Background Epratuzumab is a monoclonal antibody targeting CD22 that may affect B-cell signaling, adhesion and migration.1,2 We report immunologic response in SL0008 (NCT00660881), an open-label extension of EMBLEM™, a 12-week phase IIb study in moderate-to-severe SLE patients.
Objectives To assess the effect of long-term epratuzumab treatment on B cells and other immune parameters.
Methods EMBLEMTM patients who completed 12 weeks of blinded treatment and patients who discontinued due to lack of efficacy but completed ≥8 weeks were eligible for SL0008. Patients received 1200 mg epratuzumab at weeks 0 and 2 of repeating 12-week cycles. Immune assessments included B-cell (CD20+) and T-cell (CD3+) counts, and immunoglobulin levels. B-cell surface CD22 levels are given as mean fluorescence intensity (MFI).
Results SL0008 recruited 203 patients aged 18–68 years (mean 39 years; 95% female; 78% Caucasian). Median (range) epratuzumab exposure was 845 (75–1185) days. Median absolute B-cell counts decreased, plateauing at median (range) 50% (–94 to 286) below EMBLEMTM baseline at week 112, the last timepoint at which >50% of patients reported this endpoint (Table). CD22 expression on all B cell subsets (median MFI) remained low relative to EMBLEMTM baseline throughout SL0008. No consistent trends were seen in median absolute T-cell counts, which remained similar to EMBLEMTM baseline (3.0% [range –74 to 1608] higher at week 112). No consistent trends were observed for IgA and IgG levels but IgM levels decreased slightly (–0.21 g/L by week 112). At week 48 (including last visit data if week 48 unavailable), mean total BILAG (n=195) was 13.9 for patients with screening B-cell count <median (n=96) vs 13.2 for patients ≥median (n=99; p=0.712). Week 48 BILAG improvement rate (defined as BILAG A/B at screening to B/C/D and C/D, respectively, and no new A and ≤1 new Bs; last available value used if Week 48 unavailable; n=150) was 33.8% (24/71) for patients with screening B-cell count <median and 35.4% (28/79) for patients ≥median (p=0.833).
Conclusions Total B-cell count reductions in SL0008 remained within or slightly below normal range in most patients.3 Immunoglobulin levels remained within normal ranges.4 The moderate reduction in B-cell counts and the lack of correlation between screening counts and week 48 BILAG scores or improvements support B-cell modulation rather than depletion as a mode of action for epratuzumab.
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Disclosure of Interest V. Strand Consultant for: UCB Pharma, Abbott Immunology Pharmaceuticals, Amgen Inc., AstraZeneca, Biogen Idec, Canfite Pharma, Centocor, Inc., Cypress Biosciences, Inc., Euro-Diagnostica Inc., Fibrogen, Forest Laboratories, Genentech and Biogen IDEC Inc., 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 and Schering-Plough., P. Leszczyński Grant/research support from: UCB Pharma, Speakers bureau: UCB Pharma, M. Keiserman Grant/research support from: UCB Pharma, B. Kilgallen Shareholder of: UCB Pharma, Employee of: UCB Pharma, S. Bongardt Employee of: UCB Pharma, D. Wallace Consultant for: Bristol-Myers Squibb, Genentech and Biogen IDEC Inc, GlaxoSmithKline, Human Genome Sciences, Inc., C. Gordon Grant/research support from: Aspreva, Consultant for: Aspreva, Bristol-Myers Squibb, Genentech and Biogen IDEC Inc, Merck Pharmaceuticals, Roche and UCB Pharma