Methotrexate Response In Treatment of Ulcerative Colitis (MERIT-UC)

General Description

Compared to patients with active Crohn’s disease (CD), there are fewer therapeutic options for patients with active ulcerative colitis (UC).Because of this lack of treatment options for UC, providers and patients face a persistent need for additional effective and affordable therapies. Methotrexate (MTX) administered once weekly subcutaneously (25 mg) is an efficient therapy to induce and maintain steroid-free remission in patients with CD and may be an effective therapy for patients with UC. The Methotrexate Response in Treatment of Ulcerative Colitis (MERIT-UC) study is a double-blind, placebo-controlled, randomized, multicenter clinical trial that was established to test whether subcutaneous administration of MTX is a safe and effective therapy for UC.

Patients with active UC who failed 5-aminosalicylic acid therapy, are steroid dependent, or are not responding to therapy with either azathioprine/6-mercaptopurine or anti-TNFare enrolled. The study, designed as a drug withdrawal trial, includes two phases. In the first phase (week 0-16), the Induction Period, every patient receives a steroid taper, consisting of MTX 25 mg sq once weekly and daily folic acid 1 mg tablets for the induction of clinical response or remission. In the second phase of the trial (week 17-48), patients who respond to the open label MTX therapy and who achieve steroid remission between weeks 12-16 are randomized at week 16 to treatment with either placebo or MTX (25 mg); both are administered subcutaneously once weekly. In addition, participants receive daily folic acid 1 mg tablets and 2.4 g mesalamine, regardless of treatment group.

Objectives

The primary objective of the MERIT-UC study is to determine whether 25 mg MTX applied subcutaneously once weekly is a safe and effective therapy to induce and maintain steroid-free remission in patients with active UC. In addition to this objective, the study aims to establish a DNA, plasma and serum library to enable the evaluation of clinical and pharmacogenomic models to predict the response to MTX therapy in patients with UC.

Outcome Measure

The primary outcome measure, assessed at 48 weeks, is a composite measure of relapse-free survival, comprised of three components: 1) total week 32 Mayo score not exceeding 2 points, with all individual subscores not exceeding 1 point; 2) a stable Mayo score throughout 32 weeks of maintenance therapy without increase of 3 or more points in the partial Mayo clinic score (excluding sigmoidoscopy) compared to the partial Mayo score of the individual patient at randomization at week 16; and 3) no steroid use or other immunosuppressive medication throughout the 32 week maintenance period. Secondary outcome measures include mucosal healing, defined as an absolute subscore for endoscopy of 0 or 1 at week 48, and relapse of disease, defined as an increase of 3 or more in the partial Mayo clinic score (excluding sigmoidoscopy) with an absolute clinical Mayo score ≥ 4 or need for retreatment with steroids.

Criteria

Individuals between the ages of 18 and 70 years who met the following criteria are eligible for the study:
- Ulcerative colitis diagnosed by routine clinical, radiographic, endoscopic, and pathological criteria.
- Active UC with a Mayo score of 6 to 12 points and moderate-to severe active disease on sigmoidoscopy (Mayo endoscopic subscore of at least 2) and at least one of the following: steroid dependent UC, primary failure or loss of response to an anti-TNF (infliximab, adalimumab, golimumab) or to vedolizumab, intolerance/failure of azathioprine/6- mercaptopurine therapy in the past, or failure of 5- aminosalicylic acid therapy.

Steroid dependence is defined as a clinical response to treatment with prednisone 40 to 60 mg/day and relapse within 30 days after prednisone treatment was completed or as a requirement for a daily dosage of not less than 10 mg of prednisone and impossibility of weaning the patient off steroid without clinical relapses (two attempts to discontinue the medication within the preceding six months of the start of the study).

Exclusion criteria are documented in the study protocol.

Outcome

This study is ongoing.