Diagnostic delay of associated interstitial lung disease increases mortality in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main extra-articular organ affected is the lung, sometimes in the form of diffuse interstitial lung disease (ILD) and conditions the prognosis. A multicenter, observational, descriptive and cross-sectional study of consecutive patients diagnosed with RA-ILD. Demographic, analytical, respiratory functional and evolution characteristics were analyzed to evaluate the predictors of progression and mortality. 106 patients were included. The multivariate analysis showed that the diagnostic delay was an independent predictor of mortality (HR 1.11, CI 1.01-1.23, p = 0.035). Also, age (HR 1.33, 95% CI 1.09-1.62, p = 0.0045), DLCO (%) (HR 0.85, 95% CI 0.73-0.98, p = 0.0246), and final SatO2 (%) in the 6MWT (HR 0.62, 95% CI 0.39-0.99, p = 0.0465) were independent predictor variables of mortality, as well as GAP index (HR 4.65, 95% CI 1.59-13.54, p = 0.0051) and CPI index (HR 1.12, 95% CI 1.03-1.22, p = 0.0092). The withdrawal of MTX or LFN after ILD diagnosis was associated with disease progression in the COX analysis (HR 2.18, 95% CI 1.14-4.18, p = 0.019). This is the first study that highlights the diagnostic delay in RA-ILD is associated with an increased mortality just like happens in IPF.

Figure 1

Respiratory functional impairment of the global recruited cases differentiating between groups of progressive and non-progressive patients. FVC (%) impairment is represented in the graph (a) and DLCO (%) impairment is represented in the graph (b).

Figure 2

Kaplan–Meier curve for disease progression in RA-ILD during five years period, grouped by discontinuing or not MTX and/or LFN at the moment of ILD diagnosis (Log Rank Test: p = 0.0139).

Figure 3

Respiratory functional impairment in deceased patients. FVC (%) impairment is represented in the graph (a) and DLCO (%) impairment is represented in the graph (b).

Figure 4

Kaplan–Meier survival curves for patients with RA-ILD. Overall survival according for diagnostic delay (Log Rank Test: p = 0.0051).

Figures 5

Kaplan–Meier survival curves for patients with RA-ILD. Survival according for GAP stage (A) (Log Rank Test: p < 0.001) and for CPI with cut-off point of 50 (B) (Log Rank Test: p < 0.0001).

Figure 6

(A) ROC curve for CPI and GAP indexes. For CPI, the AUC was 0.742 and the best cut-off point for predicting survival was 50.58 (sensitivity of 50% and specificity of 96.2%). The AUC for GAP ROC curve was 0.857 with a best cut-off point of 3 (sensitivity 83.3% and specificity 85.2%). (B) Receiver operator characteristic (ROC) curves for GAP stage (I, II and III) and CPI (with a cut-off point of 50) to predict mortality in AR-ILD patients.