Subcutaneous Methotrexate Superior to Oral Version in Key Areas for Psoriasis

Subcutaneous methotrexate (MTX) may provide greater efficacy with increased response time compared to oral treatment among psoriatic patients, a recent literature review’s findings suggest, with this version overcoming certain limitations of the oral version in terms of bioavailability, intestinal absorption, and safety.1

Manuelle Viguier, MD, PhD, from the Department of Dermatology at Robert Debré University Hospital in France, led a team of investigators in the literature review that resulted in these conclusions. Viguier and colleagues highlighted the commonly observed debate over subcutaneous versus oral MTX in the dermatology field.2

“The aim of this comprehensive literature review was to analyze the available literature on subcutaneous and oral methotrexate and discuss its advantages and disadvantages in terms of efficacy, safety, patient adherence to treatment, and costs to improve patient care,” Viguier and colleagues wrote.1

The investigators set out to look into the safety, efficacy, and adherence among patients of subcutaneous MTX and to make comparisons with MTX's oral formulation for the purposes of psoriasis management. With this aim in mind, they designed a structured literature review that was conducted in accordance with systematic review principles.

A comprehensive search, study selection, and synthesis of relevant scientific publications was involved in this analysis, with the investigative team gathering the necessary data in the timeframe between January 2015 - May 2023.

The MEDLINE/PubMed and Cochrane databases were implemented by the team for their search of relevant data, following the current review protocols. They kept their search restricted to articles that were available in either French of English. Additionally, the investigators carried out a gray literature search, finding data through the targeted exploration of different topics.

There were 230 articles that the the analysis had initially involved, with a set of 2 reviewers independently assessing these data. In their initial screening, the pair would identify relevant studies through an evaluation of keywords in the titles and abstracts. Eligible studies included those involving patients diagnosed with psoriasis and undergoing MTX therapy, considering both oral and subcutaneous administration routes.

The included studies evaluated treatment efficacy, safety, and adherence, with a particular focus on gastrointestinal adverse effects, hepatotoxicity, and differences in bioavailability between the two methods of administration. After applying the predefined inclusion criteria, 32 studies were selected for final analysis.

The team systematically extracted key results from the selected trials—including information regarding trial designs, therapy outcomes, characteristics among study subjects, MTX regimens, routes of administration, and safety profiles. They then carried out a descriptive synthesis to compare findings across the different studies.

Overall, the investigative team found that only European guidelines explicitly recommend subcutaneous MTX over the option for oral administration. This recommendation, the team highlighted, likely explains why MTX's implementation is predominantly reported in European countries, as opposed to the oral version's general worldwide implementation.

They added that while the body of data was somewhat limited and heterogeneous, the investigators' assessment indicates that subcutaneous MTX may address some of the limitations linked to the use of MTX's oral formulation.

This was particularly shown to be the case in terms of bioavailability, intestinal absorption, and safety. Additionally, the evidence evaluated by the team indicates that subcutaneous MTX may offer superior effectiveness, potentially leading to a quicker and more robust response in those living with psoriasis.

“Despite the paucity and heterogeneity of the literature, available data suggest that subcutaneous MTX may overcome some of the limitations of the oral route in terms of intestinal absorption, bioavailability, and safety,” they wrote.1 “Subcutaneous application may also lead to a faster response when compared to the oral route.”

References

1. Viguier, M., Carrascosa-Carrillo, J.-M., Rakvit, P., Constantin, M.-M., Varlet, A.-A., Le Clanche, S., Verhagen, L.A.W. and Boehncke, W.-H. (2025), Comprehensive Literature Review Evaluating the Use, Safety, and Efficacy of Subcutaneous Methotrexate in the Treatment of Adult Patients With Moderate-To-Severe Plaque-Type Psoriasis. Int J Dermatol. https://doi.org/10.1111/ijd.17758.

2. S. R. Quist, J. Quist, J. Birkenmaier, T. Stauch, and H. P. Gollnick, “Pharmacokinetic Profile of Methotrexate in Psoriatic Skin via the Oral or Subcutaneous Route Using Dermal Microdialysis Showing Higher Methotrexate Bioavailability in Psoriasis Plaques Than in Non-Lesional Skin,” Journal of the European Academy of Dermatology and Venereology 30 (2016): 1537–1543.