a 50-week trial that compared combination therapy to IFX alone in 126 patients with CD who had initiated prednisone induction therapy, 15 to 40 mg daily, within 6 weeks of entry.Patients were randomly assigned to receive MTX at an initial weekly dose of 10 mg s.c., escalating to 25 mg, or placebo.Both groups received IFX; 5 mg/kg of body weight at weeks 1, 3, 7, 14 and every 8 weeks thereafter.Prednisone was tapered, beginning at week 1, and discontinued no later than week 14.The primary outcome was time to treatment failure, defined as failure to enter prednisone-free remission (CDAI <150) at week 14 or failure to maintain this remission through week 50.ATIs and trough serum IFX concentrations were measured every 8 weeks using the Prometheus® assays.RESULTS Sixty-three patients were randomized.Baseline characteristics were similar.By week 50 the actuarial rate of treatment failure was 30.6% in the combination group vs. 29.8% in the monotherapy group (P=0.63;hazard ratio 1.16, 95% CI 0.62 to 2.17).Patients who received MTX were less likely to develop antibodies to IFX (4.0% vs. 20.4%,P=0.01) than those who were assigned to placebo.The median serum trough IFX concentration was higher in patients receiving MTX, 6.35 mg per mL compared with 3.75 mg per mL, P=0.08.The proportion of patients with detectable drug at trough was also higher, 25.9% vs. 14.0%,P=0.13) in those assigned to MTX.Overall, patients who had detectable IFX at trough were more likely to be a treatment success (72.3% vs. 52.4%,P=0.08).CONCLUSIONS The combination of IFX and MTX, although safe, was no more effective than IFX alone in CD patients requiring treatment with prednisone.However, patients treated with MTX were less likely to form ATIs and have high serum trough IFX concentrations.Detectable IFX at trough was associated with treatment success independent of MTX assignment.