SAT0505 Comparison of long-term cyclophosphamide (CY) and mycophenolate mofetil (MMF) efficacy and safety in patients with systemic sclerosis (SSC) and interstitial lung disease (ILD)
Authors: O. Koneva, O. Ovsyannikova, O. Desiniva, L. Garzanova, L. Ananieva, M. Starovoytova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> CY is considered to be the drug of choice for ILD therapy in patients with SSc. However, based on published evidence, only temporary and modest improvement of pulmonary fibrosis is usually achieved, therefore search for new more effective and safe agents is ongoing, with specific attention given to MMF. <h3>Objectives</h3> To compare CY and MMF effects on SSc clinical manifestations and activity, and safety of both agents in an open prospective non-randomised study. <h3>Methods</h3> The study included patients with a documented SSc diagnosis and ILD signs based on HRCT data. All patients were treated with immunosuppressants in combination with low and medium doses of glucocorticoids. 36 pts (mean age 47±12 years, m/f 1/1,1, SSc duration 5.0±4.8 years, diffuse/limited – 1/1,6) were administered parenteral CY during 12±6 months, with a cumulative dose of 10.6±5 g. 45 pts (mean age 49±13 years, m/f – 1/10, SSc duration 7.6±6.3 years, diffuse/limited – 1/1,3) were administered MMF at 2 g/day during 13±2 months. The following parameters were monitored during the study: FVC%, DLC%, modified skin score (), activity index (EScSG), gastrointestinal tract symptoms, left ventricle ejection fraction, presence of diastolic ventricle dysfunction, <i>PASP</i> (Echo-CG), heart rhythm and conduction disoders (ECG), count of digital ulcers and necroses. <h3>Results</h3> MMF therapy led to a significant reduction of the mRSS (7.5±6.9 and 4.8±3.9, p=0.0006), EScSG (1.9±1,5 and 1.22±0.9, p=0.005), number of patients with heart conduction disorders (13/29% and 5/11%, p=0.03). The FVC improvement by ≥10% was documented in 6 (13%) pts, and DLCO – in 3 (7%); while worsening was observed in 4 (9%), and 2 (4%) cases, respectively. Mean FVC (90.3±20.8 and 92.2±21, p=0.09), and DLCO (52.2±17.4 and 51.9±17, p=0.86) values did not change significantly. CY therapy resulted in significant FVC increase (80.5±20.1 and 85.9±20.5; p=0.034), reduction of EScSG (2.8±2 and 1.4±1.2, p=0,0002) and mRSS (11,2±9,8 and 7.9±6,8, p=0,009).≥10% FVC increase was observed in 11 (31%) pts, which was significantly more than in MMF group (p=0.043). FVC loss was noticed in 2 (5.6%) cases. The median FVC increase was 5.4% (25th%=−0.6, 75th%=12.3).≥10% DLCO improvement and worsening was observed in 2 (6.7%) pts. The mean DLCO values (53,5±16,2 and 54.4±15,5) did not change significantly. The other parameters monitored did not show significant deviations during the observation period. Drug tolerability was better in MMF group: the rate of adverse drug reactions was significantly lower in MMF group (12/27%), compared to CY group (19/53%), p=0.03. <h3>Conclusions</h3> Both drugs effectively reduced mRSS and EScSG in SSc patients. However, CY more often led to a clinically significant increase in FVC, in contrast to MMF, mostly contributing to stabilisation of FVC. The obtained results justify a differentiated approach to SSc pharmacotherapy depending on disease severity. A CY induction therapy should be considered as appropriate practice in patients with more severe pulmonary disease. A MMF induction therapy should be considered in SSc patients with cardiomyopathy and mild pulmonary disease, with poor CY tolerability. In other cases, MMF should be used for maintenance therapy after induction with CY. <h3>Disclosure of Interest</h3> None declared