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

To evaluate the real-life effectiveness of methotrexate (MTX) on skin involvement in patients with early systemic sclerosis (SSc), with a focus on identifying clinical factors associated with treatment response and persistence. We performed a retrospective observational study including SSc patients with early disease (≤ 2years from first non-Raynaud’s symptom) and skin involvement, who initiated MTX monotherapy. The primary outcome was change in modified Rodnan skin score(mRSS) over time; clinically meaningful improvement was defined as ≥ 25% reduction from baseline. Longitudinal mRSS trajectories were analysed using linear mixed-effects models. Secondary outcome included MTX drug survival, defined as persistence of MTX monotherapy without addition of other immunosuppressive drugs or MTX discontinuation. Ninety-two patients were included (85% female; 79% diffuse cutaneous SSc). At 3 months, 34.2% of dcSSc patients achieved ≥ 25% reduction in mRSS from baseline, with this proportion increasing to 61.8% at 24 months among patients remaining on monotherapy (p = 0.02), and 28.8% at 24 months in an intention-to-treat analysis with non-responder imputation. Time (β=−0.092 per month, 95% CI − 0.132 to − 0.054, p < 0.001) and baseline mRSS ≥ 14 (β = 8.18, 95% CI 6.06 to 10.31, p < 0.001) were independently associated with mRSS changes. Concomitant glucocorticoid therapy was not associated with skin improvement. Patients with higher baseline skin severity (mRSS ≥ 14) had higher absolute mRSS values but shorter drug survival; disease progression accounted for 75% of MTX monotherapy discontinuations. MTX monotherapy can be associated with meaningful skin improvement in patients with early SSc, with response emerging within the first 3 months. However, high rates of treatment escalation highlight the need for careful patient selection and early reassessment to optimize therapeutic strategies. • ≥ 25% skin improvement at 24 months in 62% of patients remaining on MTX and in 29% of the whole dcSSc cohort. • Response at 3 months was maintained through 24 months in most patients remaining on treatment. • Nearly half of patients require treatment escalation, mainly due to disease progression. • Corticosteroids and MTX dosage do not independently predict mRSS trajectory.