What are the considerations for using M-Spikevax (Moderna COVID-19 vaccine)?

M-Spikevax (Moderna COVID-19 Vaccine) Considerations

M-Spikevax is specifically FDA-approved for individuals aged ≥65 years or those aged 6 months through 64 years with at least one underlying condition that increases risk for severe COVID-19 outcomes, making it distinct from the standard Spikevax formulation which is appropriate for the general adult population. 1

Key Distinction: M-Spikevax vs. Spikevax

• M-Spikevax is reserved for high-risk populations only: adults ≥65 years or younger individuals (6 months-64 years) with qualifying high-risk conditions per CDC criteria 1
• Standard Spikevax is recommended for general adult vaccination in those who don't meet M-Spikevax criteria 1
• For a patient under 65 without high-risk conditions, standard Spikevax (or other authorized COVID-19 vaccines) is the appropriate choice 1

Mechanism and Formulation

• M-Spikevax uses mRNA technology delivering genetic instructions to cells for temporary SARS-CoV-2 spike protein expression, triggering immune response without live virus components 2, 3
• The mRNA does not enter the cell nucleus or interact with DNA, and degrades within days after protein production 2, 3
• Bivalent formulations contain equal amounts of mRNA encoding spike proteins from both ancestral strain and Omicron BA.4/BA.5 sublineages 2, 3

Current Vaccination Recommendations

• All adults should receive at least 1 dose of updated (2024-2025 Formula) COVID-19 vaccine 1
• Bivalent booster doses should be administered ≥2 months after completion of any FDA-approved primary series or prior monovalent booster 4
• The vaccine manufacturer does not need to match prior vaccinations 1
• Persons with recent SARS-CoV-2 infection may consider delaying booster by 3 months from symptom onset or positive test 2

High-Risk Conditions Qualifying for M-Spikevax

• Obesity is specifically recognized as a qualifying high-risk condition for severe COVID-19 outcomes 1
• Patients with obesity are at higher risk for COVID-19 complications, making vaccination a priority 1
• Other chronic conditions increase risk, though specific qualifying conditions should follow CDC high-risk criteria 1

Efficacy and Effectiveness

• Original mRNA-1273 (Moderna) demonstrated 95.9% effectiveness at 2 months post-vaccination, declining to 80.3% at 7 months 5
• Effectiveness against hospitalization and death remains more durable than protection against infection over time 5
• Waning protection results from both declining immunity and variant emergence (particularly Delta and Omicron) 5
• Bivalent boosters were specifically developed to address immune evasion by Omicron variants 2, 3

Safety Profile and Reactogenicity

• Spikevax demonstrates higher reactogenicity compared to Pfizer-BioNTech (Comirnaty), particularly after first dose (76.1% vs 67.4% adverse effects) 6
• Second dose produces greater reactogenicity than first dose for both vaccines (Spikevax: 87.9% vs 76.1%) 6
• Most common adverse events: injection site pain, fatigue, and headache 7
• Women and individuals aged 18-55 years experience greater reactogenicity 7, 6
• Prior COVID-19 infection associated with more systemic events after first dose 7
• Myocarditis is a rare complication, highest risk in males aged 16-19 years (137 per million risk difference) 2
• Approximately 1.2% of recipients required hospitalization or emergency room visit for adverse events 7
• Overall safety profile demonstrates mRNA vaccines are safe across all population groups 8

Special Population Considerations

Immunosuppressed Patients

• Methotrexate (MTX) should be withheld for 2 weeks before and after vaccination to optimize immune response 4
• Withholding MTX beyond 2 weeks risks disease flare-up, requiring careful timing 4
• Anti-CD20 agents (rituximab) profoundly impair vaccine response even months after use: administer vaccine minimum 4 weeks before and 6 months after rituximab 4
• JAK inhibitors should be withheld 1-2 weeks on either side of vaccination, particularly when used with MTX 4
• Abatacept (subcutaneous) timing: withhold for 1 week before and after each vaccine dose 4
• Abatacept (IV) timing: administer vaccine 4 weeks after infusion, delay next infusion to 5 weeks post-previous dose 4
• TNF inhibitors, IL-17 blockers, and IL-6 inhibitors (tocilizumab) have minimal effect on vaccine response unless combined with MTX 4
• Corticosteroids >10 mg prednisolone daily impair vaccine response; consider dose tapering around vaccination 4

Other Considerations

• Co-administration with other recommended vaccines (influenza, pneumococcal) during the same visit is acceptable 1
• Pregnant women, elderly, transplant recipients, and cancer patients require special attention but vaccination remains recommended 9

Common Pitfalls to Avoid

• Do not delay vaccination in high-risk patients waiting for age 65 to receive M-Spikevax when standard Spikevax is appropriate now 1
• Do not unnecessarily prolong immunosuppressive medication holds beyond recommended timeframes, as this increases disease flare risk 4
• Do not assume vaccine manufacturer must match prior doses - any authorized vaccine is acceptable 1
• Do not dismiss reactogenicity concerns - counsel patients, especially women and younger adults, about expected higher rates of adverse effects with Spikevax 7, 6