Efficacy of non-conventional synthetic DMARDs for patients with rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

Abstract

Objectives: We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).

Methods: PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI.

Results: A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV₁ and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=-4.62, 95% CI -8.90 to -0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively.

Conclusion: ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD.

Prospero registration number: CRD42022356816.

Keywords: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Therapy; Pulmonary Fibrosis; Qualitative research.

Figure 1

Flow chart of included studies and excluded reasons.

Figure 2

(A) Meta-analysis of self-control studies to assess FVC changes in patients with RA-ILD treated with different types of ncs-DMARDs; (B) meta-analysis of self-control studies to assess FEV₁ changes in patients with RA-ILD treated with different types of ncs-DMARDs. ABA, abatacept; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; ILD, interstitial lung disease; JAKis, Janus kinase inhibitors; ncs-DMARDs, non-conventional synthetic disease-modifying antirheumatic drugs; RA, rheumatoid arthritis; RTX, rituximab; TCZ, tocilizumab; TNFis, tumour necrosis factor inhibitors.

Figure 3

(A) Meta-analysis of self-control studies to assess DLCO changes in patients with RA-ILD treated with different types of ncs-DMARDs; (B) meta-analysis of self-control studies to assess DLCO changes in patients with RA-ILD treated with different types of ncs-DMARDs after sensitivity analysis. ABA, abatacept; DLCO, diffusion lung capacity for carbon monoxide; ILD, interstitial lung disease; JAKis, Janus kinase inhibitors; ncs-DMARDs, non-conventional synthetic disease-modifying antirheumatic drugs; RA, rheumatoid arthritis; RTX, rituximab; TCZ, tocilizumab.

Figure 4

Meta-analysis of self-control studies to assess the single-group non-progression rate of HRCT in patients with RA-ILD treated with ncs-DMARDs. ABA, abatacept; ES, effect size; HRCT, high-resolution CT; ILD, interstitial lung disease; JAKis, Janus kinase inhibitors; NA, not applicable; ncs-DMARDs, non-conventional synthetic disease-modifying antirheumatic drugs; RA, rheumatoid arthritis; RTX, rituximab; TCZ, tocilizumab.

Figure 5

Meta-analysis of self-control studies to assess the single-group case fatality rate of patients due to ILD progression in patients with RA-ILD treated with ncs-DMARDs. ABA, abatacept; ES, effect size; ILD, interstitial lung disease; ncs-DMARDs, non-conventional synthetic disease-modifying antirheumatic drugs; RA, rheumatoid arthritis; RTX, rituximab; TNFis, tumour necrosis factor inhibitors.

Figure 6

Egger’s test to assess the publication bias of primary outcome. MSE, mean squared error; DLCO, diffusion lung capacity for carbon monoxide; FVC, forced vital capacity.