Investigators analyzed data from 1,784 adult patients with moderate to severe plaque psoriasis. Among them, 1,553 received adalimumab monotherapy, and 231 received adalimumab with methotrexate. The participants were drawn from a national dermatology registry between 2007 and 2021. The investigators used a target trial emulation framework to reflect key elements of a randomized trial.
At 1 year, drug survival was 78.1% in the monotherapy group and 79.1% in the combination group, with no statistically significant difference. At 3 years, survival rates were 57.2% and 59.3%, respectively, also showing no statistically significant difference.
Treatment response was assessed using the Psoriasis Area and Severity Index (PASI), specifically the proportion of patients achieving a 75% reduction from baseline (PASI75). At 1 year, PASI75 was achieved among 52.0% of patients receiving monotherapy and 49.4% of those receiving the combination therapy. At 3 years, PASI75 was 32.4% and 37.2%, respectively. These differences were not statistically significant.
Serious adverse events (SAE) occurred in 5.9% of the patients in the monotherapy group and 7.8% in the combination group after 1 year. At 3 years, SAE rates were 16.0% and 16.1%, respectively, indicating no meaningful difference in safety.
A pharmacokinetic analysis of 245 participants found that those receiving methotrexate had lower antidrug antibody (ADA) levels. Mean ADA levels were 120.9 AU/mL in the combination group vs 244.6 AU/mL in the monotherapy group. Mean adalimumab concentrations were higher with methotrexate (6.5 μg/mL vs 5.2 μg/mL), though this difference was not statistically significant. Lower ADA levels didn't lead to improved clinical outcomes.
The investigators aimed to clarify earlier findings from a randomized trial that had been limited by underenrollment. By leveraging real-world registry data and adjusting for confounding variables, the current analysis offered more precise estimates of treatment outcomes.
Despite the reduction in immunogenicity with methotrexate co-therapy, the addition of methotrexate didn't result in improved effectiveness or safety. The investigators concluded that methotrexate may not offer added clinical benefit when used alongside adalimumab for plaque psoriasis.
These results may inform treatment strategies, especially when reducing medication burden is a goal. Additional research could explore whether higher methotrexate doses or different patient populations might influence outcomes.
Full disclosures can be found in the published study.
Source: JAMA Dermatology