OP0281 PHARMACODYNAMIC EFFECT OF SEQUENTIAL BELIMUMAB (BEL) AND RITUXIMAB (RTX) THERAPY IN PATIENTS (PTS) WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): THE PHASE 3, RANDOMISED, PLACEBO-CONTROLLED BLISS-BELIEVE STUDY

Background BEL is approved for active SLE and lupus nephritis (adults only). Despite failed trials, 1 RTX remains in the treatment armamentarium. Sequential therapy offers a promising strategy to target B cells by distinct but complementary mechanisms. Objectives To assess pharmacodynamic effects of single cycle on immunologic biomarkers adults with SLE. Methods In this 104-week (wk) study ( NCT03312907 ), all pts received subcutaneous 200 mg/wk 52 wks. Pts were randomised receive intravenous (IV) 1000 mg at Wks 4 + 6 (BEL/RTX), IV PBO (BEL/PBO), or continued standard (BEL/ST). For BEL/RTX BEL/PBO pts, 52-wk treatment-free observational phase followed phase; BEL/ST 104 Changes from baseline (BL) anti-dsDNA C3/C4 levels, counts total (CD19 ) B-cell subsets (CD20 ; naïve; memory; activated B-cells), analysed. Results 292 ≥1 dose (BEL/PBO n=72; n=144; n=76). assessed Wk 52, reductions BL levels seen 3 groups significant difference between (p=0.0495). increased groups, trends greater increases versus (Table 1). At most decreased 1), differences (p<0.0001 all). During observation period, repopulation CD19 (comprising mostly naïve CD20 CD27 - towards was evident BEL/RTX, while low circulating memory cell remained relatively unchanged Table 1. Absolute changes completers* Median (25 th , 75 percentile Change n=54 n=102 n=58 n=24 n=44 n=50 Anti-dsDNA (IU/ml -9 (-83, 1) -51 (-155, -3) -5 (-61, 0) -9.5 (-197, 2) -55 (-329, -2) -6.5 (-57, -1) C3 (md/dl 8.5 (-8, 21) 15 † (0, 30) 1‡ (-6, 11) (-5.5, 19.5) 11 (-7, 27) 7.5 (-5, 23) C4 2 5) (2, 9) 2‡ (-1, 4) 1.5 (-1.5, 4.5) 8) (1, (cells/ml n=48 n=93 n=55 n=20 n=40 n=47 -57,570 (-120,810, -5861) -95,313 (-193,946, -44,240) -57,399 (-152,403, -12,562) -41,343 (-105,789, 23,819) -11,932 (-77,822, 45,773) -48,783 (-151,528, -15,603) -58,112 (-110,681, -3126) -93,482 (-189,567, -42,636) -57,428 (-147,094, -3590) -40,773 (-95,658, 25,547) -3986 (-75,942, 49,021) -45,110 (-143,321, -15,063) Naïve -60,929 (-112,623, -15,316) -61,405 (-152,261, -28,496) -62,477 (-142,009, -16,191) -22,210 (-72,131, 28,335) 6941 (-62,669, 67,355) -51,254 (-142,712, -14,736) Activated CD95 -5012 (-12,701, 278) -9991 (-17,900, -5560) -3895 (-10,068, -1347) -3834 (-13,274, 1490) -5821 (-11,216, -233) -5641 (-14,810, -3341) Memory 9,586 (1500, 30,983) -15,076 (-42,880, -6376) 5532 (-146, 14,393) -13,927 (-24,816, -3064) -11,534 (-25,646, -2958) -1229 (-8466, 7300) *Excluded analysis: who discontinued investigational product before if 104, re-started after 53; †n=101; ‡n=57. Conclusion An improvement generally observed across antibodies following BEL/ST. We believe that induced window subsequent marked reduction other subsets. Our findings underscore need better understanding bridge clinical outcomes, given did not show an disease control over BEL/PBO. References [1]Aranow C, et al. Arthritis Rheumatol 2021;73 (suppl 10). Acknowledgements This analysis GSK Study 205646 funded GlaxoSmithKline (GSK). Medical writing support provided Nicholas Thomas, PhD, Fishawack Indicia Ltd. UK, part Health, GSK. Disclosure Interests Y.K. Onno Teng Consultant of: GSK, Aurinia Pharmaceuticals, Novartis, KezarBio, Otsuka, Vifor Pharma, Grant/research from: Andre van Maurik Shareholder Employee Kenneth L Clark Norma Lynn Fox Yun Irene Gregan James Groark Robert Henderson Josephine Ocran-Appiah David Roth Don Shanahan Paul-Peter Tak Cynthia Aranow BMS, Kezar,