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

Abstract

ObjectiveTo identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE).MethodsA 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).ResultsProportion 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.ConclusionsTreatment 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.

Sensitivity to Change and Minimal Important Differences of the LupusQoL in Patients With Systemic Lupus Erythematosus

“…The BILAG‐2004 category scores A to E are based on intention to treat, where A = severe disease activity, B = moderate disease activity, C = mild, stable disease, D = inactive disease but previously affected system, and E = a system that has never been involved. Changes in overall disease activity between consecutive time points, as measured by the BILAG‐2004 index, were defined as follows: 1) deterioration, with any system changing to A from B/C/D or to B from C/D 21; 2) improvement, with all systems changing from A to B/C/D and B scores changing to C/D 22, with no deterioration in any system (one persistent B score was allowed if there was improvement from A or B in at least 1 other system); 3) persistent inactive disease, with all systems scored as C/D/E at both time points; and 4) persistent active disease, with A or B system scores remaining unchanged but without overall improvement or deterioration. When changes of activity of a single BILAG system were analyzed, the above definitions applied, but only for that system, and no persistent B score was allowable for improvement.…”

Upcoming biological therapies in systemic lupus erythematosus

“…A post hoc analyses showed that a cumulative dose of 2400 mg of epratuzumab was associated with a significantly better clinical improvement. The frequencies of AEs and SAEs, including infusion reactions, were not different across all groups of patients [15].…”

B cells biology in systemic lupus erythematosus—from bench to bedside

“…EMBLEM was a phase IIb RCT study targeting moderate to severe SLE patients and the results showed 2,400 mg (cumulative dose in four weeks) Epratuzumab was well tolerated with considerable clinical improvements. A higher proportion of responders than placebo group was observed [173], whereas both of the two phase III trials (EMBODY TM -1 and -2)have not meet their primary clinical efficacy endpoints, announced on 28 July, 2015. (http://www.ucb.com/ presscenter/News/article/UCBannounces-Phase-3-clinical-trial-program-for-epratuzumabin-Systemic-Lupus-Erythematosus-did-not-meet-primary-en dpoint-nbsp).…”