OP0068 BELIMUMAB, A BLYS-SPECIFIC INHIBITOR, REDUCES DISEASE ACTIVITY AND SEVERE FLARES IN SEROPOSITIVE SLE PATIENTS: BLISS-76 STUDY

R. F. van Vollenhoven ^1,*O. Zamani ²D. J. Wallace ³D. Tegzova ⁴J. T. Merrill ⁵W. Chatham ⁶A. Schwarting ⁷F. Hiepe ⁸A. Doria ⁹J. Sanchez-Guerrero ¹⁰S. Jeka ¹¹A. Dyczek ¹²R. A. Furie ¹³M. Petri ¹⁴D. D'Cruz ¹⁵Z. Fojtik ¹⁶L. Pineda ¹⁷Z. J. Zhong ¹⁷D. Hough ¹⁷W. Freimuth ¹⁷R. Cervera ¹⁸ and 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).

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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. (NCT00410384)

Disclosure of Interest: R. van Vollenhoven Grant / Research Support from: Abbott, GSK, HGS, Roche, Schering-Plough/MSD, Wyeth/Pfizer Consultant for: GSK, HGSO. Zamani: None DeclaredD. Wallace Consultant for: BMS, HGS Speakers Bureau: BMS, HGS, Amgen, Genentech, UCB, Forest, AbbottD. Tegzova: None DeclaredJ. Merrill Grant / Research Support from: HGS Consultant for: HGSW. Chatham Grant / Research Support from: HGSA. Schwarting: None DeclaredF. Hiepe Consultant for: HGS, GSKA. Doria Consultant for: GSK, HGS Speakers Bureau: Roche, BMSJ. Sanchez-Guerrero: None DeclaredS. Jeka: None DeclaredA. Dyczek: None DeclaredR. Furie Grant / Research Support from: HGS Consultant for: HGSM. Petri Grant / Research Support from: HGS Consultant for: HGS, GSKD. D'Cruz Grant / Research Support from: HGS Consultant for: GSKZ. Fojtik: None DeclaredL. Pineda Shareholder of: HGS Employee of: HGSZ. Zhong Shareholder of: HGS Employee of: HGSD. Hough Shareholder of: HGS, J&J, Pfizer Employee of: HGSW. Freimuth Shareholder of: HGS Employee of: HGSR. Cervera Consultant for: HGS