About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question: Policy question: Should MenACWY-TT (MenQuadfi) be included as an option for meningococcal ACWY vaccination according to currently recommended dosing and schedules?
Population: Persons aged ≥ 2 years currently recommended to receive meningococcal conjugate (ACWY) vaccines
Intervention: Vaccination with MenACWY-TT according to currently recommended dosing and schedules
Comparison(s): Vaccination with MenACWY-D and MenACWY-CRM according to currently recommended dosing and schedules
Outcome(s):1
- Short-term immune response
- Persistence of immune response
- Immune interference due to co-administration with other routine adolescent vaccines
- Serious adverse events
Background
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.
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. No changes to existing ACIP recommendations for use of meningococcal vaccines are proposed. Of note, several current ACIP recommendations for use of MenACWY vaccines are off-label for both the currently available MenACWY-CRM and MenACWY-D vaccines and for MenACWY-TT; these include the two-dose primary series for individuals with complement component deficiency, functional or anatomic asplenia, or HIV infection; booster doses in persons aged <15 years of age; and second and subsequent booster doses in individuals recommended to receive multiple booster doses due to persistent increased meningococcal disease risk. For MenACWY-D and MenACWY-CRM, use in persons aged >55 years is also off-label; however, MenACWY-TT is licensed in this age group.
A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was completed for MenACWY-TT vaccine to assess the certainty of evidence. Additional factors related to MenACWY-TT vaccination were assessed as part of the Evidence to Recommendations Framework (EtR), summarized below.
Additional background information supporting the ACIP recommendations on the use of MenACWY vaccine can be found in the Prevention and Control of Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Recommendations and Reports and Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons — Advisory Committee on Immunization Practices, 2016.22
Problem
| Criteria | Work Group Judgments | Evidence |
|---|---|---|
| Is the problem of public health importance? | Yes |
ACIP has recognized meningococcal disease as a problem of public health importance and currently recommends routine vaccination with quadrivalent conjugate (MenACWY) vaccines for adolescents and persons at increased risk of meningococcal disease. Current incidence of meningococcal disease in the United States is 0.1 cases per 100,000 population.
The Work Group was of the opinion that the question of whether to include MenACWY-TT vaccine as an option for meningococcal ACWY vaccination is probably of public health importance in the context of recent FDA licensure of MenACWY-TT.
|
Benefits and Harms
| Criteria | Work Group Judgments | Research Evidence |
|---|---|---|
| How substantial are the desirable anticipated effects? | Small | Inclusion of MenACWY-TT as an additional option for MenACWY vaccination will increase availability and choice for vaccine providers and recipients and increase security of vaccine supply. |
| How substantial are the undesirable anticipated effects? | Minimal |
The clinical trials for MenACWY-TT in healthy persons demonstrated an acceptable safety profile compared with currently available MenACWY vaccines. No serious adverse events related to the MenACWY-TT vaccine were detected in any of the clinical trials. Immune responses to MenACWY-TT were non-inferior to those induced by licensed meningococcal vaccines, showing that addition of MenACWY-TT as an option for meningococcal vaccination will not reduce individual or population protection from meningococcal disease.
Concomitant administration of MenACWY-TT with other routine adolescent vaccines demonstrated non-inferiority of the immune response to HPV, tetanus, diphtheria, and pertussis toxin. Non-inferiority criteria were not met for other pertussis antigens; however, clinical relevance of this finding is unknown and similar issues have been noted with coadministration of Tdap and other licensed MenACWY vaccines.
|
| Do the desirable effects outweigh the undesirable effects? | Favors intervention | The desirable effects of MenACWY-TT, including additional options for providers and patients, and security of the supply chain, outweigh the undesirable effects as there is currently no evidence of safety, coadministration, or other concerns for use of MenACWY-TT. |
| What is the overall certainty of this evidence for the critical outcomes? | For healthy individuals: Effectiveness of the intervention is Level 4 (Very low), Level 2 (Moderate), Level 1 (High)Safety of the intervention is Level 2 (Moderate) For individuals at increased meningococcal disease risk because of specified underlying medical conditions:
Effectiveness of the intervention is Level 4 (Very low), Level 3 (Low)
Safety of the intervention is Level 4 (Very low)
|
GRADE analysis was completed to assess certainty of evidence for inclusion of MenACWY-TT vaccine as an option for MenACWY vaccination according to currently recommended dosing and schedules.
See associated GRADE tables for additional details. |
Values
References in this table:3
| Criteria | Work Group Judgments | Research Evidence |
|---|---|---|
| Does the target population feel that the desirable effects are large relative to undesirable effects? | Yes | No data are available on values of the target population toward inclusion of MenACWY-TT as an additional option for MenACWY vaccination.
However, the high vaccination coverage of 86.6% in 2018 for at least one dose of MenACWY among adolescents demonstrates that the target population feels that the desirable effects of MenACWY vaccination outweigh the undesirable effects.3 Limited data are available on MenACWY vaccine uptake in other individuals recommended to receive MenACWY vaccine.
|
| Is there important uncertainty about or variability in how much people value the main outcomes? | Probably no important uncertainty or variability | High vaccination coverage of 86.6% in 2018 for at least one dose of MenACWY among adolescents demonstrates that the target population values the outcomes of vaccine immunogenicity and effectiveness for prevention of meningococcal disease. The Work Group feels confident that physicians and the general public also value the safety of meningococcal vaccines. |
Acceptability
| Criteria | Work Group Judgments | Research Evidence |
|---|---|---|
| Is the intervention acceptable to key stakeholders? | Yes | No data are available on the acceptance of including MenACWY-TT as an option for MenACWY vaccination among key stakeholders. However, the high vaccination coverage for at least one dose of MenACWY among adolescents demonstrates acceptance of MenACWY vaccination among adolescents. Limited data are available on MenACWY vaccine uptake in other individuals recommended to receive MenACWY vaccine. |
Resource Use
| Criteria | Work Group Judgments | Research Evidence |
|---|---|---|
| Is the intervention a reasonable and efficient allocation of resources? | Yes | MenACWY-TT cost is projected to be within 5% of currently licensed and available MenACWY conjugate vaccines in the United States. As such, resource allocation will not be substantively affected by the addition of MenACWY-TT as an option for meningococcal ACWY vaccination according to current recommendations. |
Feasibility
| Criteria | Judgments | Research Evidence |
|---|---|---|
| Is the intervention feasible to implement? | Yes | Including MenACWY-TT as an option for MenACWY vaccination will not create any new feasibility challenges. Vaccination of adolescents relies on an existing vaccination platform and high coverage with at least one dose of MenACWY in adolescents demonstrates that implementing existing recommendations in this age group has been feasible. |
Balance of Consequences
Desirable consequences probably outweigh undesirable consequences in most settings
Is there sufficient information to move forward with a recommendation? Yes
Recommendation
MenACWY-TT (MenQuadfi) should be included as an option for meningococcal ACWY vaccination according to currently recommended dosing and schedules. Inclusion of MenACWY-TT as an option does not require an ACIP vote as no new recommendations are being made; however, a VFC vote will be needed to include this vaccine as an option in the Vaccines for Children program.
This Evidence to Recommendation table is based on the GRADE Evidence to Decision framework developed through the DECIDE project. See further information. Framework last updated 19 June 2019.
View the complete list of EtR Frameworks
- 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. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.htm
- 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
- Walker TY, Elam-Evans LD, Yankey D, et al. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2018. MMWR Morb Mortal Wkly Rep 2019;68:718–723. DOI: https://dx.doi.org/10.15585/mmwr.mm6833a2