Sex: U
Vaccine: PPV
Symptoms: Adverse event
Clinical narrative: This literature study report has been received from the author in a published literature article. Background/Purpose: Intravenous (IV) belimumab 10 mg/kg was approved in subjects 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 subjects with SLE. Methods: This Phase 4, randomized, open-label study was conducted at 13 centers. Subjects were randomized (7:9) to receive a pneumococcal Vaccine, Polyvalent (23-valent) (manufacturer unknown) 4 weeks prior to (pre-belimumab cohort) or 24 weeks after (concurrent belimumab cohort) commencing 4-weekly belimumab 10 mg/kg IV treatment. All subjects received SoC. All analyses of vaccine titer were performed on the as-treated population, defined as all subjects who received 1 dose of belimumab. The primary endpoint was the proportion of subjects with positive antibody responses (>=2-fold increase from pre-vaccination levels or post-vaccination level 0.6 microg/mL if pre-vaccination levels were unquantifiable) to >=1 of the PNEUMOVAX23 serotypes 4 weeks post vaccination. Other endpoints included the proportion of subjects with positive antibody responses to >=2 to >=10 of the serotypes. Safety was assessed by monitoring adverse events (AEs). Results: A total of 79 subjects were enrolled and randomized to receive the pneumococcal Vaccine, Polyvalent (23-valent) (manufacturer unknown) (pre-belimumab cohort, n=34, concurrent belimumab cohort, n=45). The majority (87.3% [69/79]) completed the study; 10 subjects (12.7%) withdrew (subject 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 subjects 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 subjects in the pre-belimumab cohort and 85.4% (35/41) in the concurrent belimumab cohort responding to >=10 of the serotypes. The proportion of subjects 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 subjects 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 subjects 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). This report refers to four subjects of unknown age and gender in pre-belimumab cohort, who on unknown dates received pneumococcal Vaccine, Polyvalent (23-valent) (manufacturer unknown) (lot#, dose and route unknown) for prophylaxis. On unspecified date, the subjects experienced serious AEs. The outcome of serious AEs was unknown. The investigator considered the events to be serious (medically significant) and related to pneumococcal Vaccine, Polyvalent (23-valent) (manufacturer unknown). This is one of several reports received from the same literature (MARRS# 1701USA007543). Additional information has been requested. Company Causality Assessment: Based on the limited information currently available for this case, a reasonable possibility to suggest a relationship between  Pneumovax23 vaccination and the reported serious events of "adverse event" cannot be established. Patients' concurrent conditions, medical history, concomitant therapies and clinical details of the events were not reported. Company Comment- No changes to the product safety information are warranted at this time.  Merck and Co., Inc., also known as MSD, continues to monitor the safety profile of the product. Sender's Comments: US-009507513-1701USA007543.