Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension

Abstract

Objective: This extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual.

Methods: In this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period.

Results: A total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual.

Conclusion: Belimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years.

Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).

Keywords: belimumab; long-term treatment; organ damage; safety; systemic lupus erythematosus.

Fig. 1

Patient recruitment and attrition Patient disposition (A) and withdrawals per study year (B) of the six patients who were reported as withdrawing due to lack of efficacy; details are only available for three patients. These patients were withdrawn by their physicians due to disease flare ups.

Fig. 2

Cumulative AE incidence over time AE: adverse event; SAE: serious AE. ^aExcept non-melanoma skin cancer.

Fig. 3

Percentage of patients with SDI changes at week 48 of each study year Analyses are categorized by: (A) mITT and HDA populations, (B) baseline SELENA-SLEDAI score ≤9 or ≥10, (C) age at disease onset <18 or ≥18 years and (D) baseline SDI score 0 or ≥1. Data labels denote the number of patients in each group. HDA: high disease activity; mITT: modified intent-to-treat population; SDI: SLICC/ACR Damage Index; SELENA-SLEDAI: Safety of Estrogens In Lupus Erythematosus National Assessment-SLEDAI.

Fig. 4

Percentage of patients experiencing any change in prednisone dose from baseline Lines and data labels indicate percentage and number of patients, respectively, who required a change in baseline prednisone dose at each time point.