Long-term open-label continuation study of the safety and efficacy of belimumab for up to 7 years in patients with systemic lupus erythematosus from Japan and South Korea

Abstract

Objectives: To evaluate the long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) from Japan and South Korea.

Methods: In this phase III, open-label continuation study (BEL114333; NCT01597622), eligible completers of BEL113750 (NCT01345253) or BEL112341 (NCT01484496) received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint was safety. Secondary endpoints: SLE Responder Index (SRI)4 response rate, proportion of patients meeting individual SRI4 criteria, SLE flares and prednisone use. Analyses were based on observed data from the first belimumab exposure (either in parent or current study) through to study end.

Results: Of 142 enrolled patients who received belimumab, 73.2% completed the study. The study population comprised patients with moderate SLE, mean (SD) Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) baseline score of 9.3 (3.9) and 98.6% receiving corticosteroids. Most patients (97.9%) experienced adverse events (AEs); 33.8% experienced serious AEs. Increase in SRI4 (Year 1, Week 24: 47.8%; Year 6, Week 48: 68.2%) and SELENA-SLEDAI responders suggested reductions in disease activity. Proportions of patients with no worsening in Physician Global Assessment/no new organ damage remained stable throughout. Severe SLE flares occurred in 14.8% of patients. Among patients with baseline prednisone-equivalent dose >7.5 mg/day (n=81), the median (min, max) number of days anytime post-baseline that the daily dose was ≤7.5 mg/day or had been reduced by 50% from baseline was 584 (0, 2267).

Conclusions: Favourable safety profile and treatment responses were maintained for ≤7 years in patients with SLE from Japan and South Korea.

Keywords: B-lymphocytes; biological therapy; cytokines; lupus erythematosus; systemic.

Figure 1

Study design. Note: Due to the additional 6-month open-label extension for SC patients entering BEL114333, there is a 6-month offset in the data capture between the parent studies. C3/C4, complement 3/4; SC, subcutaneous; SELENA-SLEDAI, Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index; SLE, systemic lupus erythematosus.

Figure 2

Patient disposition. *One screened patient in the belimumab treatment group did not enter BEL114333 due to a serious AE of chronic pancreatitis which started during the parent Study BEL113750. Note: Study completers included all patients who transferred to a different protocol or who were still participating in the study at the time of the sponsor decision to close the study when belimumab became commercially available in Japan and South Korea. There were eight adverse events (AEs) resulting in the withdrawal of seven patients from the study: spontaneous abortion, ALT increased, angiocentric lymphoma, AST increased, asphyxia, pleurisy, bacterial pneumonia and skin ulcer. ALT, alanine aminotransferase; AST, aspartate aminotransferase; IV, intravenous.

Figure 3

SRI4 response rate during belimumab treatment over time (safety population, N=142). Baseline was defined as the last available value prior to belimumab initiation: Day 1 of the parent study for patients randomised to belimumab and Week 52 of the parent study for patients randomised to placebo. SLE, systemic lupus erythematosus; SRI, SLE Responder Index.