ABSTRACT

Impact of the Pattern of Interstitial Lung Disease on Mortality in Rheumatoid Arthritis: A systematic review and meta-analysis

Background/Purpose: Interstitial lung disease affects 10-15% of rheumatoid arthritis (RA) patients and carries poor prognosis with a median survival of less than 3 years following diagnosis. ILD can be classified into distinct patterns based on computed tomography or lung histopathology, with the usual interstitial pneumonia (UIP) pattern being the most common. While some studies have shown the UIP pattern to have a higher mortality risk, other studies have not found this association. The purpose of this study was to complete a systematic review and meta-analysis of the association between RA-ILD pattern and mortality risk.

Methods: Pubmed and Embase databases were searched for relevant, published articles from their inception to March 1^st, 2017 using the PRISMA guidelines. The MeSH terms used for the search were “rheumatoid arthritis” and “interstitial lung disease”. Inclusion criteria were assessment of ILD pattern (either radiographically or based on histopathology) as a predictor of mortality in RA patients. Studies of connective tissue disease ILD without separate analysis of RA patients were excluded. No exclusions were made based on study design, quality of the study or duration of follow-up. Data was pooled using a random effects model with inverse variance weighting. Cochran’s Q statistic and I² test were used to test for heterogeneity among the studies. The Newcastle-Ottawa scale (NOS) was used to assess the risk of bias among the included studies.

Results: Five studies fulfilled inclusion and exclusion criteria. Two of the five studies found UIP pattern to be significantly associated with worse survival. In a meta-analytic approach, the UIP pattern was associated with a 2-fold increased risk of mortality (pooled risk ratio=2.03; 95% confidence interval=1.13, 3.66) (Figure 1). The results of the meta-analysis were heterogeneous, I²=67% (p=0.02), with risk ratios for the UIP pattern ranging from 1.09 to 8.62. Three of the five studies were of high quality based on the NOS.

Conclusion: Using a meta-analytic approach, we found UIP pattern to be associated with higher mortality risk. However, there was substantial heterogeneity between studies and a limited number of studies investigating ILD pattern and mortality risk. Further study of mortality risk in RA-ILD is needed with standardized assessment of other RA and patient related factors such as age, gender, smoking history, autoantibody expression, disease activity and pulmonary function tests.

Figure 1. Pooled effect estimate of rheumatoid arthritis interstitial lung disease pattern and mortality risk.