Parenteral Methotrexate Improves Clinical Remission During Forced Corticosteroid Tapering for Patients With Ulcerative Colitis: Presented at ECCO-IBD

By Chris Berrie

BARCELONA -- February 23, 2015 -- Parenteral methotrexate is well tolerated, and provides significantly improved clinical remission compared with placebo during forced corticosteroid tapering for patients with corticosteroid-dependent ulcerative colitis (UC), according to results of a prospective study presented here at the 10th Congress of the European Crohn’s and Colitis Organisation, Inflammatory Bowel Diseases (ECCO-IBD).

Parenteral methotrexate did not, however, improve induction of remission in these patients without steroids.

Parenteral methotrexate has been shown to be effective as induction and maintenance treatment in Crohn’s disease, explained lead author Franck Carbonnel, MD, PhD, APHP Paris Sud University, Le Kremlin Bicêtre, France, speaking here on February 21. By contrast, there has only been 1 prior, randomised trial to determine methotrexate benefits for patients with UC, and, while its results were negative, Dr. Carbonnel noted, “methotrexate was given orally, probably at a suboptimal dose.”

To examine the results of parenteral methotrexate in the UC population, Dr. Carbonnel and colleagues enrolled 111 patients who had corticosteroid-dependent active or inactive UC of 6 months or longer duration who were receiving daily corticosteroids at 10 mg to 40 mg in the double-blind METEOR trial.

Following randomisation, the patients received either placebo (n = 51) or methotrexate 25 mg/week intramuscularly (IM) or subcutaneously (SC) (n = 60). For both treatment groups, this was accompanied by a forced steroid-weaning schedule at week 13.

The primary endpoint of improved induction of remission at week 16 following forced corticosteroid tapering required a total Mayo score of 2 or less with no item over 1, no immunosuppressives, no anti-tumour-necrosis factor (TNF) agents, and no colectomy. On an intention-to-treat basis, when compared with placebo, this primary endpoint was not reached (20% vs 32%; P = .15), although methotrexate provided a beneficial trend.

This methotrexate treatment showed significant benefit over placebo for the secondary endpoint of clinical remission without corticosteroids at week 16, however (23.5% vs 42%; P = .04).

The further secondary endpoint of endoscopic healing without corticosteroids at week 16 did not reach significance (25.5% vs 35%; P = .28).

There were no significant benefits over placebo for these endpoints at week 24, in improved induction of remission (33% vs 35%), clinical success (35% vs 40%), or endoscopic success (33% vs 40%).

In the safety analysis, methotrexate was well tolerated, with relatively few serious adverse events, and no safety signal, the researchers noted.

The main limitation of this study -- no central reading of endoscopic images -- was recently shown to be critical to the conduct of induction studies in UC. When questioned about this, Dr. Carbonnel stated that “a rectal bleeding score of 0 has good sensitivity and specificity for assessing mucosal healing, and the difference was statistically significant [22% vs 47%; P = .04], which may suggest that, in many patients, the mucosa had healed and this got blurred by the on-site reading of the endoscopy.”

Baseline characteristics were similar across these treatments, with a mean patient age of 42 years, about 50% female, and disease duration of 4 to 5 years. The mean Mayo score was 4.0, and Mayo endoscopy subscore was 1. Patients were receiving 25 to 30 mg/day prednisone-equivalent doses.

The METEOR study was undertaken with the support of the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) and the European Crohn’s and Colitis Organisation.

[Presentation title: Methotrexate for Corticosteroid-Dependent Ulcerative Colitis: Results of a Placebo Randomized Controlled Trial. Abstract OP023]

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