What’s the effectiveness of Covid-19 vaccination in patients with multiple sclerosis (MS) treated with high-efficacy disease-modifying therapies?

The answer appears to be dependent on which high-efficacy disease-modifying agent is being used to treat MS.  Limited data suggest that cladribine treatment does not impair humoral response to Covid-19 vaccine in patients with MS, while ocrelizumab and fingolimod have a major negative impact on vaccine responsiveness based on humoral antibody measurements.1

A study involving 125 Covid-19 MS vaccine (mRNA, Pfizer BNT162b2) recipients  (58% females, 61% relapse-remitting, 19% primary-progressive, 14% secondary-progressive, 3% clinically isolated syndrome and 2% radiologically isolated syndrome), found high levels of SARS-CoV-2 anti-spike IgG in all subjects (n=23) receiving cladribine as early as 4.4 months from last treatment dose.1

In contrast only 4% of patients with MS treated with fingolimod had a post-vaccination humoral response (time-interval from last treatment dose to vaccination not reported).  Similarly, most patients under treatment with ocrelizumab failed to develop a post-vaccination humoral response, with only 23% demonstrating a protective antibody titer (time-interval from last treatment dose 3.1-8.9 months).

These results may not be totally surprising given the attenuated humoral response to several common vaccines in patients with MS treated with ocrelizumab or fingolimod.2,3

Given the potential suboptimal response to Covid-19 vaccine in patients with MS treated with fingolimod or ocrelizumab, until further data become available, it’s fair to state that patients treated with these agents should NOT depend on vaccination to protect them from Covid-19 and that they may need to still take extra precautions during the pandemic.   

 

Bonus Pearl: Did you know that fingolimod prevents lymphocyte egression from secondary lymphoid tissue and ocrelizumab is an anti-CD20 monoclonal antibody that depletes B lymphocytes?1

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Reference

  1. Achiron A, Mandel M, Dreyer-Alster S, et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Therapeutic Adances in Neurological Disorders 2021;14:1-8. https://journals.sagepub.com/doi/full/10.1177/17562864211012835
  2. Bar-Or A, Calkwood JC, Chognot C, et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis. Neurology 2020; 95:e1999-22008. https://pubmed.ncbi.nlm.nih.gov/32727835/
  3. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology 2015;84:872-9. https://pubmed.ncbi.nlm.nih.gov/25636714/  

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the effectiveness of Covid-19 vaccination in patients with multiple sclerosis (MS) treated with high-efficacy disease-modifying therapies?

Are women at higher risk of Covid-19 vaccine-related adverse events?

Data to date shows a preponderance of Covid-19 vaccine-related adverse events (AEs) among women compared to men. This finding may be due to the generally more robust immunological response to infections and vaccines among women, increased reporting of AEs by women, genetic factors, microbiome differences as well as other factors.1-3

A CDC study involving mRNA vaccines (Pfizer and Moderna) during the 1st month of vaccination roll out in the US, found that nearly 80% of adverse events were reported by women.  The great majority (>90%) of these AEs were not serious and included symptoms such as headache, dizziness and fatigue.1

A JAMA study involving individuals receiving one of the mRNA vaccines found that 94% (Pfizer) and 100% (Moderna) of anaphylaxis events occurred among women. Of note, the median age was ~40 years  with the majority of anaphylaxis events were reported after the first dose. 2

Higher incidence of AEs following Covid-19 vaccination is not surprising and may be explained biologically. Women typically have a more robust immune response to infections and vaccination, both at the level of innate and adaptive immunity with higher antibody responses.  

These findings may be in part due to hormones such as estrogen which is known to enhance differentiation of dendritic cells and proinflammatory cytokine production. Other proposed mechanisms include differences in microbiome between sexes and sex-based genetic influences on humoral immune profile with the X chromosome expressing 10 times more genes than the Y chromosome, including genes that influence immunity.3

Bonus Pearl: Did you know that anaphylactic reaction to the mRNA Covid-19 vaccines is extremely rare, occurring in only 2-5 cases/ million!2

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References

  1. Gee J, Marquez P, Su J, et al. First month of Covid-19 vaccine safety monitoring—United States, December 14, 2020—January 13, 2021. MMWR 2021;70:283-88. https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm
  2. Shimabukuro TT, Cole M, Su JR. Reports of anaphylaxis after receipt of mRNA Covid-19 vaccines in the US—December 14, 2020-January 18, 2021. JAMA 20201;325:1101-1102. https://jamanetwork.com/journals/jama/fullarticle/2776557
  3. Fischinger S, Boudreau CM, Butler AL, et al. Sex differences in vaccine-induced humoral immunity. Semin Immunopath 2019;41:239-49. https://pubmed.ncbi.nlm.nih.gov/30547182/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Are women at higher risk of Covid-19 vaccine-related adverse events?