PMID- 26293163 OWN - NLM STAT- MEDLINE DCOM- 20160628 LR - 20221207 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 75 IP - 2 DP - 2016 Feb TI - 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. PG - 332-40 LID - 10.1136/annrheumdis-2015-207654 [doi] 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. TRIAL REGISTRATION NUMBER: NCT01205438. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ FAU - Merrill, J T AU - Merrill JT AD - Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. FAU - van Vollenhoven, R F AU - van Vollenhoven RF AD - Department of Medicine, Karolinska Institute, Stockholm, Sweden. FAU - Buyon, J P AU - Buyon JP AD - New York University School of Medicine, New York, New York, USA. FAU - Furie, R A AU - Furie RA AD - Division of Rheumatology and Allergy-Clinical Immunology, Hofstra North Shore-LIJ School of Medicine, Great Neck, New York, USA. FAU - Stohl, W AU - Stohl W AD - Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, California, USA. FAU - Morgan-Cox, M AU - Morgan-Cox M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Dickson, C AU - Dickson C AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Anderson, P W AU - Anderson PW AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Lee, C AU - Lee C AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Berclaz, P-Y AU - Berclaz PY AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Dorner, T AU - Dorner T AD - Medicine/Rheumatology and Clin Immunology, Charite Universitatsmedizin, Berlin, Germany. LA - eng SI - ClinicalTrials.gov/NCT01205438 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20150820 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Antinuclear) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Autoantibodies) RN - 0 (B-Cell Activating Factor) RN - 0 (Biomarkers) RN - 0 (Complement C3) RN - 0 (Complement C4) RN - PQP8VH3MJW (tabalumab) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antibodies, Antinuclear/blood MH - Antibodies, Monoclonal/*administration & dosage MH - Antibodies, Monoclonal, Humanized MH - Autoantibodies/blood MH - B-Cell Activating Factor/administration & dosage/*antagonists & inhibitors MH - B-Lymphocytes/metabolism MH - Biomarkers/blood MH - Black People MH - Complement C3/metabolism MH - Complement C4/metabolism MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Humans MH - Injections, Subcutaneous MH - Lupus Erythematosus, Systemic/*drug therapy/ethnology MH - Male MH - Middle Aged MH - Severity of Illness Index MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Autoimmune Diseases OT - B cells OT - Disease Activity OT - Systemic Lupus Erythematosus EDAT- 2015/08/22 06:00 MHDA- 2016/06/29 06:00 CRDT- 2015/08/22 06:00 PHST- 2015/03/25 00:00 [received] PHST- 2015/08/01 00:00 [accepted] PHST- 2015/08/22 06:00 [entrez] PHST- 2015/08/22 06:00 [pubmed] PHST- 2016/06/29 06:00 [medline] AID - annrheumdis-2015-207654 [pii] AID - 10.1136/annrheumdis-2015-207654 [doi] PST - ppublish SO - Ann Rheum Dis. 2016 Feb;75(2):332-40. doi: 10.1136/annrheumdis-2015-207654. Epub 2015 Aug 20.