been associated with the risk of relapse in patients with ulcerative colitis (UC) who are in clinical remission. We compared endoscopic and histologic grades for their ability to predict clinical relapse in this patient population. METHODS Patients with UC in clinical remission were prospectively enrolled into an observational cohort. Baseline endoscopic scores (Mayo) and histological (Geboes) grades and blood markers were collected. All subjects were followed for 12 months and relapse determined using clinical indices. RESULTS A total of 179 subjects were enrolled into the study and followed for 12 months. Clinical relapse occurred in 23%; 5% were hospitalized, and 2% underwent colectomy. In univariate analysis, the baseline Mayo endoscopy score and the Geboes histology grade were significantly associated with the later development of clinical relapse (P<0.001 for both), but only the histology grade remained significant in a multivariate model (P=0.006). The relative risk of clinical relapse was 3.5 (95% CI 1.9-6.4, P<0.0001) in subjects whose baseline Geboes grade was ≥3.1. The area under the curve was 0.73 for the Geboes histology grade to identify subjects at risk of future clinical relapse. Of the patients in clinical, endoscopic, and histological remission at baseline (n=82), only 7% had a clinical relapse over the subsequent 12 months. CONCLUSIONS Histology grade has the strongest association with the risk of clinical relapse in patients with UC who are in clinical remission. Consideration should be given to including this end point in evaluating therapy for UC.
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Affiliation(s)
- Talia Zenlea
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Eric U Yee
- Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Laura Rosenberg
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Marie Boyle
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Kavinderjit S Nanda
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Jacqueline L Wolf
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Kenneth R Falchuk
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Adam S Cheifetz
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Jeffrey D Goldsmith
- Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Alan C Moss
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA
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Shah SC, Colombel JF, Sands BE, Narula N. Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn's disease. Aliment Pharmacol Ther 2016; 43:317-33. [PMID: 26607562 DOI: 10.1111/apt.13475] [Citation(s) in RCA: 267] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 10/10/2015] [Accepted: 10/22/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clinical manifestations of Crohn's disease (CD) do not reliably correlate with endoscopic activity. While treating to achieve clinical remission (CR) has neither proven to improve CD outcomes nor alter the natural disease course, it is unclear whether targeting objective measures like mucosal healing (MH) is associated with improved long-term outcomes. AIM To perform a systematic review and meta-analysis comparing long-term outcomes in active CD patients who achieve MH compared to those who do not. METHODS We performed a systematic literature search to identify studies with prospective cohorts of active CD patients that included outcomes of patients who achieved MH at first endoscopic assessment (MH1) compared to those who did not. The primary outcome was long-term (≥50 weeks) CR. Secondary outcomes included CD-related surgery-free rate, hospitalisation-free rate and long-term MH rate. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated. RESULTS Twelve studies with 673 patients met inclusion criteria. Patients achieving MH1 had a pooled OR of 2.80 (95%CI, 1.91-4.10) for achieving long-term CR, 2.22 (95%CI, 0.86-5.69) for CD-related surgery-free rate, and 14.30 (95%CI, 5.57-36.74) for long-term MH. Sensitivity analyses suggested no difference in outcomes if MH1 was achieved on biologics vs. non-biologics. No significant publication bias or heterogeneity was detected. CONCLUSIONS Achieving MH1 is associated with increased rates of long-term clinical remission, and maintenance of mucosal healing in active Crohn's disease and may therefore be a reasonable therapeutic target.
