Dataset Information

Deep Remission With Vedolizumab in Patients With Moderately to Severely Active Ulcerative Colitis: A GEMINI 1 post hoc Analysis.

ABSTRACT:

Background and aims

This GEMINI 1 post hoc analysis evaluated vedolizumab efficacy for inducing deep remission in patients with ulcerative colitis and correlation between vedolizumab trough concentrations and deep remission rates.

Methods

Week 6 vedolizumab responders were re-randomized to placebo or vedolizumab every 8 or 4 weeks. Deep remission at Week 52 was measured using four different definitions [from most to least stringent]: [1] Mayo Clinic endoscopic score = 0, rectal bleeding score = 0 and decrease or no change from baseline in stool frequency score; [2] endoscopic score ≤1, rectal bleeding score = 0 and stool frequency score = 0; [3] endoscopic score ≤1, rectal bleeding score = 0, decrease or no change from baseline stool frequency score, and total score [endoscopic score + rectal bleeding score + stool frequency score] ≤1; and [4] endoscopic score ≤1, rectal bleeding score = 0 and stool frequency score ≤1. Steady-state trough vedolizumab serum concentrations were evaluated.

Results

At Week 6, 373 vedolizumab responders were re-randomized to maintenance placebo [n = 126] or vedolizumab every 8 [n = 122] or 4 [n = 125] weeks. Significantly more vedolizumab patients achieved deep remission at Week 52 for the most (placebo 8.7%, every 8 weeks 27.0% [p = 0.0001], every 4 weeks 28.0% [p < 0.0001]) and least (placebo 15.9%, every 8 weeks 43.4% [p < 0.0001], every 4 weeks 43.2% [p < 0.0001]) stringent definitions. Patients with higher vedolizumab trough concentration quartiles had higher deep remission rates [all definitions] compared with those with the lowest quartile or who received placebo.

Conclusion

Vedolizumab was associated with significantly higher deep remission rates than placebo at Week 52, regardless of deep remission definition [NCT00783718].

SUBMITTER: Sandborn WJ

PROVIDER: S-EPMC6357899 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Deep Remission With Vedolizumab in Patients With Moderately to Severely Active Ulcerative Colitis: A GEMINI 1 post hoc Analysis.

Sandborn William J WJ Colombel Jean-Frédéric JF Panaccione Remo R Dulai Parambir S PS Rosario Maria M Cao Charlie C Barocas Morris M Lasch Karen K

Journal of Crohn's & colitis 20190201 2

<h4>Background and aims</h4>This GEMINI 1 post hoc analysis evaluated vedolizumab efficacy for inducing deep remission in patients with ulcerative colitis and correlation between vedolizumab trough concentrations and deep remission rates.<h4>Methods</h4>Week 6 vedolizumab responders were re-randomized to placebo or vedolizumab every 8 or 4 weeks. Deep remission at Week 52 was measured using four different definitions [from most to least stringent]: [1] Mayo Clinic endoscopic score = 0, rectal bl ...[more]

PMID: 30285104

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Project description:BackgroundDue to wide-ranging impacts of Ulcerative Colitis (UC), regulatory authorities emphasize the importance of including validated patient-reported symptom severity measures in clinical trials.AimTo describe the development and validation of the Ulcerative Colitis-Symptom Questionnaire (UC-SQ).MethodsThe UC-SQ was developed in a qualitative study involving a targeted literature review, semi-structured concept elicitation interviews, and combined concept elicitation/cognitive interviews. Measurement properties, including item-level analyses, factor structure, reliability, validity, responsiveness, and clinically meaningful change were evaluated using data from a phase 2b, randomized trial in adults with UC (N = 113).ResultsFourteen symptom concepts were elicited across 22 interviews, with saturation at the fifth interview. Twenty-two items were unmodified as cognitive interview participants interpreted underlying concepts correctly. Instructions were clear and items were relevant, with appropriate response options and recall periods. Reduction to 17 items was completed prior to psychometric testing. Two items (joint pain/constipation) did not contribute to reliability in initial testing and were included as non-scored items. The 15-item UC-SQ showed evidence of internal consistency (α = 0.86) and test-retest reliability (intraclass correlation coefficient = 0.88). The UC-SQ discriminated by disease severity as defined by Mayo and Inflammatory Bowel Disease Questionnaire scores (p < 0.0001). Convergent validity was supported by strong correlations with criterion measures. The UC-SQ was responsive in patients indicating change in other measures. A 10-point decrease from baseline indicated within-patient meaningful improvement.ConclusionsThe UC-SQ is reliable, valid and responsive, with a 10-point improvement estimating within-patient clinically meaningful improvement. The tool is fit-for-purpose as a key endpoint in pivotal UC trials.

Project description:BackgroundCorticosteroid-free clinical remission is important in ulcerative colitis.ObjectiveThis GEMINI 1 post hoc analysis evaluated vedolizumab efficacy in achieving sustained corticosteroid-free clinical remission in moderately to severely active ulcerative colitis.Materials and methodsGEMINI 1 included a 6-week induction period followed by a 46-week maintenance period. Patients received stable corticosteroid dosing at baseline/during induction and tapered dosing during maintenance. Analysis groups included vedolizumab (induction and maintenance); vedolizumab/placebo (vedolizumab induction, placebo maintenance); and placebo (induction and maintenance). The primary endpoint was sustained corticosteroid-free clinical remission (partial Mayo score ≤2, no individual subscore >1, for ≥32 weeks). Multivariate analyses identified covariates associated with the primary endpoint. Safety endpoints included adverse events.ResultsBaseline demographics and concomitant corticosteroid use were similar across groups (n=454). A greater proportion (95% confidence interval) of the vedolizumab group achieved sustained corticosteroid-free clinical remission (10.2% [6.9 to 13.6]) vs the placebo group (1.4% [0.0 to 7.3]; difference 8.9% [-3.8 to 21.4]). Proportions were similar between the vedolizumab/placebo and placebo groups. Covariates associated with sustained corticosteroid-free clinical remission (odds ratio [95% confidence interval]) were treatment (vedolizumab vs placebo: 9.35 [1.25 to 71.43]; p=0.0605), anti-tumor necrosis factor alpha exposure (yes vs no: 0.26 [0.12 to 0.57]; p=0.0008), and disease duration (≤2 vs >2 years: 2.66 [0.99-7.19]; p=0.0531). Adverse events were similar across groups.ConclusionA numerically greater proportion of vedolizumab-treated patients with ulcerative colitis achieved sustained corticosteroid-free clinical remission. Vedolizumab treatment, no previous anti-tumor necrosis factor alpha exposure, and shorter disease duration were associated with sustained corticosteroid-free clinical remission.ClinicaltrialsgovNCT00783718.

Dataset Information

Deep Remission With Vedolizumab in Patients With Moderately to Severely Active Ulcerative Colitis: A GEMINI 1 post hoc Analysis.

Background and aims

Methods

Results

Conclusion

Publications

Deep Remission With Vedolizumab in Patients With Moderately to Severely Active Ulcerative Colitis: A GEMINI 1 post hoc Analysis.

Similar Datasets

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