Efficacy of methylprednisolone in very early systemic sclerosis: results of the 'Hit Hard and Early' randomized controlled trial.

Objective: We hypothesized that glucocorticoids would induce remission in very early systemic sclerosis (SSc) patients by inhibition of inflammation driving the disease. We examined the efficacy and safety of methylprednisolone in very early SSc.

Methods: In this trial adults with puffy fingers for less than 3 years, specific auto-antibodies and meeting the Very Early Diagnosis of Systemic Sclerosis criteria were randomly assigned (2:1) to methylprednisolone 1000 mg i.v. or placebo for three consecutive days three 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 [interquartile range, 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, and seven (23%) patients had a relevant pulmonary function decline. No serious adverse events were reported.

Conclusion: No clinically relevant effect of short-term methylprednisolone in patients with very early SSc was observed. A substantial proportion of patients showed disease progression.

Trial Registration: clinicaltrials.gov, NCT03059979.