Methotrexate shows real-world skin benefits in early systemic sclerosis

The research, conducted in real-life clinical practice rather than a controlled trial setting, examined how patients with early disease and skin involvement fared after starting methotrexate monotherapy, and how long they remained on the treatment.

Eighty-five percent of the participants were women, and seventy-nine percent had the diffuse cutaneous form of the disease, which is typically associated with more extensive skin thickening.

The results showed a gradual but measurable response. At three months, 34.2 percent of patients with diffuse cutaneous disease had achieved at least a twenty-five percent reduction in their skin score from baseline. Among patients who remained on methotrexate monotherapy, this proportion rose to 61.8 percent at twenty-four months, a difference the authors report as statistically significant. However, in an intention-to-treat analysis using non-responder imputation, which counts patients who discontinued treatment as non-responders, only 28.8 percent of the whole diffuse cutaneous cohort met the improvement threshold at twenty-four months.

The modelling analysis identified two factors independently associated with changes in the skin score. Time on treatment was linked to a steady decline in skin scores, with an estimated decrease of 0.092 points per month. Patients with a baseline skin score of fourteen or higher, indicating more severe skin involvement, had higher absolute skin score values throughout follow-up. Notably, concomitant glucocorticoid therapy was not associated with skin improvement, and neither corticosteroid use nor methotrexate dosage independently predicted the skin score trajectory.

Drug survival emerged as a central challenge. Patients with higher baseline skin severity had shorter time on methotrexate, and disease progression accounted for seventy-five percent of the discontinuations of methotrexate monotherapy. According to the study’s highlights, nearly half of the patients required treatment escalation, meaning that other immunosuppressive drugs were added or methotrexate was stopped altogether. This high rate of escalation underscores that methotrexate alone is not sufficient for a substantial share of patients with early diffuse disease.

Among those who stayed on treatment, the response achieved at three months was generally maintained through twenty-four months, suggesting that an early skin response may identify patients in whom monotherapy is durable. The authors conclude that methotrexate monotherapy can be associated with meaningful skin improvement in early systemic sclerosis, with response typically emerging within the first three months of treatment.

The findings carry practical implications for clinical decision-making. Because so many patients eventually need escalated therapy, the researchers emphasise the need for careful patient selection when initiating methotrexate and for early reassessment of the treatment strategy, so that patients whose disease is progressing are not left on an insufficient regimen. As a retrospective, single-cohort observational study, the analysis describes associations in routine practice rather than proving causal treatment effects, and the authors note that the high escalation rates highlight the importance of optimising therapeutic strategies in this patient group.

Subject of Research: Real-life effectiveness and drug survival of methotrexate monotherapy for skin involvement in early systemic sclerosis

Article Title: Methotrexate in early systemic sclerosis: skin outcomes and drug survival in real-life practice

Article References: Iannone, C., Magi, I., Pellico, M. R., Bochicchio, C., Minniti, A., Caporali, R., & Del Papa, N. (2026). Methotrexate in early systemic sclerosis: skin outcomes and drug survival in real-life practice. Arthritis Research & Therapy. https://doi.org/10.1186/s13075-026-03910-x

Image Credits: AI Generated

DOI: 10.1186/s13075-026-03910-x

Keywords: systemic sclerosis, scleroderma, methotrexate, modified Rodnan skin score, diffuse cutaneous systemic sclerosis, drug survival, retrospective study, rheumatology, immunosuppressive therapy, skin fibrosis, treatment escalation, observational study