A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus.

ABSTRACT: Objective Intravenous belimumab 10?mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10?mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (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 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ?2 to ?10, and ?11-23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n?=?34; belimumab-concurrent cohort, n?=?45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n?=?3; adverse event, n?=?3; lost to follow-up, n?=?2; other, n?=?2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ?1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ?10 of serotypes, approximately 80% responded to ?12 serotypes, and approximately two-thirds responded to ?16 serotypes. Little difference was observed between cohorts across a broad response, up to 23 serotypes. Eight (23.5%) patients experienced an adverse event considered by the investigator to be treatment-related in the pre-belimumab cohort and four (8.9%) in the belimumab-concurrent cohort; seven patients experienced non-fatal serious adverse events (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 the pre-belimumab and belimumab-concurrent cohorts; the proportions were also comparable across a broader response (from ?2 serotypes to 23 serotypes).

SUBMITTER: Chatham W 

PROVIDER: S-EPMC5673008 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature