Entyvio superior to Humira in moderate, severe ulcerative colitis
Entyvio conferred superior clinical remission and mucosal healing compared with Humira among patients with moderately to severely active ulcerative colitis, according to results of a phase 3b randomized trial presented at the Congress of the European Crohn’s and Colitis Organisation.
“With multiple agents available for treating ulcerative colitis, particularly the newer agents such as the biologic therapies, it is sometimes difficult to decide which treatment you should use and in what order,” Bruce E. Sands, MD, MS, chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai, told Healio Gastroenterology and Liver Disease. “The field is really lacking in direct comparisons and head-to-head trials of these agents, [and] this study was an effort to begin to address that by comparing vedolizumab to adalimumab in patients with active ulcerative colitis.”
Sands, who is a co-author of the study, and colleagues conducted a phase 3b randomized, double-blind, double-dummy, multicenter, active controlled study within 330 study sites across 37 countries to assess and compare the efficacy and safety of Entyvio (vedolizumab; Takeda) vs. Humira (adalimumab; AbbVie) in patients with moderately to severely active UC.
The VARSITY trial comprised 771 patients – 386 patients who received adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg every 2 weeks until week 50, as well as placebo intravenously at weeks 0, 2, 6 and every 8 weeks afterward until week 46; and 385 patients who received vedolizumab 300 mg at weeks 0, 2, 6 and every 8 weeks afterward until week 46, as well as placebo delivered subcutaneously at week 0 and every 2 weeks until week 50.
The proportion of patients achieving clinical remission – as defined by a complete Mayo score of 2 or less points and no individual subscore greater than 1 point at week 52 – served as the primary endpoint.
Secondary endpoints included the proportion of patients who achieved mucosal healing – as defined by a Mayo endoscopic subscore of 1 or less point at week 52.
More than half of the patients receiving adalimumab (54.4%) and vedolizumab (56.4%) presented with severe disease at baseline as defined by a Mayo score of 9 to 12.
More than a quarter of patients who received vedolizumab (31.3%) achieved clinical remission at week 52, compared with 22.5% of patients who received adalimumab (P = .0061).
“[While] this was highly statistically significant, this was also very clinically important given that drugs [have been approved] on the basis of a 10% treatment effect size in comparison to placebo,” Sands said in an interview. “So, this is an active drug compared against an active drug. It’s quite a meaningful outcome in my view and should guide practice as far as if one is looking at the first biologic therapy to treat a patient for their active UC, probably the better choice would be vedolizumab.”
Additionally, mucosal healing at week 52 was achieved in 39.7% of patients who received vedolizumab compared with 27.7% of patients who received adalimumab (P = .0005).
“When you put together superior efficacy and probably a superior safety profile, then I think most patients and most physicians would probably choose vedolizumab first,” Sands said. “One area that has made it difficult to use vedolizumab first is that insurers have often wanted other [therapies] to be tried before vedolizumab. I think this provides a very solid foundation for stating that vedolizumab should be the first choice.”
Sands noted that some people looking at these results might think vedolizumab had superior results because of the length of the study, but he said treatment differences in clinical response were noticed as early as weeks 6 through weeks 14.
“I think some people assume vedolizumab may have [had an] advantage by the later timepoint because people assume it does not work as quickly as other TNF-blockers, but in fact it was shown that actually quite early on, vedolizumab was already superior to adalimumab,” he said. – by Ryan McDonald
Schreiber S, et al. OP34. Presented at: Congress of the European Crohn’s and Colitis Organisation; March 7-9, 2019; Copenhagen, Denmark.
Disclosure: Sands reports serving as a consultant for AbbVie, Janssen and Takeda.