SC administration of vedolizumab receives FDA approval for Crohn’s disease maintenance

Crohn’s disease (CD) is an inflammatory bowel disease (IBD) with rising incidence and prevalence worldwide, characterized by abdominal pain, diarrhea, fatigue and weight loss.1,2 While corticosteroids (CS), immunomodulators and biologics are commonly used, achieving sustained remission remains variable.2,3 Vedolizumab, a monoclonal antibody that selectively blocks gut lymphocyte trafficking, is approved worldwide for treating moderate-to-severe ulcerative colitis and CD via intravenous (IV) administration.1,3 Recently, the United States (US) Food and Drug Administration (FDA) approved the subcutaneous (SC) administration of vedolizumab for maintenance therapy in moderately to severely active CD, based on results from the phase 3 VISIBLE 2 trial.1

CD is an IBD with unclear etiology, though an excessive immune response to gut bacteria in genetically predisposed individuals is suspected.2,3 During flare-ups, activated immune cells migrate into the intestinal tissue, fueling inflammation.2,3 This is facilitated by the binding of α4ß7 integrin molecules on the cell surface of T and B lymphocytes to mucosal address in cell adhesion molecule 1 (MAdCAM-1) selectively expressed on gut endothelial cells.2,3 Vedolizumab, a monoclonal antibody against the α4ß7 integrin, blocks the interaction with MAdCAM-1 and selectively suppresses gut-specific lymphocyte trafficking.2 While an IV formulation of vedolizumab has been approved for CD treatment, an SC formulation may be less time-consuming and more convenient maintenance option for patients.1 The recent approval of SC vedolizumab by the FDA thus provides CD patients with the option for an alternative route of administration for maintenance therapy.1

This approval was based on results from the VISIBLE 2 study, a randomized, double-blind, placebo-controlled, phase 3 trial that evaluated the efficacy and safety of a new SC vedolizumab formulation as maintenance treatment in CD patients.1 Eligible study participants were adults aged 18-80 years with moderate-to-severe CD that had been diagnosed at least 3 months prior.1 They must have shown inadequate response or intolerance to CS, immunomodulators and/or anti-tumor necrosis factor (anti-TNF) therapies in the past.1 The study enrolled 644 patients with moderate-to-severe CD from 169 sites in 30 countries.1 All participants received open-label IV vedolizumab 300mg at weeks 0 and 2.1 Of these, 412 (64%) achieved a clinical response (≥70-point decrease in CD Activity Index [CDAI] from baseline) by week 6.1 The 410 patients who either responded or were close to the response threshold were then randomized 2:1 to receive maintenance vedolizumab 108mg SC or placebo every 2 weeks until week 50.1 The primary endpoint was clinical remission (CDAI score ≤150) at week 52, while secondary endpoints include enhanced clinical response (≥100-point decrease in CDAI from baseline), CS-free clinical remission among patients using a CS at baseline, clinical remission in anti-TNF-naïve patients and safety.1

At week 52, significantly more patients on vedolizumab SC maintenance achieved clinical remission compared to placebo (48.0% vs. 34.3%; 95% CI: 3.8%-23.7%, p=0.008).1 Enhanced clinical response at week 52 was 52% with vedolizumab vs. 44.8% with placebo (p=0.167).1 CS-free remission at week 52 was 45.3% with vedolizumab vs. 18.2% with placebo (pnominal=0.002).1 Among anti-TNF-naïve patients, 48.6% on vedolizumab vs. 42.9% on placebo were in remission at week 52 (pnominal=0.591).1

The primary and secondary endpoint results were consistent in a post-hoc sensitivity analysis excluding 18 patients who did not meet the criteria of clinical response, as well as across subgroups.1 However, the treatment difference in clinical remission favored vedolizumab SC only in patients with colonic or ileocolonic disease, but not with ileum-only disease. Improvements were seen in biomarker endpoints at week 52, including normal fecal calprotectin in 60.5% with vedolizumab SC vs. 31.7% placebo and normalized C-reactive protein in 23.2% vs. 17.5%.1 Safety profiles were similar between arms, with injection site reaction being the only new finding, occurring in 2.9% of vedolizumab SC patients vs. 1.5% placebo.1

In summary, vedolizumab SC was found to be an effective and safe maintenance therapy in patients with CD who responded to 2 infusions of vedolizumab IV induction therapy.1 These results support vedolizumab SC as an important treatment option for CD patients who require maintenance therapy and offer the option for both IV and SC administration.1


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