Analysis: Methotrexate Does Not Enhance Adalimumab Outcomes in Psoriasis

Key Takeaways

• Methotrexate did not increase drug survival or PASI75 outcomes when added to adalimumab in plaque psoriasis.

• Adverse event rates and drug concentrations were similar across treatment groups.

• Methotrexate reduced antidrug antibody levels but did not increase efficacy. 

Concomitant methotrexate does not improve the effectiveness or persistence of adalimumab in plaque psoriasis, according to findings from a new study.

Researchers investigating whether methotrexate enhances adalimumab’s durability or efficacy in psoriasis enrolled 1,784 adults with plaque psoriasis in the study. Adalimumab therapy was administered between 2007 and 2021. Patients were categorized into two cohorts: one receiving adalimumab monotherapy (40 mg biweekly; n = 1,553), while and a cohort receiving concomitant methotrexate with the same adalimumab regimen (n = 231). The primary study outcome (adalimumab drug survival at 1 year) was similar between study groups. One-year drug survival was 78.1% (95% CI, 76.1% to 80.2%) for monotherapy and 79.1% (95% CI, 71.8% to 87.2%) for combo therapy, with difference of 1.0% (95% CI, −7.0% to 8.9%).

At one year, PASI75 response rates were 52.0% (95% CI, 47.7% to 56.3%) in the monotherapy group and 49.4% (95% CI, 31.5% to 67.3%) in the combo group. At three years, the rates dropped to 32.4% and 37.2%, respectively (not statistically significant). Serious adverse event rates didn't differ between groups. The researchers did report a significantly lower level of antidrug antibodies in the methotrexate group (−123.7 AU/mL; 95% CI, −200.5 to −46.9).

“The results of this cohort study suggest that there was no evidence of a difference in the effectiveness and persistence of adalimumab in people with psoriasis between monotherapy and adalimumab with concomitant methotrexate,” the authors wrote.

Source: Yiu Z, et al. JAMA Dermatology. 2025. doi:10.1001/jamadermatol.2025.1463