Efficacy of methylprednisolone in very early systemic sclerosis: results of the “Hit hard and early’’ randomized controlled trial

Abstract Objective We hypothesized that glucocorticoids would induce remission in very early Systemic Sclerosis patients by inhibition of inflammation driving the disease. We examined the efficacy and safety of methylprednisolone in very early Systemic Sclerosis. Methods In this trial adults with puffy fingers for less than three years, specific auto-antibodies and meeting the Very Early Diagnosis of Systemic Sclerosis criteria were randomly assigned (2:1) to methylprednisolone 1000 mg intravenously or placebo for 3 consecutive days 3 times with monthly intervals. The primary end point was nailfold capillary density at week 12. Capillary density at 52 weeks, number of megacapillaries, and patient-reported outcomes were secondary outcomes. In addition, we assessed disease progression and lung function decline over 52 weeks. We used linear regression analyses adjusted for baseline values and stratification variables to estimate differences between groups. Results Between February 2017 and February 2021, 87 patients were screened, of whom 30 (70% female, median (IQR) age 52·9 (40·8–60·8) years, median (IQR) disease duration 11.4 (4.6–18.6) months) were randomly assigned to methylprednisolone (n = 21) or placebo (n = 9). We found no difference in nailfold capillary density at 12 weeks: -0.5 (95% CI 1.1, 0.2) nor in any of the secondary outcomes. Eleven (37%) patients showed disease progression during 1 year follow up, 7 (23%) patients had a relevant pulmonary function decline. No serious adverse events were reported. Conclusions No clinically relevant effect of short-term methylprednisolone in patients with very early Systemic Sclerosis was observed. A substantial proportion of patients showed disease progression.