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

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

Abstract

Background and aims: Extraintestinal manifestations [EIMs] such as arthritis/arthralgia are common in inflammatory bowel disease. We performed post hoc analyses of data from the GEMINI studies to evaluate the effect of vedolizumab, a gut-selective anti-trafficking agent, on arthritis/arthralgia.

Methods: Sustained resolution of baseline arthritis/arthralgia, worsening of baseline arthritis/arthralgia, the occurrence of new arthritis/arthralgia, and the composite of new/worsening arthritis/arthralgia were evaluated. Cox modelling was used for time-to-event analysis. The influence of corticosteroid-tapering was also investigated.

Results: In Crohn's disease [CD] patients, vedolizumab was significantly less likely than placebo to be associated with new/worsening arthritis/arthralgia (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89). Similar incidences of sustained resolution of arthritis/arthralgia occurred with vedolizumab and placebo. In CD patients on corticosteroids at baseline, a decrease in corticosteroid dose increased the risk of new/worsening arthritis/arthralgia (odds ratio [OR], 7.49; 95% CI, 3.50-15.97) regardless of treatment; and in those achieving corticosteroid-free status, arthritis/arthralgia was less likely with vedolizumab than with placebo [HR, 0.14; 95% CI, 0.05-0.35]. In ulcerative colitis [UC] patients, vedolizumab and placebo showed a similar incidence of new/worsening of arthritis/arthralgia. In UC patients on corticosteroid at baseline, arthritis/arthralgia was more likely in those achieving corticosteroid-free status than in those continuing corticosteroids (HR 2.63 [95% CI 1.13-6.11]); and in those achieving corticosteroid-free status, the incidence of arthritis/arthralgia was similar with vedolizumab and placebo.

Conclusions: 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].

Figures

Figure 1.
Figure 1.
Kaplan–Meier analyses for [A] time to sustained resolution of baseline arthritis/arthralgia in CD [GEMINI 2], [B and C] time to occurrence of new arthritis/arthralgia in CD [GEMINI 2 and 3 respectively], [D] time to new/worsening arthritis/arthralgia in CD [GEMINI 2], and [E] time to new/worsening of arthritis/arthralgia in UC [GEMINI 1]. In GEMINI 1 and 2, the VDZ group includes both induction responders and non-responders, the VDZ/PLA group is responders only, and the PLA group is both responders and non-responders. CD, Crohn’s disease; PLA, placebo; VDZ, vedolizumab; UC, ulcerative colitis.

References

    1. Zippi M, Corrado C, Pica R, et al. . Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients. World J Gastroenterol 2014;20:17463–7.
    1. Ott C, Schölmerich J. Extraintestinal manifestations and complications in IBD. Nat Rev Gastroenterol Hepatol 2013;10:585–95.
    1. Veloso FT. Extraintestinal manifestations of inflammatory bowel disease: do they influence treatment and outcome?World J Gastroenterol 2011;17:2702–7.
    1. Vavricka SR, Schoepfer A, Scharl M, Lakatos PL, Navarini A, Rogler G. Extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2015;21:1982–92.
    1. Arvikar SL, Fisher MC. Inflammatory bowel disease associated arthropathy. Curr Rev Musculoskelet Med 2011;4:123–31.
    1. Harbord M, Annese V, Vavricka SR, et al. ; European Crohn’s and Colitis Organisation The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease. J Crohns Colitis 2016;10:239–54.
    1. Vavricka SR, Gubler M, Gantenbein C, et al. ; Swiss IBD Cohort Study Group Anti-TNF treatment for extraintestinal manifestations of inflammatory bowel disease in the Swiss IBD Cohort Study. Inflamm Bowel Dis 2017;23:1174–81.
    1. Peyrin-Biroulet L, Van Assche G, Gómez-Ulloa D, et al. . Systematic review of tumor necrosis factor antagonists in extraintestinal manifestations in inflammatory bowel disease. Clin Gastroenterol Hepatol 2017;15:25–36.e27.
    1. Roda G, Jharap B, Neeraj N, Colombel JF. 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, Andersson M, Jess T. 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. Thiebault H, Boyard-Lasselin P, Guignant C, et al. . Paradoxical articular manifestations in patients with inflammatory bowel diseases treated with infliximab. Eur J Gastroenterol Hepatol 2016;28:876–81.
    1. Rahier JF, Buche S, Peyrin-Biroulet L, et al. ; Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif [GETAID] Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy. Clin Gastroenterol Hepatol 2010;8:1048–55.
    1. Entyvio® [package insert]. Deerfield, IL: Takeda Pharmaceuticals America Inc; 2014. Available at: . Accessed December 18, 2017.
    1. Entyvio® [Summary of Product Characteristics]. Zurich, Switzerland: Takeda Pharma A/S; 2014. Available at: . Accessed December 18, 2017.
    1. Wyant T, Fedyk E, Abhyankar B. An overview of the mechanism of action of the monoclonal antibody vedolizumab. J Crohns Colitis 2016;10:1437–44.
    1. Feagan BG, Rutgeerts P, Sands BE, et al. . Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013;369:699–710.
    1. Sandborn WJ, Feagan BG, Rutgeerts P, et al. ; GEMINI 2 Study Group Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 2013;369:711–21.
    1. Sands BE, Feagan BG, Rutgeerts P, et al. . Effects of vedolizumab induction therapy for patients with Crohn’s disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology 2014;147:618–627.e3.
    1. Loftus EV Jr, Colombel JF, Feagan BG, et al. . Long-term efficacy of vedolizumab for ulcerative colitis. J Crohns Colitis 2017;11:400–11.
    1. Vermeire S, Loftus EV Jr, Colombel JF, et al. . Long-term efficacy of vedolizumab for Crohn’s disease. J Crohns Colitis 2017;11:412–24.
    1. Colombel JF, Sands BE, Rutgeerts P, et al. . The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut 2017;66:839–51.
    1. Ungaro R, Blake A, Bhayat F, et al. . A description of joint-related events in patients receiving vedolizumab from clinical and post-marketing safety experience. Inflamm Bowel Dis 2017;23:S47–S48. Abstract Poster P-135.
    1. Dulai PS, Singh S, Jiang X, et al. . The real-world effectiveness and safety of vedolizumab for moderate-severe Crohn’s disease: results from the US VICTORY Consortium. Am J Gastroenterol 2016;111:1147–55.
    1. Tadbiri S, Peyrin-Biroulet L, Serrero M, et al. ; GETAID OBSERV-IBD study group Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort. Aliment Pharmacol Ther 2018;47:485–93.
    1. Hanauer SB, Feagan BG, Lichtenstein GR, et al. ; ACCENT I Study Group Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002;359:1541–9.
    1. Feagan BG, Sandborn WJ, Gasink C, et al. ; UNITI–IM-UNITI Study Group Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 2016;375:1946–60.
    1. Juillerat P, Mottet C, Pittet V, et al. . Extraintestinal manifestations of Crohn’s disease. Digestion 2007;76:141–8.
    1. Mattheakis L, Bhandari A, Bai L, et al. . PTG-100, an oral peptide antagonist of integrin α4β7 that alters trafficking of gut homing T cells in preclinical animal models. Inflamm Bowel Dis 2016;22[suppl 1]:S48. Abstract P-126.

Source: PubMed

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