The performance of the GAP model in patients with rheumatoid arthritis associated interstitial lung disease

Abstract

Background Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Similarities have been observed between patients with idiopathic pulmonary fibrosis (IPF) and the UIP (usual interstitial pneumonia) form of RA-ILD. The GAP (gender, age, physiology) model has been shown to predict mortality in patients with IPF, but its ability to predict mortality in RA-ILD is not known. Methods We identified 309 patients with RA-ILD at 4 academic centers with ongoing longitudinal cohorts of patients with ILD. The primary endpoint was mortality. To handle missing data (n=219 subjects with complete dataset), multiple imputation by iterative chained equations was used. Using the GAP model as a baseline, we assessed improvements in mortality risk prediction achieved by incorporating additional variables. Model discrimination was assessed using the c-index, and calibration was checked by comparing observed and expected incidence of death. Results Patients had a mean age of 65 years and were predominantly female (54%). The mean forced vital capacity (FVC) % predicted was 73 and the mean diffusing capacity for carbon monoxide (DLCO) % predicted was 55. Twenty-four percent of the 236 patients with a high-resolution computed tomography scan available for review had a definite UIP pattern. The original GAP model, including gender, age, FVC%, and DLCO%, had a c-index of 0.746 in our cohort. Calibration of this model was satisfactory at 1, 2 and 3 years. Model discrimination was not meaningfully improved by adding other clinical variables. Conclusion The GAP model that was derived for IPF performs similarly as a mortality risk prediction tool in RA-ILD.

Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians

“…More recent studies tend to show longer survival which may be attributed to improved radiological techniques and increased awareness of RA-ILD leading to earlier diagnosis (Table 4). Previous studies have reported UIP as the predominant radiological pattern and predictor of mortality [14,42]; however, recent studies report a UIP proportion of 40%-54% [40,47]. A recent study showed that radiology-based prediction models in RA-ILD can identify patients with a progressive fibrosis phenotype [112], and that the visual extent of ILD in combination with FVC values, as previously seen in scleroderma [113], predicts outcome in RA-ILD.…”

“…Radiological findings in RA-ILD include ground glass-opacities, reticulation, consolidation, honeycombing, and nodules similar to other ILD subtypes [30,33,38,39]. The most common HRCT patterns in RA-ILD are UIP and NSIP, while organizing pneumonia (OP) and bronchiolitis are less common ( Figure 1) (Table 1) [8,14,[38][39][40][41][42][43][44][45][46][47]. Studies show a fairly good correlation between HRCT and histopathological findings with the least concordance in the diagnosis of UIP and NSIP [39,42,46].…”

“…A recent study showed that radiology-based prediction models in RA-ILD can identify patients with a progressive fibrosis phenotype [112], and that the visual extent of ILD in combination with FVC values, as previously seen in scleroderma [113], predicts outcome in RA-ILD. Morisset et al [47] showed that the addition of HRCT patterns to the ILD-GAP prediction model did not improve its performance.…”

Progression of fibrosing interstitial lung disease

“…Specifically, a radiological and/or histological pattern of usual intersitial pneumonia (UIP) has been associated with increased mortality with poor prognosis also seen in patients with specific radiological features of UIP such as honeycombing and traction bronchiectasis [26][27][28]. The prognostic significance of a UIP pattern is seen across ILD subtypes, indicating that morphological pattern may be more prognostically important compared to the specific etiology of the disease [9,29,30]. An acute exacerbation is the most extreme type of ILD progression, characterized by a sudden and usually severe respiratory deterioration with new bilateral opacities on high-resolution computed tomography (HRCT) [31].…”

Development and validation of a multivariate predictive model for rheumatoid arthritis mortality using a machine learning approach

“…Morisset et al . 46 developed a mortality model for patients with rheumatoid arthritis-associated interstitial lung disease. The cross-validated C-index of the final model (a multivariate CPH model) was 0.75, similar to our results.…”