0979: Belimumab Effects on Skin in Patients with Systemic Lupus Erythematosus: A Pooled Post Hoc Analysis of Five Phase 3, Randomized, Placebo-Controlled Clinical Trials

Susan Manzi¹, Jorge Sanchez-Guerrero², Naoto Yokogawa³, Joerg Wenzel⁴, Josephine C. Ocran-Appiah⁵, Munther Khamashta⁶, Julia H N Harris⁷, Bernie Rubin⁸, Norma Lynn Fox⁹, Roger A Levy¹⁰ and Victoria Werth¹¹, ¹Allegheny Health Network, Lupus Center of Excellence, Wexford, PA, ²University of Toronto, Division of Rheumatology, Department of Medicine Mount Sinai Hospital/University Health Network, Toronto, ON, Canada, ³Tokyo Metropolitan Tama Medical Center, Department of Rheumatic Diseases, Tokyo, Japan, ⁴University Hospital of Bonn, Department of Dermatology and Allergy, Bonn, Germany, ⁵GlaxoSmithKline, Clinical Science Immunology, Rockville, MD, ⁶GlaxoSmithKline, Medical Affairs, Dubai, United Arab Emirates, ⁷GlaxoSmithKline, Immunology Biostatistics, Brentford, United Kingdom, ⁸GlaxoSmithKline, US Medical Affairs and Immuno-inflammation, Durham, NC, ⁹GlaxoSmithKline, Clinical Development *At time of study, Collegeville, PA, ¹⁰GlaxoSmithKline, Global Medical Affairs, Collegeville, PA, ¹¹Philadelphia VAMC, Philadelphia, PA, USA and Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia

Background/Purpose: Mucocutaneous manifestations affect >80% of patients (pts) with SLE and can contribute to their poor quality of life through unwanted attention, self-consciousness, emotional symptoms, and functional decline.^1,2 There is emerging evidence that belimumab (BEL), in addition to standard therapy (ST), improves mucocutaneous manifestations of SLE.³ This large, integrated analysis further explored the effects of BEL on SLE disease activity within specific manifestations in the mucocutaneous system and vasculitis.

Methods: This post hoc analysis pooled data from five, Phase 3, randomized, placebo-controlled BEL trials (GSK Studies BLISS-76, BLISS-52, BLISS-NEA, BLISS-SC, and EMBRACE). Adults with SLE and a SELENA-SLEDAI score of either ≥8 (BLISS-NEA, BLISS-SC, EMBRACE) or ≥6 (BLISS-52, BLISS-76), with no selection or exclusion for any specific type of skin or vasculitic lesion at screening, were randomized to either BEL (10 mg/kg/month intravenously or 200 mg/week subcutaneously) or placebo (PBO), plus ST. The effect of BEL vs PBO on disease activity within the mucocutaneous organ system and vasculitis was measured every four weeks in the modified intention-to-treat population using items from both the SELENA-SLEDAI and the BILAG indices. Treatment differences in item resolution at Week 52 in pts with the item present at baseline (BL) were analyzed using Fisher’s exact test, provided there were at least 20 pts per arm with the item present at BL.

Results: Of 3086 included pts (BEL, n=1869; PBO, n=1217), 94.4% were female, mean (standard deviation) age was 37.0 (11.6) years (Table 1). Most pts had mucocutaneous manifestations at BL (SELENA-SLEDAI, 85.0%; BILAG [category A or B, moderate or severe activity]: 59.6%) (Table 1). At Week 52, significantly more BEL than PBO pts experienced improvements in SELENA-SLEDAI (59.4% vs 49.2%; treatment difference vs PBO 10.3%; p< 0.0001) and BILAG (54.1% vs 43.1%; treatment difference vs PBO 11.0%; p< 0.0001) mucocutaneous domains. Significant treatment differences were found in favor of BEL at Week 52 for four SELENA-SLEDAI items (vasculitis, rash, alopecia, and mucosal ulcers) and nine BILAG items (mild maculopapular eruption, localized active discoid lesions, mild alopecia, small mucosal ulceration, malar erythema, subcutaneous nodules, swollen fingers, major cutaneous vasculitis [including ulcers], and minor cutaneous vasculitis). For SELENA-SLEDAI, the largest BEL vs PBO treatment difference (25.4%) was for the vasculitis item (p<0.0001) and for BILAG; the largest BEL vs PBO treatment difference (34.1%) was for the major cutaneous vasculitis item (p=0.0039; Table 2).

Conclusion: Compared with ST alone, pts with SLE treated with BEL plus ST experienced significant improvements in specific manifestations of the mucocutaneous organ systems and vasculitis. This large integrated analysis of five Phase 3 clinical trials supports the efficacy of BEL in common mucocutaneous manifestations of SLE.Funding: GSKReferences¹Justiz Vaillant AA, et al. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2022²Yan D, et al. Lupus Sci Med. 2021;8: e000444³Tanaka Y, et al. Mod Rheumatol. 2020;30:313–20
Table 1. Patient demographics and clinical characteristics at baseline (modified intention-to-treat population, Nf3086).

*Age was imputed when full date of birth was unavailable. †A=requires disease modifying treatment, B=mild reversible problems requiring only symptomatic therapy, C=stable mild disease, D=previously affected but currently inactive, E=system never involved.

Table 2. Proportions of patients demonstrating resolution in SELENA-SLEDAI and BILAG mucocutaneous and vasculitis items at Week 52 in patients with the item present at baseline (modified intention-to-treat population; Nf3086).

*Post hoc analyses of pooled data were not sufficiently powered to examine the treatment effect of BEL on individual items and adjustments were not made for multiple comparisons; nominal p-values are provided for pairwise comparison of results between the BEL and PBO group.
Disclosures: S. Manzi, AstraZeneca, GlaxoSmithKline (GSK), Exagen Diagnostics Inc, AbbVie, HGS, Cugene, Lilly, UCB Advisory Board, Lupus Foundation of America; J. Sanchez-Guerrero, Biogen, EMD Serono, Janssen; N. Yokogawa, AbbVie, Asahi Kasei, AYUMI, BMS, Chugai, GlaxoSmithKline (GSK), Mitsubishi Tanabe, Ono, Takeda; J. Wenzel, GlaxoSmithKline (GSK); J. Ocran-Appiah, GlaxoSmithKline (GSK); M. Khamashta, GlaxoSmithKline (GSK); J. Harris, GlaxoSmithKline; B. Rubin, GlaxoSmithKline (GSK); N. Fox, GlaxoSmithKline (GSK), GlaxoSmithKlein(GSK); R. Levy, GlaxoSmithKline (GSK); V. Werth, GlaxoSmithKline, CLASI.