PMID- 23313811 OWN - NLM STAT- MEDLINE DCOM- 20140211 LR - 20211021 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 73 IP - 1 DP - 2014 Jan TI - Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. PG - 183-90 LID - 10.1136/annrheumdis-2012-202760 [doi] AB - OBJECTIVE: To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). METHODS: A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37-39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). RESULTS: Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. CONCLUSIONS: Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing. FAU - Wallace, Daniel J AU - Wallace DJ AD - David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, UCLA, Los Angeles, California, USA. FAU - Kalunian, Kenneth AU - Kalunian K FAU - Petri, Michelle A AU - Petri MA FAU - Strand, Vibeke AU - Strand V FAU - Houssiau, Frederic A AU - Houssiau FA FAU - Pike, Marilyn AU - Pike M FAU - Kilgallen, Brian AU - Kilgallen B FAU - Bongardt, Sabine AU - Bongardt S FAU - Barry, Anna AU - Barry A FAU - Kelley, Lexy AU - Kelley L FAU - Gordon, Caroline AU - Gordon C LA - eng SI - ClinicalTrials.gov/NCT00624351 GR - UL1 TR001079/TR/NCATS NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20130112 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Immunosuppressive Agents) RN - 0 (Placebos) RN - 3062P60MH9 (epratuzumab) SB - IM MH - Adult MH - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects MH - B-Lymphocytes/drug effects/immunology MH - Double-Blind Method MH - Female MH - Humans MH - Immunosuppressive Agents/*administration & dosage/adverse effects MH - Lupus Erythematosus, Systemic/*drug therapy MH - Male MH - Middle Aged MH - Placebos MH - *Severity of Illness Index MH - Treatment Outcome PMC - PMC3888603 OTO - NOTNLM OT - B cells OT - Systemic Lupus Erythematosus OT - Treatment EDAT- 2013/01/15 06:00 MHDA- 2014/02/12 06:00 CRDT- 2013/01/15 06:00 PHST- 2013/01/15 06:00 [entrez] PHST- 2013/01/15 06:00 [pubmed] PHST- 2014/02/12 06:00 [medline] AID - annrheumdis-2012-202760 [pii] AID - 10.1136/annrheumdis-2012-202760 [doi] PST - ppublish SO - Ann Rheum Dis. 2014 Jan;73(1):183-90. doi: 10.1136/annrheumdis-2012-202760. Epub 2013 Jan 12.