PO:31:173 | Methotrexate monotherapy in early systemic sclerosis: a real-life monocentric Italian experience

Claudia Iannone^1|2, Ilaria Magi^1|2, Antonina Minniti², Giuseppe Armentaro², Silvia Cavalli^1|2, Manuel Sette^1|2, Laura Giudice^1|2, Maria Rosa Pellico^1|2, Cristina Bochicchio^1|2, Roberto Felice Caporali^1|2, Nicoletta Del Papa^1|2. | ¹Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milano, Italy; ²Dipartimento di Reumatologia e Scienze Mediche, ASST G. Pini-CTO, Milano, Italy.

Abstract

Background. Systemic sclerosis (SSc) is a complex autoimmune disease with significant morbidity and mortality. Methotrexate (MTX) is one of the most prescribed immunosuppressants for SSc, particularly in patients with early diffuse cutaneous disease, with prescription rates of 30-50%. However, supporting scientific evidence remains limited. The objective of this study is to evaluate the efficacy of MTX monotherapy on the cutaneous component of SSc using the modified Rodnan Skin Score (mRSS) as the primary parameter.

Materials and Methods. A retrospective monocentric study was conducted on patients with SSc treated with MTX monotherapy within the first two years of disease onset. The mRSS, MTX dosage, and prednisone equivalent were collected at baseline and at 3, 6, 12, and 24 months. Cutaneous improvement was defined as a reduction of > or = 5 points or > or = 25% from baseline mRSS. Disease activity was assessed using the EUSTAR Activity Index. Temporal variation was evaluated through analysis of variance (ANOVA) corrected for independent variables. Kaplan-Meier analysis was applied to estimate MTX therapy persistence, and survival curves were censored at MTX monotherapy discontinuation (intolerance, disease progression, combination with an additional drug, pregnancy).

Results. The cohort included 92 patients, predominantly female (85%), with a median age of 50.75 years and a median disease duration of 1.08 years at MTX initiation. 77% had diffuse cutaneous SSc (dcSSc), and 72% were Scl70 positive (Table). Linear mixed-model analysis revealed a statistically significant variation in mRSS over time (p < 0.001). Estimated marginal means showed a progressive decline from baseline (9.745) to 24 months (6.603), with the most substantial improvement occurring after 3 months (-1.886), reaching the improvement criterion of > or = 25% (Figure 1). The EUSTAR Activity Index remained stable during follow-up (p = 0.213), consistently staying below the active disease threshold (> or = 2.5) (Figure 2). After two years of follow-up, 47 patients (51%) discontinued MTX monotherapy: 36 (39%) due to disease progression (25 cutaneous, 5 pulmonary, 6 combined) and only 9 (9.78%) due to intolerance. Rituximab was the most frequently added drug (30.43%). MTX persistence was 48.9% at 2 years, with a median survival time of 1.366 years. Patients with limited cutaneous SSc (lcSSc) showed better drug retention (median 1.749 years) compared to dcSSc patients (1.3 years). Figure 3: dcSSc (red line) and lcSSc (blue line).

Conclusions. This observational study provides evidence that MTX can be effective as monotherapy in the early treatment of cutaneous SSc, especially in diffuse involvement. The lower persistence in patients with dcSSc likely reflects the more aggressive progression of cutaneous fibrosis and extra-cutaneous involvement that requires escalation to combination therapy.

Keywords

• Real-world evidence
• Outcome measures
• Skin