Favorable Benefit: Risk Profile for Vedolizumab as Induction and Maintenance Therapy in TNF-Naïve or TNF-Failure Patients with Moderately to Severely Active Ulcerative Colitis

Analysis showed consistent treatment benefit irrespective of prior treatment history with TNF antagonist

Takeda Pharmaceutical Company  announced that an exploratory analysis of the GEMINI 1 data, evaluating Entyvio (vedolizumab) therapy in patients with ulcerative colitis (UC) based on their treatment history with tumor necrosis factor (TNF) antagonists was published in Clinical Gastroenterology and Hepatology. The sub-group analysis, compared TNF-naïve with TNF-failure patients with moderately to severely active UC. The former had never received TNF antagonist therapy whilst those who had received and failed therapy due to inadequate response, loss of response or intolerance were in the latter group. Overall, the publication reported a statistically significantly greater efficacy with vedolizumab treatment compared to placebo in both sub-groups of patients.

“Approximately 50% of patients with ulcerative colitis do not respond to TNF antagonist therapy, or lose response over time. Healthcare 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,” said Professor Brian Feagan, MD, Robarts Clinical Trials, Robarts Research Institute, at the University of Western Ontario in London, Canada. “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.”

Investigators examined primary and secondary outcomes data from the GEMINI 1 study, after 6 weeks and 52 weeks of vedolizumab therapy in patient sub-groups who were either TNF-naïve or failed TNF antagonist therapy. The analysis reported that vedolizumab treatment had statistically significantly greater efficacy compared to placebo in inducing and maintaining clinical response in both sub-groups of patients. Furthermore, greater treatment differences favoring vedolizumab treatment at week 6 were observed for TNF-naïve patients, compared to TNF-failure patients. There were no differences in adverse events among treatment groups in this study.

“Ulcerative colitis requires life-long management, and symptoms can cause patients a significant impact on their daily lives, if they are not adequately controlled. As the global burden of inflammatory bowel disease is so high, Takeda is committed to continuing our research and development efforts to help these patients,” explained Asit Parikh, MD, PhD, senior vice president, Head Gastroenterology Therapeutic Area, Takeda. “These data indicate that vedolizumab is an effective therapeutic option for ulcerative colitis and it potentially has a better effect in biologic-naïve patients, compared to those who have previously failed a TNF antagonist.”


Investigators evaluated predefined outcomes data from the GEMINI 1 clinical trial (Phase 3) of vedolizumab examining treatment with vedolizumab in patients with moderately to severely active UC.

GEMINI 1 was a multicenter, phase 3, randomized, placebo-controlled trial (additional study details further below). As part of the eligibility criteria for GEMINI 1, patients had demonstrated, within the previous 5-year period, an inadequate response to, loss of response to, or intolerance of ≥1 of the following therapies: corticosteroids (outside the United States only), immunosuppressives (azathioprine or mercaptopurine), and/or infliximab, as this was the only TNF antagonist approved for the treatment of UC at the time of enrollment.

GEMINI 1 enrolled 464 patients without prior TNF antagonist therapy (TNF-naïve) and 367 who had failed therapy because of inadequate response, loss of response or intolerance (TNF-failure). In the present analyses, the TNF-failure population comprised an aggregate of patients with inadequate response, loss of response, or intolerance to prior TNF antagonist treatment as pre-defined according to data captured on the case report form (CRF) at baseline (week 0).

The primary outcome measure for induction therapy was a clinical response at week 6. Secondary outcome measures were clinical remission and mucosal healing at week 6. For maintenance therapy, the primary outcome was clinical remission at week 52.

Efficacy outcomes in TNF-naïve and TNF-failure patient sub-groups were analyzed in terms of the absolute difference in percentages for vedolizumab and placebo and the risk ratios (RRs). The RR is a measure of treatment efficacy, adjusted for any variabilities within the patient sub-groups, with RR > 1 indicating greater efficacy with vedolizumab.

Investigators found greater absolute differences between vedolizumab and placebo for TNF-naïve patients than for TNF-failure patients at week 6 and the RRs were similar. Week 6 response rates with vedolizumab and placebo were 53.1% and 26.3%, respectively, in TNF-naïve patients (AD: 26.4%; 95% confidence interval [CI]: 12.4, 40.4; RR: 2.0; 95% CI: 1.3, 3.0) and 39.0% and 20.6%, respectively, in TNF-failure patients (AD: 18.1%; 95% CI: 2.8, 33.5; RR: 1.9; 95% CI: 1.1, 3.2).

During maintenance, the absolute differences were similar and the RRs were higher for TNF-failure patients for most outcomes. Week 52 remission rates with vedolizumab and placebo were 46.9% and 19.0%, respectively, in TNF-naïve patients (AD: 28.0%; 95% CI: 14.9, 41.1; RR: 2.5; 95% CI: 1.5, 4.0) and 36.1% and 5.3%, respectively, in TNF-failure patients (AD: 29.5%; 95% CI: 12.8, 46.1; RR: 6.6; 95% CI: 1.7, 26.5).

Vedolizumab was approved as a gut-selective humanized monoclonal antibody, available in the European Union under the trade name Entyvio (vedolizumab). Entyvio was also approved in the United States in 2014. Entyvio is now approved in 48 countries, across five continents. It is the first and only biologic therapy to be approved simultaneously for the treatment of adults with moderately to severely active UC or CD who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha antagonist.

For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO.



SOURCE Takeda Pharmaceutical Company Limited

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