CLINICAL MODIFIERS TO IMMUNOSUPPRESSION RESPONSE IN FIBROTIC HYPERSENSITIVITY PNEUMONITIS

Abstract

SESSION TITLE: Occupational and Environmental Lung Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Patients with hypersensitivity pneumonitis (HP) are often treated with immunosuppression (IS) with varied response. Nintedanib, an antifibrotic medication, is effective in progressive fibrotic interstitial lung diseases, including HP (Flaherty, et al, 2019). Given the option of treating with IS or nintedanib, it is unclear which patients should be preferentially treated with IS. We aimed to identify IS treatment effect modifier variables in patients with fibrotic HP. METHODS: This was a single center retrospective study of HP patients from 1/2004-1/2018. Patients were excluded for < 6-month follow up, exposure to IS at initial evaluation, or no fibrosis on high-resolution CT (HRCT). Patients exposed to IS (prednisone, azathioprine, or mycophenolate) were compared to those without exposure (control). To account for baseline differences between treatment groups, propensity score matching was performed; covariates included age, gender, ethnicity, smoking history, baseline forced vital capacity (FVC%), diffusion of lung for carbon monoxide (DLCO%). Potential treatment effect modifier variables were abstracted from the medical record. Transplant-free survival was assessed using multivariable Cox proportional hazards model that included an interaction term for each potential modifier and IS exposure (modifier variable x treatment); p-interaction <0.05 was considered significant for treatment effect modifier. FVC% change over 1-year from IS initiation was estimated using linear mixed-effect model with an interaction term for each potential modifier and IS exposure included as fixed effects. RESULTS: After propensity matching, there were 92 patients included (46 in the IS and 46 in the non-IS groups); there were no baseline differences (p>0.05 for all variables). None of the patient demographics, baseline lung function, peripheral blood counts, blood inflammatory markers, serologies, and HRCT features modified treatment effect of IS on transplant-free survival (p-interaction >0.05 for all variables). In patients exposed to IS, BAL lymphocyte >20% was associated with improved FVC% at 1 year (+7.5% vs -2.8, p=0.044), while traction bronchiectasis on HRCT (-4.0% vs + 7.2%, p=0.007) and usual interstitial pneumonia pattern on HRCT or pathology (-9.1% vs +1.6%, p=0.022) was associated with decline in FVC% at 1 year. CONCLUSIONS: In fibrotic HP patients, the association between IS treatment and transplant-free survival did not differ by commonly assessed baseline characteristics. However, “IPF-like features” were associated with faster FVC% decline, while “inflammatory” markers like BAL lymphocytosis was associated with improved FVC% in fibrotic HP patients exposed to IS. CLINICAL IMPLICATIONS: This study identified treatment effect modifiers to immunosuppressive therapy which may help guide treatment decisions in patients with fibrotic hypersensitivity pneumonitis. DISCLOSURES: No relevant relationships by Traci Adams, source=Web Response No relevant relationships by KIRAN BATRA, source=Web Response No relevant relationships by ESTHER DE BOER, source=Web Response No relevant relationships by Craig Glazer, source=Web Response No relevant relationships by Margaret Kypreos, source=Web Response No relevant relationships by Chad Newton, source=Web Response