Oral cyclophosphamide improves pulmonary function in scleroderma patients with fibrosing alveolitis: experience in one centre

Lung involvement constitutes nowadays the major cause of morbidity and mortality in scleroderma patients. Pulmonary fibrosis in systemic sclerosis (SSc) is thought to be the consequence of interstitial inflammation. Early diagnosis and treatment of active alveolitis is essential to prevent the deterioration of pulmonary function, improving outcome in SSc patients. The aim of the study was to investigate the effect of 1-year treatment with oral cyclophosphamide (CYC) on the evolution of interstitial lung disease in scleroderma patients with a diagnosis of active alveolitis. An open-label one-arm monocenteric study was conducted on 33 scleroderma patients with active alveolitis—defined as the presence of areas of ‘ground-glass attenuation’ on high-resolution computed tomography and a recent deterioration in lung function—treated with oral CYC 2 mg kg⁻¹ day⁻¹ for 1 year and medium-low dose steroids (prednisone 25 mg for 3 months and then tapered to 5 mg/day). Results showed that diffusing capacity for carbon monoxide (DLco) values remained stable after 6 months of treatment and significantly increased after 12 months (2.06±1.38, 2.21±1.62 and 2.39±1.64 mmol/min/kPa, at baseline/6/12 months, respectively; p<0.001 12th month vs baseline) vital capacity (VC) values slightly increased (i.e. stabilised) in the same time frame (2.46±0.71, 2.41±0.76 and 2.56±0.75 l). Accordingly, the vast majority of our patients (n=29, 87.9%) presented a DLco and/or a VC improvement or stabilisation with respect to baseline. Favourable results were more likely to be observed in patients with a lower Wells’ radiological grade (grade I). In 25 patients followed up for further 12 months after the interruption of therapy, VC and DLco remained stable. Thus, long-term therapy with oral CYC is effective in ameliorating and/or stabilising lung function in scleroderma patients with active alveolitis, with beneficial effects lasting up to 1 year after interruption. The higher efficacy in those patients with an early pulmonary disease stage and a lower radiological grade underlies the importance of an early diagnosis and intervention.