TY - JOUR
T1 - Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study
T2 - results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study
AU - Merrill, J. T.
AU - van Vollenhoven, R. F.
AU - Buyon, J. P.
AU - Furie, R. A.
AU - Stohl, W.
AU - Morgan-Cox, M.
AU - Dickson, C.
AU - Anderson, P. W.
AU - Lee, C.
AU - Berclaz, P.-Y.
AU - Dörner, T.
PY - 2016/2
Y1 - 2016/2
N2 - Objectives To evaluate the efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that neutralises membrane and soluble B-cell activating factor (BAFF). Methods This randomised, placebo-controlled study enrolled 1124 patients with moderate-to-severe systemic lupus erythematosus (SLE) (Safety of Estrogens in Lupus Erythematosus National Assessment- SLE Disease Activity Index >= 6 at baseline). Patients received standard of care plus subcutaneous study drug, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every 2 weeks (120 Q2W), 120 mg every 4 weeks (120 Q4W) or placebo. Primary endpoint was proportion achieving SLE Responder Index 5 (SRI-5) improvement at week 52. Results Clinical characteristics were balanced across groups. The primary endpoint was met with 120 Q2W (38.4% vs 27.7%, placebo; p=0.002), but not with the less frequent 120 Q4W regimen (34.8%, p=0.051). Although key secondary endpoints (time to severe flare, corticosteroid sparing and fatigue) were not met, patients treated with tabalumab had greater SRI-5 response rates in a serologically active subset and improvements in more stringent SRI cut-offs, SELENA-SLEDAI, Physician's Global Assessment, anti-double stranded DNA antibodies, complement, total B cells and immunoglobulins. The incidences of deaths, serious adverse events (AEs), and treatment-emergent AEs were similar in the 120 Q2W, 120 Q4W and placebo groups, but depression and suicidal ideation, albeit rare events, were more commonly reported with tabalumab. Conclusion SRI-5 was met with 120 Q2W and although key secondary endpoints were not met, numerous other secondary endpoints significantly improved in addition to pharmacodynamic evidence of BAFF pathway blockade. The safety profile for tabalumab was similar to placebo, except for depression and suicidality, which were uncommon
AB - Objectives To evaluate the efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that neutralises membrane and soluble B-cell activating factor (BAFF). Methods This randomised, placebo-controlled study enrolled 1124 patients with moderate-to-severe systemic lupus erythematosus (SLE) (Safety of Estrogens in Lupus Erythematosus National Assessment- SLE Disease Activity Index >= 6 at baseline). Patients received standard of care plus subcutaneous study drug, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every 2 weeks (120 Q2W), 120 mg every 4 weeks (120 Q4W) or placebo. Primary endpoint was proportion achieving SLE Responder Index 5 (SRI-5) improvement at week 52. Results Clinical characteristics were balanced across groups. The primary endpoint was met with 120 Q2W (38.4% vs 27.7%, placebo; p=0.002), but not with the less frequent 120 Q4W regimen (34.8%, p=0.051). Although key secondary endpoints (time to severe flare, corticosteroid sparing and fatigue) were not met, patients treated with tabalumab had greater SRI-5 response rates in a serologically active subset and improvements in more stringent SRI cut-offs, SELENA-SLEDAI, Physician's Global Assessment, anti-double stranded DNA antibodies, complement, total B cells and immunoglobulins. The incidences of deaths, serious adverse events (AEs), and treatment-emergent AEs were similar in the 120 Q2W, 120 Q4W and placebo groups, but depression and suicidal ideation, albeit rare events, were more commonly reported with tabalumab. Conclusion SRI-5 was met with 120 Q2W and although key secondary endpoints were not met, numerous other secondary endpoints significantly improved in addition to pharmacodynamic evidence of BAFF pathway blockade. The safety profile for tabalumab was similar to placebo, except for depression and suicidality, which were uncommon
KW - Adolescent
KW - Adult
KW - African Continental Ancestry Group
KW - Aged
KW - Antibodies, Antinuclear
KW - Antibodies, Monoclonal
KW - Autoantibodies
KW - B-Cell Activating Factor
KW - B-Lymphocytes
KW - Biomarkers
KW - Clinical Trial, Phase III
KW - Complement C3
KW - Complement C4
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Drug Administration Schedule
KW - Female
KW - Humans
KW - Injections, Subcutaneous
KW - Journal Article
KW - Lupus Erythematosus, Systemic
KW - Male
KW - Middle Aged
KW - Multicenter Study
KW - Randomized Controlled Trial
KW - Severity of Illness Index
KW - Treatment Outcome
KW - Young Adult
U2 - https://doi.org/10.1136/annrheumdis-2015-207654
DO - https://doi.org/10.1136/annrheumdis-2015-207654
M3 - Article
C2 - 26293163
SN - 0003-4967
VL - 75
SP - 332
EP - 340
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 2
ER -