Subcutaneous Methotrexate More Effective than oral route in psoriasis but Linked to Higher Adverse Effects: Study
A new study published in the Journal of the European Academy of Dermatology and Venereology revealed that subcutaneous methotrexate (MTX) improves treatment efficacy for psoriasis compared to oral MTX but also carries a higher risk of adverse effects. Oral MTX showed higher discontinuation due to ineffectiveness, whereas subcutaneous MTX had more discontinuations related to side effects.
From July 2012 to January 2023, this study included 406 patients diagnosed with plaque, erythrodermic, or guttate psoriasis. All participants were new to methotrexate, biologic therapies, and apremilast, and began treatment with MTX monotherapy. Among them, 58.1% received oral methotrexate (MTX-PO), while 41.9% were administered the drug subcutaneously (MTX-SC).
At the start of treatment, the median Psoriasis Area and Severity Index (PASI) score stood at 11, which indicated moderate to severe disease activity. Additionally, 67.3% of patients reported a Dermatology Life Quality Index (DLQI) score of 6 or higher, which reflected a notable impact of psoriasis on daily living.
To assess how long patients remained on methotrexate without discontinuing due to inefficacy or side effects, this research used Kaplan–Meier curves and Cox regression analyses. After adjusting for potential confounding factors like age, disease severity, and comorbidities, the results showed no statistically significant difference in overall MTX survival between oral and subcutaneous administration routes (p = 0.15).
The patients receiving subcutaneous methotrexate (MTX-SC) were less likely to stop treatment due to a lack of effectiveness, suggesting that the injectable form may offer slightly better therapeutic stability. On the other hand, discontinuation due to intolerance like side effects or adverse reactions, was more common in the MTX-SC group than in those taking the drug orally.
While the choice between oral and subcutaneous methotrexate did not significantly alter overall treatment persistence, clinicians might consider patient tolerance and response patterns when selecting a route of administration. The study noted certain limitations, including a relatively small sample size, which could have limited the statistical power to detect smaller differences. Overall, these findings reinforced the role of methotrexate as a cornerstone therapy for psoriasis, with both oral and subcutaneous forms showing comparable long-term adherence.
Source:
Paris, C., Curmin, R., Gouillon, L., Giboin, C., De Rycke, Y., Bachelez, H., Beneton, N., Beylot-Barry, M., Dupuy, A., Joly, P., Mahé, E., Paul, C., Richard, M.-A., Sbidian, É., Viguier, M., Chosidow, O., Tubach, F., Jullien, D., & PSOBIOTEQ study group. (2025). Impact of methotrexate administration route on drug survival in psoriasis: Results from PSOBIOTEQ. Journal of the European Academy of Dermatology and Venereology: JEADV, jdv.70044. https://doi.org/10.1111/jdv.70044
