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MERIT-UC Interim Reports – 2013

Report April 2013

Executive Summary for CCFA: Status Merit-UC April 2013

Hans Herfarth

Study in ClinicalTrials.gov

There are fewer therapeutic options for patients with active ulcerative colitis (UC) compared to patients with active Crohn’s disease (CD) and we are facing a persistent unmet need for additional effective and affordable therapies for patients with UC. Methotrexate (MTX) 25 mg once weekly administered subcutaneously (sq) or intramuscularly (im) is an efficient therapy to induce and maintain steroid free remission in patients with CD. Only one small prospective placebo controlled trial investigating the oral administration of 12.5 mg MTX once weekly compared to placebo has been conducted. The results did not demonstrate superiority of MTX compared to placebo. We conducted a systematic literature research to identify published clinical efficacy data of MTX in patients with UC and found several retrospective and prospective case series demonstrating clinical efficacy of MTX, when the drug was administered in a comparable dose and similar route (im or sq) as in CD. The conflicting data of the only placebo controlled trial and the published clinical experience may be explained by the fact, that MTX has a known dose response curve as shown in patients with CD or rheumatoid arthritis and also has a significant lower bioavailability if applied orally especially in higher doses such as the one used in CD. We therefore hypothesize that MTX presents an effective therapy for patients with UC if administered in a similar fashion as in CD patients.

Related Publications

Herfarth HH, Long MD, Isaacs KL; Methotrexate: Underused and Ignored?  Dig Dis DOI: 10.1159/000342735, in press 2012

Herfarth HH, Osterman MT, Isaacs KL, Lewis JD, Sands BE; Efficacy of methotrexate in ulcerative colitis: Failure or promise. Inflamm Bowel Dis 2010;16:1421-30.

Aims of MERIT-UC

MERIT-UC is a NIH funded multi-center prospective placebo controlled study to investigate the safety and efficacy of 25 mg MTX applied subcutaneously once weekly in patients with active UC, who are either steroid dependent or are intolerant or not responding to 5-ASA’s or azathioprine/6-mercaptopurine therapy or have no response/ lost response to infliximab prior to the study inclusion.

The aims of the trial are:

1)    To evaluate the safety and tolerability of 25 mg MTX applied sq once weekly over a time period of 48 weeks.

2)    To evaluate the relapse-free survival of MTX maintenance therapy compared to placebo over a time period of 32 weeks.

3)    To evaluate the efficacy of MTX over a time period of 16 weeks to induce steroid free remission.

4)    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.

 

Active Sites in MERIT-UC

Currently we have 34 active sites and 1 site preparing to join the consortium (if you want to see who is participating check the CRA website www.CCFACRA.org). We are still looking for new sites.  If you are or know a site that might be interested, please contact Hans Herfarth, PI of MERIT-UC: hherf@med.unc.edu).

 

Recruitment

So far we have screened 79 patients for the study and included 45 into the open label induction period. We hope to reach the first aim of the study – an interim analysis of 75 patients completing open label induction period – in the next 9-12 months.