A Randomized Trial of Methotrexate in Combination With Infliximab for the Treatment of Crohn's Disease

Abstract

Both methotrexate (MTX) and infliximab (IFX) are effective therapies for active Crohn’s disease (CD); however, it is unknown whether the combination is superior to IFX alone. METHODS: We conducted a 50-week, double-blind, multicenter, controlled trial that compared combination therapy to IFX alone in patients with active CD. Eligible patients had initiated prednisone induction therapy within 6 weeks. Patients previously treated with IFX and those at risk for MTX or IFX toxicity were excluded. Patients were randomly assigned to receive MTX 25 mg subcutaneously weekly or placebo (PBO). Both groups received IV IFX, 5 mg/kg, at weeks 1, 3, 7, and every 8 weeks thereafter. Hydrocortisone 200 mg IV was administered pre-IFX infusion. Prednisone was tapered, beginning at week 1, to discontinuation by no later than week 14. The primary outcome was time to treatment failure, (failure to enter prednisone-free remission [Crohn’s Disease Activity Index (CDAI) 150] at week 14 or failure to maintain remission through week 50]. RESULTS: Sixty-three patients were randomized to each group. The demographics of the 2 groups were similar (baseline CDAI, 207.8 MTX vs 207.6 PBO; mean age 40.4 years MTX vs 38.5 years PBO; prednisone dose, 26.9 mg MTX vs 31.4 mg PBO). By week 50, 30.6% of patients in the MTX group had failed treatment compared with 29.8% of those assigned to PBO (P .63). Prespecified subgroup analyses failed to show an effect of treatment in patients with short duration of disease or an elevated C-reactive protein. No differences were observed in CDAI or SF-36 scores. Combination therapy was well tolerated (any infection, 58.7% MTX vs 61.9% PBO). CONCLUSIONS: The combination of IFX and MTX, although safe, was no more effective than IFX alone in CD patients requiring treatment with prednisone.