Adverse Events of Special Interest, SLE Medication Utilization, Hospitalizations, and Organ Damage: Results from a Phase 4, Randomized, Double-Blind, Placebo-Controlled, 52-week Study of Belimumab in Adults with Active, Autoantibody-Positive SLE

Saira Sheikh¹, Morton Scheinberg ², Cheng-Chung Wei ³, Dana Tegzova ⁴, William Stohl ⁵, Ricardo Acayaba de Toledo ⁶, Tamara Mucenic ⁷, Mauricio Abello Banfi ⁸, Kathleen Maksimowicz-McKinnon ⁹, Carlos Abud-Mendoza ¹⁰, Sandra Navarra ¹¹, Mercedes Garcia ¹², Ignacio Garcia-De La Torre ¹³, Josep Ordi Ros ¹⁴, Roger Abramino Levy ¹⁵, Damon L Bass ¹⁵, Jorge Ross Terrés ¹⁶, Raj Punwaney ¹⁶, Julia Harris ¹⁷, Alireza Nami ¹⁸, Amy Pierce ¹⁹, Kevin Thorneloe ²⁰, Beulah Ji ¹⁷ and David Roth ¹⁶, ¹University of North Carolina, Chapel Hill, NC, ²Centro de Pesquisas Clinicas do Hospital Abreu Sodré, São Paulo, Brazil, ³Chung Shan Medical University, Taichung City, Taiwan (Republic of China), ⁴Institute of Rheumatology, Prague, Czech Republic, ⁵University of Southern California Keck School of Medicine, Los Angeles, CA, ⁶Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil, ⁷Hospital Moinhos Angeles de Vento, Porto Alegre, Brazil, ⁸Centro Integral de Reumatología del Caribe, Barranquilla, Colombia, ⁹Henry Ford Hospital, Wayne State University, Detroit, MI, ¹⁰Hospital Central “Dr Ignacio Morones Prieto”, Unidad Regional de Reumatologia y Osteoporosis, Hospital Central and Facultad de Medicina de la Universidad Autónoma de San Luis Potosí, San Luis Potosi, Mexico, ¹¹University of Santo Tomas Hospital, Manila, Philippines, ¹²Hospital San Martín, La Plata, Argentina, ¹³Centro de Estudios de Investigación Básica y Clínica, S.C., Guadalajara, Jalisco, Mexico, ¹⁴Hospital Vall d'Hebron, Barcelona, Spain, ¹⁵GlaxoSmithKline, Collegeville, PA, ¹⁶GSK, Collegeville, PA, ¹⁷GSK, Uxbridge, Middlesex, United Kingdom, ¹⁸Joint Muscle Medical Care and Research Institute, Charlotte, NC, ¹⁹ViiV Healthcare, Research Triangle Park, NC, ²⁰GSK, Collegeville, NC

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: corticosteroids, organ and belimumab, Safety

Session Information

Date: Sunday, November 10, 2019

Title: 3S081: SLE – Clinical I: Clinical Trials (857–862)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Belimumab (BEL), approved in active, autoantibody-positive SLE, has demonstrated a positive efficacy/safety profile while suggesting potential for steroid sparing and reduced organ damage accrual. BASE, a placebo-controlled study, evaluated all-cause mortality and adverse events of special interest (AESIs), and limited efficacy endpoints.

Methods: Adults who met ACR SLE criteria were randomized (1:1) to monthly BEL 10 mg/kg IV or placebo (PBO) plus standard of care for 48 weeks. There was no minimum disease activity required or exclusions for psychiatric conditions, and no protocol mandated corticosteroid (CS) taper or assessment of change in disease activity. For primary endpoints of mortality and AESIs (reported previously), differences in rates (95% CI) were assessed vs PBO on-treatment (first to last dose +28 days). Serious suicidal ideation/behavior and self-injury events on-treatment, and C-SSRS suicidal ideation/behavior on-study (first dose to end of Week 52 follow up) were assessed (differences calculated post hoc). Percentages of patients with baseline CS dose >7.5 mg/day whose dose to treat SLE reduced by ≥25% to ≤7.5 mg/day (Weeks 40‒52), SLE immunomodulator use (baseline vs treatment completion), study hospitalizations, and organ damage accrual (Week 52), were assessed.

Results: Baseline demographics and disease activity/characteristics were similar between groups. All-cause mortality was also similar (Figure); most deaths were due to infections (9 [0.45%] BEL, 3 [0.15%] PBO). On-study deaths occurred in 13 (0.65%) BEL and 22 (1.10%) PBO patients (difference [95% CI]: –0.45 [–1.03, 0.13]). Rates of on-treatment AESIs were similar, except for serious depression and serious infusion/hypersensitivity reactions (Figure).

On-treatment serious suicidal ideation/behavior and self-injury sponsor-adjudicated events occurred in 15 (0.75%) BEL and 5 (0.25%) PBO patients (difference [95% CI]: 0.50 [0.06, 0.94]); on-study suicidal ideation/behavior (C-SSRS) occurred in 48 (2.43%) BEL and 39 (1.96%) PBO patients (difference [95% CI]: 0.47 [–0.44, 1.38]). There were no suicide-related deaths.

Efficacy endpoints were assessed in those receiving ≥1 dose (intent-to-treat; 2001 BEL, 2002 PBO). More BEL vs PBO patients had a SLE CS dose reduction (Table). SLE immunomodulator use did not change vs baseline. Hospitalizations were similar between groups. BEL impact on organ damage, if any, was minimal.

Conclusion: In the largest, double-blind, placebo-controlled SLE study to date, on-treatment all-cause mortality, infection, and malignancy AESI rates were similar between BEL and PBO; imbalances were observed in serious depression, serious suicidal ideation/behavior and self-injury events, and serious infusion/hypersensitivity reactions. BEL reduced SLE CS use in high-dose patients; the effect was small and without supporting parallel disease activity measures. There was no change in SLE immunomodulator use, no differences in hospitalizations, and organ damage impact was minimal, as in other BEL studies.

We acknowledge the BASE participants and Study Group. Study funding: GSK. Medical writing support: Louisa McKay, PhD, Fishawack Indicia Ltd, UK (funded by GSK).

Figure: Prespecified AESI endpoints in the BASE study -on-treatment period: as-treated population-

Table. Efficacy endpoints in the BASE study -ITT population-

Disclosure: S. Sheikh, GSK, 5; M. Scheinberg, None; C. Wei, AbbVie, 2, 5, BMS, 2, 5, Celgene, 2, 5, Chugai, 5, Eisai, 5, Janssen, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, Sanofi-Aventis, 5, TSH Biopharm, 2, 5, UCB Pharma, 2, 5; D. Tegzova, None; W. Stohl, GlaxoSmithKline, 2, Janssen R&D, 5, Janssen Research & Development, 5; R. Acayaba de Toledo, GlaxoSmithKline, 2, AbbVie, 2, 5, Pfizer, 2, Roche, 2, Novartis, 2, 8, Janssen, 5, 8, UCB Pharma, 8; T. Mucenic, GlaxoSmithKline, 2, Janssen, 2, 5, 8, Roche, 2, 5, 8, Eli Lilly, 2, Pfizer, 2, 8, Amgen, 2, UCB Pharma, 5, 8, Novartis, 5, 8, AbbVie, 8; M. Abello Banfi, None; K. Maksimowicz-McKinnon, AstraZeneca, Gilead, GSK, Merck, 9, ChemoCentryx, 5; C. Abud-Mendoza, Pfizer, 5, 8, Eli Lilly, 5, 8, Takeda, 5, 8; S. Navarra, Abbott, 8, Abbott, Astellas, Johnson & Johnson, Novartis, Pfizer, 8, Astellas, 8, Johnson & Johnson, 8, Novartis, 8, Pfizer, 8; M. Garcia, None; I. Garcia-De La Torre, None; J. Ordi Ros, GlaxoSmithKline, 5; R. Levy, GlaxoSmithKline, 1, 3, 4; D. Bass, GlaxoSmithKline, 1, 3, 4; J. Ross Terrés, GlaxoSmithKline, 1, GlaxoSmithKline at the time of study, 3; R. Punwaney, GlaxoSmithKline, 1, 3; J. Harris, GlaxoSmithKline, 1, 3, 4; A. Nami, None; A. Pierce, GlaxoSmithKline, 1, 4, ViiV Healthcare, 3; K. Thorneloe, GlaxoSmithKline, 1, 3, 4; B. Ji, GlaxoSmithKline, 1, 3, 4; D. Roth, GlaxoSmithKline, 1, 3, 4.

To cite this abstract in AMA style:

Sheikh S, Scheinberg M, Wei C, Tegzova D, Stohl W, Acayaba de Toledo R, Mucenic T, Abello Banfi M, Maksimowicz-McKinnon K, Abud-Mendoza C, Navarra S, Garcia M, Garcia-De La Torre I, Ordi Ros J, Levy R, Bass D, Ross Terrés J, Punwaney R, Harris J, Nami A, Pierce A, Thorneloe K, Ji B, Roth D. Adverse Events of Special Interest, SLE Medication Utilization, Hospitalizations, and Organ Damage: Results from a Phase 4, Randomized, Double-Blind, Placebo-Controlled, 52-week Study of Belimumab in Adults with Active, Autoantibody-Positive SLE [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/adverse-events-of-special-interest-sle-medication-utilization-hospitalizations-and-organ-damage-results-from-a-phase-4-randomized-double-blind-placebo-controlled-52-week-study-of-belimumab-in/. Accessed .

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