The American Academy of Neurology (AAN) has issued a practice guideline update for vaccine-preventable infections and immunizations for individuals with multiple sclerosis (MS), its first since 2002. A subcommittee of the AAN — tasked with developing, disseminating and implementing these guidelines — found improvements and additions to the previously issued recommendations. The guideline has been endorsed by the Multiple Sclerosis Association of America and by the Consortium of Multiple Sclerosis Centers. Complete findings, including rationale and recommendations, were published in Neurology.
The AAN’s 2002 guideline statement, “Immunization in multiple sclerosis: a summary of published evidence and recommendations” did not evaluate the effectiveness of immunization in patients with MS who are receiving disease-modifying therapies (DMTs). This update aimed to evaluate and incorporate new evidence, vaccines, and DMTs.
“We reviewed all of the available evidence and for people with MS, preventing infections through vaccine use is a key part of medical care,” said guideline lead author Mauricio F. Farez, MD, MPH, of the FLENI Institution in Buenos Aires, Argentina, and a member of the American Academy of Neurology. “People with MS should feel safe and comfortable getting their recommended vaccinations.”
Recommendations were developed based on evidence from a systematic review (developed in accordance with the development process and AAN guidelines from 2011), as well as strong related evidence, previously established principles of care, and inferences made by the panel. The strength of these findings, risk-benefit ratio, variation in patient preferences, feasibility/availability, and patient cost informed the level of each recommendation issued.
The review included randomized control trials, cohort studies and case-control studies published between 1990 and March 2018. Inclusion criteria required that studies described incidence, prevalence and effect of vaccine-preventable illnesses, and the risk of developing MS or relapse of the disease. Other criteria required the inclusion of studies with a sample size ≥10 and studies that evaluated the interaction between DMTs and vaccine efficacy. Unless safety data or laboratory reference standards were included, the panel excluded case reports and case series from their review.
The following is a summary of the recommendation statements endorsed by the guideline subcommittee. For more information, including a description of the process by which evidence was classified, how conclusions were derived, and how recommendations were established, refer to the full guideline publication.
Recommendation for general care for individuals with MS when considering immunization and vaccine-preventable infections.
1a. There is no definite evidence suggesting that vaccination increases the risk for MS, although a link cannot be completely excluded, given the lack of relevant data. However, vaccinations against human papilloma virus infection, tetanus toxoid, pertussis, and smallpox were associated with a lower likelihood of a subsequent MS diagnosis. Vaccine preventable infections can be associated with morbidity and mortality, therefore clinicians should discuss evidence from the systematic review regarding immunization in MS with their patients (Level B).
1b. Patients with MS are often concerned about the safety of immunizations and may have questions regarding immunizations, including any effects on the course of their illness, interactions with MS treatments, adverse effects, and payer coverage. Clinicians should explore patients’ opinions, preferences, and questions regarding immunizations at clinic visits to effectively address the optimal immunization strategy for each patient, keeping with the patient’s MS status, values, and preferences (Level B).
2. Although there is no evidence that MS alone increases the risk of acquiring vaccine-preventable infections, individuals with MS have at least the same risk as unvaccinated individuals without MS. Therefore, clinicians should recommend that patients with MS follow all vaccine standards (eg, those issued by the United States Center for Disease Control and Prevention, the World Health Organization, and local regulatory bodies), unless there is a specific contraindication (eg, active treatment with immunosuppressive or immunomodulating [ISIM] agents) (Level B).
3. Prevalence of vaccine-preventable diseases and respective seropositivity vary by country and region, as do recommendations for immunization. In cases where local risk for infection is particularly high, vaccination benefits for people with MS—including with live vaccines for those receiving immunomodulatory therapy—may outweigh the risks. Clinicians should weigh local risk for vaccine-preventable diseases when counseling individuals with MS regarding vaccination (Level B).
4. Because of the known risks for exacerbation of MS and other morbidity as a result of influenza infection and no identified risks for exacerbation as a result of the vaccine, benefits of influenza vaccination outweigh the risks in most scenarios. Clinicians should recommend that patients with MS receive the influenza vaccination annually, unless there is a specific contraindication (eg, previous severe reaction) (Level B).
