Efficacy and safety of upadacitinib in refractory interstitial lung disease with idiopathic inflammatory myopathies: a retrospective study.

Abstract

To assess the efficacy and safety of upadacitinib(UPA) in patients with refractory idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) following conventional therapy failure. We conducted a single-center retrospective cohort study of IIM-ILD patients initiating UPA after conventional therapy failure. Clinical characteristics, pulmonary function tests (PFTs), high-resolution computed tomography (HRCT) Warrick scores, and therapeutic regimens were collected at baseline and follow-ups. Patients receiving conventional treatment were included as the control group following propensity score matching (PSM, 1:2). Treatment responses and adverse events were analyzed and compared. Among 28 UPA-treated patients (mean age 57, 87.5% female), 16 had complete paired data of PFTs and/or HRCT both at baseline and after treatment. After mean 7.4 months, lung function improved: the mean FVC increased from 1.84-2.13 L (p= 0.0069), FVC% from 63.5% to 76.77% (p= 0.0004). HRCT Warrick scores remained stable overall, with some patients showing radiographic improvement. Inflammatory indicators, including IL-6 (14.06-8.44 pg/ml, p= 0.039) and serum ferritin (240.30-188.15 µg/l, p= 0.018), decreased significantly after treatment. Further PSM analysis (n = 16 UPA vs 32 controls) showed notably lower post-treatment IL-6 (8.44 vs 20.60 pg/ml, p= 0.0012) and lower glucocorticoid dose (7.50 vs 12.50 mg, p= 0.017). No significant differences in PFTs or HRCT scores were found between groups. Infections occurred in 6/28 (21.4%), all recovered well. UPA significantly improved lung function, reduced glucocorticoid dependence, and suppressed systemic inflammation in refractory IIM-ILD with acceptable safety, supporting its use as a promising therapeutic option in IIM-ILD patients after conventional treatment failure.