Adalimumab plus methotrexate lowers treatment failure 2-fold in pediatric Crohn’s
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Key takeaways:
- Adding methotrexate to adalimumab therapy significantly reduced treatment failures for patients with pediatric Crohn’s disease.
- No differences were reported between infliximab combination therapy and monotherapy.
Combination therapy with adalimumab plus low-dose methotrexate induced a two-fold reduction of treatment failure among pediatric patients with Crohn’s disease, according to research published in Gastroenterology.
“Tumor necrosis factor inhibitors (TNFi), including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease therapy; however, non-response and loss of response are common,” Michael D. Kappelman, MD, MPH, professor of pediatric gastroenterology at University of North Carolina at Chapel Hill, told Healio. “As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare TNFi with oral methotrexate to TNFi monotherapy.”
Kappelman and colleagues enrolled 297 pediatric patients with CD (mean age 13.9 years, 35% girls), randomly assigning 156 patients to the combination therapy group (110 received infliximab; 46 received adalimumab), and 141 patients to the TNFi monotherapy group (102 received infliximab; 39 received adalimumab). The researchers followed patients for 12 to 36 months to analyze composite indicator of treatment failure. Additional studied outcomes included anti-drug antibodies and patient reported outcomes of pain interference and fatigue.
“Among adalimumab, but not infliximab, initiators, [pediatric patients with CD] treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile,” Kappelman said.
According to study results, there was no difference in time to treatment failure among infliximab initiators between the combination and monotherapy groups (HR = 0.93; 95% CI, 0.55-1.56). However, among adalimumab initiators, combination therapy was significantly associated with a longer time to treatment failure (HR = 0.4; 95% CI, 0.19-0.81).
Kappelman and colleagues reported that patients who received combination therapy with either infliximab (OR = 0.72; 95% CI, 0.49-1.07) or adalimumab (OR = 0.71; 95% CI, 0.24-2.07) had decreased anti-drug antibody development, though they noted this trend was “not significant.”
Furthermore, 30% of patients experienced treatment failure, including 27% who received infliximab and 36% who received adalimumab. Additionally, patients who received combination therapy experienced less treatment failure (26%) vs. those who received monotherapy (34%).
Kappelman and colleagues noted the most common indicator of treatment failure was hospitalization for active inflammatory bowel disease after week 25. Time to treatment failure did not differ between groups (HR = 0.69; 95% CI, 0.45-1.05).
“We believe that all patients with pediatric Crohn’s disease should be starting on adalimumab, and their parents should be informed of the improved effectiveness when combined with low-dose oral methotrexate,” Kappelman told Healio. “Those without contraindications should be offered combination therapy, and shared decision-making should be incorporated into final treatment decisions. In contrast, most patients starting infliximab are not likely to experience added benefits from low dose oral methotrexate.”
He continued: “The evaluation and comparison of additional strategies to further optimize response to adalimumab, including proactive therapeutic drug monitoring, warrant additional research.”
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