Treatment of scleroderma-related interstitial lung disease with mycophenolate mofetil for two years or cyclophosphamide for one year both significantly improve lung function, according to the SLS II trial just published in the Lancet.
The findings support the potential effectiveness of both approaches, and also the current preference for mycophenolate because of its better tolerability and toxicity profile, the US research team said.
SLS II, conducted in 126 patients meeting clearly-defined criteria for dyspnoea, pulmonary function and high-resolution CT findings, was the first randomised comparison of mycophenolate and cyclophosphamide, prompted by the results of a series of retrospective and observational analyses and the earlier SLS I study.
SLS I identified benefits of one year’s treatment with cyclophosphamide compared to placebo, but an editorial commented that the effect was small, of dubious clinical relevance, and did not persist.
However it said the follow-up SLS II study was a “triumph of intelligent recruitment and study design”, showing clear evidence of improvement in both treatment groups and unequivocal data that mycophenolate is better tolerated.
Mycophenolate, an immunosuppressant with anti-fibrotic and immunomodulatory properties, was associated with significantly lower rates of leucopenia and thrombocytopenia in the study, and also with lower rates of withdrawal from treatment.
“Prospective, observational studies have suggested that mycophenolate is safe, well tolerated, and might prevent pulmonary function deterioration in scleroderma-related interstitial lung disease,” the researchers said.
“Cyclophosphamide was included as an active comparator because it is the only drug that has been found in previous randomised controlled trials to have efficacy.”
Concurrent improvements in skin scores noted in the study suggested an overall systemic benefit of mycophenolate.
“The key message is that mycophenolate mofetil is tolerable and could be valuable in treating lung fibrosis in systemic sclerosis,” the editorial said.
“Now might be the time to accept this conclusion and move on with testing more innovative therapies to achieve greater clinical improvements and to better define patients that are most likely to respond.”
Progressive interstitial lung disease is the leading cause of death in systemic sclerosis, and few treatment options are available.