PMID- 26338095 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 in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study. PG - 323-31 LID - 10.1136/annrheumdis-2015-207653 [doi] 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 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. TRIAL REGISTRATION NUMBER: NCT01196091. 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 - Isenberg, D A AU - Isenberg DA AD - University College Hospital to University College London, London, UK. FAU - Petri, M AU - Petri M AD - Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Kalunian, K AU - Kalunian K AD - Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, California, USA. FAU - Tanaka, Y AU - Tanaka Y AD - The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan. FAU - Urowitz, M B AU - Urowitz MB AD - University of Toronto, Toronto Western Hospital, Toronto, Canada. FAU - Hoffman, R W AU - Hoffman RW AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Morgan-Cox, M AU - Morgan-Cox M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Iikuni, N AU - Iikuni N AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Silk, M AU - Silk M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Wallace, D J AU - Wallace DJ AD - Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA. LA - eng SI - ClinicalTrials.gov/NCT01196091 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150903 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 CIN - Ann Rheum Dis. 2016 Feb;75(2):e10. PMID: 26487652 CIN - Ann Rheum Dis. 2016 Feb;75(2):e11. PMID: 26530320 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over 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- 2015/09/05 06:00 MHDA- 2016/06/29 06:00 CRDT- 2015/09/05 06:00 PHST- 2015/03/25 00:00 [received] PHST- 2015/08/13 00:00 [accepted] PHST- 2015/09/05 06:00 [entrez] PHST- 2015/09/05 06:00 [pubmed] PHST- 2016/06/29 06:00 [medline] AID - annrheumdis-2015-207653 [pii] AID - 10.1136/annrheumdis-2015-207653 [doi] PST - ppublish SO - Ann Rheum Dis. 2016 Feb;75(2):323-31. doi: 10.1136/annrheumdis-2015-207653. Epub 2015 Sep 3.