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OP0044 Effects of Atacicept on Disease Activity in Patients with Moderate to Severe Systemic Lupus Erythematosus: APRIL-SLE Randomized Trial
  1. C. Gordon1,
  2. D. Isenberg2,
  3. Y. Li3,
  4. S. Wax4,
  5. D. Wofsy5,
  6. C. Pena Rossi6
  1. 1Rheumatology Research Group, School of Immunity and Infection, University of Birmingham, Birmingham
  2. 2Centre for Rheumatology, University College London, London, United Kingdom
  3. 3R&D Global BioStatistics
  4. 4Global Clinical Development Center, Immunology, EMD Serono Inc, Rockland
  5. 5Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, United States
  6. 6Merck Serono S.A, Merck Serono S.A, Geneva, Switzerland

Abstract

Background Atacicept is a fusion protein that inhibits B-cell stimulating factors BLyS and APRIL. Levels of these factors are elevated in systemic lupus erythematosus (SLE). Atacicept 150 mg (A150) was associated with a reduction of BILAG A and B flares in APRIL-SLE study.

Objectives We examined the efficacy of atacicept in preventing flares of SLE disease activity by BILAG organ system and by modified SELENA SLEDAI flare index and assessed corticosteroid use during a previously reported trial of atacicept versus placebo.

Methods Subjects with active SLE (≥1 BILAG A and/or B) were recruited and treated with corticosteroid taper for 12 weeks. Only subjects reaching BILAG C or D at weeks 10 and 12 were randomized then at baseline 1:1:1 to receive placebo (PLC), atacicept 75 mg (A75) or 150 mg (A150) twice weekly for every 4 weeks then weekly for 48 weeks. All patients received standard of care (SOC). The analysis was performed in the modified intention-to-treat (mITT) population (all subjects who received study medication). BILAG and SELENA SLEDAI flares and corticosteroid usage were assessed 4 weekly.

Results The A150 arm was terminated early due to 2 fatal pulmonary infections. A lower proportion of subjects with ≥1 BILAG system A or B flare was observed in A150, A75, vs PLC: 30/144 (20.8%), 61/157 (38.9%) vs 64/154 (41.6%). The proportion of subjects with a BILAG flare in each organ system was reduced in A150 compared to PLC, with the exception of vasculitis, which had a similar proportion between groups. BILAG flares (A or B) were most commonly observed in mucocutaneous in PLC, A75, and A150: 27/154 (17.5%), 33/157 (21.0%), and 13/144 (9.0%) and musculoskeletal systems 28/154 (18.2%), 34/157 (21.7%), and 13/144 (9.0%). Proportions of subjects who had severe SELENA SLEDAI flare1 during treatment in a post-hoc analysis were 19%, 11% (OR 0.50, p=0.05), and 13% (OR 0.49, p=0.04) for PLC, A75, and A150, respectively. There was a dose proportional decrease in the number of subjects who had at least one increase in steroid dose, as well as in the number who had an increase of ≥20 mg/day (Table).

Table 1.

Corticosteroid exposure post-randomization, mITT population

Conclusions A reduction of individual BILAG system and severe SELENA SLEDAI flares was associated with A150 treatment. A150 was also associated with a reduction in corticosteroid use. These results warrant further studies to further assess the safety and efficacy of atacicept in SLE patients.

References

  1. Buyon J et al. Ann Intern Med 2005;142:953–62.

Acknowledgements Merck Serono S.A. Geneva, Switzerland: an affiliate of Merck KGaA, Darmstadt, Germany.

Disclosure of Interest C. Gordon Consultant for: Merck Serono S.A., D. Isenberg Consultant for: Merck Serono. S.A., Y. Li Employee of: EMD Serono Inc, S. Wax Employee of: EMD Serono Inc, D. Wofsy Consultant for: Merck Serono S.A., C. Pena Rossi Employee of: Merck Serono. S.A.

DOI 10.1136/annrheumdis-2014-eular.4384

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