| 1. |
- Caron, Bénédicte, et al.
(författare)
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IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis : the PROCTRIAL Consensus
- 2022
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:11, s. 2169-2627.e1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the PROCTRIAL (Definition and endpoints for ulcerative PROCtitis in clinical TRIALs) initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults.METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity is proposed. Secondary endpoints which should be evaluated include endoscopic remission, histological remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life.CONCLUSION: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the PROCTRIAL consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.
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| 2. |
- D'Amico, Ferdinando, et al.
(författare)
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Practical Management of Biosimilar Use in Inflammatory Bowel Disease (IBD) : A Global Survey and an International Delphi Consensus
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:19
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Tidskriftsartikel (refereegranskat)abstract
- As the patents for biologic originator drugs expire, biosimilars are emerging as cost-effective alternatives within healthcare systems. Addressing various challenges in the clinical management of inflammatory bowel disease (IBD) remains crucial. To shed light on physicians' current knowledge, beliefs, practical approaches, and concerns related to biosimilar adoption-whether initiating a biosimilar, transitioning from an originator to a biosimilar, or switching between biosimilars (including multiple switches and reverse switching)-a global survey was conducted. Fifteen physicians with expertise in the field of IBD from 13 countries attended a virtual international consensus meeting to develop practical guidance regarding biosimilar adoption worldwide, considering the survey results. This consensus centered on 10 key statements covering biosimilar effectiveness, safety, indications, rationale, multiple switches, therapeutic drug monitoring of biosimilars, non-medical switching, and future perspectives. Ultimately, the consensus affirmed that biosimilars are equally effective and safe when compared to originator drugs. They are considered suitable for both biologic-naïve patients and those who have previously been treated with originator drugs, with cost reduction being the primary motivation for transitioning from an originator drug to a biosimilar.
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| 3. |
- Danese, Silvio, et al.
(författare)
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Unmet Medical Needs in Ulcerative Colitis : An Expert Group Consensus
- 2019
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Ingår i: Digestive Diseases. - : S. Karger. - 0257-2753 .- 1421-9875. ; 37:4, s. 266-283
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC.METHODS: PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings.RESULTS: In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients' daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs.CONCLUSIONS: These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC.
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| 4. |
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| 5. |
- Kim, HoUng, et al.
(författare)
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The Future of Biosimilars : Maximizing Benefits Across Immune-Mediated Inflammatory Diseases
- 2020
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Ingår i: Drugs. - : Adis International. - 0012-6667 .- 1179-1950. ; 80:2, s. 99-113
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Tidskriftsartikel (refereegranskat)abstract
- Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars-biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators-can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.
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| 6. |
- Reinisch, Walter, et al.
(författare)
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Clinical Practice of Adalimumab and Infliximab Biosimilar Treatment in Adult Patients With Crohn's Disease
- 2021
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott-Raven Publishers. - 1078-0998 .- 1536-4844. ; 27:1, s. 106-122
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of tumor necrosis factor (TNF) inhibitors has significantly changed the treatment landscape in Crohn's disease (CD). The overall therapeutic achievements with TNF inhibitors such as infliximab, adalimumab, and certolizumab pegol paved the way to push the boundaries of treatment goals beyond symptomatic relief and toward cessation of objective signs of inflammation, including endoscopic remission. Even though these agents are widely used for the treatment of moderate to severe CD, heterogeneity still exists in translating evidence-based guidelines on the use of anti-TNF agents into actual treatment algorithms in CD. This might be due to several reasons including disparities in health expenditure policies; lack of harmonization between countries; and variations in assessment of disease severity, use of disease monitoring tools, or application of treatment targets by physicians. With the advent of biosimilars, patent-free versions of reference biologics are now available to minimize health inequalities in drug availability. In this context, this article aims to provide practical clinical guidance for the use of infliximab and adalimumab biosimilars in patients with moderate to severe CD by outlining different clinical scenarios that patients may encounter during their treatment journey.
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| 7. |
- Schreiber, Stefan, et al.
(författare)
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Defining Comprehensive Disease Control for use as a Treatment Target for Ulcerative Colitis in Clinical Practice : International Delphi Consensus Recommendations
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:1, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Treatment of ulcerative colitis (UC) requires a patient-centric, definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process.METHODS: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before round 3. Consensus was met if ≥ 67% of the panel agreed. Statements without consensus in rounds 1 and 2 were revised or discarded after round 3.RESULTS: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials (rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use), with additional patient-reported symptoms (bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance). The panel agreed on scoring systems and thresholds for many aspects.CONCLUSIONS: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multi-component tool and adopt comprehensive disease control as a treatment target in clinical practice and trials.
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| 8. |
- Siegel, Corey A., et al.
(författare)
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Development of an index to define overall disease severity in IBD
- 2018
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Ingår i: Gut. - London, United Kingdom : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 67:2, s. 244-254
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.Methods: Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.Results: For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.Conclusions: Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.
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| 9. |
- Ungaro, Ryan C., et al.
(författare)
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Deep Remission at 1 Year Prevents Progression of Early Crohn's Disease
- 2020
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Ingår i: Gastroenterology. - : W. B. Saunders Company. - 0016-5085 .- 1528-0012. ; 159:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD).METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period.RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome.CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.
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