Background Treatment with epratuzumab, a humanized monoclonal antibody targeting CD22 on B cells, has been associated with improvements in disease activity in patients (pts) with moderate-to-severe systemic lupus erythematosus (SLE) with an acceptable safety/tolerability profile and moderate reductions in B cell levels.
Objectives To assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of epratuzumab in Japanese pts with moderate-to-severe SLE in addition to standard of care treatments.
Methods Japanese pts were randomized 1:1:1:1:1 to placebo (PBO) or epratuzumab (100mg/400mg/1200mg every other week [wk] [Q2W] or 600mg every wk [QW]) for a 4-wk dosing period at the beginning of the 12-wk study. Pts had moderate-to-severe SLE (BILAG A disease activity in ≥1 or BILAG B disease activity in ≥2 body systems). Levels of plasma epratuzumab, human anti-human antibodies (HAHA) to epratuzumab, B cells, T cells and mean fluorescence intensity (MFI) of B cell CD22 were measured and results summarized using descriptive statistics. PK parameters were computed by non-compartmental methods. Adverse events (AEs) and laboratory parameters were assessed.
Results 19 of 20 randomized pts (95.0%) completed the study; 1 pt (1200mg Q2W group) discontinued due to an AE. PK appeared to be linear: after first and last epratuzumab infusion Cmax and AUCτ increased proportionally to dose (Table). t1/2 was approximately 13 days and similar across groups. No pts were HAHA positive during the study (antibody concentration >2-fold the limit of quantitation; 62ng/mL). There were small-to-moderate decreases in total B cell (CD20+) counts in all epratuzumab groups (median change from baseline: -43.2% to 10.0%), no trend was seen with dose or regimen. Total T cell (CD3+) counts showed no consistent trends in any treatment group. A pharmacological effect on median CD22 MFI was observed in all epratuzumab groups: Wk1 median change from baseline was -3360 to -4092 on total B cells (CD19+CD22+) and -2147 to -2805 on memory B cells (CD19+IgD+CD27+). Decreases were maintained in 400mg Q2W/1200mg Q2W/600mg QW groups whilst increasing towards baseline in the 100mg Q2W group after Wk4 (median change on memory B cells: -954 and -674 at Wks 8 and 12, respectively). All PBO pts and 13/16 epratuzumab pts reported ≥1 AE, all mild-moderate in intensity. Most commonly reported AEs were in the system organ class of infections and infestation (7/16 pts; 43.8%). Serious AEs were reported in 2/16 pts in epratuzumab treatment groups: 1 incidence each of drug hypersensitivity and Herpes zoster. Epratuzumab was well-tolerated with no new safety signals identified.
Conclusions PK of epratuzumab appeared to be linear after first and last infusions in Japanese pts with moderate-to-severe SLE. Treatment with epratuzumab was associated with downregulation of CD22 as indicated by decreased CD22 MFI, with small to moderate decreases in total B cell count. Epratuzumab was well tolerated in Japanese SLE pts.
Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.
Disclosure of Interest J. Yamamoto Employee of: UCB Pharma, R. Lledo-Garcia Employee of: UCB Pharma, T. Tsuru Consultant for: UCB Pharma, Y. Tanaka Grant/research support: Bristol-Myers Squibb, Mitsubishi-Tanabe, Abbvie, MSD, Chugai, Astellas, Daiichi-Sankyo, Consultant for: Abbott Japan, Abbvie, Asahi-Kasei, Astellas, Astra-Zeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, MSD, Pfizer, Takeda, Speakers bureau: Mitsubishi-Tanabe, Eisai, Chugai, Abbott Japan, Astellas, Daiichi-Sankyo, Abbvie, Janssen, Pfizer, Takeda, Astra-Zeneca, Eli Lilly Japan, GlaxoSmithKline, Quintiles, MSD, Asahi-Kasei, T. Koike Consultant for: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin, UCB Pharma, Speakers bureau: UCB Pharma, Pfizer, Chugai, Abbott, Mitsubishi-Tanabe, Takeda, Eisai, Santen, Astellas, Taisho-Toyama, Bristol-Myers Squibb, Teijin and Daiichi-Sankyo