Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) for Use of Serogroup B Meningococcal (MenB) Vaccines in Persons at Increased Risk for Serogroup B Meningococcal Disease

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Introduction

In October 2014, the Food and Drug Administration (FDA) licensed the first serogroup B meningococcal (MenB) vaccine (MenB-FHbp [Trumenba®, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc., Philadelphia, Pennsylvania]) as a 3-dose series. The FDA licensed a second MenB vaccine (MenB-4C [Bexsero®, Novartis Vaccines, Siena, Italy]) in January 2015 as a 2-dose series. Both vaccines were approved for use in persons aged 10 through 25 years. Evidence of benefits and harms were reviewed in accordance with GRADE methods[1]. The primary policy question was “Should MenB vaccines be administered routinely to all persons aged ≥10 years at increased risk for serogroup B meningococcal disease or at increased risk for serogroup B disease because of an outbreak?”

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Methods for GRADE

The benefits outcomes considered for each vaccine included short-term immunogenicity (1 month after vaccination) and persistence of immunogenicity (11-24 months after vaccination, if data available). The harms outcome considered for each vaccine included occurrence of serious adverse events (SAEs) after vaccination.

Safety and immunogenicity data from seven clinical trials (6 RCTs and one immunogenicity extension study) of MenB-4C [2-7] (Novartis, unpublished data) and nine clinical trials (6 RCTs and 3 open label studies) of MenB-FHbp [8-13] (Pfizer unpublished data) were considered in the assessment.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 (11-24 months after vaccination, if data available) were based on demonstration of immune response, as measured by serum bactericidal activity using human complement (hSBA) against a small number of serogroup B strains. In studies supporting US 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) (see package inserts; Trumenba [10 pages] and Bexsero [10 pages]). The LLOQ was defined as the lowest amount of the antibody in a sample that can be reliably quantified.

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Results

Table 1a: Use of MenB-4C (Bexsero®) in Persons at Increased Risk: Evidence Table

Table 1a Footnotes

Table 1b: Use of MenB-4C (Bexsero®) During Outbreaks: Evidence Table

Table 1b Footnotes

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

Table 2a: Use of MenB-FHbp (Trumenba®) in Persons at Increased Risk: Evidence Table

Table 2a Footnotes

Table 2b: Use of MenB-FHbp (Trumenba®) During Outbreaks: Evidence Table

Table 2b Footnotes

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

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Summary

The evidence type for both vaccines was determined to be type 2 (moderate level of evidence) for use in outbreak settings, and type 3 (low level of evidence) for use in persons at increased risk of serogroup B meningococcal disease; the recommendation was designated Category A (recommended for all persons in an age- or risk-factor-based group). The GRADE methodology is not entirely objective and there are areas in the methodology that are subject to interpretation by the evaluator. A head to head comparison of the two vaccines was not done because the vaccines target different antigens. Certain groups of individuals are known to be at increased risk for meningococcal disease and are currently recommended to be routinely vaccinated with a quadrivalent meningococcal conjugate vaccine (MenACWY) which protects against serogroups A, C, W, and Y. Many of these groups are also at increased risk for serogroup B meningococcal disease. On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) recommended use of MenB vaccines among certain groups of persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease; these persons include those with persistent complement component deficiencies; persons with anatomic or functional asplenia; microbiologists routinely exposed to isolates of Neisseria meningitidis; and persons identified to be at increased risk because of a serogroup B meningococcal disease outbreak. Available immunogenicity and safety data support the use of MenB vaccines in groups at increased risk for serogroup B meningococcal disease. Both MenB vaccines are approved for use in individuals aged 10 through 25 years; however, due no theoretical differences in safety for those aged >25 years as compared to those aged 10 through 25 years, the ACIP supported routine use of MenB vaccines in persons aged ≥10 years at increased risk for meningococcal disease, including in persons at increased risk because of a serogroup B meningococcal disease outbreak. These recommendations do not apply to children younger than 10 years of age.

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References

1. Ahmed F, Temte J, Campos-Outcalt D, Schunemann H, ACIP Evidence Based Recommendations Work Group. Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC). Vaccine 2011;29:9171-6
2. Santolaya ME, O’Ryan ML, Valenzuela MT, Prado V, Vergara R, Munoz A, et al. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet. 2012 Feb 18;379(9816):617-24
3. Santolaya ME, O’Ryan M, Valenzuela MT, Prado V, Vergara RF, Munoz A, et al. Persistence of antibodies in adolescents 18-24 months after immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine. Hum Vaccin Immunother. 2013 Nov;9(11):2304-10
4. Kimura A, Toneatto D, Kleinschmidt A, Wang H, Dull P. Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine and a quadrivalent meningococcal CRM197 conjugate vaccine against serogroups A, C, W-135, and Y in adults who are at increased risk for occupational exposure to meningococcal isolates. Clin Vaccine Immunol. 2011 Mar;18(3):483-6
5. Read RC, Baxter D, Chadwick DR, Faust SN, Finn A, Gordon SB, et al. Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial. Lancet. 2014 Dec 13;384(9960):2123-31
6. Block SL, Szenborn L, Daly W, Jackowska T, D’Agostino D, Han L, et al. A comparative evaluation of two investigational meningococcal ABCWY vaccine formulations: Results of a phase 2 randomized, controlled trial. Vaccine. Poster presentation at Infectious Disease Week 2014, October 8-12. Philadelphia, PA.
7. Toneatto D, Ismaili S, Ypma E, Vienken K, Oster P, Dull P. The first use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in humans. Hum Vaccin. 2011 Jun; 7(6):646-53
8. Marshall HS, Richmond PC, Nissen MD, Wouters A, Baber J, Jiang Q, et al. A phase 2 open-label safety and immunogenicity study of a meningococcal B bivalent rLP2086 vaccine in healthy adults. Vaccine. 2013 Mar 15; 31(12):1569-75
9. Sheldon EA, Schwartz H, Jiang Q, Giardina PC, Perez JL. A phase 1, randomized, open-label, active-controlled trial to assess the safety of a meningococcal serogroup B bivalent rLP2086 vaccine in healthy adults. Hum Vaccin Immunother. 2012 Jul; 8(7):888-95
10. Richmond PC, Marshall HS, Nissen MD, Jiang Q, Jansen KU, Garces-Sanchez M, et al. Safety, immunogenicity, and tolerability of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised, single-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012 Aug; 12(8):597-607
11. Vesikari T, Wysocki J, Kieninger D, Beeslaar J, Eiden JJ, Jiang Q, et al., editors. Immunogenicity, Safety, and Tolerability, of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly with Diphtheria, Tetanus, Acellular Pertussis and Inactivated Poliomyelitis Vaccine to Healthy Adolescents. 32nd Annual Meeting of the European Society of Paediatric Infectious Disease; 2014; Dublin,  Ireland
12. Bhuyan P, Eiden J, Jones TR, York LJ, Ginis J, Jansen KU, et al., editors. Immunogenicity of Human Papilloma Vaccine Coadministered With an Investigational Bivalent rLP2086 Vaccine Against Meningococcal Serogroup B in Healthy Adolescents. IDWeek 2014; Philadelphia, PA.
13. Vesikari T, Diez-Domingo J, Ostergaard L, Beeslaar J, Eiden J, Jiang Q, et al., editors. Safety and Immunogenicity of an Investigational Meningococcal Serogroup B Bivalent rLP2086 Vaccine in Healthy Adolescents. 32nd Annual Meeting of the European Society for Paediatric Infectious Diseases; 2014; Dublin, Ireland.

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