Effect of Sequential Intravenous Pulse Cyclophosphamide-Azathioprine in Systemic Sclerosis-Interstitial Lung Disease: An Open-Label Study

Abstract

Systemic sclerosis (SSc) is a rare connective tissue disorder of unknown aetiology. Pulmonary involvement contributes substantially to its morbidity and mortality. Treatment of pulmonary disease due to SSc remains unsatisfactory. We examined the effect of sequential six-month intravenous pulse therapy with cyclophosphamide (CYC) followed by azathioprine and low-dose corticosteroids on SSc associated interstitial lung disease (SSc-ILD). In a single-centre, prospective, observational, open-labelled study; nine patients (eight females, one male) with SSc-ILD were treated with intravenous pulse CYC (600mg/m(2) body surface area) at monthly interval for six cycles with oral prednisolone 10mg daily. Subsequently, azathioprine (2-3mg/Kg) was administered while continuing with the same dose of prednisolone. Primary end-points were forced vital capacity (FVC) and high resolution computed tomography (HRCT) scan of thorax score. Secondary end-points were quality of life measured by health assessment questionnaire-disability index (HAQ-DI) and six-minute walk distance (6WMD) test. After one year of observation, the FVC showed significant improvement (p=0.003). The 6WMD also improved significantly (p=0.0028). However, change in HRCT scan scoring and HAQ-DI score was not significant. Intravenous, pulse CYC followed by azathioprine along with low-dose corticosteroids produces significant improvement in FVC and 6WMD at 12-month follow-up without significant change in radiological manifestations and health status.