Dual targeting of joint and lung disease: efficacy of tofacitinib plus iguratimod combination in progressive fibrosing rheumatoid arthritis-associated interstitial lung disease

Objective To evaluate the efficacy and safety of tofacitinib (TOF) plus iguratimod (IGU) in treating progressive fibrosing rheumatoid arthritis-associated interstitial lung disease (PF-RA ILD). Methods This historical-controlled study enrolled 28 PF-RA ILD patients (13 received TOF plus IGU; 15 received the biologic/conventional synthetic disease-modifying anti-rheumatic drugs (b/csDMARDs). Disease activity, pulmonary function (PFTs), high-resolution computed tomography (HRCT) scores, and safety were assessed longitudinally and between groups. Results Baseline characteristics were comparable ( P >0.05). The TOF plus IGU group showed significant improvements: C-reactive protein (CRP) decreased (30.5 ± 23.1 to 5.1 ± 3.3 mg/L, P < 0.05), erythrocyte sedimentation rate: 46.2 ± 18.8 to 20.1 ± 18.9 mm/h, P = 0.012). The disease activity score 28-joint count with CRP declined from high to low activity, and rheumatoid factor titers dropped (79.7 ± 64.2 to 23.4 ± 21.7 IU/mL at 12 months, P = 0.023). Similarly, anti-cyclic citrullinated peptide levels declined from 157 ± 57.5 RU/mL to 109.8 ± 32.6 RU/mL at 6 months ( P = 0.028). Pulmonary function improved, with forced vital capacity increasing from 79.5 ± 12.9% to 85.3 ± 13.6% at 6 months ( P = 0.008). HRCT fibrosis scores decreased from 9.6 ± 2.5 to 5.1 ± 1.6 ( P = 0.026). Compared to controls, TOF plus IGU demonstrated superior outcomes: lower CRP (8.5 vs 20.2 mg/L, P = 0.002), higher diffusing capacity for carbon monoxide at 3 months (73.1 ± 19.6% vs 61.1 ± 14.5%, P = 0.045), and lower fibrosis scores at 12 months (5.1 vs 7.5, P = 0.004). At 12 months, imaging stability/regression occurred in 92.3% vs 60.0% ( P = 0.047). All TOF plus IGU patients tapered prednisone. No thromboembolic events or severe infections occurred. Conclusion TOF plus IGU demonstrated dual efficacy in controlling synovitis and lung fibrosis, with a favorable safety profile.