Sustained Clinical Remission With Vedolizumab in Patients With Moderate-to-Severe Ulcerative Colitis

Brian G Feagan, Stefan Schreiber, Douglas C Wolf, Jeffrey L Axler, Arpeat Kaviya, Alexandra James, Rebecca I Curtis, Parnia Geransar, Andreas Stallmach, Robert Ehehalt, Bernd Bokemeyer, Javaria Mona Khalid, Sharon O'Byrne, Brian G Feagan, Stefan Schreiber, Douglas C Wolf, Jeffrey L Axler, Arpeat Kaviya, Alexandra James, Rebecca I Curtis, Parnia Geransar, Andreas Stallmach, Robert Ehehalt, Bernd Bokemeyer, Javaria Mona Khalid, Sharon O'Byrne

Abstract

Background: Sustaining clinical remission is an important treatment goal in moderate-to-severe UC. This post hoc exploratory analysis assessed the long-term efficacy of vedolizumab in the subset of patients with UC in the GEMINI 1 study who were in clinical remission by week 14 after 3 induction doses, administered at weeks 0, 2, and 6.

Methods: Sustained clinical remission (primary endpoint) was evaluated using 2 definitions: (1) a partial Mayo Score (pMS) of ≤2 with no subscore >1 and (2) a rectal bleeding subscore (RBS) of 0 throughout weeks 14, 26, 38, and 52.

Results: The proportion of patients in clinical remission at week 14 was significantly higher in patients receiving vedolizumab (n = 620) compared with placebo (n = 149) (pMS: 32.7% vs 20.1% [percentage-point difference (∆) 12.6%; 95% confidence interval [CI], 5.2-20.0]; RBS: 47.3% vs 28.9% [∆18.4%; 95% CI, 10.1-26.7]). Of patients in clinical remission at week 14, a significantly higher proportion of vedolizumab-treated patients achieved sustained clinical remission compared with placebo (pMS: 66.5% vs 26.7%; ∆39.8%; 95% CI, 22.7-56.9; RBS: 56.7% vs 20.9%; ∆35.7%; 95% CI, 22.3-49.1). Findings were consistent in tumor necrosis factor (TNF) antagonist-naive and antagonist-failure patients.

Conclusion: Compared with placebo, 35%-40% more patients receiving a full induction course of vedolizumab had sustained clinical remission after 52 weeks of therapy. This result was observed irrespective of TNF antagonist treatment history. Clinical remission at week 14 may therefore be a predictor for sustained clinical remission with vedolizumab.

Trial registration: ClinicalTrials.gov NCT00783718 NCT00790933.

Keywords: TNF antagonist; remission; ulcerative colitis; vedolizumab.

© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.

Figures

FIGURE 1.
FIGURE 1.
Design of GEMINI 1 and patient disposition. GEMINI 1 study design and disposition of patients with moderate-to-severe UC failing conventional therapy. Cohort 1, randomized to double-blind vedolizumab or placebo at weeks 0 and 2; cohort 2 (required to ensure sufficient sample size in maintenance phase) received open-label vedolizumab at weeks 0 and 2. The 2 cohorts were integrated for the maintenance phase (up to week 52) based on clinical response* at week 6. Vedolizumab nonresponders received open-label vedolizumab Q4W, while responders were re-randomized to double-blind vedolizumab Q4W, Q8W, or placebo. Patients discontinuing vedolizumab induction (cohort 1: n = 7; cohort 2: n = 36) or placebo (n = 14) were re-assigned to open-label vedolizumab Q4W maintenance (nonresponder) or to the placebo group, respectively (stippled arrows). *Reduction from baseline in total MS of ≥3 points and ≥30% decrease from baseline, with ≥1-point decrease in RBS or an absolute ≤1-point RBS. †Sustained clinical remission (weeks 14, 26, 38, and 52) assessed according to 2 definitions: (1) pMS ≤2 points and no individual subscore >1 point, and (2) RBS of 0. Data substitution from GEMINI LTS was performed for 3.4% (n = 21), 16.3% (n = 101), 18.2% (n = 113), and 16.1% (n = 100) of the combined VDZ group at weeks 14, 26, 38, and 52, respectively. Abbreviations: DB, double-blind; OL, open-label.
FIGURE 2.
FIGURE 2.
Sustained clinical remission based on (A) pMS (≤2 points and no individual subscore >1 point) or (B) RBS of 0 at weeks 14, 26, 38, and 52. Data substitution from the GEMINI LTS study was performed for 3.4% (n = 21), 16.3% (n = 101), 18.2% (n = 113), and 16.1% (n = 100) of the combined VDZ group at weeks 14, 26, 38, and 52, respectively. The n value in each bar indicates patients who were in clinical remission at week 14. *Indicates significance based on the 95% CI for percentage-point difference between combined VDZ and PLA groups.

