Journal Article

AB0519 LONG-TERM SAFETY OF BELIMUMAB AMONG ADULT PATIENTS WITH SLE: POOLED DATA FROM THREE OPEN-LABEL EXTENSION STUDIES OVER 11+ YEARS

Wallace, D.J., Khamashta, M., Mian, A., Atsumi, T., Henning, C., Tektonidou, M., Curtis, P., Cervera, R.

2023

Overview

Belimumab is approved for the treatment of systemic lupus erythematosus (SLE) in >75 countries [1]. Clinical trials and long-term extension (LTE) studies have demonstrated the consistent safety profile of belimumab in patients with SLE receiving standard therapy (ST) [2-4]. A pooled analysis of LTE studies could provide a more robust dataset to explore the long-term safety of belimumab. To evaluate the long-term safety of belimumab in adult patients with SLE using pooled data from three multicentre, LTE studies. This post hoc analysis pooled data from three belimumab LTE studies: LBSL02 LTE (Phase 2; GSK Study 112626) [2], BLISS-76 LTE (including US patients only; Phase 3; GSK Study 112233) [3], and BLISS-52 + BLISS-76 LTE (excluding US patients from BLISS-76; Phase 3; GSK Study 112234) [4]. Patients were eligible for LTE studies if they completed treatment through Week 72 (LBSL02 and BLISS-76 trials), or Week 48 (BLISS-52 trial). LBSL02 LTE also required an improvement in physician global assessment at Week 72 or 68 versus at first belimumab dose. From the start of each LTE, all enrolled patients received open-label belimumab 10 mg/kg intravenously every 28 days plus ST, regardless of study drug allocation in prior trials. Adverse events (AEs) were assessed at each infusion visit and summarised (based on observed data) any time post baseline (first belimumab dose in prior trial or LTE), and in each year. In total, 1304 patients were enrolled into the three LTE studies and 1299 (99.6%) received ≥1 dose of study drug (pooled safety population). Cumulative belimumab treated patient-years was 7040.1. Overall, 604 (46.5%) patients completed their respective studies. The main reasons for withdrawal included ‘withdrawal by patient’ (18.3%) and ‘AE’ (10.6%). In the pooled safety population, 1054 (81.1%) and 618 (47.6%) patients received steroids and immunosuppressants at baseline, respectively. Over 11+ years, 1267 (97.5%) patients had ≥1 AE (incidence generally decreased yearly; Table 1), while 525 (40.4%) had ≥1 serious AE (SAE) and 139 (10.7%) experienced ≥1 AE resulting in study drug discontinuation (incidence of each was stable over time). By system organ class, infections and infestations were the most frequent AE, SAE, and AE resulting in study drug discontinuation. The most common AE of special interest was post-infusion systemic reactions (9.7 events per 100 patient-years). There were 21 (1.6%) deaths in total, 3 (0.2%) were considered possibly related to study drug (cardiogenic shock, lung infection pseudomonal, and pneumonia cytomegaloviral [all n=1]). Among a large, pooled population of patients with SLE treated with belimumab plus ST for over 11+ years, the incidence of AEs generally decreased or remained stable over time. No new safety concerns were observed. This analysis was limited by use of a self-selected population that had not withdrawn from prior trials, and the open-label nature of the study. [1]Levy RA et al. Lupus 2021;11:1705–21 [2]Wallace DJ et el. Arthritis Rheumatol 2019;7:1125–34 [3]Furie RA et al. Arthritis Rheumatol 2018;6:868–77 [4]van Vollenhoven RF et al. Rheumatol 2020;2:281–91 Study funded by GSK (GSK Studies 112626, 112233 and 112234). Medical writing support was provided by Robert Bloxham, PhD, Fishawack Indicia Ltd, UK, part of Fishawack Health, and was funded by GSK. Aneela Mian Shareholder of: GSK, Employee of: GSK, Paula Curtis Shareholder of: GSK, Employee of: GSK, christine henning Shareholder of: GSK, Employee of: GSK, MUNTHER KHAMASHTA Shareholder of: GSK, Employee of: GSK, Ricard Cervera Speakers bureau: GSK, Consultant of: GSK, Grant/research support from: GSK, Daniel J. Wallace Speakers bureau: GSK, Consultant of: GSK, Grant/research support from: GSK, Maria Tektonidou: None declared, Tatsuya Atsumi Speakers bureau: GSK, Consultant of: GSK, Grant/research support from: GSK. Table 1Incidence of treatment-emergent AEs over time* (pooled safety population, N=1299)n (%)Any time post baseline†(N=1299)Year 0–1 (N=1299)Year 2–3 (N=1140)Year 4–5 (N=867)Year 6–7 (N=541)Year 8–9 (N=175)Year 10–11 (N=131)Year 11+ (N=88)AEs1267 (97.5)1168 (89.9)907 (79.6)631 (72.8)361 (66.7)160 (91.4)105 (80.2)45 (51.1)Serious AEs525 (40.4)152 (11.7)141 (12.4)91 (10.5)59 (10.9)28 (16.0)14 (10.7)7 (8.0)AEs resulting in study drug discontinuation139 (10.7)18 (1.4)30 (2.6)12 (1.4)8 (1.5)3 (1.7)2 (1.5)0 (0.0)Deaths21 (1.6)3 (0.2)3 (0.3)2 (0.2)2 (0.4)0 (0.0)0 (0.0)0 (0.0)*AEs occurred on or after first belimumab dose (in prior trial or LTE); post hoc data shown for every other year†Post-baseline data include follow-up visits. Data from Year 0 up to last visit in the treatment period are shown by years of study participation. Note: patients may be counted in ≥1 year interval

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Arthritis / Bronchopulmonary infection / Clinical trials / Drug dosages / Drug withdrawal / Immunosuppressive agents / Lupus / Monoclonal antibodies / Patients / Population studies / Safety / Steroid hormones / Stockholders / Systemic lupus erythematosus