The ASTIS trial targets patients with early diffuse systemic sclerosis at risk of early mortality. These include patients with disease duration of ⩽4 years, a modified Rodnan skin score (mRSS) of at least 15 (out of a maximum of 51), evidence of heart, lung, or kidney disease; and patients with a maximum disease duration of 2 years, an mRSS of 20 or more plus laboratory signs of acute phase reaction. Exclusion criteria are end stage organ failure, extensive pretreatment with cyclophosphamide (over 5 g intravenously or 3 months’ oral treatment), and common reasons that preclude participation in a trial.