Background Epratuzumab is a monoclonal antibody that targets CD22 on B cells. In EMBLEM™ (dose-ranging Phase 2b study [NCT00624351]), and its open-label extension (OLE; SL0008 [NCT00660881]), epratuzumab produced sustained and clinically relevant improvements in disease activity in patients (pts) with moderate-to-severe systemic lupus erythematosus (SLE) as measured by the primary endpoint of the OLE, British Isles Lupus Assessment Group (BILAG) response. BILAG response also forms the basis of the BILAG-Based Composite Lupus Assessment (BICLA), the primary endpoint in EMBLEM™ and in current Phase 3 studies, consisting of BILAG improvement without worsening, no worsening in SLEDAI or Physician Global Assessment (PGA) scores, and no treatment failure.
Objectives To correlate the British Isles Lupus Assessment Group (BILAG) response, a component of the BICLA composite responder index, with clinical and laboratory parameters during open-label therapy with epratuzumab.
Methods Pts from any EMBLEM™ arm (including placebo) completing 12 weeks (wks) of blinded treatment, and those who discontinued due to lack of efficacy but completed ≥8 wks, were eligible for entry into the OLE, in which all pts received 1200mg epratuzumab at Wks 0 and 2 of repeating 12-wk cycles. A post-hoc analysis was undertaken to evaluate the changes in relevant clinical and laboratory parameters in BILAG responders (R) vs non-responders (NR) at OLE Wks 48 and 96 compared to EMBLEM™ baseline. BILAG response was defined as all BILAG A scores at study entry improved to B/C/D; all Bs improved to C/D; no new BILAG A or ≥2 new B scores. Non-response was defined as lack of improvement or worsening; pts who withdrew prior to assessment were also classified as NR.
Results Of 203 pts who entered the OLE, 80 (39%) achieved a BILAG response at Wk48 (123 were non-responders), and 72 (35%) achieved a BILAG response at Wk96 (130 were non-responders; one pt attended the visit but did not record any BILAG component scores and was excluded from the analysis at this timepoint). At both Wks 48 and 96, responders had significantly greater reductions in SLEDAI, PGA and Patient Global Assessment (PtGA) scores, and improvements in greater numbers of BILAG organ domains than non-responders. Although not statistically significant, responders had a greater reduction in concomitant steroid doses. Laboratory parameters associated with BILAG response included greater decreases in absolute B cell (CD19+) and T cell (CD3+) counts, and smaller increases in protein/creatinine ratios. Results are summarized in the table.
Conclusions Pts achieving a BILAG response in the OLE SL0008 study were also more likely to achieve improvements in a range of clinical and laboratory parameters, including SLEDAI, PGA and PtGA scores and absolute B cell (CD19+) and T cell (CD3+) counts. This substantiates the value of the BICLA composite endpoint, the cornerstone of which is BILAG improvement without worsening.
Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.
Disclosure of Interest : R. Furie Consultant for: UCB Pharma, M. Petri Grant/research support: UCB Pharma, Consultant for: UCB Pharma, C. Gordon Consultant for: GlaxoSmithKline, MedImmune, Merck Serono, Paraxel and UCB Pharma, V. Strand Consultant for: UCB Pharma, C. Galateanu Employee of: UCB Pharma, S. Bongardt Employee of: UCB Pharma, W. Koetse Shareholder of: UCB Pharma, Employee of: UCB Pharma, D. Wallace Consultant for: Bristol-Myers Squibb, Genentech, Biogen IDEC Inc, GlaxoSmithKline, Human Genome Sciences Inc, MedImmune, Novo Nordisk, UCB Pharma