Phase 3, long-term, open-label extension period of safety and efficacy of belimumab in patients with systemic lupus erythematosus in China, for up to 6 years

Abstract

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

Methods: In this phase 3, open-label extension period, eligible completers of study BEL113750 (NCT01345253) received intravenous belimumab 10 mg/kg monthly for ≤6 years. The primary endpoint was safety. Secondary endpoints included the SLE Responder Index (SRI)-4 response rate, severe SLE flares and changes in prednisone use. Analyses were based on observed data from the first dose of belimumab through to study end.

Results: Of the 424 patients who received belimumab, 215 (50.7%) completed the study, 208 (49.1%) withdrew and 1 patient died. Overall, 359/424 (84.7%) patients had adverse events (AEs), and 96/424 (22.6%) had serious AEs. 26/424 (6.1%) patients discontinued study treatment/withdrew from the study due to AEs. Postinfusion systemic reaction rate was 1.5 events/100 patient-years. Herpes zoster infection rate was 3.0 events/100 patient-years, of which 0.4 events/100 patient-years were serious events. One papillary thyroid cancer and one vaginal cancer were reported in year 0-1 and year 3-4, respectively. There were no completed suicides/suicide attempts and no reports of serious depression. The proportion of SRI-4 responders increased progressively (year 1, week 24: 190/346 (54.9%); year 5, week 48: 66/82 (80.5%)). Severe flares were experienced by 55/396 (13.9%) patients. For 335 patients with baseline prednisone-equivalent dose >7.5 mg/day, the number of patients with a dose reduction to ≤7.5 mg/day increased over time (year 1, week 24: 30/333 (9.0%); year 5, week 48: 36/67 (53.7%)).

Conclusions: Favourable safety profile and disease control appeared to be maintained in patients with SLE in China for ≤6 years, consistent with previous belimumab studies.

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

Conflict of interest statement

Competing interests: FZ is a Principal Investigator at GSK. JZ, YL, GW, MW, YS, JG and XL have no conflict of interest to declare. DB, PC, KD, JL, PM and DAR are employees of GSK and hold stocks and shares in the company. MC and RK were employees of GSK and held stocks and shares in the company at the time of study.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Study design.C, complement; IV, intravenous; OL, open-label; SELENA-SLEDAI, Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index; SLE, systemic lupus erythematosus.

Figure 2

(A) Patient disposition and (B) withdrawals per study year (safety population; N=424).*One patient did not receive OL belimumab and was excluded from the safety population. The patient was withdrawn from the OL period due to an ongoing non-SAE that started during the double-blind period (considered by the investigator to be unrelated to study treatment).†Patients who entered the OL period were considered to have completed the OL period of the study if they transferred to another study or were still participating at the time of the sponsor decision to close/terminate the study. Year 4+ represents year 4–5 and year 5–6 of belimumab treatment.OL, open-label; SAE, serious adverse event.

Figure 3

SRI-4 response rate during belimumab treatment over time (efficacy population; N=399).Note: Baseline was defined as the last available value prior to belimumab initiation: day 1 for patients randomised to belimumab in the double-blind period and week 52 for patients randomised to placebo in the double-blind period. The observed proportion of SRI-4 responders was assessed at weeks 24 and 48 visits of each study year. The SRI-4 was defined as a ≥4-point reduction from baseline in SELENA-SLEDAI, no worsening in PGA (<0.3-point increase from baseline), and no new BILAG 1A/2B organ domain scores.BILAG, British Isles Lupus Assessment Group; IV, intravenous; PGA, Physician’s Global Assessment; SELENA-SLEDAI, Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index; SRI-4, Systemic Lupus Erythematosus Responder Index≥4-point reduction in Systemic Lupus Erythematosus Disease Activity Index.

Figure 4

Percentage of patients with and without SDI worsening (change >0) from baseline at week 48 of each study year (efficacy population; N=399).Note: Observed case data are presented. The index is cumulative, once an item had been scored, it continued to be scored at all subsequent visits. Baseline was defined as the last available value prior to belimumab initiation: day 1 for patients randomised to belimumab in the double-blind period and week 52 for patients randomised to placebo in the double-blind period.SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.