Long-Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus: A Continuation of a Seventy-Six-Week Phase III Parent Study in the United States

Abstract

Objective: We undertook this US multicenter continuation study (GlaxoSmithKline study BEL112233; ClinicalTrials.gov identifier: NCT00724867) to assess long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) who completed the Study of Belimumab in Subjects with SLE 76-week trial (ClinicalTrials.gov identifier: NCT00410384).

Methods: Patients continued to receive the same belimumab dose plus standard therapy; patients previously receiving placebo received 10 mg/kg belimumab. The primary outcome measure was long-term safety of belimumab (frequency of adverse events [AEs] and damage assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], evaluated every 48 weeks [1 study year]). Other assessments included the SLE Responder Index (SRI), flare rates (using the modified SLE Flare Index [SFI]), prednisone use, and B cell levels.

Results: Of 268 patients, 140 completed the study and 128 withdrew. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) at baseline was 7.8 ± 3.86. The mean ± SD SDI score increased by 0.4 ± 0.68 from its value at baseline (1.2 ± 1.51). The overall incidence of treatment-related and serious AEs remained stable or declined through study year 7. An SRI response was achieved by 41.9% and 75.6% of patients at the study year 1 and study year 7 midpoints, respectively. At the study year 7 midpoint, relative to baseline, 78.2% had achieved a ≥4-point reduction in the SELENA-SLEDAI score, 98.4% had no new British Isles Lupus Assessment Group (BILAG) A organ domain score and no more than 1 new BILAG B organ domain score, 93.7% had no worsening in the physician's global assessment of disease activity, 20.6% had experienced ≥1 severe SFI flare, the mean decrease in prednisone dose was 31.4%, and the median change in CD20+ B cell numbers was -83.2%.

Conclusion: These long-term exposure results confirm the previously observed safety and efficacy profiles of belimumab in patients with SLE.

© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Figures

Figure 1

Disposition of the systemic lupus erythematosus (SLE) patients and enrollment by treatment in the Study of Belimumab in Subjects with SLE 76‐week (BLISS‐76) trial. This continuation study (GlaxoSmithKline [GSK] study BEL112233) was designed to end either after 5 calendar years from the date of enrollment of the last patient or when fewer than 100 patients remained in the trial, whichever occurred first. Patients at non‐US sites were not eligible for enrollment into this study and had the opportunity to enroll in another open‐label, long‐term continuation study, GSK study BEL112234. For patients who received placebo in the parent study (BLISS‐76; GSK study BEL110751), baseline was the last assessment prior to their first dose of belimumab, at the start of the continuation study. For patients who received belimumab in the parent study, baseline was the latest assessment prior to commencing the parent study. One patient who withdrew from the continuation study reported an adverse event (AE) leading to discontinuation, but the investigator‐recorded reason for withdrawal was “physician decision.”

Figure 2

Efficacy end points. A, Systemic Lupus Erythematosus Responder Index (SRI) response. B, Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) score. C, British Isles Lupus Assessment Group (BILAG) score. In A and B, patients with baseline SELENA–SLEDAI scores of <4 were excluded from the analyses. No new A/2B scores = no new BILAG A organ domain score and no more than 1 new BILAG B organ domain score. D, Physician's global assessment of disease activity (PGA) score. Y1W24 = year 1, week 24.

Figure 3

Mean percentage change from baseline in prednisone dose. Y1W24 = year 1, week 24.