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Affiliation(s)
- S C Shah
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - J-F Colombel
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - B E Sands
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - N Narula
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Qiu Y, Chen BL, Mao R, Zhang SH, He Y, Zeng ZR, Chen MH. Early Thiopurines Versus Conventional Step-Care Therapy for Modifying the Disease Course of Early Crohn's Disease: A Tertiary Referral Center Cohort Study. Medicine (Baltimore) 2015; 94:e1148. [PMID: 26252273 PMCID: PMC4616617 DOI: 10.1097/md.0000000000001148] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The impact of thiopurines (TP) on the long-term outcome of early Crohn disease (CD) is still controversial. The present study designed as a comparison of conventional step-care to alternative treatment paradigms for disease progression.This longitudinal cohort study examined the established CD patients from a university-based inflammatory bowel disease referral center. Outcomes of mucosal healing (MH), CD-related surgery or hospitalization, and clinical remission were compared based on timing of initiation of TP therapy. The cumulative incidence of events was estimated by Kaplan-Meier method.One-hundred ninety patients with early CD were included. After a median follow-up of 57 months (interquartile range, 31.3-76.2), 29 patients undergone abdominal surgeries, 48 patients hospitalized, and 68 patients experienced clinical flares. A higher cumulative proportion of patients in the top-down (TD) group achieving MH than both the accelerated step-up (AC) group and conventional management (CM) group at month 36 (78.8% vs 39.9% and 42.2%, respectively; P = 0.001). There was a trend, albeit not significant, for an increased proportion of patients free of CD-related intestinal surgery in the TD group at month 60 (P = 0.16). However, among secondary outcomes, an early TP-based AC or TD strategy was not associated with improvement in clinical remission rates compared with a CM strategy at month 60 (P = 0.79). No significant difference was observed between early TP and CM for rates of MH, CD-related intestinal surgery or hospitalization, and clinical remission.Both AC and CM strategy were minimally effective for disease modification. TD strategy has the potential of achieving higher rates MH. Our results support the TD strategy in patients with early CD at risk for a disabling course.
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Affiliation(s)
- Yun Qiu
- From the Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
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Bouguen G, Levesque BG, Feagan BG, Kavanaugh A, Peyrin-Biroulet L, Colombel JF, Hanauer SB, Sandborn WJ. Treat to target: a proposed new paradigm for the management of Crohn's disease. Clin Gastroenterol Hepatol 2015; 13:1042-50.e2. [PMID: 24036054 DOI: 10.1016/j.cgh.2013.09.006] [Citation(s) in RCA: 201] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2013] [Revised: 08/26/2013] [Accepted: 09/01/2013] [Indexed: 02/07/2023]
Abstract
The traditional management of Crohn's disease, which is based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of Crohn's disease and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity by using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high-risk patients. This review evaluates current literature on this topic and proposes a definition for the concept of treating to targets for Crohn's disease.
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Affiliation(s)
- Guillaume Bouguen
- Division of Gastroenterology, University of California San Diego, La Jolla, California; Service des Maladie de l'Appareil Digestif et INSERM U991, Centre Hospitalier Universitaire Pontchaillou et Université de Rennes 1, Rennes, France
| | - Barrett G Levesque
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Brian G Feagan
- Robarts Clinical Trials, University of Western Ontario, London, Ontario, Canada
| | - Arthur Kavanaugh
- Division of Rheumatology, University of California San Diego, La Jolla, California
| | - Laurent Peyrin-Biroulet
- INSERM U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Vandoeuvre-les-Nancy, France
| | | | | | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California.
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Magalhães J, Castro FDD, Carvalho PB, Moreira MJ, Cotter J. Quality of life in patients with inflammatory bowel disease: importance of clinical, demographic and psychosocial factors. ARQUIVOS DE GASTROENTEROLOGIA 2015; 51:192-7. [PMID: 25296078 DOI: 10.1590/s0004-28032014000300005] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2014] [Accepted: 05/14/2014] [Indexed: 12/16/2022]
Abstract
CONTEXT Inflammatory bowel disease causes physical and psychosocial consequences that can affect the health related quality of life. OBJECTIVES To analyze the relationship between clinical and sociodemographic factors and quality of life in inflammatory bowel disease patients. METHODS Ninety two patients with Crohn's disease and 58 with ulcerative colitis, filled in the inflammatory bowel disease questionnaire (IBDQ-32) and a questionnaire to collect sociodemographic and clinical data. The association between categorical variables and IBDQ-32 scores was determined using Student t test. Factors statistically significant in the univariate analysis were included in a multivariate regression model. RESULTS IBDQ-32 scores were significantly lower in female patients (P<0.001), patients with an individual perception of a lower co-workers support (P<0.001) and career fulfillment (P<0.001), patients requiring psychological support (P = 0.010) and pharmacological treatment for anxiety or depression (P = 0.002). A multivariate regression analysis identified as predictors of impaired HRQOL the female gender (P<0.001) and the perception of a lower co-workers support (P = 0.025) and career fulfillment (P = 0.001). CONCLUSIONS The decrease in HRQQL was significantly related with female gender and personal perception of disease impact in success and social relations. These factors deserve a special attention, so timely measures can be implemented to improve the quality of life of patients.
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Affiliation(s)
- Joana Magalhães
- Gastrentroenterology Department, Centro Hospitalar do Alto Ave, E.P.E., Guimarães, Guimarães, Portugal
| | - Francisca Dias de Castro
- Gastrentroenterology Department, Centro Hospitalar do Alto Ave, E.P.E., Guimarães, Guimarães, Portugal
| | - Pedro Boal Carvalho
- Gastrentroenterology Department, Centro Hospitalar do Alto Ave, E.P.E., Guimarães, Guimarães, Portugal
| | - Maria João Moreira
- Gastrentroenterology Department, Centro Hospitalar do Alto Ave, E.P.E., Guimarães, Guimarães, Portugal
| | - José Cotter
- Gastrentroenterology Department, Centro Hospitalar do Alto Ave, E.P.E., Guimarães, Guimarães, Portugal
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Mucosal healing did not predict sustained clinical remission in patients with IBD after discontinuation of one-year infliximab therapy. PLoS One 2014; 9:e110797. [PMID: 25330148 PMCID: PMC4203839 DOI: 10.1371/journal.pone.0110797] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 09/17/2014] [Indexed: 12/13/2022] Open
Abstract
Aim To assess the endoscopic activity and Clinical activity after a one-year period of infliximab therapy and to evaluate the association between mucosal healing and need for retreatment after stopping infliximab in patients with Inflammatory bowel disease (IBD). Methods The data from 109 patients with Crohn’s disease (CD) and 107 patients with Ulcerative colitis (UC) received one-year infliximab were assessed. The primary endpoint of the study was the proportion of clinical remission, mucosal healing and full remission in IBD after the one-year period of maintenance infliximab therapy. The secondary endpoint was the frequency of relapses in the next year. Results A total of 84.4% (92/109) CD patients and 81.3% (87/107) UC patients achieved clinical remission, 71.56% (78/109) of CD patients and 69.16% (74/107) of UC patients achieved mucosal healing, 56.88% (62/109) of CD patients and 54.21% (58/107) of UC patients achieved full remission at the end of the year of infliximab therapy. Infliximab therapy was restarted in the 10.19% (22/216) patients (13 CD, 9 UC) who achieved mucosal healing, and 13.89% (30/216) patients (18 CD, 12 UC) who achieved clinical remission and 6.48% (14/216) patients (8 CD, 6 UC) who achieved full remission had to be retreated within the next year. Neither clinical remission nor mucosal healing was associated with the time to restarting Infliximab therapy in IBD. Conclusion Mucosal healing did not predict sustained clinical remission in patients with IBD in whom the infliximab therapies had been stopped. And stopping or continuing infliximab therapy may be determined by assessing the IBD patient’s general condition and the clinical activity.
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Abstract
OBJECTIVE The aim of the study was to prospectively evaluate clinical and mucosal responses to the specific carbohydrate diet (SCD) in children with Crohn disease (CD). METHODS Eligible patients with active CD (Pediatric Crohn's Disease Activity Index [PCDAI] ≥ 15) underwent a patency capsule and, if passed intact, capsule endoscopy (CE) was performed. Patients taking SCD were monitored for 52 weeks while maintaining all prescribed medications. Demographic, dietary, and clinical information, PCDAI, Harvey-Bradshaw Index (HBI), and Lewis score (LS) were collected at 0, 12, and 52 weeks. CEs were evaluated by an experienced reader blinded to patient clinical information and timing. RESULTS Sixteen patients were screened; 10 enrolled; and 9 completed the initial 12-week trial-receiving 85% of estimated caloric needs before, and 101% on the SCD. HB significantly decreased from 3.3 ± 2.0 to 0.6 ± 1.3 (P = 0.007) as did PCDAI (21.1 ± 5.9 to 7.8 ± 7.1, P = 0.011). LS declined significantly from 2153 ± 732 to 960 ± 433 (P = 0.012). Seven patients continued the SCD up to 52 weeks; HB (0.1 ± 0.4) and PCDAI (5.4 ± 5.5) remained improved (P = 0.016 and 0.027 compared to baseline), with mean LS at 1046 ± 372 and 2 patients showed sustained mucosal healing. CONCLUSIONS Clinical and mucosal improvements were seen in children with CD, who used SCD for 12 and 52 weeks. In addition, CE can monitor mucosal improvement in treatment trials for pediatric CD. Further studies are critically needed to understand the mechanisms underlying SCD's effectiveness in children with CD.
