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GEMINI: Entyvio benefits IBD patients long-term, regardless of anti-TNF history
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Three new studies demonstrate long-term clinical benefits of Entyvio in patients with inflammatory bowel disease, regardless of their previous exposure to anti-TNF therapy.
Entyvio (vedolizumab, Takeda) is a gut-selective humanized monoclonal antibody that targets the alpha-4/beta-7 integrin. It is approved in more than 50 countries and is the only biologic approved for both patients with moderate-to-severe active ulcerative colitis and Crohn’s disease for whom other therapies have failed, according to a press release from the manufacturer.
GEMINI LTS
Researchers have reported interim analyses from the ongoing phase 3 open-label GEMINI long-term safety (LTS) study with data spanning from May 2009 through June 2013. GEMINI LTS enrolled patients who completed or withdrew early from the GEMINI I, II and III trials, and also vedolizumab-naive patients. All patients received vedolizumab every 4 weeks in GEMINI LTS.
The results from the interim analyses indicate long-term benefits of vedolizumab therapy in both moderate-to-severe active ulcerative colitis and Crohn’s disease, regardless of prior anti-TNF exposure, according to investigators.
Edward V. Loftus
“Given that ulcerative colitis and Crohn’s are chronic diseases, it is imperative we evaluate a treatment’s efficacy and safety over the long-term to assess its continued benefit for patients,” Edward V. Loftus, MD, professor of medicine in the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., said in the press release. “These latest findings, reflecting continuous use of vedolizumab for up to 3 years, are encouraging and provide additional information about the potential benefit for vedolizumab as a long-term treatment option for people with ulcerative colitis and Crohn’s disease.”
As of June 27, 2013, 63% of the UC efficacy population (n = 845) were continuing treatment. Of induction responders with data available, 88% of 136 were in remission after 104 weeks and 96% of 73 were in remission at 152 weeks.
Of 32 patients who withdrew from maintenance dosing every 8 weeks before week 52 of GEMINI I, increasing dosing to every 4 weeks increased response rates from 19% to 41% and increased remission rates from 6% to 28% after 52 weeks. The observed benefits were similar in both anti-TNF failure and naive patients, and the investigators also observed durable health-related quality of life improvements.
The Crohn’s disease GEMINI LTS safety population consisted of 1,349 patients, 1,297 of whom were included in the efficacy population. Of 120 GEMINI II week-6 responders who received continuous treatment, 83% were in remission after 104 weeks, and 89% of 70 were in remission at 152 weeks.
Of 57 patients who withdrew early from maintenance dosing every 8 weeks in GEMINI II, increasing dosing to every 4 weeks increased response rates from 39% to 47% and increased remission rates from 4% to 32% at week 52. Like the UC cohort, these observed benefits were similar in both anti-TNF failure and naive patients, and durable health-related quality of life improvements were also observed.
Of 212 patients who completed GEMINI II and received an additional 100 weeks of treatment (week 152 of GEMINI LTS), 74% were in remission, including 66% of 113 who had prior anti-TNF failure and 82% of 84 who were anti-TNF naive. Long-term health-related quality of life improvements were also observed in these subgroups.
GEMINI I
A post hoc analysis of data from GEMINI I — a phase 3 multicenter randomized placebo-controlled trial of vedolizumab in patients with UC — also showed significantly greater efficacy for induction and maintenance was achieved with vedolizumab compared with placebo in both anti-TNF failure and naive patients.
Brian Feagan
“Approximately 50% of patients with ulcerative colitis do not respond to TNF antagonist therapy, or lose response over time. Health care professionals realize that failure of TNF antagonist treatment can be a predictor of poor prognosis and these patients need alternative approaches to achieve sustained remission of symptoms,” Brian Feagan, MD, from Robarts Clinical Trials, Robarts Research Institute, at the University of Western Ontario in London, Canada, said in a press release from Takeda.
Feagan and colleagues evaluated outcomes in 464 patients without prior exposure to anti-TNFs and in 367 with previous anti-TNF failure.
At week 6, 53.1% of anti-TNF naive patients had response with vedolizumab compared with 26.3% with placebo (absolute difference = 26.4%; 95% CI, 12.4-40.2; RR = 2; 95% CI, 1.3-3), and 39% of anti-TNF failure patients had response with vedolizumab compared with 20.6% with placebo (absolute difference = 18.1%; 95% CI, 2.8-33.5; RR = 1.9; 95% CI, 1.1-3.2). Absolute differences in efficacy between vedolizumab and placebo were greater for the anti-TNF naive patients, while RRs for efficacy were similar.
Conversely, absolute differences were similar and RRs were higher for anti-TNF failure patients for most outcomes during maintenance therapy. Week 52 remission rates were 46.9% with vedolizumab vs. 19% with placebo in anti-TNF naive patients (absolute difference = 28%; 95% CI, 14.9-41.1; RR = 2.5; 95% CI, 1.5-4) and 36.1% vs. 5.3% in anti-TNF failure patients (absolute difference = 29.5%; 95% CI, 12.8-46.1; RR = 6.6; 95% CI, 1.7-26.5). Adverse events were also comparable between groups.
“These efficacy findings underscore the importance of vedolizumab as a treatment for appropriate patients with moderate to severely active ulcerative colitis, both as first-line biologic therapy in both patients who have never received TNF antagonist treatment or who have failed these agents,” Feagan said in the press release. – by Adam Leitenberger
References:
Feagan BG, et al. Clin Gastroenterol Hepatol. 2016;doi:10.1016/j.cgh.2016.08.044.
Loftus EV Jr., et al. J Crohns Colitis. 2016;doi:10.1093/ecco-jcc/jjw177.
Vermeire S, et al. J Crohns Colitis. 2016;doi:10.1093/ecco-jcc/jjw176.
Disclosures: Feagan reports he has received financial support for research from Abbott/AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Millennium, Pfizer, Receptos, Roche/Genentech, Sanofi, Santarus, Tillotts, UCB Pharma; has received lecture fees from Abbott/AbbVie, JnJ/Janssen, Takeda, UCB Pharma, Warner Chilcott; has served as a consultant for Abbott/AbbVie, Actogenix, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics Inc., Avir Pharma, Axcan, Baxter Healthcare Corp., Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharmaceuticals, GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharmaceuticals, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Hakko Kirin Co., Ltd., Lexicon, Lilly, Merck, Millennium, Nektar, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Roche/Genentech, Salix Pharmaceuticals, Serono, Shire, Sigmoid Pharma, Synergy Pharmaceuticals Inc., Takeda, Teva, TiGenix, Tillotts, UCB Pharma, Vertex Pharmaceuticals, Warner Chilcott, Wyeth, Zealand, Zyngenia; has served on advisory boards for Abbott/AbbVie, Amgen, AstraZeneca, Avaxia Biologics Inc., Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Ferring Pharmaceuticals, JnJ/Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharmaceuticals, Takeda, Teva, TiGenix, Tillotts, UCB Pharma; and holds a directorship as CEO and Senior Scientific Director at Robarts Clinical Trials Inc, Western University, London, Ontario. Loftus reports he has received financial support for research from AbbVie, Janssen, UCB, Takeda, Pfizer, GlaxoSmithKline, Amgen, Bristol-Myers Squibb, Genentech, Robarts Clinical Trials, Gilead and Receptos, and has also served as a consultant for AbbVie, Janssen, UCB, Takeda, Immune Pharmaceuticals, Celgene, MedImmune, Theradiag, Genentech, Seres Health, Sun Pharmaceuticals and Bristol-Myers Squibb. Please see the full studies for all other researchers’ relevant financial disclosures.