The Scleroderma Lung Study II (SLS II) was presented by Dr. Phil Clements (abstract #1075). It is important to find more effective therapies in the treatment of SSc ILD that are safe. For this study, patients had to have <7 years of SSc and FVC between 45 and 80% predicted and HRCT evidence of ILD.
The SLS II compared oral cyclophosphamide at 2 mg/kg/d to mycophenylate mofetil (MMF) at 1.5 g/d. Cyclophosphamide was given for 1 year and then no treatment whereas MMF was given for 2 years. The strange thing is that these authors knew that if cyclophoshapmide is given as induction and there is then no maintenance therapy, that patients will regress. Thus not surprisingly, the patients had equal improvement but the transition dyspnea index and modified Rodnan Skin Score (MRSS) seemed numerically better in cyclophosphamide-treated patients (reduction of 6 units with cyclo vs. 3 with MMF). There were more discontinuations in the cyclophosphamide group (out of a total of 142 patients, 106 completed 2 years, and 36 dropped out in the cyclophosphamide group vs 20 in the MMF group).
What is the take home message?
I question the ethics of good clinical trials that demand bad clinical practice – the regression to the mean with cyclophosphamide discontinuation in year 2 was known PRIOR to recruitment in this study.
Despite that, cyclophosphamide looked actually more efficacious but it did not reach statistical significance, although there were more drop-outs.
With this study, I have no idea of what to use in year 2 of immune suppression but it looks like oral cyclophosphamide is not a bad idea for one year of treatment. The study does not answer what to do with maintenance therapy – maybe MMF? Maybe azathioprine? Maybe rituximab, etc. Unfortunately, this study doesn't answer the questions that were raised with the initial SLS study.
Dr. Janet Pope is Professor of Medicine at Western University and Division Head of Rheumatology. Dr. Pope's research interests include epidemiologic studies in scleroderma, classification criteria in systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.View Full Bio