Cyclophosphamide for scleroderma lung disease.

2707 age readers to recommend topics of interest and have established a separate e-mail address ([email protected]) for readers to submit their ideas or comments regarding the new series. Clinically significant interstitial lung disease affects patients with systemic sclerosis (scleroderma) and is a cause of morbidity and mortality in approximately 40 percent of these patients. 1 Management of this condition remains difficult and controversial. 2,3 In this issue of the Journal, Tash-kin and colleagues 4 report the results of a multi-center, placebo-controlled trial of oral cyclophos-phamide in patients with well-defined, symptomatic scleroderma-related interstitial lung disease and alveolitis. They document small but statistically significant improvements in lung function and symptoms with cyclophosphamide administered over the course of one year — the first positive results of a placebo-controlled trial in this field. How should these results be translated into clinical care? In this trial, a change in the expected annual decline in the forced vital capacity (FVC, expressed as a percentage of the predicted value) was the primary end point. Although the dropout rate was higher than anticipated (approximately 33 percent of the patients did not complete one year of cyclophosphamide therapy), the statistical analysis allowed the calculation of longitudinal changes in the FVC in the majority of the patients. This analysis showed an adjusted difference of 2.53 percent in the FVC favoring cy-clophosphamide (P = 0.03). This modest difference was less than that anticipated by the investigators — a 9 percent annual decline in the FVC, as derived from published case series. In the majority of the patients in the two study groups, the change in the predicted value of the FVC was less than 5 percent, which is close to the expected natural variability in the percentage of the predicted FVC. 5 In contrast, no significant treatment related difference was noted in the diffusing capacity for carbon monoxide, a measure that is considered by some to be a better longitudinal marker of disease progression than the change in the FVC. 2,6 The explanation of this modest effect remains conjectural, but the size of the effect may reflect the patient population studied. Previous investigators have suggested that progressive scleroderma-related interstitial lung disease is more likely to develop in patients with low pulmonary function at presentation or rapid disease progression during the first five years after the onset of the first scleroderma-related symptom. 7 In the patients in the current trial, the duration …