Methotrexate no better than placebo for steroid-free response, remission in UC

Last Updated: 2018-07-26

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Subcutaneous methotrexate (MTX) may not work better than placebo as maintenance therapy for ulcerative colitis (UC), researchers have found.

"The MERIT-UC trial showed that MTX was not superior to placebo in maintaining a steroid-free response or remission among patients who achieved steroid-free response during induction therapy," co-author Dr. Edward L. Barnes of the University of North Carolina at Chapel Hill told Reuters Health by email.

"Although there was no benefit in efficacy compared to placebo, over the trial period no new safety signals were detected with MTX in this study; however, a numerically higher incidence of nausea was noted among patients treated with MTX than with placebo," he added.

Dr. Barnes and colleagues, whose findings appeared online July 2 in Gastroenterology, recruited 179 patients to take part in the 48-week study at 37 sites in the United States. All participants had active UC (Mayo score 6-12 and endoscopy subscore 2 or higher) after undergoing conventional or biological therapy. For 16 weeks, all patients received open-label subcutaneous MTX.

By week 16, 91 (51%) patients responded, and over the next 32-weeks, 84 of them were randomized into one of two groups: 44 patients continued MTX (25 mg/week) and 40 were given placebo.

At week 48, the authors compared the percentage of patients in the MTX and placebo groups who remained relapse free without taking steroids or other medications.

During the 32-week maintenance period, 66% of patients in the MTX group and 60% in the placebo group had a UC relapse (P=0.75). At week 48, 27% taking MTX and 30% on placebo were in steroid-free clinical remission and did not need additional therapies (P=0.86).

"Given that there have been many questions about the role of MTX in patients with ulcerative colitis, the drug's lack of ability to maintain a therapeutic effect, compared to placebo, would suggest that this may not be an optimal therapy choice for patients with mild to moderate ulcerative colitis," Dr. Barnes advised.

Dr. Tanvi Dhere, an associate professor of medicine at Emory University School of Medicine, in Atlanta, who was not involved in the trial, echoed Dr. Barnes' assessment, but added a cautious note.

"The results of the study, which were eagerly anticipated, tell us that parenteral methotrexate may not be an ideal option as monotherapy to treat patients with mild to moderate active UC who are failing standard therapies," she said.

"However, one cannot completely discount the benefits of methotrexate in patients with inflammatory bowel disease, especially when considering its use in combination with biologics," she noted. "Methotrexate has been shown to prevent immunogenicity against biologic agents and to help boost biologic drug levels."

"The MERIT-UC trial included over 50% of patients who had previously failed biologic agents and/or azathioprine/6-mercaptopurine. Future studies looking at the efficacy of parenteral methotrexate in less medically refractory patients, including biologic and azathioprine/6-mercaptopurine-naive mild to moderate UC patients, are warranted," Dr. Dhere said.

Dr. Alyssa M. Parian, an assistant professor of medicine at Johns Hopkins Hospital in Baltimore, who also was not involved in the research, said, "This study was important to perform to determine if MTX is a medication we should or should not be using in our UC patients as single therapy since there have been some observational studies suggesting it may be effective."

"As a strength, this was a randomized, prospective, double-blind study which is of higher quality than retrospective and observational studies. It was a smaller study but still had adequate power to detect a difference," Dr. Parian told Reuters Health by email.

Dr. Jordan Axelrad, a gastroenterologist at the Inflammatory Bowel Center at NYU Langone Health in New York City, said, "These data are critical to understanding the full role of methotrexate in the treatment of ulcerative colitis."

"Although methotrexate is used in several autoimmune diseases and felt to be a safer alternative to biologic therapies or other antimetabolites, such as thiopurines, we now have more definitive evidence against its use for maintenance of remission in ulcerative colitis," Dr. Axelrad, who did not take part in the study, told Reuters Health by email.

The study did not have commercial funding.

SOURCE: https://bit.ly/2LCRsyM

Gastroenterology 2018.