Intravenous Cyclophosphamide Infusion and miRNA-29A, miRNA-16, IL-6, TGF-β1 Responses in Systemic Sclerosis Patients with Interstitial Lung Disease

Background: Systemic sclerosis (SSc) is characterised by organ fibrosis, microvascular damage and immunological dysregulation. With an aetiology that remains poorly understood, increasing evidence suggests that epigenetic alterations and inflammatory mechanisms play crucial roles in the pathogenesis of SSc. Objective: To evaluate the effects of intravenous cyclophosphamide (CYC) versus conventional disease-modifying antirheumatic drugs (DMARDs) on miRNA-29a, miRNA-16, interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-β1) levels in SSc-associated interstitial lung disease (SSc-ILD). Methods: This quasi-experimental study included 67 patients meeting the 2013 American College of Rheumatology/European League Against Rheumatism criteria with high-resolution computed tomography-confirmed ILD. Treatment allocation was not randomised; patients received either intravenous CYC ( n = 32) or conventional DMARDs ( n = 35) based on clinical indications. Serum miRNA-29a, miRNA-16, IL-6, TGF-β1 and forced vital capacity (FVC) were quantified at baseline and 6 months. Results: Modulations in miRNA-29a and miRNA-16 were not statistically significant ( P > .05). However, IL-6 significantly declined in both CYC ( P = .001) and DMARD ( P = .019) groups, although the difference between groups was not statistically significant ( P = .051). TGF-β1 levels also decreased significantly across the study population ( P = .004). These shifts were accompanied by highly significant intragroup FVC improvements ( P < .001). FVC improved from 51.35% to 78.75% in the CYC group and from 83.20% to 96.30% in the DMARD group, with no significant intergroup difference ( P = .099). Conclusion: Intravenous CYC substantially reduces TGF-β1 and IL-6 in SSc-ILD, effectively attenuating systemic inflammatory and fibrotic drivers. While CYC demonstrated a stronger trend in IL-6 suppression compared to DMARDs, it did not significantly modulate upstream epigenetic precursors, such as miRNA-29a and miRNA-16.