Efficacy and Safety of Adalimumab as Monotherapy Versus Adalimumab With Methotrexate for Psoriasis: A Systematic Review

Adalimumab is a common biologic used for the management of moderate-to-severe plaque psoriasis. Despite the known importance of adding methotrexate to adalimumab in reducing immunogenicity and improving clinical response, the extent of its benefit remains unclear. This review aimed to systematically compare adalimumab with and without methotrexate, considering their efficacy and safety in the management of psoriasis. This systematic review included randomized controlled trials, long-term follow-up studies, and observational cohorts that investigated adalimumab monotherapy with adalimumab plus methotrexate in adult patients diagnosed with plaque psoriasis. Data on clinical efficacy using Psoriasis Area and Severity Index (PASI), drug survival, and safety outcomes were extracted and summarized. A total of 128 records were initially identified through database searching. After removal of duplicates and screening of titles and abstracts, 45 full-text articles were assessed for eligibility, of which five studies met the predefined inclusion criteria and were included in the final analysis. The studies showed that the addition of methotrexate reduced the antidrug antibody formation and improved the serum level of adalimumab. Additionally, higher early PASI75 achievement was observed at early follow-up periods (approximately 5-16 weeks, depending on study design), with only modest numerical improvements in select studies. Considering safety profiles, the results were comparable between groups, with rare serious adverse events reported. However, the rate of discontinuation because of adverse events was higher with combination therapy. Addition of methotrexate to adalimumab therapy for the management of psoriasis may reduce immunogenicity and optimize the drug pharmacokinetics; however, it does not show a significant advantage considering clinical efficacy or long-term treatment persistence. Therefore, according to the study findings, the combination therapy should be selectively used in patients with suboptimal response or in those with suspected immunogenicity, while retaining the standard use of adalimumab monotherapy for the rest of the patients.