科研之友
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摘要
Objective Intravenous belimumab 10mg/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 10mg/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 level0.6 mu g/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).
- 出版日期2017-12
