AB1079 BELIMUMAB VERSUS PLACEBO IMPROVES DISEASE ACTIVITY AND REDUCES CUMULATIVE GLUCOCORTICOID DOSE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS WHO WERE TREATMENT RESPONDERS: RESULTS OF A LARGE INTEGRATED ANALYSIS
Authors: K. Costenbader, M. Aringer, K. Yamaoka, R. A. Levy, J. H. N. Harris, S. Hadlington, A. S. Carroll, W. Stohl
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The systemic lupus erythematosus (SLE) Responder Index (SRI), a composite outcome, was the primary endpoint in several clinical trials that demonstrated superiority of belimumab (BEL) over placebo (PBO) in patients with SLE on standard therapy (ST).<sup>1–5</sup> In pooled data from these trials, 42% of PBO-treated patients and 55% of BEL-treated patients were SRI responders (BEL vs PBO odds ratio, OR [95% confidence interval, CI]: 1.70 [1.46, 1.98], p&lt;0.0001); leading to a more focused evaluation of potential differences in outcomes between BEL- and PBO-treated responders. Combining three frequently used SLE assessment tools (Safety of Estrogens in Lupus National Assessment–SLE Disease Activity Index [SELENA-SLEDAI], British Isles Lupus Activity Group [BILAG], Physician Global Assessment [PGA]), the SRI consistently measures disease change, and can be used with other SLE disease measures to further differentiate treatment effect, such as change in glucocorticoid (GC) use, which is particularly relevant in the context of the EULAR 2023 guidelines.<sup>6</sup> <h3>Objectives:</h3> To determine whether the degree of response among SRI responders treated with BEL plus ST is greater than in SRI responders receiving PBO plus ST. <h3>Methods:</h3> This <i>post hoc</i> analysis examined pooled data for adults with active SLE from five Phase 3, randomised trials (BLISS-52 [NCT00424476], BLISS-76 [NCT00410384], North East Asia [NCT01345253], BLISS-SC [NCT01484496] and EMBRACE [NCT01632241])<sup>1–5</sup> treated with BEL (10 mg/kg/month intravenously or 200 mg/week subcutaneously) or PBO, plus ST. SRI responders met the following at Week 52: ≥4-point reduction in SELENA-SLEDAI score, no new BILAG A, ≤1 BILAG B, and no worsening of PGA. We evaluated the change from baseline to Week 52 in: SELENA-SLEDAI, clinical SELENA-SLEDAI (excludes serology), time to first severe SELENA-SLEDAI flare index (SFI) flare, and GC use, in SRI responders treated with BEL versus PBO, plus ST. <h3>Results:</h3> Of 1512 SRI responders (BEL, n=1011; PBO, n=501), 95% and 94% were female and mean (standard deviation, SD) age was 36.4 (11.4) and 37.4 (11.7) years, respectively (<b>Table 1</b>). Further baseline characteristics, including SLE disease duration, SELENA-SLEDAI score and medication use are presented in <b>Table 1</b>. More BEL than PBO SRI responders had a ≥5-, ≥6-, ≥7- and ≥8-point reduction in SELENA-SLEDAI score from baseline to Week 52: BEL vs PBO ORs (95% CIs): 1.60 (1.23, 2.07), p=0.0004; 1.45 (1.12, 1.87), p=0.0043; 1.31 (1.03, 1.66), p=0.0304; and 1.34 (1.05, 1.71), p=0.0198, respectively (<b>Table 2</b>). Differences between treatment groups for clinical SELENA-SLEDAI score were not statistically significant. BEL-treated SRI responders had greater mean cumulative GC dose reduction than PBO-treated responders (p=0.0170). Similar proportions of BEL-treated (n=49/1011, 4.8%) and PBO-treated (n=25/501, 5.0%) SRI responders experienced a severe SFI flare, and BEL vs PBO time to first severe SFI flare hazard ratio (95% CI) was 0.99 (0.61, 1.61), p=0.9582. <h3>Conclusion:</h3> SRI responders treated with BEL plus ST achieved both a greater degree of response on disease activity and significant reduction in GC use, compared with those receiving PBO plus ST but had a similar risk of having a severe SFI flare. This large analysis provides further evidence for the added benefit of BEL for patients with active SLE. <h3>REFERENCES:</h3> [1] Navarra SV, et al <i>Lancet</i> 2011;377:721 [2] Furie R, et al <i>Arthritis Rheum</i> 2011;63(12):3918 [3] Zhang F, et al <i>Ann Rheum Dis</i> 2018;77:355 [4] Stohl W, et al <i>Arthritis Rheum</i> 2017;69(5):1016 [5] Ginzler E, et al <i>Arthritis Rheum</i> 2022;74(1):112 [6] Fanouriakis A, et al <i>Ann Rheum Dis</i> 2024;83:15 <h3>Acknowledgements:</h3> This analysis was funded by GSK. Editorial support (GSK-funded): Tasmin Long, PgCert, and Evelin O. Szalai, PhD, Fishawack Indicia Ltd, UK, part of Avalere Health. <h3>Disclosure of Interests:</h3> Karen Costenbader GSK, BMS, Amgen, AstraZeneca, Cabaletta Bio, Gilead, Exagen, Merck, Martin Aringer GSK, GSK, Kunihiro Yamaoka GSK, GSK, Pfizer, Astellas, AYUMI, Chugai, Mitsubishi-Tanabe, Eisai, Roger A. Levy GSK, GSK, Julia H. N. Harris GSK, GSK, Sam Hadlington GSK, Angela S. Carroll GSK, GSK, William Stohl Investigator-initiated from GSK.