R.F. van Vollenhoven1, O. Zamani2, D.J. Wallace3, D. Tegzova4, J.T. Merrill5, W. Chatham6, A. Schwarting7, F. Hiepe8, A. Doria9, J. Sanchez-Guerrero10, S. Jeka11, A. Dyczek12, R.A. Furie13, M. Petri14, D. D'Cruz15, Z. Fojtik16, L. Pineda17, Z.J. Zhong17, D. Hough17, W. Freimuth17, R. Cervera18, BLISS 76 Study Group. 1The Karolinska Institute, Stockholm, Sweden; 2Rheuma Zentrum Favoriten, Vienna, Austria; 3David Geffen School of Medicine, Cedars-Sinai–UCLA, West Hollywood, CA, United States; 4Inst of Rheumatology, Prague, Czech Republic; 5OMRF, Oklahoma City, OK; 6UAB, Birmingham, AL, United States; 7University Hospital, Rheumatology Ctr, Mainz; 8Charité, Berlin, Germany; 9University of Padova, Padova, Italy; 10INCMNSZ, Mexico City, Mexico; 11SPZOZ, Bydgoszczy; 12Malopolskie Ctr Med, Krakow, Poland; 13NSLIJHS, Lake Success, NY; 14School of Medicine, JHU, Baltimore, MD, United States; 15Rayne Institute, St Thomas Hospital, London, United Kingdom; 16University Hospital, Brno, Czech Republic; 17HGS, Rockville, MD, United States; 18Hospital Clinic, Barcelona, Catalonia, Spain

Objectives: To assess the efficacy and safety of belimumab, a BLyS-specific inhibitor, in seropositive SLE patients.
Methods: In BLISS-76, a 76-wk double-blind, international, phase 3 study, 819 seropositive SLE patients (ANA ≥1:80 and/or anti-dsDNA ≥30 IU/mL) with SELENA-SLEDAI (SS) score ≥6 on stable therapy (≥30 d) were randomized to belimumab (1 or 10 mg/kg iv) plus standard of care (SOC) vs placebo plus SOC on days 0, 14, 28, then q28d for 72 wks. Efficacy analyses included SS, BILAG, and SS Flare Index (SFI). Primary endpoint was % SLE Responder Index (SRI) response at 52 wks: SS improvement (≥4-point decrease), no new BILAG 1 A or 2 B flares, and no >0.3-point Physician's Global Assessment (PGA) worsening vs baseline.
Results: Mean values for baseline disease characteristics across treatment groups were similar: disease duration 7.5 yrs; antimalarial use 63%; steroid use 76% with prednisone-equivalent dose of steroid ≥7.5 mg/d in 46%; immunosuppressant use 56%; proteinuria (>0.5 g/24 hr) 16%; low C4 53%; SS 9.7; BILAG 1 A or 2 B 64%; ANA+ 92%; anti-dsDNA+ 64%. SRI response rates were 34% on placebo, 41% on 1-mg/kg (p=0.104 vs placebo) and 43% on 10-mg/kg belimumab (p=0.021 vs placebo). Significant improvements were also seen in at least 1 of the belimumab groups for: SS ≥4-point reduction; no >0.3-point worsening in PGA; reduction in severe flares; improvement in SF-36 Physical Component Summary (PCS), and FACIT-Fatigue. Statistically significant PGA improvement and steroid dose reduction were not seen with belimumab treatment. Overall AEs, deaths, serious AEs, infections, and lab abnormalities were comparable in the belimumab and placebo groups. Serious or severe infusion reactions were modestly increased with belimumab compared with placebo. Six malignancies occurred (1 on placebo, 3 on 1 mg/kg, 2 on 10 mg/kg).

Conclusion: In BLISS-76, belimumab significantly improved the SRI response rate and reduced SLE disease activity and severe SLE flare rates in seropositive SLE patients. Overall AEs, including serious AEs and infections, were comparable in the belimumab and placebo groups.
Disclosure of Interest: R. van Vollenhoven Grant/Research Support from: Abbott, GSK, HGS, Roche, Schering-Plough/MSD, Wyeth/Pfizer, Consultant for: GSK, HGS, O. Zamani: None Declared, D. Wallace Consultant for: BMS, HGS, Speakers Bureau: BMS, HGS, Amgen, Genentech, UCB, Forest, Abbott, D. Tegzova: None Declared, J. Merrill Grant/Research Support from: HGS, Consultant for: HGS, W. Chatham Grant/Research Support from: HGS, A. Schwarting: None Declared, F. Hiepe Consultant for: HGS, GSK, A. Doria Consultant for: GSK, HGS, Speakers Bureau: Roche, BMS, J. Sanchez-Guerrero: None Declared, S. Jeka: None Declared, A. Dyczek: None Declared, R. Furie Grant/Research Support from: HGS, Consultant for: HGS, M. Petri Grant/Research Support from: HGS, Consultant for: HGS, GSK, D. D'Cruz Grant/Research Support from: HGS, Consultant for: GSK, Z. Fojtik: None Declared, L. Pineda Shareholder of: HGS, Employee of: HGS, Z. Zhong Shareholder of: HGS, Employee of: HGS, D. Hough Shareholder of: HGS, J&J, Pfizer, Employee of: HGS, W. Freimuth Shareholder of: HGS, Employee of: HGS, R. Cervera Consultant for: HGS

Citation: Ann Rheum Dis 2010;69(Suppl3):74

Session: Abstract Session: Lupus, antiphospholipid syndrome and Sjögren's: predictors, pathways, treatment


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