Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal (PRESS): an open-label, multicentre, non-inferiority, randomised controlled study in China

Objectives To explore the relapse rate after glucocorticoid (GC) withdrawal with or without hydroxychloroquine (HCQ) maintenance in sustained clinically inactive systemic lupus erythematosus (SLE). Methods The PRESS trial is a multicentre, 33-week, open-label, three-arm, non-inferiority designed, randomised controlled trial. SLE patients with sustained clinically inactive disease who were maintained on low-dose GC plus HCQ therapy were screened and qualified patients were randomly assigned to three groups: drug-free group (both GC and HCQ withdrawal); HCQ group (discontinued GC but maintained HCQ); dual maintenance group (both GC and HCQ continued). The primary endpoint was to compare the proportion of patients experiencing a relapse as defined by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index flare index by 33 weeks. Two parallel non-inferiority analyses were performed (drug-free group vs dual maintenance group and HCQ group vs dual maintenance group). Results From 3 November 2016 to 13 August 2021, 333 participants complied with the protocol after randomisation were analysed. The relapse rates in the three groups were 26.1%, 11.2% and 4.7%, respectively. Compared with dual maintenance group, drug-free group failed to achieve non-inferiority significance (relapse rate difference 21.4%; 95% CI 12.3% to 30.5%; P non-inferiority =0.238), whereas HCQ group achieved non-inferiority (relapse rate difference 6.5%; 95% CI −0.5% to 13.5%; P non-inferiority =0.034). HCQ group also exhibited fewer relapses than drug-free group (p=0.006). Adverse events were similar among all three groups. Conclusions GC withdrawal may be feasible in sustained clinically inactive SLE patients. HCQ maintenance can exert a protective role in preventing disease relapse after GC withdrawal. Trial registration number NCT02842814 .