Douglas C. Wolf

Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease.

Sustaining clinical remission is an important treatment goal in moderate-to-severe UC. This post hoc exploratory analysis assessed the long-term efficacy of vedolizumab in the subset of patients with UC in the GEMINI 1 study who were in clinical remission by week 14 after 3 induction doses, administered at weeks 0, 2, and 6. Sustained clinical remission (primary endpoint) was evaluated using 2 definitions: (1) a partial Mayo Score (pMS) of ≤2 with no subscore >1 and (2) a rectal bleeding subscore (RBS) of 0 throughout weeks 14, 26, 38, and 52. The proportion of patients in clinical remission at week 14 was significantly higher in patients receiving vedolizumab (n = 620) compared with placebo (n = 149) (pMS: 32.7% vs 20.1% [percentage-point difference (∆) 12.6%; 95% confidence interval [CI], 5.2–20.0]; RBS: 47.3% vs 28.9% [∆18.4%; 95% CI, 10.1–26.7]). Of patients in clinical remission at week 14, a significantly higher proportion of vedolizumab-treated patients achieved sustained clinical remission compared with placebo (pMS: 66.5% vs 26.7%; ∆39.8%; 95% CI, 22.7–56.9; RBS: 56.7% vs 20.9%; ∆35.7%; 95% CI, 22.3–49.1). Findings were consistent in tumor necrosis factor (TNF) antagonist-naive and antagonist-failure patients. Compared with placebo, 35%–40% more patients receiving a full induction course of vedolizumab had sustained clinical remission after 52 weeks of therapy. This result was observed irrespective of TNF antagonist treatment history. Clinical remission at week 14 may therefore be a predictor for sustained clinical remission with vedolizumab.

Background: Histological remission (HR) has been reported as a positive prognostic indicator of clinical activity in ulcerative colitis (UC). The TOUCHSTONE open-label extension (OLE) is an opportunity to examine the impact of histologic remission on UC activity during a long-term evaluation of efficacy and safety of ozanimod 1 mg. TOUCHSTONE was a randomized, double-blind, placebo-controlled phase 2 trial designed to assess the efficacy and safety of ozanimod 0.5 mg and 1 mg versus placebo during induction and maintenance in patients with moderate to severe UC [1], and established that ozanimod induced and maintained clinical response, clinical remission (CR), endoscopic mucosal healing, and HR through weeks 8 and 32. Methods: A total of 197 patients were randomized (1:1:1) and treated with daily ozanimod at 0.5 mg, 1 mg, or placebo in TOUCHSTONE. Of the initial 197 patients randomized, 170 (86%) entered OLE and received daily ozanimod 1 mg, and 131 (77%) and 105 (62%) completed assessments at weeks 44 and 80. In this analysis, HR was defined as a Geboes score 3× ULN were seen in 3% of patients. Conclusions: Histological remission is predictive of CR in patients with UC receiving ozanimod 1 mg in OLE. All patients, whether naïve to or having received ozanimod in TOUCHSTONE, showed additional improvements in CR upon continued treatment with ozanimod 1 mg in OLE. Patients naïve to ozanimod had a rapid improvement in CR over the first 8 weeks of treatment with ozanimod 1 mg in OLE. References: [1] Sandborn WJ, Feagan BG, Wolf DC, et al. (2016), Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med, 1754–62

On August 24, 1998, infliximab, an antibody to tumor necrosis factor alpha (anti-TNF) became the first biologic approved for inflammatory bowel disease (IBD). At that time, the approval was limited to induction therapy for moderate to severe luminal and fistulizing Crohn's disease; no Federal Drug Agency (FDA) approval for maintenance therapy was given. The anti-TNFs have changed the course of Crohn's disease and ulcerative colitis for many patients over the past 17 years. The benefit derived from these biologic drugs, the induction and maintenance of response and remission, and improvement of quality of life, are well known. With the advent of biosimilars, a new type of biologic has arrived. Biosimilars are biological medicines that are developed after the patent on a reference biologic has expired.¹ Biosimilars to infliximab have been approved by the European Medicines Agency (EMA) and used...