Preventive effects of early immunosuppressive treatment on the development of interstitial lung disease in systemic sclerosis

Background: Hypothesizing that early treatment yields improved prognosis, we aimed to investigate how the timing of immunosuppressive treatment relates to interstitial lung disease (ILD) development and the course of pulmonary function in systemic sclerosis (SSc). Methods: A cohort was created using data from the EUSTAR database and Nijmegen Systemic Sclerosis cohort, including adult patients who started their first immunosuppressive treatment (i.e. mycophenolate mofetil, methotrexate, cyclophosphamide, tocilizumab or rituximab) after SSc diagnosis, and no signs of ILD on high-resolution CT. ILD-free survival and the course of forced vital capacity (FVC) % predicted were assessed for up to 5years’ follow-up comparing patients who started early (disease duration ≤3years) vs late with immunosuppression. Results: 1052 patients met the eligibility criteria. The early treatment group (n=547, 52%) showed a higher prevalence of male sex, diffuse cutaneous subtype (53.1% vs 36.5%), and anti-topoisomerase-I antibody (ATA, 51.1% vs 42.7%). Most patients were treated with methotrexate (60.1%), whereas only a few patients were treated with biologics (1.7%). The incidence of ILD was 46.6% after mean (s.d.) 3.6 (1.4) years; the hazards ratio for ILD in the early treatment group was 1.13 (95% CI: 0.93, 1.38) after adjustment for confounders. FVC % predicted trajectories were comparable between groups. Conclusion: Our findings did not confirm a preventive role of early initiation of immunosuppressive therapy vs late initiation on ILD development. However, our findings should be interpreted with caution, considering the high inflammatory, ATA-positive enriched nature of the cohort, confounding by indication, and that very few patients were treated with biologics.