SAT0193 A PHASE 3, OPEN-LABEL, CONTINUATION STUDY EVALUATING LONG-TERM SAFETY AND EFFICACY OF BELIMUMAB IN PATIENTS FROM JAPAN AND KOREA WITH SYSTEMIC LUPUS ERYTHEMATOSUS, FOR UP TO 7 YEARS

Background:Systemic lupus erythematosus (SLE) is an autoimmune disorder more prevalent in the Asian population vs Caucasians. Belimumab (BEL), a monoclonal antibody targeting B-lymphocyte stimulator, is approved in patients (pts) ≥5 years with active, autoantibody-positive SLE.Objectives:Evaluate long-term safety and efficacy of intravenous (IV) BEL + standard SLE therapy (SST) in pts with SLE in Japan/Korea.Methods:In this Phase 3, multicentre, open-label (OL) study (BEL114333;NCT01597622), eligible (≥18 years of age) completers of the double-blind phase of GSK study BEL113750 in Japan and South Korea or the subcutaneous OL phase of GSK Study BEL112341 in Japan, received monthly BEL 10 mg/kg IV plus SST. Primary endpoints: safety assessments. Key secondary endpoints: SRI4 response rate at each scheduled visit (observed data), defined as a ≥4-point reduction from baseline in SELENA-SLEDAI score, no worsening in PGA (<0.3-point increase from baseline) and no new BILAG 1A/2B organ domain scores; time to first severe SFI flare over time. Endpoints were analysed relative to first BEL dose (parent or current study). No follow-up data were collected after study withdrawal.Results:Overall, 142 pts were enrolled (Japan n=72; Korea n=70), 104 (73.2%) completed the study, 1 (0.7%) died and 37 (26.1%) withdrew.Overall, 139 (97.9%) pts had ≥1 adverse event (AE) (Table). Most frequent AEs included: nasopharyngitis (60.6%); headache (28.2%); cough, herpes zoster and viral upper respiratory tract infection (18.3% each). Serious AEs (SAEs) occurred in 48 (33.8%) pts. Most common SAEs were infections and infestations, reported in 24 (16.9%) pts (Table). During this study, the annual incidence of AEs, including SAEs and AESI, remained stable or declined, with no trends of clinical concerns regarding the incidence of Grade 3 or 4 values for laboratory parameters. There was 1 transient positive immunogenicity result of no clinical concern.Table.The proportion of SRI4 responders was 47.8% at Year 1 (Week 24) and tended to increase numerically up to 84.6% at Year 7 (Week 48). The proportion of pts with a ≥4-point decrease from baseline in SELENA-SLEDAI score numerically increased from 51.5% at Year 1 (Week 24) to 84.6% at Year 7 (Week 48). Proportion of pts with no PGA worsening was 91.3-100% and the proportion with no new BILAG 1A/2B organ domain scores was 93.3-100% up to Year 7 (Week 48). A total of 21 (14.8%) pts had 24 severe SFI flares.Conclusion:BEL was well tolerated as add-on therapy to SST for ≤7 years in pts with SLE from Japan/Korea. Safety results were consistent with the known BEL safety profile.Study funding: GSK.Disclosure of Interests:Yoshiya Tanaka Grant/research support from: Received research grants from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Ono, Speakers bureau: Received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Teijin, Sang-Cheol Bae: None declared, Damon Bass Shareholder of: GSK, Employee of: GSK, Myron Chu Shareholder of: GSK, Employee of: GSK, Paula Curtis Shareholder of: GSK, Employee of: GSK, Kathleen DeRose Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Regina Kurrasch Shareholder of: GSK, Employee of: GSK, Jenny Lowe Shareholder of: GSK, Employee of: GSK, Paige Meizlik Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK

SAT0505 PLUTO TRIAL OF INTRAVENOUS BELIMUMAB IN PAEDIATRIC PATIENTS WITH CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS (cSLE): PATIENT RESPONSES OVER TIME

