Methotrexate Adds No Benefit to Adalimumab in Psoriasis

TOPLINE:

In adults with psoriasis, adding methotrexate to adalimumab did not improve effectiveness or drug survival compared with adalimumab alone, according to a UK cohort study of patients with plaque psoriasis.

METHODOLOGY:

• Researchers emulated a target trial using data on 1784 patients with moderate to severe plaque psoriasis treated with systemic medications from the British Association of Dermatologists Biologic and Immunomodulators Register between 2007 and 2021.
• Participants received either adalimumab monotherapy (n = 1553) or adalimumab plus methotrexate (n = 231).
• The primary outcome was the difference in adalimumab drug survival at 1 year.
• Secondary outcomes were the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI 75), adverse events, and adalimumab drug and antidrug antibody levels.

TAKEAWAY:

• Drug survival was not significantly different with combination therapy compared with adalimumab alone at 1 year (79.1% vs 78.1%) and 3 years (59.3% vs 57.2%).
• At 1 year, PASI 75 was achieved by 52% vs 49.4% of patients in the monotherapy group vs the combination therapy group. Rates were 32.4% vs 37.2%, respectively, at 3 years.
• Serious adverse event rates were similar between the two treatment groups: At 1 year, 7.8% vs 5.9% in the combination group vs the monotherapy group.
• The combination therapy group had a lower antidrug antibody level (mean difference, −123.7 AU/mL) and numerically higher estimated drug concentration level (1.3 mcg/mL) than the monotherapy group.

IN PRACTICE:

“This target trial emulation cohort study did not find evidence that adding methotrexate to adalimumab was beneficial for treating plaque psoriasis,” the study authors wrote. “Future studies evaluating the effect of concomitant methotrexate should either focus on high (> 10 mg/wk) dosing regimens with biologics other than adalimumab for treating plaque psoriasis or with adalimumab for other inflammatory skin diseases,” they added.

SOURCE:

The study was led by Zenas Yiu, PhD, Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, University of Manchester, Manchester, England, and was published online on June 4 in JAMA Dermatology.

LIMITATIONS:

Most of the study participants deviated from treatment allocation and had missing outcome data, leading to inaccuracy of relative treatment effects measured by PASI and pharmacokinetic outcomes. Effect estimates in the intervention group lacked precision across all outcomes. Quality-of-life outcomes and baseline adjustment were omitted due to high levels of missing data. As an observational study, participants were unblinded to treatment allocation, introducing potential detection bias.

DISCLOSURES:

This study was supported by the National Institute for Health and Care Research Manchester Biomedical Research Centre. Several authors reported receiving grants or personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.