ORLANDO – In patients with Crohn’s disease, a response to the investigational monoclonal antibody vedoluzimab within 6 weeks of initiating therapy was predictive of a continued response to the drug, even at lower doses.
Among patients in the GEMINI II trial with a documented response to vedoluzimab after 6 weeks, 32% of those who were then randomized to receive the drug once every 8 weeks for an additional 46 weeks had a corticosteroid-free clinical remission of Crohn’s disease (CD), as did 29% of those who continued to receive the same dose every 4 weeks and 16% of those on placebo, said Dr. William Sandborn at the annual Digestive Disease Week.
However, the rate of durable clinical remissions, defined as clinical remissions at 80% or more of study visits, was comparable for both dosing groups and the placebo group.
Dr. William J. Sandborn
"Patients who had a clinical response to vedolizumab by week 6 then went on to have stable clinical remission rates throughout the maintenance phase and significantly higher clinical remission rates than placebo by week 52," said Dr. Sandborn of the University of California, San Diego.
Vedolizumab is an investigational, gut-selective monoclonal antibody targeting the alpha-4 beta-7 integrin. In GEMINI II, the drug was shown to be more effective than placebo for induction and maintenance therapy of CD.
For this analysis, the researchers dug deeper into the data from GEMINI II and looked at maintenance-phase outcomes for those patients who had a clinical response to the drug by week 6 of the trial.
Patients in the trial were adults 18-80 years old with a diagnosis of CD at least 3 months before study entry, moderate to severe CD as determined by a CD Activity Index (CDAI) score of 220-450 at screening, and either intolerance of or an inadequate response to purine antimetabolites or anti–tumor necrosis factor (anti-TNF) agents.
A clinical response to vedolizumab was defined as at least a 70-point decline in CDAI score from baseline value at week 6 following two induction doses of therapy. Patients were randomized on a 1:1:1 basis to receive vedolizumab via infusion every 8 weeks, the same dose every 4 weeks, or placebo until week 52.
Patients who did not have a clinical response by week 6 were treated with open-label vedolizumab at the 300-mg dose every 8 weeks until week 52, and were assessed with those patients who had been on placebo throughout the induction and maintenance phases.
CDAI scores among 153 patients on placebo stabilized at 26 weeks, but continued to decline through week 52 among patients on vedolizumab at both dosing frequencies (154 patients in each dosing group). Rates of clinical remission (CDAI score of 150 or lower) remained relatively stable among patients on vedolizumab, but declined among those on placebo.
A corticosteroid-free remission was seen at week 52 in 32% of patients on the 8-week schedule and in 16% of those on placebo (P = .015). The remission rate was 29% for those on the 4-week schedule (P vs. placebo = .045).
In addition, 21% of those on vedolizumab every 8 weeks had durable clinical remissions, as did 16% of those on the every-4-week dose and 14% of those on placebo. There were no statistically significant differences among the three groups.
In the question-and-answer session following presentation of the results, an attendee commented that "it’s a little disturbing that the more frequent dose seemed to be numerically inferior to the less-frequent dose at virtually every measured outcome."
Dr. Sandborn said that the investigators have extensively examined that question and determined that "there’s noise around the measurements, but you couldn’t draw any firm statistical conclusions."
The study was funded by Millennium/Takeda. Dr. Sandborn disclosed serving as a consultant and receiving grant and research support from the combined companies.
