Background Two RCT and several open-labeled studies demonstrated various efficacy of cyclophosphamide (CYC) for treatment of Systemic sclerosis-associated interstitial lung disease (SSc-ILD) with follow up for 1-4 years.
Objectives To analyze the changes in pulmonary function tests, pulmonary artery pressure (PAP) estimated by Doppler echocardiography, and skin involvement measured by modified Rodnan’ skin score (mRSS) at 4-years, and 7-years follow-up after completion of at list 6 monthly treatments intravenous (IV) CYC of SSc-ILD.
Methods The data on pts with active SSc-ILD (ground glass opacities and/or pulmonary fibrosis (PF) on chest HRCT and reduction in FVC and/or DLCO for more than 10% during 2 consecutive visits) who started IV CYC before year 2007 were analyzed. Student T-test, Mann-Whitney U-test and Wilcoxon Signed Ranks tests were used for statistical analysis with significance measured by p<0.05.
Results A total of 225 SSc pts were registered in the EUSTAR database at our site, 41pts were had an active ILD, data on 28 pts started CYC before year 2007 (17/28- before year 2004) were eligible. Age, disease duration, and follow-up period were (mean +/- SD) 50.7 +/- 12.7 years (yrs), 16.3 +/- 17.9 months, 6.5 +/- 6 yrs respectively. Eight pts died (6 pts due to SSc). Mean cumulative CYC dose was 8.96 +/- 3.8 G; in 12 pts the treatment was followed by another non-biological DMARD. Three pts developed adverse events: 2-pneumonia, 1-hepatitis B reactivation and ankle Kaposi sarcoma, 1-premature menopause. Main changes in FVC, DLCO, PAP and mRSS were observed in first 4 yrs after CYC treatment with mild additional reduction in the next three yrs. Annual changes rate in FVC, DLCO, mRSS, and PAP are presented in Table 1. Among presenting features only elevated CK correlated with FVC, DLCO and PAP (p=0.04, p=0.026 and p=0.028 respectively). Reduction in mRSS was significant (p=0.023) at any cumulative CYC dose, but not changes in FVC, DLCO and PAP.
Conclusions Course of CYC IV infusions did not prevent FVC and DLCO reduction as well as PASP elevation in the next 4 yrs of follow-up. CYC rapidly and significantly improved mRSS. Cumulative doses of CYC above 6G had not additional influence on FVC and DLCO. In SSc-ILD follow-up longer than 4 years indicates a need for maintenance therapy after stabilization of pulmonary function tests with CYC.
Disclosure of Interest: None Declared