References

    1. Taft TH, Keefer L. A systematic review of disease-related stigmatization in patients living with inflammatory bowel disease. Clin Exp Gastroenterol. 2016;9:49–58.
    1. Bressler B, Marshall JK, Bernstein CN, et al. ; Toronto Ulcerative Colitis Consensus Group Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto Consensus. Gastroenterology. 2015;148:1035–1058.e3.
    1. Tabatabaeian M, Afshar H, Roohafza HR, et al. . Psychological status in Iranian patients with ulcerative colitis and its relation to disease activity and quality of life. J Res Med Sci. 2015;20:577–584.
    1. Harbord M, Eliakim R, Bettenworth D, et al. . Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management. J Crohns Colitis. 2017;11:769–784.
    1. Scarpa M, Castagliuolo I, Castoro C, et al. . Inflammatory colonic carcinogenesis: a review on pathogenesis and immunosurveillance mechanisms in ulcerative colitis. World J Gastroenterol. 2014;20:6774–6785.
    1. Castaño-Milla C, Chaparro M, Gisbert JP. Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther. 2014;39:645–659.
    1. Cohen RD, Yu AP, Wu EQ, et al. . Systematic review: the costs of ulcerative colitis in Western countries. Aliment Pharmacol Ther. 2010;31:693–707.
    1. Kawalec P. Indirect costs of inflammatory bowel diseases: Crohn’s disease and ulcerative colitis. A systematic review. Arch Med Sci. 2016;12:295–302.
    1. Ramos A, Calvet X, Sicilia B, et al. . IBD-related work disability in the community: prevalence, severity and predictive factors. A cross-sectional study. United European Gastroenterol J. 2015;3:335–342.
    1. Rocchi A, Benchimol EI, Bernstein CN, et al. . Inflammatory bowel disease: a Canadian burden of illness review. Can J Gastroenterol. 2012;26:811–817.
    1. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. . Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324–1338.
    1. Roda G, Jharap B, Neeraj N, et al. . Loss of response to anti-TNFs: definition, epidemiology, and management. Clin Transl Gastroenterol. 2016;7:e135.
    1. Nyboe Andersen N, Pasternak B, Friis-Møller N, et al. . Association between tumour necrosis factor-α inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study. Bmj. 2015;350:h2809.
    1. Danese S, Fiorino G, Peyrin-Biroulet L, et al. . Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis. Ann Intern Med. 2014;160:704–711.
    1. Rutgeerts P, Sandborn WJ, Feagan BG, et al. . Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.
    1. Sandborn WJ, Feagan BG, Marano C, et al. ; PURSUIT-Maintenance Study Group Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109.e1.
    1. Soler D, Chapman T, Yang LL, et al. . The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330:864–875.
    1. Fedyk ER, Wyant T, Yang LL, et al. . Exclusive antagonism of the α4 β7 integrin by vedolizumab confirms the gut-selectivity of this pathway in primates. Inflamm Bowel Dis. 2012;18:2107–2119.
    1. Entyvio [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2014.
    1. Entyvio [Summary of Product Characteristics]. Taastrup, Denmark: Takeda Pharma A/S; 2014.
    1. Feagan BG, Rutgeerts P, Sands BE, et al. ; GEMINI 1 Study Group Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.
    1. Sandborn WJ, van Assche G, Reinisch W, et al. . Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–265.e1.
    1. Reinisch W, Sandborn WJ, Panaccione R, et al. . 52-week efficacy of adalimumab in patients with moderately to severely active ulcerative colitis who failed corticosteroids and/or immunosuppressants. Inflamm Bowel Dis. 2013;19:1700–1709.
    1. Loftus EV, Colombel JF, Feagan B, et al. . Long-term effectiveness and safety of vedolizumab in patients with ulcerative colitis: 5-year cumulative exposure of GEMINI 1 completers rolling into the GEMINI open-label extension study. Gastroenterology. 2017;152(suppl 1):S602. Abstract Su1934.
    1. Vickers AD, Ainsworth C, Mody R, et al. . Systematic review with network meta-analysis: comparative efficacy of biologics in the treatment of moderately to severely active ulcerative colitis. PLoS One. 2016;11:e0165435.
    1. Colombel JF, Keir ME, Scherl A, et al. . Discrepancies between patient- reported outcomes, and endoscopic and histological appearance in UC. Gut. 2017;66:2063–2068.
    1. Dhanda AD, Creed TJ, Greenwood R, et al. . Can endoscopy be avoided in the assessment of ulcerative colitis in clinical trials?Inflamm Bowel Dis. 2012;18:2056–2062.
    1. US Department of Health and Human Services. Ulcerative Colitis: Clinical Trial Endpoints—Guidance for Industry. August 2016. . Accessed March 20, 2018.
    1. Ng SC, Palo W, Blake A, et al. . Vedolizumab clinical and post-marketing safety experience of opportunistic infections. Gastroenterology. 2017;152(Suppl 1):S575–S576. Abstract Su1865.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa