GRADE: Inclusion of MenACWY-TT (MenQuadfi) as an option for meningococcal serogroup A, C, W, and Y (MenACWY) vaccination according to currently recommended dosing and schedules

Grading of Recommendations, Assessment, Development, and Evaluation

Printer friendly version of this page

Introduction

Meningococcal disease is an uncommon but severe bacterial infection that can progress rapidly. One in ten persons with meningococcal disease die despite proper antibiotic treatment, and one in five survivors have long-term sequelae.

Despite the current low incidence of meningococcal disease in the United States, certain groups are at increased risk for meningococcal disease. Serogroup A, C, W, Y (MenACWY) meningococcal vaccines are currently recommended for use in adolescents aged 11 – 18 years, persons with certain underlying conditions (persistent complement component deficiency, complement inhibitor (e.g., eculizumab [Soliris®]) use, anatomic or functional asplenia, and HIV), microbiologists with routine exposure to Neisseria meningitidis isolates, persons at increased risk due to a meningococcal disease outbreak caused by serogroup A, C, W, or Y, persons who travel to or reside in countries where meningococcal disease is endemic or hyperendemic, unvaccinated or under-vaccinated college freshmen living in residence halls, and military recruits. (1,2)

MenACWY-TT (MenQuadfi, Sanofi-Pasteur) is a MenACWY conjugate vaccine that was approved in the United States in April 2020 for use in individuals aged 2 years or older. Considering availability of the newly licensed MenACWY-TT vaccine, the ACIP Meningococcal Vaccines Work Group assessed data related to potential benefits and harms of including MenACWY-TT as an option for meningococcal ACWY vaccination, including through the Vaccines for Children (VFC) program, according to currently recommended dosing and schedules.

A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was completed for the MenACWY-TT vaccine to assess the certainty of evidence for outcomes associated with this vaccine. Additional factors related to potential use of the MenACWY-TT vaccine were assessed as part of the Evidence to Recommendations Framework (EtR).

Top of Page

Methods for GRADE

A systematic review and GRADE of the evidence for MenACWY-TT vaccine was conducted and presented to ACIP in June 2020.  No conflicts of interest were reported by CDC staff or the ACIP Meningococcal Vaccines Work Group members involved in the GRADE analysis. As a basis for the GRADE analysis, the policy question consisting of the population, intervention, comparison, and outcomes of interest was defined (Table 1).

Table 1: Policy question and definition of the Population, Intervention, Comparison, and Outcome for GRADE analysis.

Bold font indicates outcomes with evidence included in the GRADE analysis

A search was conducted for studies in any language from PubMed, Medline, Embase, CINAHL, Cochrane, Scopus, clinicaltrials.gov, and clinicaltrialsregister.eu databases using search string: MenACYW-TT, MenACYWTT, MenACYW TT, MCV4-TT, MCV4TT, MCV4 TT, MenQuadfi, and “vaccin*” and “(immunogenicity or efficacy or effectiveness or impact or safety or adverse event*)”. Efforts were made to obtain unpublished or other relevant data from the manufacturer.

Studies were included that presented primary data on MenACWY-TT (MenQuadfi).

One hundred forty-nine references were identified. After screening titles and abstracts, 10 studies were included in the GRADE analysis. Characteristics of these studies are presented in Table 2.

Of note, the data reviewed and included in GRADE do not include evidence related to those individuals recommended to receive meningococcal vaccines based on underlying medical conditions, as these groups were excluded from the evaluated studies. The GRADE tables reflect this consideration.

Beneficial and harmful outcomes for the GRADE assessment were selected by the Work Group during Work Group calls. The Work Group deemed serogroup A, C, W, and Y meningococcal disease, short-term immunogenicity, coadministration with routine adolescent vaccines, and serious adverse events (SAEs) to be critical outcomes (Table 1). Persistence of the immune response was deemed an important outcome. Short-term immunogenicity, persistence of the immune response, coadministration with routine adolescent vaccines, and SAEs were included in the evidence profiles; no data were available on prevention of serogroup A, C, W, and Y meningococcal disease.

Because of the absence of data on use of MenACWY-TT among individuals with underlying medical conditions, two GRADE analyses were conducted for each of the four included outcomes: one for healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions, and one for individuals at increased meningococcal disease risk because of underlying medical conditions. This resulted in a total of 8 GRADE tables.

Table 2. Study References

Table 3: Characteristics of the included studies for MenACWY-TT (MenQuadfi)

Table 3 Footnotes

Top of Page

Short-term immunogenicity (Tables 4-15)

Table 4. Summary data on short-term immunogenicity of MenACWY-TT (MenQuadfi)

Table 4 Footnotes

Table 5. Short-term immunogenicity data from Study MET54, conducted in persons aged 12-24 months

Table 5 Footnotes

Table 6. Short-term immunogenicity data from Study MET51, conducted in persons aged 12-23 months

Table 6 Footnotes

Table 7. Short-term immunogenicity data from Study MET35, conducted in persons aged 2-9 years

Table 7 Footnotes

Table 8. Short-term immunogenicity data from Study MET50, conducted in persons aged 10-17 years

Table 8 Footnotes

Table 9. Short-term immunogenicity data from Study MET43, conducted in persons aged 10-17

Table 9 Footnotes

Table 10. Short-term immunogenicity data from Study MET43, conducted in persons aged 18-55

Table 10 Footnotes

Table 11. Short-term immunogenicity data from Study MET44, conducted in persons aged 56+

Table 11 Footnotes

Table 12. Short-term immunogenicity data from Study MET49, conducted in persons aged 56+

Table 12 Footnotes

Table 13. Short-term immunogenicity data from Study MET56^, conducted in persons aged 15+

Table 13 Footnotes

Table 14. GRADE table short-term immunogenicity of MenACWY-TT vaccination in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions:

Table 14 Footnotes

Table 15. GRADE table: short-term immunogenicity of MenACWY-TT vaccination in individuals at increased meningococcal disease risk because of underlying medical conditions:

Table 15 Footnotes

Top of Page

Serious adverse events (Tables 16-18)

Table 16. Data on serious adverse events following vaccination with MenACWY-TT (MenQuadfi)

Table 16 Footnotes

Table 17. GRADE table: Safety of MenACWY-TT in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions

Table 17 Footnotes

Table 18. GRADE tables: Safety of MenACWY-TT in individuals at increased meningococcal disease risk because of underlying medical conditions

Table 18 Footnotes

Top of Page

Persistence of immune response (Tables 19-21)

Table 19. Data on persistence of the immune response to of MenACWY-TT (MenQuadfi) in 4-5 year olds vaccinated three years previously with MenACWY-TT or MCV4-TT

Table 19 Footnotes

Table 20. GRADE table: Persistence of MenACWY-TT in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions

Table 20 Footnotes

Table 21. GRADE table: Persistence of MenACWY-TT in individuals at increased meningococcal disease risk because of underlying medical conditions

Table 21 Footnotes

Top of Page

Immune interference due to coadministration with routine adolescent vaccines (Tables 22-25)

Table 22. Data on immune interference due to coadministration with routine adolescent vaccines (Study MET50): Response to quadrivalent HPV vaccine

Table 22 Footnotes

Table 23. Data on immune interference due to coadministration with routine adolescent vaccines (Study MET50): Response to quadrivalent Tdap vaccine

Table 24. GRADE table: Coadministration of routine adolescent vaccines with MenACWY-TT in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions

Table 24 Footnotes

Table 25. GRADE tables: Coadministration of routine adolescent vaccines with MenACWY-TT in individuals at increased meningococcal disease risk because of underlying medical conditions

Table 25 Footnotes

Summary

To summarize the GRADE assessment for use of MenACWY-TT, for healthy individuals the certainty of evidence was rated as 1 for short term immunogenicity, 4 for persistence of the immune response, and 2 for coadministration of routine adolescent vaccines and serious adverse events; however, for people with underlying medical conditions increasing their risk of meningococcal disease, quality of evidence is a 3 for short term immunogenicity and 4 for the other outcomes.

Table 26. GRADE Summary of Evidence table for use of MenACWY-TT in healthy individuals (including adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions) and individuals at increased meningococcal disease risk due to underlying medical conditions.

ACIP reviewed the results of both the GRADE analysis and the Evidence to Recommendations framework in June 2020 and voted to include MenACWY-TT (MenQuadfi) as an option for meningococcal serogroup A, C, W, and Y (MenACWY) vaccination for children aged ≥2 years in the Vaccines for Children (VFC) program according to currently recommended dosing and schedules.Top of Page

References

1. Prevention and Control of Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Recommendations and Reports March 22, 2013 / 62(RR02);1-22. www.cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.htm
2. MacNeil JR, Rubin LG, Patton M, Ortega-Sanchez IR, Martin SW. Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons — Advisory Committee on Immunization Practices, 2016. MMWR Morb Mortal Wkly Rep 2016;65:1189–1194. DOI: https://dx.doi.org/10.15585/mmwr.mm6543a3

Top of Page