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THU0387 Effects of Blisibimod, An Inhibitor of B Cell Activating Factor, On Patient Reported Outcomes and Disease Activity in Patients with Systemic Lupus Erythematosus
  1. M. Petri1,
  2. R.S. Martin2,
  3. C. Hislop2,
  4. M.A. Scheinberg3,
  5. R.A. Furie4
  1. 1Johns Hopkins University School of Medicine, Baltimore
  2. 2Anthera Pharmaceuticals, Inc, Hayward, United States
  3. 3Rheumatology Hospital Abreu Sodre Pesquisa Clínica, São Paulo, Brazil
  4. 4North Shore–Long Island Jewish Health System, Great Neck, United States

Abstract

Background Blisibimod (A-623, AMG 623), a potent and selective inhibitor of B-cell activating factor (BAFF), was evaluated in the phase 2b clinical trial PEARL-SC (NCT01162681) in patients with systemic lupus erythematosus (SLE). Effects of blisibimod on disease activity and safety were reported previously [1].

Objectives To conduct secondary endpoint analyses of the effects of subcutaneously-administered blisibimod on patient-reported outcomes from the PEARL-SC trial.

Methods 547 SLE patients who met the ACR classification criteria, had anti-double-stranded DNA or anti-nuclear antibodies, and SELENA-SLEDAI score ≥6 at baseline, were randomized in the PEARL-SC study 1:1 to receive placebo or blisibimod administered at 1 of 3 dose levels, 100 mg weekly (QW), 200 mg QW, or 200 mg every 4 weeks for up to 52 weeks (with a median of 37 weeks) or until the last subject completed 6 months of study drug therapy. Patient self-reported outcomes were evaluated using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and disease activity was evaluated utilizing both SELENA-SLEDAI and BILAG.

Results Significant improvements in measures of disease activity in subjects with severe disease (defined as baseline SELENA-SLEDAI score≥10 and receiving steroids), especially at the highest blisibimod dose of 200mg QW, were reported previously [1]. Approximately 76% of subjects had SELENA-SLEDAI musculoskeletal involvement at enrollment, and 89% of subjects had mucocutaneous involvement. At Week 24, approximately 12% and 39% of subjects randomized to the 200mg QW blisibimod arm had musculoskeletal or mucocutaneous organ involvement, compared with approximately 15% and 42% respectively in the placebo arm (p<0.2 to p<0.05 across manifestations evaluated over Weeks 12 through 24). Improvements in self-reported fatigue were observed amongst subjects randomized to blisibimod based on the FACIT-Fatigue scale, especially in the 200mg QW group (N=80) where favorable effects of blisibimod compared with placebo were observed as early as Week 8, and a mean 6.9-point improvement from baseline was reported at Week 24 compared to 4.4 with placebo (N=229). These effects meet the criteria for minimal clinically-important improvement difference of 5.9 defined by Goligher and colleagues [2] for patients with SLE.

Conclusions Fatigue remains a debilitating manifestation of lupus. In this trial, blisibimod showed a tendency toward improved mucocutaneous and musculoskeletal disease activity as well as patient self-reported fatigue. These data support further evaluation of blisibimod in patients with SLE.

References

  1. Furie RA, Leon G, Thomas M, Petri MA, et al. A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study. Ann Rheum Dis. 2014.

  2. Goligher EC, Pouchot J, Brant R, Kherani RB et al. Minimal clinically important difference for 7 measures of fatigue in patients with systemic lupus erythematosus. J Rheumatol. 2008;35(4):635-42.

Acknowledgements We wish to thank all of the patients, Investigators and clinical teams involved in the PEARl-SC trial.

Disclosure of Interest M. Petri Consultant for: Anthera Pharmaceuticals, R. Martin Shareholder of: Anthera Pharmaceuticals, Employee of: Anthera Pharmaceuticals, C. Hislop Shareholder of: Anthera Pharmaceuticals, Employee of: Anthera Pharmaceuticals, M. Scheinberg: None declared, R. Furie Consultant for: Anthera Pharmaceuticals

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