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.