AB1033 UNDERSTANDING THE IMPACT OF BELIMUMAB ON EARLY (≤2 YEARS) SYSTEMIC LUPUS ERYTHEMATOSUS IN ADULTS: BeEARLY, A PHASE 4, PROSPECTIVE, OPEN-LABEL STUDY
Authors: M. Petri, K. Costenbader, M. Mosca, S. Collingborn, R. A. Levy, C. O’shea, H. A. Quasny
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Approximately 40% of patients with systemic lupus erythematosus (SLE) develop organ damage within the first 5 years of diagnosis due to uncontrolled disease activity and cumulative steroid exposure, resulting in a greater risk of early mortality.<sup>[1]</sup> Timely intervention with disease-modifying biologics such as belimumab (BEL) in the early stages of SLE might modify the disease course and prevent irreversible organ damage while avoiding the need for high-dose glucocorticoids (GCs) or immunosuppressants (IS). Previous studies suggested that BEL may have benefit when used earlier in the course of the disease, especially in patients with minimal or no organ damage at baseline who received BEL within 2 years of classification.<sup>[2,3]</sup> However, the use of BEL early in the treatment pathway has been limited in clinical practice, with the majority of BEL use following the failure of ≥2 IS. <h3>Objectives:</h3> Present the design of the BeEARLY (BEL in Early SLE) study, which will evaluate the efficacy and safety of BEL in adult SLE patients with early disease. <h3>Methods:</h3> In this Phase 4, prospective, open-label, single-arm, 3-year clinical study (GSK Study 219240), approximately 350 adult patients with active, autoantibody-positive, early SLE (≤2 years since diagnosis) with no organ damage and with inadequate response to initial standard therapy (ST; with/without conventional IS) will be enrolled. Key eligibility criteria are shown in <b>Table 1</b>. Eligible participants will receive open-label BEL 200 mg/week subcutaneously as an add-on to their initial ST for 52 weeks (Part A), with a long-term extension of up to 104 weeks (end of study is the safety follow-up visit after Week 156; Part B). Key primary and secondary endpoints are shown in <b>Table 2</b>. Participants will be required to taper the average oral GC (OGC; prednisone equivalent) dose from Week 12 to ≤7.5 mg/day by Week 26, and to ≤5 mg/day by Week 48 at the discretion of the investigator if they continue to maintain stable disease control on ≤7.5 mg/day. No changes in OGC dose will be permitted between Weeks 48 and 52. An optional taper of concomitant IS may be attempted after the Week 52 study visit (in participants receiving concomitant IS) if the participant has met Definition Of Remission in SLE (DORIS) criteria for ≥6 months. Safety follow-up will continue for 4 weeks after the clinical study intervention is discontinued. Descriptive summaries will be performed for all endpoints. <h3>Results:</h3> Data for the primary endpoint are estimated to be available in 2027. <h3>Conclusion:</h3> This clinical open-label trial will investigate the efficacy and safety of subcutaneous BEL in adults with early, active SLE, using relevant disease activity endpoints such as Lupus Low Disease Activity State (LLDAS)<sup>[4]</sup>, DORIS<sup>[5]</sup> and Cutaneous Lupus Disease Area and Severity Index (CLASI)<sup>[6]</sup> achieved with the prednisone equivalent target dose of ≤5 mg/day. The open-label design was selected as several other treatment options are available, and BEL is an approved biological therapy in the population under study in this proposed trial. It is expected that early administration of BEL will benefit participants' short-term outcomes, such as improvements in disease activity, quality of life, and reduction in OGC use, as well as long-term outcomes, including attainment of remission and prevention of organ damage progression. <h3>REFERENCES:</h3> [1] Urowitz MB, et al <i>Arthritis Care Res</i> 2012;64:132 [2] Gatto M, et al <i>Arthritis Rheumatol</i> 2020;72(8):1314 [3] Petri M, et al <i>Ann Rheum Dis</i> 2022;81:323 [4] Golder V, et al <i>Lancet Rheumatol</i> 2019;1:e95 [5] van Vollenhoven RF, et al <i>Lupus Sci Med</i> 2021;8:e000538 [6] Chakka S, et al <i>Ann Transl Med</i> 2021;9(5):431 <h3>Acknowledgements:</h3> The study (GSK Study 21940) was funded by GSK. Medical writing support was provided by Olga Conn, Fishawack Indicia Ltd, UK, part of Avalere Health, and funded by GSK. <h3>Disclosure of Interests:</h3> Michelle Petri BPR Scientific Advisory Committee, Alexion, Amgen, AnaptysBio, Argenx, AstraZeneca, Aurinia, Biogen, Caribou Biosciences, CVS Health, EMD Serono, Eli Lilly, Emergent Biosolutions, GSK, IQVIA, Janssen, Kira Pharmaceuticals, MedShr, Sanofi, and SinoMab, AstraZeneca, Aurinia, Eli Lilly, Exagen, GSK, Janssen, and Thermofisher, Karen Costenbader GSK, BMS, Amgen, AstraZeneca, Cabaletta Bio, Gilead, Exagen, Merck, Marta Mosca GSK, AstraZeneca, Otsuka, Janssen, AbbVie, Lilly, GSK, AstraZeneca, Otsuka, UCB, AbbVie, Idorsia, GSK, Sophie Collingborn Veramed Is also a complimentary worker on assignment with GSK and a Contractor from Veramed, Roger A. Levy GSK, GSK, Ciara O'Shea GSK, GSK, Holly A. Quasny GSK, GSK.