Effectiveness of Cyclophosphamide and Immunosuppressants in Systemic Sclerosis-associated Interstitial Lung Disease: A Meta-analysis.

Objective: The present meta-analysis compares the effectiveness of cyclophosphamide (CYC) as an immunosuppressant in systemic sclerosis-associated interstitial lung disease (SSc-ILD) with placebo, and other immunosuppressants.

Methodology: The study involved randomized trials and observational studies identified through a systematic literature search using various databases, such as Elton B Stephens Company (EBSCO) Medline/PubMed, Scopus, Web of Science, Google Scholar, PubMed Central, Cochrane Library, and ScienceDirect. These studies compared the effectiveness of CYC with placebo or other immunosuppressants in terms of lung parameters. Meta-analysis and network meta-analysis were conducted to evaluate the effectiveness of the treatments.

Results: Upon comparison, azathioprine (AZA) was favored over CYC for forced vital capacity (FVC) (d = 1.02, p = 0.00) and diffusing capacity of the lungs for carbon monoxide (DLCO) (d = 0.88, p = 0.00). No significant difference in FVC between CYC and mycophenolate mofetil (MMF) was found, although CYC was slightly preferred (d = -0.12, p = 0.60). CYC was beneficial over placebo in reducing the Dyspnea Index score (d = 0.78, p = 0.00) but not in improving DLCO. Network analysis revealed that CYC had the highest FVC outcome p-scores (0.6559), while rituximab (RTX) had the lowest (0.3410). For DLCO, AZA had the highest p-score (0.5707), followed by placebo (0.5180).

Conclusion: While suggesting the potential benefits of CYC and AZA, the study findings do not decisively support the superiority of CYC over other treatments for most SSc-ILD lung function parameters. This emphasizes the need for rigorous, ongoing research to refine treatment strategies and address unresolved questions regarding the efficacy and safety profile of CYC.