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Ananthakrishnan AN, Cheng SC, Cai T, Cagan A, Gainer VS, Szolovits P, Shaw SY, Churchill S, Karlson EW, Murphy SN, Kohane I, Liao KP. Serum inflammatory markers and risk of colorectal cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014; 12:1342-8.e1. [PMID: 24407106 PMCID: PMC4085150 DOI: 10.1016/j.cgh.2013.12.030] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Accepted: 12/21/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel diseases (IBDs) (Crohn's disease, ulcerative colitis) are at increased risk of colorectal cancer (CRC). Persistent inflammation is hypothesized to increase risk of CRC in patients with IBD; however, the few studies in this area have been restricted to cross-sectional assessments of histologic severity. No prior studies have examined association between C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) elevation and risk of CRC in an IBD cohort. METHODS From a multi-institutional validated IBD cohort, we identified all patients with at least one measured CRP or ESR value. Patients were stratified into quartiles of severity of inflammation on the basis of their median CRP or ESR value, and subsequent diagnosis of CRC was ascertained. Logistic regression adjusting for potential confounders was used to identify the independent association between CRP or ESR elevation and risk of CRC. RESULTS Our study included 3145 patients with at least 1 CRP value (CRP cohort) and 4008 with at least 1 ESR value (ESR cohort). Thirty-three patients in the CRP cohort and 102 patients in the ESR cohort developed CRC during a median follow-up of 5 years at a median age of 55 years. On multivariate analysis, there was a significant increase in risk of CRC across quartiles of CRP elevation (P(trend) = .017; odds ratio for quartile 4 vs quartile 1, 2.72; 95% confidence interval, 0.95-7.76). Similarly higher median ESR was also independently associated with risk of CRC across the quartiles (odds ratio, 2.06; 95% confidence interval, 1.14-3.74) (P(trend) = .007). CONCLUSIONS An elevated CRP or ESR is associated with increased risk of CRC in patients with IBD.
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Affiliation(s)
- Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
| | - Su-Chun Cheng
- Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
| | - Tianxi Cai
- Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
| | - Andrew Cagan
- Research IS and Computing, Partners HealthCare, Charlestown, Massachusetts
| | - Vivian S Gainer
- Research IS and Computing, Partners HealthCare, Charlestown, Massachusetts
| | - Peter Szolovits
- Massachusetts Institute of Technology, Cambridge, Massachusetts
| | - Stanley Y Shaw
- Harvard Medical School, Boston, Massachusetts; Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts
| | - Susanne Churchill
- i2b2 National Center for Biomedical Computing, Brigham and Women's Hospital, Boston, Massachusetts
| | - Elizabeth W Karlson
- Harvard Medical School, Boston, Massachusetts; Division of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Shawn N Murphy
- Harvard Medical School, Boston, Massachusetts; Research IS and Computing, Partners HealthCare, Charlestown, Massachusetts; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts
| | - Isaac Kohane
- Harvard Medical School, Boston, Massachusetts; i2b2 National Center for Biomedical Computing, Brigham and Women's Hospital, Boston, Massachusetts; Children's Hospital Boston, Boston, Massachusetts
| | - Katherine P Liao
- Harvard Medical School, Boston, Massachusetts; Division of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts
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Abstract
PURPOSE OF REVIEW Low-grade inflammation can persist in many patients with inflammatory bowel disease (IBD) who have otherwise obtained clinical remission. This review will summarize the prognostic implications of this finding for patients. RECENT FINDINGS At least 40% of patients with IBD in clinical remission have ongoing histological evidence of inflammation, despite continued use of maintenance therapy. Follow-up endoscopy and biopsy is the current gold standard for identifying these patients. Recent studies have suggested that an elevated C-reactive protein is associated with underlying histological abnormalities in this setting. Patients with histological inflammation at baseline are at increased risk of clinical relapse, hospitalization, surgery, and colon cancer in observational longitudinal studies. Even when endoscopic healing has been achieved, the presence of underlying architectural changes on biopsies can identify patients at a higher risk of complications. Prospective studies to determine if 'histological healing' provides additional outcome benefits beyond endoscopic or clinical remission alone have not been performed to date, but warrant inclusion in future trials. SUMMARY Chronic low-grade inflammation is common in patients with IBD in clinical remission. Clinicians should actively try to identify these patients and consider a lower threshold for intervention to reduce their higher risk of adverse outcomes over time.
