Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study

摘要: Objectives Evaluate efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that binds neutralises membrane soluble B-cell activating factor (BAFF) versus placebo plus standard care (SoC) in patients with systemic lupus erythematosus (SLE). Methods This phase III, 52-week study randomised 1164 moderate-to-severe SLE (Safety Estrogens Lupus Erythematosus National Assessment—SLE Disease Activity Index ≥6 at baseline). Patients received SoC subcutaneous injections tabalumab or placebo, starting loading dose (240 mg) week 0 followed by 120 mg every two weeks (120 Q2W, n=387), four weeks Q4W, n=389) Q2W (n=388). Primary endpoint: proportion achieving Responder 5 (SRI-5) response 52. Results Similar proportions each group achieved SRI-5 52 Q2W: 31.8%; 120 Q4W: 35.2% placebo: 29.3%). Key secondary endpoints were not met. In sensitivity analysis excluding who decreased antimalarials immunosuppressants, was Q4W (37.0% vs 29.8% placebo; p=0.021), but (34.1%; p=0.171). Significant reductions anti-dsDNA antibodies, increases C3 C4, total B cells immunoglobulins observed tabalumab. No differences between treatment groups percentage deaths 0.8%; 0.5%; 0.5%), serious adverse events (AEs) (range 11.1–14.4%) treatment-emergent AEs 81.1–82.3%). Conclusions Tabalumab had biological activity—changes anti-dsDNA, complement, immunoglobulins—consistent BAFF pathway inhibition. clinical did achieve statistical significance. Safety profiles similar placebo. Trial registration number NCT01196091.