A Phase 3 Trial of Telitacicept for Systemic Lupus Erythematosus

BACKGROUND: Telitacicept, a new dual inhibitor of the cytokines B-lymphocyte stimulator (BLyS) and APRIL (a proliferation-inducing ligand), showed efficacy in adults with active systemic lupus erythematosus (SLE) in a phase 2b trial when added to standard therapy. METHODS: We conducted a phase 3 trial in China in which participants with active SLE were randomly assigned (in a 1:1 ratio) to receive telitacicept (160 mg) or placebo subcutaneously once weekly for 52 weeks, in addition to standard therapy. The primary end point at week 52 was a response on the modified SLE Responder Index 4 (SRI-4), with a response on this composite measure defined as a reduction of at least 4 points in the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score (ranging from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group index, and no worsening in the Physician's Global Assessment score. RESULTS: Of 433 adults screened, 335 underwent randomization (167 to the telitacicept group and 168 to the placebo group). At week 52, significantly more participants receiving telitacicept had a response on the modified SRI-4 than those receiving placebo (67.1% vs. 32.7%; adjusted difference, 34.5 percentage points; 95% confidence interval [CI], 24.3 to 44.7; P<0.001). A reduction of at least 4 points from baseline in the SELENA-SLEDAI score had occurred in 70.1% of the telitacicept group and in 40.5% of the placebo group (difference, 29.6 percentage points; 95% CI, 13.1 to 46.1). Adverse events that were considered by the investigator to be related to the trial regimen were more common with telitacicept than with placebo (74.9% vs. 50.0%). Such events that occurred more frequently in the telitacicept group than in the placebo group included upper respiratory tract infection (31.7% vs. 19.0%), a reduced serum IgG level (15.6% vs. 1.2%), a reduced serum IgM level (15.0% vs. 0.6%), and injection-site reactions (12.6% vs. 0.6%). CONCLUSIONS: In this 52-week trial involving participants with active SLE who were receiving background therapy, the incidence of a clinical response was higher with telitacicept than with placebo. However, the incidence of upper respiratory infections, reduced immunoglobulin levels, and injection-site reactions was also higher with telitacicept. (Funded by RemeGen; 18C010 ClinicalTrials.gov number, NCT04082416.).