Background:Belimumab (BEL) is a human monoclonal antibody that specifically inhibits B-cell activating factor (BAFF). PLUTO is an ongoing trial evaluating efficacy and safety of intravenous (IV) BEL in children ≥5 years of age with cSLE. Efficacy, and safety endpoints of PLUTO have been reported;1briefly, numerically more BEL vs PBO pts met the primary and major secondary efficacy endpoints. We present patient (pt) response to BEL over time.Objectives:To evaluate changes in SLE Responder Index (SRI) 4 and SRI6 responses, and disease activity over 52 weeks, in paediatric pts receiving BEL, or placebo (PBO), plus standard SLE therapy (SST).Methods:PLUTO (GSK Study BEL114055,NCT01649765) is a Phase 2, randomised, double-blind, placebo-controlled study. Pts 5–17 years of age with active cSLE were randomised to monthly BEL 10 mg/kg IV, or PBO, plus SST. Endpoints assessed: SRI4 and SRI6 response rate, mean percentage and absolute change from baseline in Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLE Disease Activity Index (SLEDAI) and Physicians’ Global Assessment (PGA) scores, and percentage of pts with no new British Isles Lupus Assessment Group (BILAG) 1A/2B organ domain scores compared with baseline, all by study visit. The last-observation-carried-forward (LOCF) principle (missing values imputed using the last available non-missing value) was applied to pts who withdrew or received protocol-prohibited medication or a dose of allowable medication that resulted in treatment failure prior to the Week (Wk) 52 visit. Descriptive statistics were used.Results:A total of 93 pts (94.6% female, mean [SD] age 14.0 [2.49] years) were randomised for the intention-to-treat (ITT) population: 53 to BEL and 40 to PBO. Mean (SD) BEL and PBO baseline scores were 10.3 (3.34) and 10.4 (3.63) for SELENA-SLEDAI and 1.3 (0.43) and 1.4 (0.42) for PGA, respectively. Pt number with at least BILAG 1A/2B organ domain involvement at baseline was 37 (69.8%) for BEL and 29 (72.5%) for PBO. SRI4 and SRI6 responses over 52 weeks were mostly numerically higher with BEL than PBO; more BEL than PBO pts were SRI4 and SRI6 responders at Wk 52 (Figure 1). Unadjusted mean (SE) percentage changes from baseline over time in SELENA-SLEDAI and PGA scores generally favoured BEL over PBO, as did unadjusted mean (SE) absolute changes (Figure 2). Wk 52 adjusted mean (95% CI) percentage treatment difference vs PBO was -4.0% (-21.8, 13.9) for SELENA-SLEDAI and -6.1% (-23.9, 11.7) for PGA, while Wk 52 adjusted mean (95% CI) treatment difference vs PBO was -0.7 (-2.4, 1.1) for SELENA-SLEDAI and -0.1 (-0.3, 0.1) for PGA. Over the study duration, numerically more BEL than PBO pts had no new BILAG 1A/2B organ domain scores (Figure 2).Figure 1.SRI4 and SRI6 response by study visitFigure 2.SELENA-SLEDAI and PGA score mean percentage and absolute change from baseline, and no new BILAG 1A/2B organ domain scores compared with baseline, all by study visitConclusion:In line with the main analyses performed at Wk 52,1further analyses of responses over time in SRI4, SRI6 and disease activity generally favoured BEL over PBO. Combined, these results continue to support the efficacy profile of IV BEL in the treatment of children with cSLE.References:[1]Brunner HI,et al.Arthritis Rheumatol.2018;70(59): 3224–5, Abst. 2867Acknowledgments:We acknowledge all PLUTO investigators (PRINTO, PRCSG and otherwise affiliated). Study funding: GSK.Disclosure of Interests:Nicolino Ruperto Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Eli-Lilly, EMD Serono, GSK, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi and Takeda, Liza McCann: None declared, Syuji Takei Grant/research support from: Eisai, Consultant of: Novartis, Bristol-Myers Squibb, Speakers bureau: GSK, Sanofi, Tanabe-Mitsubishi, Novartis, Chugai, Ono, Abbvie, Eli-Lilly, Bristol-Myers Squibb, Clarissa Pilkington: None declared, Damon Bass Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Mohamed Okily Shareholder of: GSK, Employee of: GSK, Gina Eriksson Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, Hermine Brunner Consultant of: Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer, and UCB Biosciences, Speakers bureau: GSK, Roche, and Novartis

Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials

ObjectiveTo evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity.MethodsData obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) organ domain scores.ResultsAt baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA–SLEDAI, and immunological by SELENA–SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA–SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA–SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA–SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains.ConclusionsBelimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.