By Marilynn Larkin
NEW YORK (Reuters Health) - 30/1/2019
In patients with moderate to severe Crohn's disease who've been taking stable doses of steroids, adding vedolizumab may help induce a clinical response or remission, researchers say.
"It's interesting that the patients all had stable doses of corticosteroids and were not fully responsive to that, but did better with the addition of vedolizumab," Dr. Bruce Sands of Icahn School of Medicine at Mount Sinai in New York City told Reuters Health by phone. "It's not clear what that mechanism might be."
Dr. Sands and colleagues conducted a post hoc exploratory analysis of data from the placebo-controlled GEMINI 2 and GEMINI 3 trials, which assessed outcomes after vedolizumab induction therapy over six- and 10-week periods, respectively. Patients had a mean age of about 38 and close to half were men.
Roughly 45% of patients in GEMINI 2 and 52% of patients in GEMENI 3 had been taking steroids.
Efficacy endpoints were clinical remission (Crohn's Disease Activity Index score no higher than 150 points) and enhanced clinical response (decrease of at least 100 points from baseline).
As reported online January 4 in Inflammatory Bowel Diseases, vedolizumab plus corticosteroids resulted in higher clinical remission rates than placebo plus corticosteroids at week six in GEMINI 2 (19% vs. 4.6%) and at weeks six (19.8% vs. 10.2%) and 10 (34.2% vs. 11.1%) in GEMINI 3.
Further, compared to patients in the vedolizumab group who were not also taking corticosteroids, more patients receiving vedolizumab plus steroids achieved clinical remission at week six in GEMINI 2 (19% vs. 10.9%) and at week 10 in GEMINI 3 (34.2% vs. 22.2%).
The combination also resulted in significantly higher enhanced clinical response rates compared to placebo plus corticosteroids at all timepoints in both studies. Similarly, more patients receiving vedolizumab plus corticosteroids achieved higher enhanced response rates at week six in GEMINI 2 (36% vs. 27.7%) and at week 10 in GEMINI 3 (53.2% vs. 42.3%) than patients receiving vedolizumab alone.
Adverse event rates were similar across groups.
"We can't say from these data that initiation of steroids to boost the effects of vedolizumab is the right thing to do, but we wouldn't be concerned about adding vedolizumab if patients are already on steroids," Dr. Sands said. "Since vedolizumab has a steroid-sparing effect, this seems to be a winning combination."
Dr. Richard Bloomfeld, Director of the Inflammatory Bowel Disease Clinic at Wake Forest Baptist Health in Winston-Salem, North Carolina, said in an email to Reuters Health, "While it is not surprising that those who received a stable dose of steroids plus vedolizumab had better outcomes than those who received a stable dose of steroids plus placebo, it is interesting that those who received a stable dose of steroids plus vedolizumab tended to do better than those who received vedolizumab alone."
In line with Dr. Sands' comment, Dr. Bloomfeld noted, "The nature of this analysis comparing patients who were on baseline steroids to those who were not prevents us from drawing any conclusions about whether there is benefit to starting steroids during induction with vedolizumab."
"We await further data on whether the benefits of continuing baseline steroids during induction with vedolizumab is maintained after the steroids are tapered off," he said. "Physicians must remain mindful of the toxicities associated with prednisone use."
Takeda funded the preparation of the article. Dr. Sands and a coauthor receive fees from Takeda. Four coauthors were company employees during the study.
SOURCE: http://bit.ly/2MJ2b99 Inflamm Bowel Dis 2019.