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

TL;DR

Combining tofacitinib and iguratimod effectively treats joint and lung disease in rheumatoid arthritis patients with lung fibrosis, with minimal side effects.

Contribution

Demonstrates the efficacy of combining tofacitinib and iguratimod for progressive fibrosing rheumatoid arthritis-associated interstitial lung disease.

Findings

The combination therapy significantly reduced inflammation markers and lung fibrosis scores.

Patients on the combination therapy showed improved pulmonary function and imaging stability.

No severe infections or thromboembolic events occurred in the treatment group.

Abstract

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).

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.

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.

TOF plus IGU demonstrated dual efficacy in controlling synovitis and lung fibrosis, with a favorable safety profile.