Vedolizumab was not superior to placebo for inducing remission at 6 weeks in patients with Crohn’s disease who failed to respond to anti–tumor necrosis factor therapy, according to findings from the double-blind, phase III GEMINI 3 trial.
However, therapeutic benefit from the humanized, anti–alpha-4 beta-7 integrin, immunoglobulin G1 monoclonal antibody did become apparent by week 10, Dr. Bruce E. Sands of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues report in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2014.05.008).
Source: American Gastroenterological Association
The investigators randomized 315 patients with moderately to severely active Crohn’s disease who failed anti-TNF therapy to receive 300 mg of vedolizumab (158 patients) or placebo (157 patients) intravenously at weeks 0, 2, and 6. The results showed that 15.2% of the vedolizumab group was in remission at week 6, compared with 12.1% of the placebo group (relative risk, 1.2). At week 10, 26.6% of patients in the vedolizumab group, compared with 12.1% of those in the placebo group, were in remission (RR, 2.2), the investigators reported.
More patients in the vedolizumab group did, however, achieve at least a 100-point decrease in the Crohn’s Disease Activity Index (CDAI) score at both 6 weeks (39.2% vs. 22.3% of placebo patients; RR, 1.8) and 10 weeks (46.8% vs. 24.8%; RR, 1.4), they said.
The incidence and type of adverse events were similar in both groups.
GEMINI 3 was conducted between November 2010 and April 2012 at 107 sites in North America, Europe, Asia, Africa, and Australia. Participants were aged 18-80 years with moderately to severely active Crohn’s disease (defined in part by a CDAI score of 220-400 points), with known involvement of the ileum and/or colon at 3 or more months before enrollment.
Remission was defined by a CDAI score of 150 points or less.
Treatment with TNF antagonists has improved the care of patients with Crohn’s disease that is refractory to other treatments, but in controlled trials anti-TNF therapy failed in about two-thirds of patients. Treatment is also associated with an increased risk of serious infections in some patients. Natalizumab, another treatment used in Crohn’s disease, has been limited by its association with an increased risk of progressive multifocal leukoencephalopathy.
"Because of these limitations with TNF antagonists and natalizumab, therapies for patients with TNF antagonist failure are needed, and those that selectively inhibit lymphocyte trafficking to the gut may yield important safety benefits," the investigators said.
Vedolizumab was shown in the pivotal GEMINI 2 study to be safe and effective for induction and maintenance in patients with moderately to severely active Crohn’s disease who failed one or more prior therapies; GEMINI 3 specifically focuses on patients with prior TNF antagonist failure.
"The results of this short-term study support the safety of vedolizumab in patients with Crohn’s disease and are consistent with the drug’s postulated gut-selective mechanism of action," the investigators said.
Furthermore, several prespecified outcomes suggest that in addition to leading to clinical remission in the TNF antagonist–naive patients with Crohn’s disease, vedolizumab may lead to clinical remission at 10 weeks in those who failed TNF antagonist therapy.
"These clinically relevant response kinetics have potential implications for bridging induction therapy to vedolizumab maintenance therapy, which has established efficacy, in patients with this lifelong condition," they concluded.
This study was funded by Millennium Pharmaceuticals (doing business as Takeda Pharmaceuticals). Dr. Sands reported receiving consulting and advisory board fees, as well as clinical research/institutional grant support from AbbVie, Janssen, and Takeda. Detailed disclosures for all authors are available with the full text of the article.