Use of Leflunomide in patients with hypersensitivity pneumonitis
Description
In this study, we evaluated the tolerability and effectiveness of leflunomide (LEF) in patients with HP by longitudinal analysis of pulmonary function changes. We hypothesized that LEF would be an alternative steroid sparing immunomodulatory drug for treating HP with a beneficial effect on pulmonary function. A retrospective review was performed utilizing electronic medical records at the Cleveland Clinic (Ohio, USA). A search was performed for patients with the ICD Code for HP (ICD-9 495.8 or ICD-10 J67/J67.8/J67.9) and prescriptions of LEF from 2002 to 2018. Patients were included if they received treatment with LEF and had at least one pulmonary function test before and after the initiation of LEF. Patients who had follow-up for at least 3 months while on treatment were included for analysis of effectiveness. We stratified patients according to the presence or absence of significant (> 20%) fibrosis. We studied the effect of leflunomide on FVC and DLCO trajectory and reported the changes at 12 months. We also assessed the dose of prednisone after LEF was started. We extracted other clinical data from the electronic medical chart including demographics (age, sex, weight, ethnicity), dose of corticosteroid at LEF initiation and treatment history, tobacco use, antigen exposure history, reason for starting LEF, and diagnostic studies such as CT or HRCT, surgical lung biopsy. We also evaluated the side effects of LEF reported by patients and indication of LEF. A linear mixed-effects model (LMM) was used to compare the change in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) before and after LEF administration. The change in FVC and DLCO after 12 months of LEF initiation was estimated using the LMM, as the net difference in the observed change and the counterfactual change that would have been expected had treatment not been initiated. The actual and counterfactual trajectories of mean FVC and DLCO, centered on month of LEF initiation were plotted. The covariance used for the mixed effect model is ‘variance components’. The random term is ‘intercept’. In order to assess whether weight loss associated with prednisone dosage reduction was the case of pulmonary function test (PFT) improvements, a Pearson correlation coefficient and linear regression model was constructed to check the relationship between weight change and FVC change. A generalized mixed model with Poisson distribution was used to assess the change in corticosteroid dosage before and after LEF initiation.