NEW YORK (Reuters Health)—Parenteral methotrexate was no better than placebo for achieving steroid-free remission of ulcerative colitis (UC) in the METEOR trial.
But the drug should not be abandoned in all UC patients, researchers say.
“Although METEOR failed to reach its primary endpoint, an important secondary endpoint was met. Our study suggests that methotrexate should be considered as an alternative to azathioprine in patients with steroid-dependent UC,” Dr. Franck Carbonnel of the University of Paris-Sud, France, tells Reuters Health by email.
METEOR was a randomized, controlled, double-blind study of 111 patients with steroid-dependent UC at 26 medical centers in six European countries from 2007 to 2013.
Participants were receiving 10–40 mg/d prednisone/prednisolone at baseline and were randomized to receive either placebo (n=51) or methotrexate (n=60) 25 mg weekly intramuscularly or subcutaneously for 24 weeks.
Patients were to continue to receive steroids for 13 weeks, with researchers tapering the dose down weekly. In cases of relapse, patients received 20 mg/day and then increased systemic steroid therapy if necessary.
At Week 16, 19 methotrexate patients (31.7%) and 10 placebo patients (19.6%) had achieved steroid-free remission, defined as Mayo Clinic Score 2 or less on a 12-point scale with no item being >1, the primary endpoint. This difference was not statistically significant (p=0.15), the researchers reported in Gastroenterology, online Nov. 26.
The only outcome with a statistically significant difference was a secondary endpoint of clinical remission without steroids at Week 16, achieved by 25 patients (41.7%) on methotrexate and 12 (23.5%) in the placebo group (p=0.04).
Four placebo and six methotrexate patients experienced severe adverse events, and 40 patients (16 methotrexate, 24 placebo) discontinued the trial due to adverse events or disease activity.
“Our study failed to show that parenteral methotrexate is beneficial for induction of steroid-free remission in UC. However, methotrexate induced clinical remission without steroids at week 16 more frequently than placebo, and was associated with better control of disease-related symptoms. Additional studies are required to define the potential benefit of methotrexate as a maintenance therapy,” the researchers conclude.
“At the moment there is insufficient data to document its effect on mucosal healing and maintenance treatment,” Dr. Carbonnel says.
What is needed now, Dr. Carbonnel says, is a clinical trial of methotrexate as a maintenance treatment in UC to try and find biomarkers, such as gene polymorphisms, to predict response/remission.
The study did not have commercial support.
