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OP0119 Pharmacodynamic Effects of Atacicept in SLE Patients: 52-Week Data from the April-SLE Trial
  1. D. Wofsy1,
  2. C. Gordon2,
  3. D. Licu3,
  4. S. Copt3,
  5. C. Pena Rossi3,
  6. D. Isenberg4
  1. 1University of California, San Francisco, San Francisco, United States
  2. 2University Of Birmingham, Birmingham, United Kingdom
  3. 3Merck Serono S.A.†, Geneva, Switzerland
  4. 4University College London, London, United Kingdom

Abstract

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

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