TY - JOUR
T1 - Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus
T2 - Results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study
AU - Isenberg, D. A.
AU - Petri, M.
AU - Kalunian, K.
AU - Tanaka, Y.
AU - Urowitz, M. B.
AU - Hoffman, R. W.
AU - Morgan-Cox, M.
AU - Iikuni, N.
AU - Silk, M.
AU - Wallace, D. J.
N1 - Funding Information:
The authors would like to thank all of the ILLUMINATE-1 investigators for their participation, Dr Pierre-Yves Berclaz of Eli Lilly and Company (Indianapolis, IN) for assistance with trial design and execution, Rebecca Taha, Steven Watts, Tammy Forrester and Allen Nyhuis of Eli Lilly and Company (Indianapolis, IN) for assistance with statistical analyses, and Kelly Guerrettaz and Cindi Wood of inVentiv Health Clinical (Princeton, NJ) for assistance with manuscript writing and editing, respectively. Eli Lilly and Company.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Objectives. 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). Methods. 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. Results. 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 treatmentemergent AEs (range 81.1.82.3%). Conclusions. 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.
AB - Objectives. 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). Methods. 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. Results. 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 treatmentemergent AEs (range 81.1.82.3%). Conclusions. 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.
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U2 - 10.1136/annrheumdis-2015-207653
DO - 10.1136/annrheumdis-2015-207653
M3 - Article
C2 - 26338095
AN - SCOPUS:84954302328
SN - 0003-4967
VL - 75
SP - 323
EP - 331
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 2
ER -