BELIMUMAB (FULLY HUMAN MONOCLONAL ANTIBODY TO BLYS) IMPROVED OR STABILIZED SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) DISEASE ACTIVITY AND REDUCED FLARE RATE DURING 3 YEARS OF THERAPY

R. Furie, M. Petri, M.H. Weisman, E.M. Ginzler, J. McKay, W. Stohl, V. Strand, C.A. Pineau, K. Latinis, J. Zhong, J. Klein, W. Freimuth, LBSL02/99 Study GroupNSLIJHS, Lake Success, NY; JHU, Baltimore, MD; Cedars-Sinai, Los Angeles, CA; SUNY Downstate, Brooklyn, NY; OK Ctr for Arth Ther and Res, Tulsa, OK; USC, Los Angeles, CA; Stanford Univ., Palo Alto, CA; MUHc, Montreal, QC, Canada; Kansas Univ., Kansas City, KS; HGS, Rockville, MD; HGS, Rockville, MD, United StatesObjectives: Assess the effectiveness of belimumab over 3 years therapy in SLE patients using a novel SLE Responder Index (SRI) and traditional SLE disease activity/flare indices.Methods: 449 SLE subjects with SELENA SLEDAI (SS) ≥4 enrolled in a 52 week (wk) double-blind trial of belimumab (1, 4, 10 mg/kg, monthly) vs placebo. At wk 56, all placebo subjects received belimumab (10 mg/kg), whereas belimumab subjects remained on their current dose or increased to 10 mg/kg at the investigator's discretion. At wk 76, all remaining subjects (n=296) received 10 mg/kg in a continuation trial. All subjects were evaluated every 1-3 months using the SS, Physician's Global Assessment (PGA; 0-3 units), BILAG, SLE Flare Index (SFI) and autoantibody titers; however, only seropositive subjects at baseline (ANA ≥1:80 or anti-dsDNA Ab ≥30IU; 72% [n=321]of the original cohort) were included in this analysis. The percentage of subjects who had at least one flare as defined by the SFI was determined for each of the 6 month treatment periods. SRI definition: a) improvement in SS score (≥4 decrease), b) no new BILAG 1A or 2B flares and c) no PGA worsening (<0.3 pt increase). SRI was determined at 6 month intervals.Results: Baseline values in the original cohort (n=449) were: mean SS score=9.6; subjects with ≥1 BILAG A or 2 BILAG B values=68%; mean PGA=1.5; subjects with anti-dsDNA Ab=50%, RNP Ab= 47%, SS-A Ab=39%, aCl Ab=28%. SRI rates in all seropositive subjects treated with belimumab were 46% and 49% at wks 52 and 56, respectively (vs placebo: 29% and 35%; p<0.05). They increased to 55% by wk 76 and were maintained at 55% after 160 wks of therapy (ITT analysis). Of the seropositive subjects who received 160 wks of uninterrupted therapy (n=170), 65% responded as determined by the SRI. The SRI rates at wks 52 and 160 for all subjects with autoantibodies at baseline were: anti-dsDNA (47%, 53%), RNP (42%, 52%), SS-A (41%, 49%), and aCL (51%, 54%). The SRI is more sensitive than the SS alone for detecting clinical improvement with no worsening. In seropositive belimumab-treated subjects, flare rates at wks 28 and 56 were 72% and 62%, respectively (vs placebo 76% and 74%); this rate declined to 7% at 3 years. Parameter response Wk 52 p-value Wk 76 Wk 128 Wk 160 placebo belimumab belimumab belimumab belimumab Subject (ITT LOCF) n=86 n=235 n=235 n=235 n=235 SRI 29.1% 46.0% 0.0058 55.3% 54.0% 55.0%  SS improvement ≥4 39.5% 49.4% 0.1169 57.9% 58.3% 62.1%  No new BILAG 1A/2B 81.4% 91.5% 0.0152 94.0% 93.6% 95.2%  No PGA worsening 76.7% 90.2% 0.0027 92.8% 91.1% 92.1% Flares  Active subjects n=86 n=235 n=187 n=156 n=125  SS Flares 74% 62% NS 57% 31% 7%  Severe SS Flares 11% 8% NS 4% 4% 0% Conclusion: In seropositive subjects, belimumab treatment resulted in sustained improvement in SLE disease activity through 3 years of continuous treatment. The frequency of flares as measured by the SLE Flare Index declined in the 3 years that subjects remained on belimumab therapy.Citation: Ann Rheum Dis, volume 67, supplement II, year 2008, page 53Session: Abstract Session: Lupus – from clinic to new treatments