Related Experiment Video
Updated: May 31, 2026
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Orelabrutinib for systemic lupus erythematosus: A randomised, double-blind, placebo-controlled study
Ru Li1, Xue Li1, Xiaoxia Zhu2
1Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, China.
Objectives:
Orelabrutinib is an oral, highly selective, irreversible inhibitor of Bruton's tyrosine kinase (BTK). Preclinical mechanistic studies have demonstrated its therapeutic potential in systemic lupus erythematosus (SLE).
Methods:
A multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase Ib/IIa study was conducted in 11 centres in China. Patients diagnosed with SLE were randomised 1:1:1:1 to receive oral orelabrutinib at 50 mg, 80 mg, and 100 mg or placebo once daily for 12 weeks, respectively. This trial is registered with ClinicalTrials.gov, NCT04305197.
Results:
Between July 9, 2020 and September 29, 2021, 60 patients were randomised, with 55 patients who completed 12 weeks of treatment. Adverse events (AEs) were mostly mild or moderate. In all evaluable patients, the SLE Response Index (SRI)-4 rates at week 12 were 50%, 62%, and 64% for orelabrutinib at 50 mg, 80 mg, and 100 mg, respectively, compared with 36% for placebo, indicating dose-dependent improvement. Among patients with baseline SLEDAI-2K > 8, significantly higher SRI-4 responses were noted with orelabrutinib at 50 mg (80%, p = 0·048), 80 mg (83%, p = 0·048), and 100 mg (100%, p = 0·029) compared to placebo (0%). SRI-6 responses at week 12 were 36%, 39%, and 21% for orelabrutinib at 50 mg, 80 mg, and 100 mg, respectively, compared with 7% for placebo. Reduced proteinuria, anti-dsDNA, IgG, and IgM and increased C4 were observed with orelabrutinib treatment.
Conclusions:
Orelabrutinib was well tolerated and potentially efficacious in patients with SLE.
