Incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

Abstract

Introduction: Acute exacerbation (AE) is a devastating complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and leads to high mortality. This study aimed to investigate the incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease (AE-RA-ILD).

Methods: PubMed, EMBASE, Web of Science, and Medline were searched through 8 February 2023. Two independent researchers selected eligible articles and extracted available data. The Newcastle Ottawa Scale was used to assess the methodological quality of studies used for meta-analysis. The incidence and prognosis of AE-RA-ILD were investigated. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) and pooled odds ratios (ORs) with 95% CIs were calculated to explore the risk factors of AE in RA-ILD.

Results: Twenty-one of 1,589 articles were eligible. A total of 385 patients with AE-RA-ILD, of whom 53.5% were male, were included. The frequency of AE in patients with RA-ILD ranged from 6.3 to 55.6%. The 1-year and 5-year AE incidences were 2.6-11.1% and 11-29.4%, respectively. The all-cause mortality rate of AE-RA-ILD was 12.6-27.9% at 30 days and 16.7-48.3% at 90 days. Age at RA diagnosis (WMD: 3.61, 95% CI: 0.22-7.01), male sex (OR: 1.60, 95% CI:1.16-2.21), smoking (OR: 1.50, 95% CI: 1.08-2.08), lower forced vital capacity predicted (FVC%; WMD: -8.63, 95% CI: -14.68 to - 2.58), and definite usual interstitial pneumonia (UIP) pattern (OR: 1.92, 95% CI: 1.15-3.22) were the risk factors of AE-RA-ILD. Moreover, the use of corticosteroids, methotrexate, and biological disease-modifying anti-rheumatic drugs, was not associated with AE-RA-ILD.

Conclusion: AE-RA-ILD was not rare and had a poor prognosis. Age at RA diagnosis, male sex, smoking, lower FVC%, and definite UIP pattern increased the risk of AE-RA-ILD. The use of medications, especially methotrexate and biological disease-modifying anti-rheumatic drugs, may not be related to AE-RA-ILD.

Registration: CRD42023396772.

Keywords: Acute exacerbation; Interstitial lung disease; Meta-analysis; Rheumatoid arthritis.

Fig. 1

Study flow diagram. RA: Rheumatoid arthritis; RA-ILD: Rheumatoid arthritis-associated interstitial lung disease; AE: acute exacerbation

Fig. 2

Forest plots for the correlation of age at RA diagnosis (A), age at ILD diagnosis (B), male sex (C), and smoking history (D) with AE in RA-ILD. RA: rheumatoid arthritis; ILD: interstitial lung disease; AE: acute exacerbation; RA-ILD: rheumatoid arthritis-associated interstitial lung disease

Fig. 3

Forest plots for the correlation of FVC% (A), DLCO% (B), UIP-like pattern (C), and definite UIP pattern (D) with AE in RA-ILD. FVC%: percentage predicted forced vital capacity; DLCO%:  percentage predicted diffusing capacity of the lung for carbon monoxide; UIP: usual interstitial pneumonia

Fig. 4

Forest plots for the correlation of corticosteroids (A), MTX (B), bDMARDs (C), and tumor necrosis factor inhibitors (D) with AE in RA-ILD. MTX: methotrexate; bDMARDs: biological disease-modifying anti-rheumatic drugs; AE: acute exacerbation; RA-ILD: rheumatoid arthritis-associated interstitial lung disease