Background/Purpose: Systemic Sclerosis (SSc) is a connective tissue disease that is often complicated by secondary interstitial lung disease (SSc-ILD). Due to its high morbidity and mortality, there is an on-going effort to find a specific therapy for SSc-ILD. The standard of therapy in recent years has been an immunosuppressive therapy (IST) with cyclophosphamide (CYC). Although increasing data suggest the efficacy of mycophenolate mofetil (MMF) and other ISTs, there have been very few randomized controlled trials (RTCs) to show their efficacy. In this study we will analyze the current standard of therapy in SSc-ILD in SSc centers that participated in the DeSScipher Project on SSc-ILD.

Methods: 1,447 adult SSc patients, who participated in the DeSScipher Project, met the ACR/EULAR 2013 classification criteria and had a diagnosis of SSC-ILD proven by chest X-ray or computed tomography were included in our study. Clinical parameters, medical therapies and lung function were assessed at baseline and 12 +/- 3 months later.

Results: Out of the 1,447 patients included in the study, 781 patients (54%) received ISTs. Of those only 95 patients (12%) received CYC, either as monotherapy (47, 6%) or as combination therapy (48, 6%) (combination therapy referring to any additional IST excluding glucocorticoids (GCs) < 8 mg/day or anti-malaria agents). MMF was more prevalent with 239 patients (31%), 169 (22%) on monotherapy and 70 (9%) on combination therapy. Newer therapies such as rituximab (RTX) were less frequent with 50 (6%) patients, 14 (2%) on monotherapy and 36 (5%) on combination therapy. For Tocilizumab (TOC) we found 19 (2%) patients in total, 6 (1%) on monotherapy and 13 (1%) on combination therapy. Out of the patients with SSc-ILD receiving IST there was a total of 239 (31%) patients receiving IST combination therapy. Comparing patients receiving CYC +/- other IST to patients receiving MMF, RTX or TOC either as monotherapy or as combination therapy, they are similar in age (53.7±12.7 yrs vs. 54.2±12.8 yrs in CYC), but have shorter disease duration regarding SSc (5.9±6.9 yrs in CYC vs. 8.7±6.9 yrs, p<0.001) and ILD (3.3±5.7 yrs in CYC vs. 5.9±7.8 yrs, p<0.001), similar FVC (80.8±21.4% in CYC vs. 83.1±21.5%) and higher mRSS (13.3 in CYC vs. 8.9±8.7, p<0.001). Interestingly, over the course of 1 year +/- 3 months patients on any combination therapy showed slightly better results in terms of FVC and mRSS compared to patients on monotherapy (ΔFVC 2.3% vs. 1.5%; ΔmRSS -1.7 vs. -0.9).

Conclusion: This study highlights the heterogeneity of ISTs in current clinical practice for the treatment of SSc-ILD. There is a high prevalence of immunosuppressive combination therapies that are not supported by any RTCs. Such combination therapy seems to have a beneficial effect on both FVC and mRSS. However, the difference is below a clinically meaningful improvement of 5% FVC. Also, these data have to be interpreted with caution, because groups are not yet adjusted for baseline characteristics.