Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials

Feagan, Brian G.; Sandborn, William J.; Colombel, Jean–Frédéric; Byrne, Sharon O'; Khalid, Javaria Mona; Kempf, Christian; Geransar, Parnia; Bhayat, Fatima; Rubin, David T.

doi:10.1093/ecco-jcc/jjy125

Cited by 65 publications

(56 citation statements)

References 26 publications

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“…In VERSIFY, a substantial proportion of patients with baseline EIMs, such as arthritis/arthralgia, had their symptoms resolve and few patients developed new EIMs consistent with the findings in the GEMINI studies. 46 Our study has some limitations. First, VERSIFY was an open-label study with no comparator arm.…”

Section: Discussionmentioning

confidence: 89%

Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn’s Disease

et al. 2019

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BACKGROUND & AIMS: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy. METHODS: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less). RESULTS: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naïve to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations. CONCLUSIONS: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD. ClinicalTrials.gov no: NCT02425111.

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Section: Discussionmentioning

confidence: 89%

Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn’s Disease

et al. 2019

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“…Feagan et al have performed post hoc analyses of data from the GEMINI studies to evaluate the effect of VDZ on arthritis/arthralgia. 56 In this study, sustained resolution of baseline arthritis/arthralgia, worsening, and the occurrence of new arthritis/arthralgia were evaluated. In patients with UC, VDZ and placebo showed a similar incidence of new/ worsening of arthritis/arthralgia.…”

Section: Eimmentioning

confidence: 99%

<p>Vedolizumab in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Safety, Efficacy, and Place of Therapy</p>

Takatsu¹,

Hisabe²,

Higashi³

et al. 2020

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Introduction: Selective blockade of the integrins and mucosal adhesion molecules is a promising therapeutic strategy for ulcerative colitis (UC). Vedolizumab (VDZ), a humanized IgG1 monoclonal antibody against α4β7 integrin, selectively blocks the trafficking of the leukocytes into the gastrointestinal tract through its binding with the α4β7 integrin. Aim: In this review, we provide an overview of the unique mechanism of VDZ, along with its efficacy, safety, and pharmacokinetic and pharmacodynamic data obtained from clinical trials, observational studies, and meta-analyses. Evidence Review: A positive exposure-efficacy relationship with regard to clinical remission and clinical response was apparent in VDZ induction therapy. No drug-specific safety signals are currently available. Place in Therapy: VDZ has been shown to be effective as firstor second-line induction and maintenance therapy in UC. Conclusion: VDZ is a safe and effective treatment option for patients with UC. Prolonged VDZ induction therapy may contribute to improved outcomes in patients with UC, particularly those previously treated with tumor necrosis factor-α. Prospective head-to-head study of VDZ and other biologics would alter the positioning of VDZ much more clearly.

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“…Since those initial studies, several others have attempted to address practical clinical questions such as the sustainability of the clinical response, the need for dosing changes, and VDZ efficacy in Crohn's disease. Moreover, controversy exists within the literature regarding whether VDZ use may result in new or worsening arthralgias [4][5][6].…”

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confidence: 99%

“…A prospective study reported clinical benefit of IBD-associated spondylarthritis in VDZtreated patients, with no new or exacerbation of arthritis and/ or sacroiliitis [4]. Furthermore, a post hoc analysis of the GEMINI trials showed that when compared with placebo, treatment with VDZ reduced the likelihood of new or worsening arthralgias [5]. When comparing anti-TNF exposed and anti-TNF-naïve patients, the former had a greater likelihood of new or worsening arthritis or arthralgias-independent treatment with VDZ or placebo.…”

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confidence: 99%

“…Specifically evaluating arthralgias, studies tying VDZ to spondyloarthropathies (SpAs) and peripheral arthritis have mostly been published as case series [4]. Nevertheless, studies not showing this association were retrospective and not designed to evaluate VDZ-induced arthritis [5]. It is also possible that previous studies on this topic combine multiple distinct forms of arthritis.…”

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confidence: 99%

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Vedolizumab (VDZ) for UC and CD: Still Safe and Effective After All These Years

Bach

Taleban

2020

Dig Dis Sci

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Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials

Abstract: Vedolizumab therapy was associated with a reduced likelihood of new/worsening arthritis/arthralgia in CD and no increased incidence of these events in UC. Studies included (ClincialTrials.gov, number): GEMINI 1 (NCT00783718); GEMINI 2 (NCT00783692); GEMINI 3 (NCT01224171).

Cited by 65 publications

References 26 publications

Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn’s Disease

Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn’s Disease

<p>Vedolizumab in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Safety, Efficacy, and Place of Therapy</p>

Vedolizumab (VDZ) for UC and CD: Still Safe and Effective After All These Years

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