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

**Authors:** Yuan Zhu, Yingzi Ye, Wanlin Zhou, Xu Zheng, Weilin Xie, Zhiying Wu

PMC · DOI: 10.3389/fimmu.2025.1624125 · 2026-01-16

## 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.

## Key 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.

## Linked entities

- **Chemicals:** tofacitinib (PubChem CID 9926791), iguratimod (PubChem CID 124246)
- **Diseases:** rheumatoid arthritis (MONDO:0008383), interstitial lung disease (MONDO:0015925)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** joint and lung disease (MESH:D008171), ILD (MESH:D017563), infections (MESH:D007239), thromboembolic (MESH:D013923), synovitis (MESH:D013585), fibrosis (MESH:D005355), RA (MESH:D001172)
- **Chemicals:** TOF (MESH:C479163), IGU (MESH:C519076), prednisone (MESH:D011241), csDMARDs (-), cyclic citrullinated peptide (MESH:C487763)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12855111