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Endoscopic assessment and treating to target increase the likelihood of mucosal healing in patients with Crohn's disease. Clin Gastroenterol Hepatol 2014; 12:978-85. [PMID: 24246770 DOI: 10.1016/j.cgh.2013.11.005] [Citation(s) in RCA: 100] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Revised: 10/02/2013] [Accepted: 11/04/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Mucosal healing has been proposed as a goal for treatment because it is associated with improved clinical outcomes of patients with Crohn's disease (CD). However, little is known about the feasibility or probability of achieving mucosal healing in clinical practice. We evaluated the feasibility of treating patients to achieve mucosal healing based on endoscopic evaluation (treating to target). METHODS We reviewed the endoscopic outcomes of 67 patients with CD who had lesions detected by endoscopy. Patients underwent 2 to 4 subsequent endoscopic evaluations at the University of California San Diego and were followed up from 2011 through 2012; data were collected on therapies and patient management. The cumulative incidences of mucosal healing and endoscopic improvement were estimated using the Kaplan-Meier method. Factors independently associated with mucosal healing were identified using a Cox proportional hazards model. RESULTS After a median follow-up period of 62 weeks, 34 patients (50.7%) had mucosal healing and 41 patients (61.1%) had endoscopic improvement. The cumulative probabilities of mucosal healing were 12.7% and 45.0% at 24 and 52 weeks of treatment, respectively. Factors associated with mucosal healing were as follows: fewer than 26 weeks between endoscopic procedures (hazard ratio, 2.35; 95% confidence interval, 1.15-4.97; P = .035) and adjustment to medical therapy when mucosal healing was not observed (hazard ratio, 4.28; 95% confidence interval, 1.9-11.5; P = .0003). CONCLUSIONS In an endoscopic study of patients with CD, we found that assessment of endoscopic disease activity and adjustments to medical therapy (treat to target) increase the likelihood of mucosal healing.
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Farkas K, Lakatos PL, Szűcs M, Pallagi-Kunstár &E, Bálint A, Nagy F, Szepes Z, Vass N, Kiss LS, Wittmann T, Molnár T. Frequency and prognostic role of mucosal healing in patients with Crohn’s disease and ulcerative colitis after one-year of biological therapy. World J Gastroenterol 2014; 20:2995-3001. [PMID: 24659890 PMCID: PMC3961969 DOI: 10.3748/wjg.v20.i11.2995] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Revised: 09/28/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC).
METHODS: The data from 41 patients with CD and 22 patients with UC were assessed. Twenty-four CD patients received infliximab, and 17 received adalimumab. The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC.
RESULTS: Mucosal healing was achieved in 23 CD and 7 UC patients. Biological therapy had to be restarted in 78% of patients achieving complete mucosal healing with CD and in 100% of patients with UC. Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC.
CONCLUSION: Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.
