Impact of the pattern of interstitial lung disease on mortality in rheumatoid arthritis: A systematic literature review and meta-analysis

https://doi.org/10.1016/j.semarthrit.2019.04.005Get rights and content

Abstract

Objective

An important extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD). The relationship between the usual interstitial pneumonia (UIP) pattern and mortality in patients with RA is unclear. The purpose of this study was to complete a systematic literature review and meta-analysis on the association between RA-ILD pattern and mortality risk.

Methods

We performed a systematic literature review through December 12, 2018. Study characteristics, unadjusted and adjusted relative risks (RR) of mortality for ILD pattern were extracted from the identified studies and quality assessments were performed. RR for mortality (RA-UIP vs. other RA-ILD) was pooled using inverse variance weighting and random effects models.

Results

Ten retrospective cohort studies met our eligibility criteria. A total of 1256 RA-ILD patients were included with 484 total deaths. Meta-analysis yielded a pooled RR of 1.66 (95% confidence interval1.07 to 2.56) for death among those with UIP RA-ILD compared with other patterns. In sub-group analysis when pooling studies comparing UIP to NSIP pattern of RA-ILD, the RR was 2.39 (95% CI 0.86–6.68).

Conclusion

Through a systematic literature review and meta-analysis, we found UIP pattern to be associated with a higher mortality risk in RA-ILD compared to other patterns of RA-ILD although more recent studies emphasize the importance of pulmonary physiology and the extent of lung involvement as significant predictors of mortality rather than the pattern of RA-ILD. Recognizing the small number of studies satisfying eligibility and inconsistent accounting for confounders, further study of mortality risk in RA-ILD is needed with standardized assessment of various RA, ILD, and patient-related factors.

Section snippets

Background

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis, affecting up to 1% of the general population [1]. Extra-articular features, especially pulmonary manifestations, can significantly increase morbidity and mortality among RA patients [2]. Consequently, lung disease has been identified to be the most over-represented cause of death in two recent reports of large U.S. cohorts [3], [4].

One of the most common forms of lung involvement in RA is interstitial lung disease

Data sources and search

Systematic literature searches were developed and conducted by a health sciences librarian trained in systematic reviews (HH). Searches were conducted within PubMed, Embase (Elsevier), and Cochrane Central Register of Controlled Trials (Wiley) using both subject headings and keywords. The searches were conducted from inception through September 12, 2017 and were limited to English. All identified studies were combined in a single reference manager file (EndNote) and duplicates were identified

Results

A total of 1719 articles were identified and 92 full text articles were assessed after records were screened. The most frequent reasons for exclusion upon full text review were lack of ILD pattern description and lack of mortality data. One of the studies was excluded because it focused primarily on a group comparison of UIP with “overlap syndromes” vs. NSIP and cryptogenic organizing pneumonia (COP) [5]. Ten studies fulfilled our eligibility criteria and were included in the meta-analysis (

Discussion

In this systematic literature review and meta-analysis including 10 studies and 1256 RA patients with ILD, we observed that the mortality risk ratio for UIP pattern of ILD in RA-ILD is higher as compared to other patterns of ILD, although there was substantial heterogeneity. We tried to address the heterogeneity by sub-group analysis of UIP versus NSIP pattern or other referent group but the results did not change. Recent studies have shown that the extent of lung involvement and pulmonary

Conclusions

In summary, our results highlight the impact the UIP pattern of ILD has on the survival of RA patients. Using a meta-analytic approach, we found UIP pattern to be associated with a higher mortality risk compared to other patterns of RA-ILD. However, there was substantial heterogeneity and a limited number of included studies. Also, when accounting for pulmonary physiology, studies did not find a difference in mortality between the two ILD patterns. This highlights the importance of the

Declaration of Competing Interest

All the authors have no conflicts of interest and did not receive any funding or honorarium from any sources.

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