Recommendation regarding immunization in the setting of immunosuppressive or immunomodulating medication use.
5a. Clinicians should counsel patients with MS on the risks for infection associated with specific ISIM medications. Further, counselling is also recommended regarding treatment-specific vaccination protocols—to ensure accordance with prescribing instructions for each respective ISIM medication—when such treatments are being considered for use (Level B).
5b. Physicians should assess or reassess the vaccination status of patients with MS before prescribing ISIM therapy and should vaccinate patients with MS, according to local regulatory standards. Physicians should be guided by treatment-specific risks for infection, as per prescribing information inserts, which commonly recommend a period of at least 4 to 6 weeks before initiating ISIM therapy (Level B).
5c. ISIM medications used to treat MS are associated with severe occurrences, severe recurrences, or both for vaccine-preventable infections, including varicella-zoster and hepatitis B. Manufacturers’ package inserts contain information on treatment-specific guidance for immunization with live vaccines for prophylaxis of these infections, and clinicians are recommended to adhere to this guidance. Clinicians may discuss the advantage of vaccination with patients as soon as possible after MS diagnosis, regardless of initial therapeutic plans, to prevent future delays in initiation of ISIM therapies (Level C based on variation in patient preferences).
6a. Clinicians must screen for certain infections (eg, hepatitis, tuberculosis, and varicella-zoster) specific to intended ISIM medications, according to prescribing information (Level A) and should also treat patients who test positive for latent infections (eg, hepatitis and tuberculosis) accordingly before initiating MS treatments (Level B based on feasibility and cost relative to benefit).
6b. In high-risk populations or in countries with high infection burden, clinicians must screen for latent infections (eg, hepatitis and tuberculosis) before starting MS treatment with ISIM medications, even when not specifically mentioned in prescribing information (Level A). Clinicians should consult infectious disease or other specialists (eg, liver specialists) regarding treatment of patients who screen positive for a latent infection before treating them with ISIM medications (Level B).
7a. Although there is no evidence that patients with MS receiving ISIM therapy have an increased risk for morbidity as a result of immunization with live vaccines, clinicians should recommend against the use of live-attenuated vaccines in people with MS who currently receive ISIM therapies or have recently discontinued these therapies (Level B based on importance of outcomes).
7b. When the risk for infection is high, clinicians may recommend using live-attenuated vaccines, if killed vaccines are unavailable for people with MS who are currently receiving ISIM therapies (Level C based on variation in patient preferences, benefit relative to harm, and importance of outcomes).
Recommendation regarding immunization for individuals with MS during a relapse.
8. The guideline panel did not identify evidence that suggests vaccination increases the risk for relapse or worsens relapse severity, but studies are limited. However, experts remain concerned that vaccines may worsen relapse severity if administered to patients who are actively experiencing an MS relapse. As such, clinicians should delay vaccinations in this population, until clinical resolution or until the relapse is no longer active (eg, the relapse is no longer progressive but may be associated with residual disability), often many weeks after relapse onset (Level B).
As a result of the increasing body and utility of ISIMs for MS and other chronic diseases, the panel highlighted a need for further research that focuses on the safety, efficacy and possible complications associated with the use of such medications, especially in cases where immunizations are required. The panel recommends developing high quality prospective cohort studies that focus on the risks related to infectious diseases in patients with MS. Results pertaining to the subsequent effect on short- and long-term disability would significantly aid development of future guideline recommendations in this population.
1. Farez MF, Correale J, Armstrong MJ, et al. Practice guideline update summary: vaccine preventable infections and immunization in multiple sclerosis [published online August 28, 2019]. Neurology. doi:10.1212/WNL.0000000000008157
2. AAN Issues Guideline On Vaccines And Multiple Sclerosis. [press release]. Minneapolis, MN: PRNewswire; August 28, 2019. https://www.prnewswire.com/news-releases/aan-issues-guideline-on-vaccines-and-multiple-sclerosis-300908216.html. Accessed August 29, 2019.