Background Tabalumab is a human IgG4 monoclonal antibody that binds and neutralizes membrane and soluble BAFF.

Objectives Two trials, involving >2000 patients (pts) with SLE, evaluated the efficacy and safety of subcutaneous tabalumab + standard of care (SoC) versus placebo (pbo) + SoC at 52 weeks (wks).

Methods ANA-positive pts were enrolled with active, moderate-to-severe SLE (baseline SELENA-SLEDAI score ≥6). Pts with severe active renal or CNS disease were excluded. Pts received a loading dose (240 mg or pbo) at Wk 0, followed by 120 mg tabalumab every 2 wks (120 Q2W), 4 wks (120 Q4W), or pbo. Primary endpoint: proportion of pts achieving SLE Responder Index 5 (SRI-5) response at Wk 52. Key secondary endpoints: time to severe flare, corticosteroid sparing, and worst fatigue over last 24 hours (hrs). Subgroup analyses based on background SoC, complement, and anti-dsDNA were conducted.

Results Baseline disease activity and clinical characteristics were balanced across groups in both trials. SRI-5 was not met in Trial 1, but was met in Trial 2 for the 120 Q2W dose (p=0.002; Table). Key secondary efficacy endpoints did not achieve statistical significance. Subgroup analysis showed that baseline antimalarial (AM) use did not reduce SRI-5 response rates. Reduction in anti-dsDNA was observed as well as increases in complement C3 and C4 and reduction in total B cells and immunoglobulins (Ig). The safety profile of the tabalumab and pbo groups was similar across both trials.

Conclusions Tabalumab had biologic activity consistent with BAFF inhibition, as shown by anti-dsDNA, complement, B cell, and Ig changes. The primary endpoint was met in 1 of 2 trials for the 120 Q2W dose.

Disclosure of Interest D. Isenberg Consultant for: Eli Lilly and Company, J. Merrill Grant/research support from: GlaxoSmithKline, Consultant for: Eli Lilly and Company, GlaxoSmithKline, Anthera Pharmaceuticals, EMD Serono, Speakers bureau: GlaxoSmithKline, R. Hoffman Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, M. Linnik Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, M. Morgan-Cox Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, M. Veenhuizen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, N. Iikuni Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Dickson Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, M. Silk Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, D. Wallace Consultant for: Eli Lilly and Company, T. Dörner Consultant for: Eli Lilly and Company, UCB, Roche/Chugai Pharmaceutical Co. Ltd., Sanofi