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.
OBJECTIVE
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).


METHODS
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 treatment-emergent 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.


BACKGROUND
NCT01196091.
University College Hospital to University College London, London, UK.
D A
DA
Isenberg
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
M
M
Petri
Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, California, USA.
K
K
Kalunian
The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Y
Y
Tanaka
University of Toronto, Toronto Western Hospital, Toronto, Canada.
M B
MB
Urowitz
Eli Lilly and Company, Indianapolis, Indiana, USA.
R W
RW
Hoffman
Eli Lilly and Company, Indianapolis, Indiana, USA.
M
M
Morgan-Cox
Eli Lilly and Company, Indianapolis, Indiana, USA.
N
N
Iikuni
Eli Lilly and Company, Indianapolis, Indiana, USA.
M
M
Silk
Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
D J
DJ
Wallace
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D001402:B-Lymphocytes / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D044383:Black People; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; C575974:tabalumab
Autoimmune Diseases; B cells; Disease Activity; Systemic Lupus Erythematosus