GEMINI: Entyvio maintenance unaffected if immunosuppression stopped
HONOLULU — Discontinuation of immunosuppressants did not significantly impact the efficacy of Entyvio maintenance therapy in patients with inflammatory bowel disease, according to post hoc analyses of the GEMINI 1 and 2 trials presented at ACG 2015.
“Because of the natural history experiment due to regulatory requirements in the U.S. … immunosuppression was stopped in both of these trials in American patients as opposed to the rest of the world, so we really have an opportunity to look at what happened, respectively, in the two jurisdictions and see what inferences we can make about immunosuppression concomitant to vedolizumab therapy,” Brian Feagan, MD, from Robarts Research Institute, University of Western Ontario, said during his presentation. “So the aim of the study was to evaluate the effects of discontinuing immunosuppressants on the efficacy, pharmacokinetics and immunogenicity in patients who responded to vedolizumab induction therapy.”
At 6 weeks, Entyvio [vedolizumab, Takeda] responders were re-randomized to placebo or vedolizumab every 4 or 8 weeks for 46 weeks, at which point U.S. patients stopped immunosuppressant therapy, while patients outside of the U.S. were allowed to continue using immunosuppressants at stable doses. Patients were re-randomized to the following:
- placebo at U.S. centers; UC, n = 10; Crohn’s, n = 5;
- vedolizumab at U.S. centers; UC, n = 18; Crohn’s, n = 9;
- placebo at non-U.S. centers; UC, n = 41; Crohn’s, n = 44;
- vedolizumab at non-U.S. centers; UC, n = 70; Crohn’s, n = 94.
Feagan and colleagues stratified patients with baseline immunosuppressant use based on region and performed post hoc analyses of efficacy, vedolizumab serum concentration and immunogenicity.
They found that clinical remission and response, mucosal healing in UC and steroid-free remission rates at week 52 were numerically higher in patients who received vedolizumab regardless of their immunosuppressant use at baseline. Furthermore, patients in and outside of the U.S. had comparable mean trough concentrations at week 46, and centers in and outside of the U.S. had comparable numbers of patients who tested positive for anti-vedolizumab antibodies during maintenance.
“In conclusion, discontinued immunosuppressant use upon response to vedolizumab induction did not appear to substantially affect the efficacy of vedolizumab maintenance therapy in patients with UC,” Feagan said. “However, there was a modest trend favoring continued immunosuppressant use during vedolizumab maintenance in Crohn’s disease, and … we should really be generating a dedicated trial to look at combination therapy with vedolizumab.” – by Adam Leitenberger
Feagan B, et al. Abstract 21. Presented at: ACG 2015; Oct. 19-21, 2015; Honolulu, HI.
Disclosures: Feagan reports numerous financial disclosures, including that he received financial support for research and served as a consultant for Millenium and Takeda, and served on the advisory board for Takeda, which funded the study. Please see the abstract for a full list of all other researchers’ relevant financial disclosures.