Real‐world evidence for vedolizumab: Understanding the landscape

Vedolizumab is a monoclonal antibody that selectively inhibits the migration of α4-β7 positive inflammatory cells to the gastrointestinal tract. In the GEMINI 1 randomized double-blinded placebo-controlled trial of vedolizumab in ulcerative colitis (UC), the response rate was 47.1% at week six and, for patients receiving vedolizumab every 8 weeks, 56.6% at week 52. Of interest, however, is that despite a clinical remission rate of 16.9% at week six there was a mucosal healing rate of 40.9% at the same time point. Again, after 52 weeks of treatment, 41.8% of patients were in clinical remission, but 51.6% had complete mucosal healing. These findings suggest that symptoms of post-inflammatory irritability of the bowel may reduce the perceived clinical response rates.1 In the GEMINI 2 randomized double-blind placebo-controlled trial of vedolizumab in Crohn's disease (CD), the remission rate was 14.5% at week six and 39% at week 52 with 8-weekly vedolizumab treatment.2 Since the pivotal Phase III studies, there have been several publications from various centers that have collected real-life data for the management of UC and CD with vedolizumab. A systematic pooled analysis of nine studies that included 1565 (571 UC and 994 CD) adult patients with inflammatory bowel disease identified that in CD, vedolizumab achieved a 54% clinical response and 22% remission at week six and 49% responded and 32% were in remission by week 14. This was similar to the findings at week 52 where 45% of patients were responding and 32% were in clinical remission. In UC, vedolizumab achieved a 43% clinical response and 25% remission at week six and 51% responded and 30% were in remission by week 14. This was similar to the findings at week 52 where 48% of patients were responding and 39% were in clinical remission.3 What appear to be better findings, however, were seen in a retrospective study of 27 centers from Finland that included 247 patients (139 UC and 108 CD), in which clinical remission was achieved at 6 months in 42% of treatment persistent patients with CD and 73% of treatment persistent patients with UC.4 More recently, there have been numerous abstracts presented from many countries around the world. From the Netherlands, endoscopic response to vedolizumab therapy was observed in 8/15 (47%) patients with CD and 9/11 (82%) patients with UC, but the clinical remission rates were < 50% in both CD and UC.5 In Scotland, 340 patients (203 CD and 137 UC) experienced lower hospitalization rates and steroid usage associated with vedolizumab treatment.6 In Spain, a study of 274 patients (144 CD and 130 UC) identified that vedolizumab was more likely to be effective in UC than CD, if the patients were anti-tumor necrosis factor naïve and if they had mild or moderate disease, instead of severe disease.7 In Ireland, a study of 39 UC patients treated with vedolizumab resulted in clinical response rates of 47% at 3 months and 46% at 6 months.8 In Canada, endoscopic remission was 41% at 6 months and 48% at 12 months in UC, while clinical response was 62% and 63%, respectively.9 In Canada, endoscopic remission was lower for patients with CD with 21% in remission at 6 months and 19% in remission at 12 months with a clinical response of 23% at both time points.10 In Australia, vedolizumab has been approved, under the Pharmaceutical Benefits Scheme, for the treatment of moderate-to-severe UC and CD since August 2015. An assessment of response/remission is required at 12 weeks of therapy prior to the approval for further treatment. Data, including demographics, Montreal classification, family and smoking history, indication for vedolizumab, concomitant inflammatory bowel disease medications, prior exposure to anti- tumor necrosis factor medications, and adverse events, have been prospectively collected at 12 inflammatory bowel disease centers in Australia, the United Kingdom (UK), and Hong Kong. To date, 279 UC patients (191 Australian, 84 UK, 4 and Hong Kong) have been assessed and have demonstrated a response rate at 3 months of 79% (220/279) and remission rate of 55% (155/281). Remission at 6 months was 61% (144/235) and 12 months (117/196) was 60%. There was an endoscopic remission rate of 48% (60/124) at 6 months. There was a greater rate of remission at 12 months if patients were on combination therapy with an immunosuppressive medication (36% [37/104] vs 17% [13/79] P = 0.03). There were, however, no significant differences observed between the Australian and UK data, suggesting that there was no site or country bias in determining response and remission rates. Colectomy was undertaken in 11% (33/291). For CD, 22 Australian patients were in remission at commencement of vedolizumab and were changed to the medication due to side effects from their previous therapy. At 3 months, all patients were still in remission, at 6 months, 93% (13/14) were responding, and at 12 months, 75% (9/12) were still responding and remained on treatment. Four CD patients had a stoma, and three of the four remained on vedolizumab at 12 months; 113 Australian CD patients were commenced on vedolizumab for active inflammation. At 3 months, 96% (108/113) had demonstrated a response (Crohn's disease activity index drop of > 100) while 89% (101/113) were in clinical remission (Crohn's disease activity index < 150). By 6 months, five patients had lost response. At 12 months, 60 patients were still on vedolizumab, and all were continuing to respond, and all but two were in clinical remission. Further work and analysis still need to be undertaken, but the results certainly indicate efficacy of vedolizumab that may be higher than expected from the Phase III studies. In conclusion, in real-life practice, vedolizumab appears to be a highly effective treatment in both UC and CD, while the combination of immunosuppressive therapies with vedolizumab still needs to be further investigated. IL has received funding for auditing vedolizumab outcomes in Australia for Takeda. He serves on the advisory boards of Takeda, Janssen-Cilag, AbbVie, Gilead, Pfizer and Schering-Plough. He has received honoraria from Takeda, Janssen-Cilag, AbbVie, Gilead, Pfizer and Schering-Plough for presenting at educational events.

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