Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) for Use of Serogroup B Meningococcal (MenB) Vaccines in Adolescents and Young Adults (Including College Students)

Introduction

Two serogroup B meningococcal (MenB) vaccines have recently been licensed for use in the U.S. (MenB-FHbp [Trumenba, Wyeth Pharmaceuticals, Inc.] and MenB-4C [Bexsero, Novartis Vaccines]). Both vaccines were approved for use in persons aged 10 through 25 years. MenB-FHbp was licensed as a three-dose series and MenB-4C was licensed as two-dose series. Evidence of benefits and harms were reviewed in accordance with GRADE methods1. The primary policy question was “Should MenB vaccines be administered routinely to all adolescents and young adults (including college students)?”

Methods for GRADE

The benefits outcomes considered for each vaccine included short-term immunogenicity (1 month after vaccination), persistence of immunogenicity (11–48 months after vaccination, if data available), and MenB immunogenicity with concomitant vaccines. The harms outcome considered for each vaccine included occurrence of serious adverse events (SAEs) after vaccination and safety of concomitant administration with other vaccines.

Immunogenicity and safety data from five clinical trials (3 randomized controlled trials (RCT), 1 randomized uncontrolled trial, and 1 immunogenicity extension study) of MenB-4C23456 and seven clinical trials (5 RCTs and 2 open label studies) of MenB-FHbp78910 (Pfizer, unpublished data) were considered in the assessment. The evidence type for each outcome was derived through a review of study design, risk of bias, inconsistency, indirectness, imprecision and other considerations (strength of association, dose response gradient and opposing plausible residual confounding or bias).

Estimates of short-term immunogenicity and persistence of immunogenicity (11–48 months after vaccination, if data available) were based on demonstration of immune response, as measured by human serum bactericidal activity (hSBA) against a small number of serogroup B strains. In studies supporting U.S. licensure, immunogenicity was assessed by the proportion of subjects who achieved a ≥4-fold increase in hSBA titer for each of the strains tested, and the proportion of subjects who achieved a titer greater than or equal to the lower limit of quantitation (LLOQ) of the assay for all strains (composite response). The LLOQ was defined as the lowest amount of the antibody in a sample that can be reliably quantified.

Results

Table 1a: Use of MenB-4C (Bexsero®) in adolescents and young adults (including college students): Evidence Table

Table 1a Footnotes

^* No formal statistical hypothesis testing or sample size calculation planned in the protocol for one study. Potential selection bias for participants in the other study – downgraded by 1

^** High heterogeneity, I-squared > 90% across all strains – downgraded by 1

^*** Studies assessed correlate of protection and not directly efficacy – downgraded by 1

^# The CI around the effect estimate includes both effect and non-effect – downgraded by 1

^## Strong strength of association. RR ranges between 4.44 and 5.19 – upgraded by 1

Table 1b: Considerations for Vaccine Use: MenB-4C (Bexsero®)

Table 2a: Use of MenB-FHbp (Trumenba®) in adolescents and young adults (including college students): Evidence Table

Table 2a Footnotes

⁺ Concomitant administration with Tdap/IPV or 4vHPV

^* Very small sample size

^** Significant heterogeneity; I-square ranges between 43-81% – Downgraded 1

^*** Studies assessed correlate of protection and not directly efficacy – downgraded by 1

^*# The CI around the effect estimate includes both effect and non-effect in two strains not common in the U.S.

^# The CI around the effect estimate includes both effect and non-effect – downgraded by 1

^## Very strong strength of association: relative risk ranges between 4.64 between 12.26 – upgraded by 1

Table 2b: Considerations for Vaccine Use: MenB-FHbp (Trumenba®)

Summary

After reviewing the available data, including the result of the GRADE analysis, the Advisory Committee on Immunization Practices (ACIP) recommended that adolescents and young adults aged 16 through 23 years may be vaccinated with a MenB vaccine to provide short term protection against most strains of serogroup B meningococcal disease. The preferred age for MenB vaccination is 16 through 18 years of age (recommendation Category B). Category B recommendations are made for individual clinical decision making. See the Use of MenB vaccines in adolescents and young adults (including college students) ACIP recommendation.