Background Epratuzumab is a monoclonal antibody targeting CD22. In EMBLEM™ (a dose-ranging phase IIb study), epratuzumab produced clinically relevant improvements in disease activity in patients with moderate-to-severe systemic lupus erythematosus (SLE).1 SL0008 (NCT00660881) was an open-label extension of EMBLEM™.
Objectives To assess longer-term efficacy of epratuzumab in patients with moderate-to-severe SLE.
Methods Patients from any EMBLEM™ arm completing 12 weeks’ blinded treatment and patients who discontinued due to lack of efficacy but completed ≥8 weeks were eligible. In SL0008, all patients received 1200mg epratuzumab at weeks 0 and 2 of repeating 12-week cycles. Evaluation visits were at weeks 4 and 8 of each cycle. Efficacy endpoints included BILAG improvement, SLEDAI assessment score, Physician Global Assessment (PGA) score and combined treatment response (defined as BILAG improvement without worsening, no SLEDAI worsening, no PGA worsening, relative to EMBLEM™ baseline).
Results 203 patients participated in SL0008: 95% female (n=192), 78% Caucasian (n=158), mean±SD age 39±11 years. 35 (17%) and 168 (83%) received placebo and epratuzumab (at various doses), respectively, for 12 weeks in EMBLEM™. The median (range) duration of epratuzumab exposure was 845 (75–1185) days. BILAG improvements were observed between EMBLEM™ baseline and week 108, the last timepoint when >50% of patients reported data for this endpoint. Median BILAG total score decreased by 64%. Median (range) BILAG total score was 25.0 (12–61) at EMBLEM™ baseline, 14.0 (0–57) at SL0008 screening, 9.0 (0–52) at week 48, 9.0 (0–52) at week 96 and 9.0 (0–52) at week 108. Epratuzumab treatment was associated with improvements in BILAG grade distribution across most body systems. At week 108, 60.3% of patients responded to treatment, according to combined treatment response criteria (Table). Median (range) SLEDAI total score was 12.0 (6–39) at EMBLEM™ baseline, 10.0 (0–34) at SL0008 screening, 6.0 (0–30) at week 48, 5.0 (0–22) at week 96 and 4.0 (0–24) at week 108. Median (range) PGA total score was 50.0 (9–90) at EMBLEM™ baseline, 31.0 (0–96) at SL0008 screening, 18.0 (0–81) at week 48, 19.0 (0–73) at week 96 and 17.5 (0–69) at week 108.
Conclusions Epratuzumab was associated with sustained improvements in disease activity in patients with moderate-to-severe SLE. Responder rates were sustained beyond 2 years or increased during open-label treatment, particularly in patients previously treated with placebo.
Wallace DJ, et al. Ann Rheum Dis, Online First 12 January 2013. DOI: 10.1136/annrheumdis-2012-202760.
Disclosure of Interest C. Gordon Grant/research support from: Aspreva, Consultant for: Aspreva, Bristol-Myers Squibb, Genentech, Biogen IDEC Inc, Merck Pharmaceuticals, Roche, UCB Pharma, M. Clowse Consultant for: UCB Pharma, F. Houssiau Grant/research support from: UCB Pharma, Consultant for: UCB Pharma, M. Petri Grant/research support from: UCB Pharma, Consultant for: UCB Pharma, B. Kilgallen Shareholder of: UCB Pharma, Employee of: UCB Pharma, K. Kalunian Grant/research support from: Genentech, Biogen IDEC Inc, Cephalon, Cypress, MedImmune, Novo Nordisk, UCB Pharma, Consultant for: Bristol-Myers Squibb, Genentech, Biogen IDEC Inc, Anthera, MedImmune, Novo Nordisk, Zymogenetics, Serono, UCB Pharma, V. Strand Consultant for: Abbott Immunology Pharmaceuticals, Amgen Inc, AstraZeneca, Biogen Idec, Canfite Pharma, Centocor Inc, Cypress Biosciences Inc, Euro-Diagnostica Inc, Fibrogen, Forest Laboratories, Genentech, Human Genome Sciences Inc, Incyte, Novartis Pharmaceuticals Corporation, Alder, CBio, Chelsea, Crescendo, Idera, Jazz Pharmaceuticals, Lexicon Genetics, Logical Therapeutics, Lux Biosciences, NovoNordisk, Nuon, Ono, SKK, Pfizer Inc, Rigel Pharma, Roche, Sanofi-Aventis, Savient Pharmaceuticals, Schering-Plough and UCB Pharma, S. Bongardt Employee of: UCB Pharma, D. Wallace Consultant for: Bristol-Myers Squibb, Genentech, Biogen IDEC Inc, GlaxoSmithKline, Human Genome Sciences Inc, MedImmune, Novo Nordisk and UCB Pharma