Systematic review and meta-analysis of the risk of rheumatoid arthritis-associated interstitial lung disease related to anti-cyclic citrullinated peptide (CCP) antibody

OBJECTIVE: To clarify the risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) related to anti-cyclic citrullinated peptide (CCP) antibody. ELIGIBILITY CRITERIA: Patients with RA with and without ILD were eligible. The primary outcome was the prevalence or incidence of ILD. Primary studies of any design aside from a case report were eligible. INFORMATION SOURCES: Medline, EMBASE, Science Citation Index Expanded and Cochrane Central Register of Controlled Trials were searched from the inception through 12 November 2019. DATA EXTRACTION AND RISK OF BIAS: Two reviewers independently selected eligible reports, extracted relevant data and assessed risk of bias using a modified Quality in Prognostic Studies tool. DATA SYNTHESIS: Meta-analysis was conducted using a random-effects model. QUALITY OF EVIDENCE: The Grades of Recommendation, Assessment, Development and Evaluation system was applied. RESULTS: Among 29 out of 827 records retrieved through electronic databases and four additional reports identified from other sources, 29 studies were focused for the review. A total of 10158 subjects were included and the mean age at inclusion was between 45.8 and 63.9 years. The mean RA duration was between 4.3 and 14.9 years. The positivity of anti-CCP antibody ranged from 50.7% to 95.8%. All studies except for two were deemed as high risk of bias. A pooled analysis of univariate results demonstrated that the presence of anti-CCP antibody was significantly associated with RA-ILD with an OR of 2.10 (95% CI: 1.59 to 2.78). Similarly, the titre of anti-CCP antibody was significantly higher for RA-ILD with a standardised mean difference of 0.42 (95% CI: 0.20 to 0.65). These results were confirmed by multivariate analysis in the majority of studies and consistent by any subgroup and sensitivity analyses. CONCLUSION: The presence and higher titres of anti-CCP antibody were suggested to be significantly associated with an increased risk of RA-ILD. However, the quality of evidence was rated as low or very low.