Background RA patients suffer from many extra-articular manifestations including cardiovascular and interstitial lung disease (ILD), that is a significant cause of morbidity and mortality. RA-ILD is observed in only 5% of chest radiographs, but in 50% of chest CT scans, and up to 80% of biopsies. Studies have found that the risk factors for its development include smoking, male gender, etc.
Objectives The aim of this meta-analysis was to assess all available literature in order to determine whether it is possible to establish a significant link between RA, ILD, and biological or non-biological therapy.
Methods A search was made of the EMBASE, MEDLINE, AMED, CINAHL and Web of Knowledge databases using the terms rheumatoid arthritis OR arthritis AND interstitial lung disease AND (smoking OR age OR gender OR treatment DMARDs, anti-TNF drugs). Google Scholar was also searched. The entire search was limited to humans and the English language.The titles of the articles were independently screened by two reviewers disagreements were solved by consensus. If consensus could not be found it was planned a third reviewer to decide.After duplicates had been removed, two reviewers independently screened the remaining texts on the basis of their abstracts, and the selected full texts were separately read by two reviewers in order to ensure they met the criteria. The extraction was made independently by two reviewers, and the results were subsequently compared.
Results The literature search provided 2190 citations. 12 additional citations were found by manually searching the reference lists of the included articles. 2136 of the initially returned citations were excluded after reviewing the abstract and/or full text because not matching inclusion criteria. Finally, 54 articles were included in the meta-analysis. The articles described a total of 363849 patients (including 24406 with ILD) who received all types of DMARDs. The prevalence of ILD among the RA patients was 5.0% (CI 95% 4.0-6.0%) in the cohort and pharmacovigilance studies, and 2% (CI 1.0-4.0%) in the RCTs. It was understimated in the RCTs because ILD was a secondary outcome, the short observational period and small number of the patients, but the RCTs also demonstrated a trend towards an increased risk. ILD was associated with an increased risk of mortality (RR 4.49; CI 1.84-11.02) regardless of the type of drugs used. The prevalence of ILD was 7% among the RA patients treated with DMARDs, and 4% among those treated with anti-TNF drugs. There was an increased risk of ILD among male patients (RR 4.03; CI 1.59-10.18), anti-CCP-positive patients (RR 2.73; CI 0.91-8.23), smokers (RR 2.50; CI 0.62-10.09), and patients treated with MTX (RR: 1.15; CI 1.0-1.32). The prevalence of ILD was almost four times higher in male than in female patients, and 2.5 times higher in smokers than in non-smokers.
Conclusions RA is associated with the development of ILD, but its prevalence varies depending on the type of study. RA patients with ILD are at increased risk of death. This risk is almost four times higher than in patients without ILD regardless of the drugs used. The risk factors associated with developing ILD are male gender, smoking, anti-CCP positivity and MTX therapy. Patients with these characteristics should be carefully monitored.
Disclosure of Interest None declared
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