In patients with symptomatic systemic sclerosis (SSc)-related interstitial lung disease (ILD), 1-year treatment with the immunosuppressant cyclophosphamide (CYC) is associated with short-term improvements in forced vital capacity (FVC)%-predicted and the modified Rodnan skin score (mRSS), but not in the diffusing capacity of the lungs for carbon monoxide (DLCO)%-predicted. A comparison of the Scleroderma Lung Study (SLS) I and SLS II was conducted, with results published in the Journal of Rheumatology.

Investigators sought to compare efficacy and safety outcomes between the cyclophosphamide groups of SLS I and SLS II. A total of 79 participants were enrolled in SLS I, and 69 participants were enrolled in SLS II. In both studies, all patients were randomly assigned to oral cyclophosphamide for 1 year and were then followed up for an additional year off therapy (in SLS II, the participants received placebo in year 2). Eligibility criteria for both studies were nearly identical. Individuals assigned to cyclophosphamide in SLS I and SLS II exhibited similar baseline demographic features, except for a slight age difference (mean age in SLS I, 48.4±12.3 years; mean age in SLS II, 52.2±9.6 years).

The primary study outcome was FVC%-predicted. Secondary outcomes included DLCO%-predicted, Transition Dyspnea Index, mRSS, and safety. The FVC%-predicted, mRSS, and duration of disease were similar in the cyclophosphamide groups of each trial. Among patients in the cyclophosphamide group in SLS I, however, lower DLCO%-predicted and a trend toward more extensive quantitative ILD compared with those in the cyclophosphamide group of SLS II were reported. In addition, the Baseline Dyspnea Index was lower in the SLS I cyclophosphamide group than in the SLS II group.

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After adjustment for baseline disease severity, no significant differences were observed with respect to FVC%-predicted (P =.535) or DLCO%-predicted (P =.172) in the SLS I and SLS II cyclophosphamide treatment groups. In both groups, treatment with cyclophosphamide was associated with a significant improvement in FVC%-predicted from 3 to 12 months (P =.024), but no significant improvement was reported beyond this point. Moreover, cyclophosphamide therapy had no effect on DLCO%-predicted in either treatment group.

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The investigators concluded that treatment with 1 year of oral cyclophosphamide was associated with similar improvements in lung function in both SLS I and SLS II, but these effects were not sustained following cessation of the therapy. These findings imply that an alternative effective and safe treatment is still needed for patients with SSc-related ILD, with continued immunosuppression beyond 1 year suggested as a means of attaining a sustained response in these individuals.


Volkmann ER, Tashkin DP, Sim M, et al. Cyclophosphamide for systemic sclerosis-related interstitial lung disease: a comparison of Scleroderma Lung Study I and II [published online February 15, 2019]. J Rheumatol. doi:10.3899/jrheum.180441