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FRI0396 Double-blind comparison of mycophenolate mofetil and oral cyclophosphamide for treatment of scleroderma-related interstitial lung disease (scleroderma lung study [SLS] II): rationale, design, methods, baseline characteristics and patient disposition
  1. D. Khanna1,
  2. M. Roth2,
  3. D. Furst2,
  4. P. Clements2,
  5. J. Goldin2,
  6. E. Arriola2,
  7. J. Kotlerman2,
  8. C.-H. Tseng2,
  9. G. Kim2,
  10. R. Elashoff2,
  11. D. Tashkin2,
  12. Scleroderma Lung Study II Research Group
  1. 1Univ. of Michigan, Ann Arbor
  2. 2UCLA, Los Angeles, United States

Abstract

Background Cyclophosphamide (CYC), is the only therapy that has been shown thus far to be efficacious in scleroderma-related interstitial lung disease (SSc-ILD). However, the utility of CYC is constrained by its toxicity, which limits treatment to only ≤1 year. Findings from several uncontrolled studies in small numbers of patients with SSc-ILD (n≤17) suggest that mycophenolate mofetil (MMF) is a safe and effective treatment for SSc-ILD.

Methods SLS II is a double-blind, double-dummy, parallel-group randomized controlled trial (DB DD PG RCT) comparing the efficacy and safety of MMF (titrated to 3 g/d over 2 years) versus oral CYC (titrated to 2 mg/kg/d for 1 year followed by placebo for another year) in patients with active SSc-ILD (target enrollment 150 patients). Key eligibility criteria included adults, 7 yrs, any ground glass opacity (GGO) as an indication of “active” disease, and FVC% between 40-80% predicted. Procedures: Spirometry, lung volumes, DLCO, SGRQ, SF-12, modified Rodnan skin score (mRSS), and cough questionnaire at screening and/or baseline and every 3 months for 2 yrs; BDI (baseline); TDI every 3 months for 2 yrs; HRCT (screening and 2 years ;central reading center); toxicity monitoring. Statistical analysis: Primary endpoints: FVC % pred at 2 yrs, adjusted for baseline FVC % pred and “fibrosis” score on screening HRCT and toxicity outcomes over 2 yrs.

Results Baseline results are presented in Table 1. Premature discontinuation of study drug (38/130) – due to drug toxicity (13/38); failure to return for 24-month visits (12/26 due); SAEs (38) – 5 felt to be study-related; 1/130 treatment failure (defined by 15% pred decrease in FVC sustained for ≥1 mo).

Conclusions A DB DD RCT of oral CYC for 1 yr versus MMF for 2 yrs in patients with progressive SSc-ILD is feasible with a low rate (10%) of discontinuations due to drug toxicity overall. Extent of ILD on HRCT is significantly, albeit modestly, correlated with physiologic impairment, supporting the use of change in HRCT scores from baseline as a key endpoint.

Disclosure of Interest: None Declared

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