Immunization with inactivated vaccines while receiving the disease-modifying therapy natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows.
The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.
On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.
“We observed seroprotection rates exceeding 90% for hepatitis A, hepatitis B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain, told Medscape Medical News. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.”
The study was published online on April 12 in JAMA Network Open.
A Controversial Issue
Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions. Additionally, the immunogenicity of vaccines can be compromised by immunosuppressive agents, particularly anti-CD20 therapies like rituximab, ocrelizumab, or ofatumumab, researchers note.
As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression.
Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors write. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.
The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Carvajal said.
High Seroprotection Rate
Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.
Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).
The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.
They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.
The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.
There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P =.004) and median number of new T2 lesions (P =.01).
There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
‘Viable Option’
The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.
The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Carvajal said.
Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.
This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.
Commenting on the findings for Medscape Medical News, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”
This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.”
“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy.
This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.
Batya Swift Yasgur MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
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