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


Evaluate efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that binds and neutralises membrane and soluble B-cell activating factor (BAFF) versus placebo plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE).



 This phase III, 52-week study randomised 1164 patients with moderate-to-severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment—SLE Disease Activity Index ≥6 at baseline). Patients received SoC plus subcutaneous injections of tabalumab or placebo, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every two weeks (120 Q2W, n=387), 120 mg every four weeks (120 Q4W, n=389) or placebo Q2W (n=388). Primary endpoint: proportion of patients achieving SLE Responder Index 5 (SRI-5) response at week 52.



Similar proportions of patients in each group achieved SRI-5 response at week 52 (120 Q2W: 31.8%; 120 Q4W: 35.2% and placebo: 29.3%). Key secondary endpoints were not met. In a sensitivity analysis not excluding patients who decreased antimalarials or immunosuppressants, SRI-5 response was achieved with 120 Q4W (37.0% vs 29.8% placebo; p=0.021), but not 120 Q2W (34.1%; p=0.171). Significant reductions in anti-dsDNA antibodies, increases in C3 and C4, and reductions in total B cells and immunoglobulins were observed with tabalumab. No differences were observed between treatment groups in percentage of deaths (120 Q2W: 0.8%; 120 Q4W: 0.5%; placebo: 0.5%), serious adverse events (AEs) (range 11.1–14.4%) or treatment-emergent AEs (range 81.1–82.3%).



 Tabalumab had biological activity—changes in anti-dsDNA, complement, B cells and immunoglobulins—consistent with BAFF pathway inhibition. Key clinical efficacy endpoints did not achieve statistical significance. Safety profiles were similar with tabalumab and placebo.

Trial registration number NCT01196091.

全身性エリテマトーデス患者に対するタバルマブ(tabalumab)皮下注射治療の有効性と安全性、52週、第III相、他施設共同・無作為・プラセボ対照二重盲検試験 (ILLUMINATE-1)




B細胞膜上に存在するB細胞活性化因子(B-cell activating factor: BAFF)あるいは可溶性BAFFに結合して中和するヒトIgG4モノクローナル抗体タバルマブ(tabalumab)の、有効性と安全性を検討する。


これは第III相試験である。中等度~重度疾患活動性を有する全身性エリテマトーデス患者1164名を無作為に、標準治療(standard of care: SoC)+タバルマブ、標準治療+プラセボ(placebo)に振り分けた。タバルマブは、初回240 mgを皮下投与し、以後、2週間毎に120 mgを投与した。主要評価項目(primary endpoint)を、52週におけるSLE Responder Index 5(SRI-5)の達成率とした。


SRI-5を達成した比率は、タバルマブ群とプラセボ群で差がなかった (120 Q2W: 31.8%, 120 Q4W: 35.2% and placebo: 29.3%)。マバルマブ群で抗ds-DNA抗体の低下と、補体の上昇が認められた。治験期間中の死に至った症例数に違いはなく、重篤な有害事象にも差はなかった。





結果は、生物学的活性に基づき血液検査の改善を認めたものの、疾患活動性自体は、SLE Responder Index(SRI)で評価すると抑えることができませんでした。