Background SLE is associated with abnormal B cell activity, including elevated titers of IgG and anti-dsDNA antibodies (abs), and decreased complement levels. Atacicept is a fusion protein that inhibits the B cell stimulating factors BLyS and APRIL.
Objectives To analyze changes in biomarkers reflecting disease activity and protective abs in response to atacicept treatment.
Methods Patients with active SLEdefined as≥1 A and/or B BILAG score, and positive for ANA/anti-dsDNA abs, were treated with a corticosteroid taper for 10 weeks. Patients reaching BILAG C or D in all organ systems, and stable for 2 weeks, were randomized at baseline 1:1:1 to receive placebo (PBO) or atacicept 75 or 150 mg. Study drug was given SC twice weekly for 4 weeks, then weekly for 48 weeks.
Results 461 subjects were randomized and analyzed. The 150 mg arm was terminated early due to 2 fatal pulmonary infections. Efficacy and safety data are presented elsewhere. One subject in the 75 mg treatment group developed serum IgG levels below 3 g/L and was discontinued from the study. In neither of the 2 fatal pneumonias did the IgG level decrease below 14.6 g/L (ref range, 5.65-17.65 g/L).
Atacicept induced changes in pharmacodynamic and disease-related markers as shown in the Table. For treatment completers (analyzed at Week 52), the proportion of patients in the PBO, atacicept 75 mg and 150 mg groups whose anti-tetanus abs fell from above protective threshold at baseline to below at Week 52 were 1.9% (2/107), 9.9% (10/101) and 8.8% (5/57). The corresponding values for anti-pneumococcal abs were 3.9% (4/102), 10.4% (11/106) and 10.5% (6/57) respectively. There were no shifts in anti-diphtheria titer status.
Conclusions In subjects who received atacicept, but not PBO, following steroid treatment, there were declines in IgG, IgA, and IgM, as well as mature B cells and plasma cells. In subjects with abnormal values at screening, atacicept was associated with favorable effects on anti-dsDNA and complement levels.
Acknowledgements †An affiliate of Merck KGaA, Darmstadt, Germany
Disclosure of Interest D. Wofsy Consultant for: Merck Serono SA, C. Gordon Consultant for: Merck Serono SA, D. Licu Employee of: Merck Serono SA, S. Copt Employee of: Merck Serono SA, C. Pena Rossi Employee of: Merck Serono SA, D. Isenberg Consultant for: Merck Serono SA