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Stewart MJ, Kutcher M, Storr M, Seow CH. Interventions for induction of mucosal healing in ulcerative colitis. Hippokratia 2014. [DOI: 10.1002/14651858.cd010997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Michael J Stewart
- Cedars-Sinai Medical Center; Inflammatory Bowel Disease Center; Los Angeles California USA
| | - Matthew Kutcher
- Dalhousie University; Faculty of Medicine; Halifax Nova Scotia Canada
| | - Martin Storr
- University of Munich; Department of Medicine; Marchioninistr 15 Munich Germany 81377
| | - Cynthia H Seow
- University of Calgary; Departments of Medicine & Community Health Sciences; TRW Building Rm 6D18 3280 Hospital Drive NW Calgary Alberta Canada T2N 4Z6
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Interventions for maintenance of mucosal healing in ulcerative colitis. Hippokratia 2014. [DOI: 10.1002/14651858.cd010998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Abstract
Inflammatory bowel diseases (IBDs; e.g., Crohn's disease [CD] and ulcerative colitis [UC]) are chronic immunologically mediated diseases characterized by frequent relapses, often requiring hospitalization and surgery. There is substantial heterogeneity in the progressive natural history of disease with cumulative accrual of bowel damage and impairment of functioning. Recent advances in therapeutics have significantly improved our ability to achieve disease remission; yet therapies remain expensive and are associated with significant side effects precluding widespread use in all patients with IBD. Consequently, algorithms for the management of patients with IBD require a personalized approach incorporating an individual's projected likely natural history, the probability of response to a specific therapeutic agent and an informed approach to management of loss of response to current therapies.
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Affiliation(s)
- Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 165 Cambridge Street, 9th Floor, Boston, MA 02114, USA.
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Abstract
IMPORTANCE Treatment of Crohn disease is rapidly evolving, with the induction of novel biologic therapies and newer, often more intensive treatment approaches. Knowing how to treat individual patients in this quickly changing milieu can be a challenge. OBJECTIVE To review the diagnosis and management of moderate to severe Crohn disease, with a focus on newer treatments and goals of care. EVIDENCE REVIEW MEDLINE was searched from 2000 to 2011. Additional citations were procured from references of select research and review articles. Evidence was graded using the American Heart Association level-of-evidence guidelines. RESULTS Although mesalamines are still often used to treat Crohn disease, the evidence for their efficacy is lacking. Corticosteroids can be effectively used to induce remission in moderate to severe Crohn disease, but they do not maintain remission. The mainstays of treatment are immunomodulators and biologics, particularly anti-tumor necrosis factor. CONCLUSION AND RELEVANCE Immunomodulators and biologics are now the preferred treatment options for Crohn disease.
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Affiliation(s)
- Adam S Cheifetz
- Division of Gastroenterology, Rabb-Rose 425, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA.
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Garg V, Shen X, Cheng Y, Nawarskas JJ, Raisch DW. Use of number needed to treat in cost-effectiveness analyses. Ann Pharmacother 2013; 47:380-7. [PMID: 23463742 DOI: 10.1345/aph.1r417] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE To review the use of number needed to treat (NNT) and/or number needed to harm (NNH) values to determine their relevance in helping clinicians evaluate cost-effectiveness analyses (CEAs). DATA SOURCES PubMed and EconLit were searched from 1966 to September 2012. STUDY SELECTION AND DATA EXTRACTION Reviews, editorials, non-English-language articles, and articles that did not report NNT/NNH or cost-effectiveness ratios were excluded. CEA studies reporting cost per life-year gained, per quality-adjusted life-year (QALY), or other cost per effectiveness measure were included. Full texts of all included articles were reviewed for study information, including type of journal, impact factor of the journal, focus of study, data source, publication year, how NNT/NNH values were reported, and outcome measures. DATA SYNTHESIS A total of 188 studies were initially identified, with 69 meeting our inclusion criteria. Most were published in clinician-practice-focused journals (78.3%) while 5.8% were in policy-focused journals, and 15.9% in health-economics-focused journals. The majority (72.4%) of the articles were published in high-impact journals (impact factor >3.0). Many articles focused on either disease treatment (40.5%) or disease prevention (40.5%). Forty-eight percent reported NNT as a part of the CEA ratio per event. Most (53.6%) articles used data from literature reviews, while 24.6% used data from randomized clinical trials, and 20.3% used data from observational studies. In addition, 10% of the studies implemented modeling to perform CEA. CONCLUSIONS CEA studies sometimes include NNT ratios. Although it has several limitations, clinicians often use NNT for decision-making, so including NNT information alongside CEA findings may help clinicians better understand and apply CEA results. Further research is needed to assess how NNT/NNH might meaningfully be incorporated into CEA publications.
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Affiliation(s)
- Vishvas Garg
- Pharmacoeconomics, Epidemiology, Pharmaceutical Policy, and Outcomes Research program, Department of Pharmacy Practice and Administrative Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
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