Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival

Background Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD-pulmonary hypertension (PH)). Aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis (DNSS). Research Question Does SSc-associated ILD with or without PH affect survival differently and are there any risk factors that have an additional impact? Study Design and Methods Clinical data of 5,831 SSc patients were collected in the DNSS registry, Kaplan-Meier estimates were used to compare overall survival (OS) in patients with SSc-ILD with PH (ILD-PH) and without PH (ILD-w/o-PH) to patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival. Results Clinical data of 3,257 patients with a mean follow-up years of 3.45±1.63 have been included in our analysis. At baseline, ILD was present in 34.5%, while PH (w/o-ILD) had a lower prevalence with 4.5%. At the end of follow-up, 47.6% of SSc patients had ILD, 15.2% ILD-PH, and 6.5% PAH. ILD was more frequent in the diffuse cutaneous form (57.3%), while PAH did not differ significantly between SSc subtypes. Significant differences in baseline characteristics between PAH vs. ILD-PH vs. ILD-w/o-PH were found for age at diagnosis, gender, SSc-subsets, antibody-status, FVC, DLCO and therapy. OS at 5 years was 96.4% for patients without pulmonary involvement and differed significantly between patients with ILD-w/o-PH, PAH, being worst in patients with ILD-PH. Female gender (HR 0.3), a higher BMI (HR 0.9) and higher DLCO values (HR 0.98) were associated with a lower mortality risk. Interpretation ILD is the most prevalent pulmonary involvement in SSc, while the combination of ILD and PH is associated with the most detrimental survival.