Abstract Rationale Idiopathic interstitial pneumonia (IP) comprises a heterogeneous subset of interstitial lung diseases (ILDs), posing therapeutic challenges due to variable disease trajectory and unpredictable treatment response. We aimed to understand whether interstitial pneumonia with autoimmune features (IPAF) classification is associated with differential survival with immunosuppressant exposure among patients with idiopathic IP. We hypothesized that patients meeting IPAF classification would demonstrate improved transplant-free survival with immunosuppressant exposure compared to unexposed patients. Methods We conducted a retrospective, multi-center cohort study of patients with idiopathic IP across international academic centers. The primary objective was to determine whether IPAF classification modified the association between immunosuppressant exposure and two-year transplant-free survival. Immunosuppressant exposure was defined as initiation of mycophenolate or azathioprine within two years of registry enrollment. To minimize confounding by indication, inverse probability of treatment weighting (IPTW) using propensity scores was employed. Weighted multivariable Cox proportional hazards regression models with robust variance estimation were constructed, with immunosuppressant exposure treated as a time-dependent covariate. Due to potential differences between centers, each center was analyzed individually and meta-analyzed using a random effects model. The primary outcome was two-year transplant-free survival. Secondary outcomes included survival modification by IPAF domain and imaging pattern. Results Among 2645 patients meeting inclusion criteria, 416 were immunosuppressant-exposed within two years of registry enrollment and 2229 were unexposed. IPAF criteria were systematically applied using available clinical data. IPAF was considered present when any two IPAF domains were satisfied and absent when any two domains were not satisfied. In patients meeting IPAF criteria, immunosuppressant exposure was not associated with improved transplant-free survival compared to unexposed patients (hazard ratio (HR) 1.33, 95% confidence interval (CI) 0.39-4.53, Figure 1). IPAF classification did not modify the effect of immunosuppressant exposure on survival among idiopathic IP patients (pinteraction=0.58). The presence of the individual IPAF domains also did not modify the impact of immunosuppression on two-year transplant-free survival. Exposure was associated with worse survival among IPAF patients with usual interstitial pneumonia (UIP) on imaging (HR 2.17, 95% CI 1.03-4.58). Conclusion We provide robust evidence that IPAF classification is not associated with differential response to immunosuppressant exposure, challenging its clinical utility for treatment decision-making in idiopathic IP. We also find that immunosuppressant use may cause higher mortality risk in idiopathic IP patients meeting IPAF criteria with UIP on imaging, thus highlighting the potential adverse impact of using immunosuppression in patients with idiopathic UIP. This abstract is funded by: None
Hammoud et al. (Fri,) studied this question.