Subcutaneous Vedolizumab Shows Promise for Ulcerative Colitis

Issue: December 2018

Vedolizumab delivered subcutaneously for maintenance of ulcerative colitis, differing from the current intravenous delivery, showed similar efficacy to traditional delivery and superiority to placebo in a study presented during UEG Week 2018.

Perspective from Stephen B. Hanauer, MD

“The VISIBLE 1 results highlight that the investigational subcutaneous formulation of vedolizumab helped patients with moderately to severely active ulcerative colitis achieve and maintain clinical remission, mucosal healing and durable clinical response, after responding to vedolizumab IV induction therapy. These data indicate that the subcutaneous formulation of vedolizumab had an efficacy and safety profile similar to the IV reference arm, and further add to the collective dataset for vedolizumab in ulcerative colitis,” William J. Sandborn, MD, director of the Inflammatory Bowel Disease Center at University of California San Diego, said in a press release.

This randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial (VISIBLE 1) assessed vedolizumab subcutaneous (SC) as maintenance treatment in adult patients with active UC. After traditional vedolizumab therapy for 6 weeks, patients with a clinical response (Mayo score reduction 3 points, 30% from baseline, reduction in rectal bleeding score; n = 216) underwent randomization to either vedolizumab SC (108 mg every 2 weeks), vedolizumab IV (300 mg every 8 weeks) or placebo for up to 52 weeks.

After 52 weeks, 42.6% of patients receiving vedolizumab IV remained in clinical remission. Similarly, 46.2% of patients receiving vedolizumab SC remained in clinical remission vs. 14.3% receiving placebo (P < .001). In subgroup analysis, Sandborn and colleagues showed higher clinical remission rates with vedolizumab SC compared with placebo in both patients who were anti-TNF-alpha-naive (vedolizumab 53.7% vs. placebo 18.9%; P < .001) and those who previously failed anti-TNF-alpha (vedolizumab 33.3% vs. placebo 5.3%; P = .023).

Looking at the key secondary endpoints of mucosal healing (56.6% vs. 21.4%) and durable clinical response (64.2% vs. 28.6%), vedolizumab SC was “significantly superior” to placebo for both (P < .001), according to the abstract, while anti-vedolizumab antibodies was similar (5.7% for vedolizumab SC; 5.6% for vedolizumab IV).

“Vedolizumab SC 108 mg every 2 weeks was efficacious, generally safe and well-tolerated as maintenance therapy in UC patients following induction with vedolizumab IV 300 mg,” the researchers wrote in the abstract. “The new SC formulation of vedolizumab showed an efficacy and safety profile similar to that of the currently available IV formulation and consistent with that previously reported for vedolizumab IV.” – by Katrina Altersitz

Reference: Sandborn WJ, et al. LB03. Presented at: UEG Week Vienna 2018; Oct. 20-24, 2018.

Disclosures: Sandborn reports receiving research grants from AbbVie, Atlantic Healthcare Limited, Amgen, Celgene/Receptos, Genentech, Gilead Sciences, Janssen, Lilly and Takeda; consulting fees from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Conatus, Cosmo, Escalier Biosciences, Ferring, Genentech, Gilead, Janssen, Lilly, Miraca Life Sciences, Nivalis Therapeutics, Novartis Nutrition Science Partners, Oppilan Pharma, Otsuka, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix, Shire, Seres Therapeutics, Sigmoid Biotechnologies, Takeda, Tigenix, Tillotts Pharma, UCB Pharma and Vivelix; and holds stock options from Escalier Biosciences, Oppilan Pharma, Precision IBD, Progenity and Ritter Pharmaceuticals.

Perspective

Stephen B. Hanauer, MD

The reported study of subcutaneous vedolizumab vs. intravenous infliximab presented at UEGW provides an alternative route of administration for an important inductive and maintenance therapy for patients with ulcerative colitis refractory to conventional agents and TNF inhibitors. The results with vedolizumab IV every 8 weeks were replicated with every 2-week subcutaneous administration. Vedolizumab is recognized as an effective and safe biologic in the setting of moderate-severe ulcerative colitis with very good maintenance results that are not “burdened” by black box warnings regarding infections or malignancies. While the regimen of 30-minute intravenous infusions at baseline, week 2, week 6 and every 8 weeks allows less than 3 hours a year in infusion centers, many patients would prefer the “liberty” of self-administration; even at a more frequent interval.

Providing different administration options with equivalent efficacy and safety is in line with the concept and relevance of our shared decision-making approaches to ulcerative colitis patients who require both induction and long-term maintenance therapy.

Stephen B. Hanauer, MD

Clifford Joseph Barborka Professor of Medicine

Northwestern University Feinberg School of Medicine

Medical Director, Digestive Health Center

Disclosures: Hanauer reports financial relationships with AbbVie, Actavis, Amgen, Arena, Astra Zeneca, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Catabasis, Celltrion, Cubist, Ferring, Genentech, Entera Health, GlaxoSmithKline, Hospira, Janssen, Lilly, Novartis, Novo Nordisk and Pfizer.