Oral low-dose methotrexate improves infliximab pharmacokinetics, immunogenicity, and endoscopic outcomes in Crohn's disease: a propensity score-adjusted real-world study.

INTRODUCTION

The effectiveness of infliximab in Crohn's disease is often compromised by immunogenicity. Oral low-dose methotrexate may offer a promising strategy to optimize infliximab therapy, yet its real-world effectiveness and safety remain uncertain.

AIM: This study aimed to compare the effectiveness and safety of infliximab plus oral low-dose methotrexate versus infliximab monotherapy.

METHOD: In this single-center retrospective cohort study, 119 patients with Crohn's disease received either infliximab monotherapy (n = 99) or combination therapy with oral low-dose methotrexate (10-15 mg/week; n = 20). The primary outcome was endoscopic remission (Simple Endoscopic Score for Crohn's Disease ≤ 2) at week 26. Propensity score methods, including nearest-neighbor matching and inverse probability of treatment weighting, were used to adjust for confounding. Conditional and weighted logistic regression were used to estimate treatment effects.

RESULTS

After propensity score adjustment, combination therapy was associated with a significantly higher rate of endoscopic remission (aOR 3.70, 95% CI 1.16-11.75; P = 0.027). No significant differences were observed in endoscopic response or clinical outcomes. In a pharmacokinetic subgroup, combination therapy resulted in numerically higher infliximab trough concentrations and no detectable anti-drug antibodies (0% vs. 16.7%). Higher trough concentrations were associated with endoscopic remission (P = 0.033). The incidence of elevated liver enzymes was higher in the combination group (20.0% vs. 4.0%), but this difference was not statistically significant after adjustment (P = 0.058).

CONCLUSION

In patients with Crohn's disease, oral low-dose methotrexate combined with infliximab was associated with significantly improved endoscopic remission at week 26 compared to infliximab monotherapy, without a statistically significant increase in adverse events.