Efficacy of different pharmacological therapies for diffuse cutaneous systemic sclerosis: a systematic review and network meta-analysis.

OBJECTIVE

This study aims to compare the effectiveness of different pharmacological therapies for diffuse cutaneous systemic sclerosis (dcSSc) through a network meta-analysis (NMA).

METHODS

Randomized controlled trials (RCTs) on pharmacological interventions for dcSSc were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science up to 2026. A Bayesian network meta-analysis was carried out using Markov Chain Monte Carlo (MCMC) methods via R software and its GeMtc package. Outcomes assessed included Modified Rodnan Skin Score (MRSS), pulmonary functions (forced vital capacity [FVC], and diffusing capacity of the lung for carbon monoxide [DLCO]), and Health Assessment Questionnaire (HAQ). Effect sizes were reported as standardized mean differences (SMDs) with corresponding 95% credible intervals (95% CrIs).

RESULTS

A total of 20 RCTs involving 1,760 patients and 16 interventions were included. The results revealed that rituximab was the most effective intervention for reducing MRSS (SMD = - 3.4, 95% CrI (- 4.2, - 2.7)), followed by cyclophosphamide (CTX) (SMD = - 2.8, (- 3.3, - 2.2)), and belimumab (SMD = - 1.5, (- 2.5, - 0.39)). Belimumab (SMD = 1.9, (0.75, 3.1)) and CTX (SMD = 1.3, (0.86, 1.8)) topped FVC improvement. Methotrexate (MTX) was the most effective for enhancing DLCO (SMD = 0.52, (0.046, 0.99)). Belimumab (HAQ: SMD = - 3.8, (- 5.5, - 2.1)) and CTX (HAQ: SMD = - 2.9, (- 3.4, - 2.3)) were significantly effective in lowering HAQ scores.

CONCLUSION

B-cell-targeted therapies (e.g., rituximab and belimumab) seemed to outperform other therapeutic agents in lowering MRSS and HAQ scores. Conventional immunosuppressants (e.g., CTX and MTX) might be more effective in enhancing pulmonary functions. Treatment strategies should be tailored according to the extent and severity of organ involvement.