Dr Mauricio F FarezMauricio F. Farez, MD, MPH
The American Academy of Neurology (AAN) has released a new practice guideline regarding the use of vaccination and immunization in patients with multiple sclerosis (MS), advising that these patients should receive their recommended vaccines, including yearly influenza vaccinations.1

Additionally, the authors noted that, although the data is limited, there is no evidence that vaccination increases the risk of MS exacerbation. They recommended that clinicians should delay vaccination in those who are experiencing a relapse, and should discuss the evidence with their patients and explore their opinions, preferences, and questions.

“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 AAN, in a statement.2 “People with MS should feel safe and comfortable getting their recommended vaccinations.”

This was an update to the 2002 guidelines.Farez told NeurologyLive that despite the 17-year gap between these guidelines and their predecessor, there still a lack of good-quality evidence for most immunization regarding their effect and/or impact in MS. "Nevertheless, over the years, there is more and more evidence at least that most of them do not increase the risk of developing MS," he said.

Farez and colleagues conducted a systematic review of available literature in an attempt to address a number of clinical inquiries in MS. Those questions included the prevalence of vaccine-preventable infections in MS, their impact on the risk of developing MS or exacerbating the disease, if attenuated live and inactivated vaccines are as effective as they are in the general population, and if MS treatment reduces vaccine effectiveness. Ultimately, the review included data from 52 full-text articles, after combing through more than 4000.

The review showed that in those with MS, vaccination against human papillomavirus (HPV; Class I study: odds ratio [OR], 0.28; 95% CI, 0.12–0.70; Class II study: OR, 0.31; 95% CI 0.13–0.73), tetanus toxoid (Class II studies meta-analysis: OR, 0.61; 95% CI, 0.49–0.76, I2 = 0), pertussis (Class II studies meta-analysis: OR, 0.30; 95% CI, 0.20–0.56, I2 = 0), and smallpox (Class 1 study: OR, 0.23; 95% CI, 0.09–0.59) were all associated with a lower likelihood of subsequent MS diagnosis.

“After reviewing all the available evidence, we found that there is not enough information to say whether or not vaccinations trigger or worsen MS flares,” said Farez in a statement. “Still, experts in MS urge their patients to hold off on scheduling their vaccinations if they are having an MS flare simply to avoid the potential for any complications.”

The authors wrote that vaccine-preventable infections such as influenza and zoster can be associated with morbidity and mortality in MS. As unvaccinated individuals and those with MS receiving immunosuppressive therapy are at a higher risk of acquiring these infections, vaccination of these patients should have both personal and population-level benefits.

“Patients with MS are often concerned about the safety of immunizations and may have questions regarding immunizations, including their effect on MS, interactions with MS treatments, adverse effects, and payer coverage,” Farez and colleagues wrote. “An ongoing dialogue regarding immunization will help clinicians to understand patients’ beliefs and preferences and help patients make choices regarding immunizations.”

Despite evidence suggesting that some vaccines may not work well enough to prevent infections for some patients who take certain MS medications. Specifically, those taking  glatiramer acetate (Class I and II studies meta-analysis: OR, 0.39; 95% CI, 0.21–0.74; I2 = 0%), fingolimod (Class I studies meta-analysis: OR, 0.35; 95% CI, 0.21–0.57; I2 = 0%), and mitoxantrone (Class II study meta-analysis OR, 0.11; 95% CI, 0.03–0.45, I2 = 0%) may have insufficient responses to vaccinations. Due to limited evidence, the jury remains out on other therapies such as natalizumab, dimethyl fumarate, alemtuzumab, and interferon ß.

Notably, Farez and coauthors suggested that this systematic review highlighted a need to improve consistent weaknesses across study methodologies, as well as a lack of data altogether in many areas. Statistical imprecision, mostly related to low sample size, was also deemed an important factor in restricting conclusions.

As new immunomodulating and immunosuppressive treatments for MS are being quickly developed, the group noted that as some of these agents have comparable mechanisms of action, they “[believe] that the recommendations here are sufficiently broad.”

To conclude, the authors noted that many areas of needed research remain, including long-term prospective cohort studies in immunosuppressive agents, cohort studies of infection risk in this population, and the impact of short- and long-term disability on immunization. Additionally, funding, governance, physician and institutional involvement, and research protections are needed to maximize care and the effect of future research.

"Immunization status and vaccinations is a must-have conversation with MS patients, in particular to those newly diagnosed or about to start MS drugs," Farez told NeurologyLive. "What’s important to remember is that doctors and patients should discuss about vaccines at the very beginning of the diagnostic process. This is important so that MS patients feel safe and comfortable getting their recommended vaccinations after understanding that preventing infections through vaccine use is a key part of medical care."

The entire guideline, published in Neurology®, can be accessed by clicking here.
REFERENCES
1. Farez MF, Correale J, Armstrong AJ, et al. Practice guideline update summary: Vaccine preventable infections and immunization in multiple sclerosis. Neurology. 2019;93:1-11. doi: 10.1212/WNL.0000000000008157.
2. AAN Issues Guideline on Vaccines and Multiple Sclerosis [press release]. Minneapolis, MN: AAN; Published August 28, 2019. prnewswire.com/news-releases/aan-issues-guideline-on-vaccines-and-multiple-sclerosis-300908216.html. Accessed August 28, 2019.
3. Rutschmann OT, McCrory DC, Matchar DB. Immunization panel of the multiple sclerosis council for clinical practice G. Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002;59:1837–1843.