Background/Purpose: Interstitial lung disease (ILD) is a leading cause of mortality in myositis. Clinical trials in myositis-associated ILD (MA-ILD) are lacking due to the absence of validated outcome measures. Serial pulmonary function tests (PFTs) predict outcome in ILD; however, the degree of change in PFT variables that predict survival has not been studied in MA-ILD. We investigated PFT variable changes over 1 year that predict disease outcome for use in future clinical trials.

Methods: MA-ILD patients were identified from a prospective myositis database (1985-2014). Myositis was defined using the Bohan and Peter classification criteria (probable or definite) oranti-synthetase syndrome. The latter was defined by the presence of an anti-synthetase antibody and at least one associated clinical feature. ILD was defined by radiographic fibrosis consistent with ILD. Clinical variables and relative and absolute % change in FVC, FEV-1 and DLCO over 1 year were analyzed for prediction of survival and event-free survival. Relative percent change was defined as [(baseline Ð follow-up)/baseline] x 100, and absolute change was defined as baseline Ð follow-up. Independent variables (relative and absolute % decline in FVC, FEV-1, DLCO by 5/7.5/10/15% over 1 year) were used to predict survival and event-free survival. Event was defined as death or lung transplant. The same independent PFT predictors were evaluated after controlling for baseline PFT values, age, gender and ethnicity. Kaplan Meier and Cox Proportional Hazard model were used for analysis.

Results: 121 MA-ILD patients were identified; 63% (76/121) were female and 87% (101/116) Caucasian with a mean (SD) age at ILD diagnosis of 48 (13.2) years. 104 patients met criteria for anti-synthetase syndrome and 106 (88%) possessed at least one myositis specific antibody. There were 29 events (25 death/9 transplant) with a median (IQR) follow up time of 6.0 (5.2) years from first visit. A relative decline in FVC of 15%, 10% and 7.5%, an absolute decline in FVC of 7.5%, and a relative decline in FEV-1 of 10% predicted survival with HR of 9.2, 8.8, 6.8, 8.9, and 3.5 respectively (p<0.01), after controlling for baseline FVC or FEV-1, age at first visit, gender and race (Figure 1). A relative decline in FVC of 15% and 10%, an absolute decline in FVC of 7.5%, and a relative decline in FEV-1 of 10% predicted event-free survival with similar results as above. Relative or absolute declines in %DLCO were not predictive of survival or event- free survival.

Conclusion: Relative declines of 15% and 10% in FVC over 1 year are the best candidates for predicting survival and event-free survival in MA-ILD. Clinical trials for MA-ILD should be done using outcome criteria of 10-15% change in FVC over 1 year. 

Figure 1. Kaplan Meier curve for survival outcome in patients with FVC ³10% decline in 1 year of follow up.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-decline-in-pulmonary-function-over-one-year-predicts-outcome-in-myositis-associated-interstitial-lung-disease/