Background/Purpose:  Intravenous (IV) belimumab 10 mg/kg is approved in patients with active, autoantibody-positive systemic lupus erythematosus (SLE) as add-on to standard SLE therapy (SoC). This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with SLE.

Methods:  This Phase 4, randomized, open-label study (GSK Study 115470; NCT01597492) was conducted at 13 centers in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination 4 weeks prior to (pre-belimumab cohort) or 24 weeks after (concurrent belimumab cohort) commencing 4-weekly belimumab 10 mg/kg IV treatment. All patients received SoC. All analyses of vaccine titer were performed on the as-treated population, defined as all patients who received ≥1 dose of belimumab. The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels or post-vaccination level ≥0.6 μg/mL if pre-vaccination levels were unquantifiable) to ≥1 of the 23 pneumococcal vaccine serotypes 4 weeks post-vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10 of the serotypes. Safety was assessed by monitoring adverse events (AEs).

Results:  A total of 79 patients were enrolled and randomized to receive the pneumococcal vaccine (pre-belimumab cohort, n=34, concurrent belimumab cohort, n=45). The majority (87.3% [69/79]) completed the study; 10 patients (12.7%) withdrew (patient request, n=3; AEs, n=3; lost to follow-up, n=2; other, n=2). At Week 4 post-vaccination, 97.0% (32/33) of patients in the pre-belimumab cohort and 97.6% (40/41) in the concurrent belimumab cohort had a positive response to ≥1 of the 23 pneumococcal serotypes (as-treated population). Similarly, little difference was observed across a broader response, with 87.9% (29/33) of patients in the pre-belimumab cohort and 85.4% (35/41) in the concurrent belimumab cohort responding to ≥10 of the serotypes. The proportion of patients with an AE considered by the investigator to be treatment-related was 23.5% (8/34) in the pre-belimumab cohort and 8.9% (4/45) in the concurrent belimumab cohort. There were seven patients with non-fatal serious AEs (pre-belimumab cohort, 11.8% [n=4], concurrent belimumab cohort; 6.7% [n=3]), and no deaths were reported.

Conclusion: The proportion of patients generating a response to ≥1 pneumococcal serotype did not differ between those who were vaccinated prior to commencing belimumab and those who were vaccinated after treatment with belimumab for 24 weeks. No significant difference was also observed across a broader response (from ≥2 serotypes to ≥10 serotypes). Study funded by GSK and Human Genome Sciences, Inc. Nicole Cash, MRes, PhD, Fishawack Indicia Ltd, UK, provided submission and editorial assistance, funded by GSK.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-phase-4-multicenter-randomized-open-label-study-to-evaluate-the-effect-of-belimumab-on-vaccine-responses-in-patients-with-systemic-lupus-erythematosus/