Background In the METEOR trial, methotrexate (MTX) induced steroid free clinical remission but not endoscopic healing in a significantly higher percentage of pat. compared to placebo (P). We conducted a randomized, multicenter P-controlled trial to determine the efficacy and safety of MTX in maintaining steroid free remission in pat. with moderately-severely active UC, who had responded and were able to discontinue steroids after open label induction with steroids and MTX. Methods: The 48-week (wk) trial comprised a 16-wk open label induction period followed by a 32-wk double-blind P-controlled maintenance period (MP). Pat. with active UC (Mayo score 6-12 with endoscopy subscore ≥2) despite previous conventional or biological therapy were included and treated with open label MTX 25 mg/wk subcutaneously and a 12-wk steroid taper. At wk 16, responders were randomly assigned to either continue MTX 25 mg/wk or P until wk 48. All pat. received 2.4 g mesalamine daily. We compared the efficacy of treatment by analyzing the proportion of pat. who remained relapse free during the 32-wk MP defined by a clinical Mayo score ≤ 2 at wk 32 without increase ≥3 points during MP and no use of steroids or other medications to control disease activity during MP. Results: Fifty-one percent (91/179) of patients responded and 30% (53/179) achieved remission at wk 16. Of 91 pat. with steroid free response, 7 pat. declined randomization and 84 pat. were randomized in the P controlled MP. In the P and MTX arm, 63% (25/40) and 66% (29/44) of pat. experienced a relapse (p=0.75) (fig.1). At wk 48, 75% (12/16) and 85% (12/15) of pat. on P and MTX, respectively, were in steroid free clinical remission. No new safety signals were detected. Conclusion: Although when combined with a standardized steroid taper, parenteral MTX 25 mg/wk induced a steroid free response and remission rate in a substantial proportion of pat. with active UC, it was not superior to P in preventing relapse of disease.
