Challenges and insights in immunization in patients with demyelinating diseases: a bench-to-bedside and evidence-based review

ABSTRACT

Background: Infections are among the main causes of death in patients with demyelinating diseases of the central nervous system (CNSDD). Vaccines are effective methods in reducing hospitalization and death from infectious diseases, but they are challenging in patients with CNSDD because of autoimmunity and immunosuppression. Objectives: To summarize the pathophysiological rationale and main evidence for vaccine recommendations in patients with CNSDD. Methods: Specialists with different backgrounds on the subject: a neurologist specialized in demyelinating diseases, an infectious diseases specialist and an immunologist, presented a critical narrative review of vaccination literature in patients with CNSDD, highlighting which vaccines should or should not be administered and the best time for it. Results: Patients with DDSNC are at increased risk of vaccine-preventable viral and bacterial infections. Vaccines can prevent herpes zoster, hepatitis B reactivation, HPV-associated warts and tumors, viral and bacterial pneumonia, and meningitis. Live attenuated virus vaccines should not be used when the patient is on immunosuppression. Vaccines should be avoided during relapses. The greatest vaccine efficacy is given before treatment or at the end of medication. Conclusion:  Patients with DDSNC need differentiated immunization in relation to additional vaccines, contraindicated vaccines and timing of vaccination.

RESUMO

Antecedentes: Infecções estão entre as principais causas de morte de pacientes com doenças desmielinizantes do sistema nervoso central (DDSNC). Vacinas são métodos eficazes para reduzir internação e morte por doenças infecciosas, porém são desafiadoras em pacientes com DDSNC tanto pela autoimunidade quanto pela imunossupressão. Objetivos: Resumir o racional fisiopatológico e as principais evidências para as recomendações de vacinas em pacientes com DDSNC. Métodos: Especialistas com diferentes formações no tema: um neurologista especialista em doenças desmielinizantes, um infectologista e um imunologista, apresentam uma revisão crítica narrativa da Literatura de vacinação em pacientes com DDSNC, com destaque a quais vacinas devem ou não ser administradas e o melhor momento para isso. Resultados: Pacientes com DDSNC têm risco aumentado para infecções imunopreveníveis virais e bacterianas. Vacinas podem prevenir herpes zooster, reativação de hepatite B, verrugas e tumores associados ao HPV, pneumonias virais e bacterianas, além de meningites. Vacinas de vírus vivos atenuados não devem ser usadas quando o paciente está em uso de imunossupressão. Vacinas devem ser evitadas durante surtos. A maior eficácia vacinal é dada antes do tratamento ou ao final de doses de medicações. Conclusão: Os pacientes com DDSNC necessitam de imunização diferenciada em relação a vacinas adicionais, vacinas contraindicadas e melhor momento de vacinação.

Keywords:

Vaccines - Demyelinating Diseases - Multiple Sclerosis - Immunization - Neuromyelitis Optica

Palavras-chave:

Vacinas - Doenças Desmielinizantes - Esclerose Múltipla - Imunização - Neuromielite Óptica

Authors’ contributions:

GDS: drafted the original manuscript and contributed to the study design; VFO: contributed to the original draft of the manuscript; LOM: revised the manuscript for intellectual content.

Publication History

Received: 15 March 2022

Accepted: 29 April 2022

Article published online:
06 February 2023

• References

• 1 Luna G, Alping P, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M. et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol 2020; 77 (02) 184-191 https://doi.org/10.1001/jamaneurol.2019.3365
• 2 Harding K, Zhu F, Alotaibi M, Duggan T, Tremlett H, Kingwell E. Multiple cause of death analysis in multiple sclerosis: a population-based study. Neurology 2020; 94 (08) e820-e829 https://doi.org/10.1212/WNL.2022s1212022s1218907
• 3 Du Q, Shi Z, Chen H, Zhang Y, Wang J, Qiu Y. et al. Mortality of neuromyelitis optica spectrum disorders in a Chinese population. Ann Clin Transl Neurol 2021; 8 (07) 1471-1479 https://doi.org/10.1002/acn3.51404
• 4 Roush SW, Murphy TV. Vaccine-Preventable Disease Table Working Group. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA 2007; 298 (18) 2155-2163 https://doi.org/10.1001/jama.298.18.2155
• 5 Becker J, Ferreira LC, Damasceno A, Bichuetti DB, Christo PP, Callegaro D. et al. Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system. Arq Neuropsiquiatr 2021; 79 (11) 1049-1061 https://doi.org/10.1590/0004-282X-ANP-2021-0162
• 6 Jakimovski D, Weinstock-Guttman B, Ramanathan M, Dwyer MG, Zivadinov R. Infections, vaccines and autoimmunity: a multiple sclerosis perspective. Vaccines (Basel) 2020; 8 (01) 50-50 https://doi.org/10.3390/vaccines8010050
• 7 Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med 2018; 378 (02) 169-180 https://doi.org/10.1056/NEJMra1401483
• 8 McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA 2021; 325 (08) 765-779 https://doi.org/10.1001/jama.2020.26858
• 9 Lucchinetti CF, Guo Y, Popescu BFG, Fujihara K, Itoyama Y, Misu T. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol 2014; 24 (01) 83-97 https://doi.org/10.1111/bpa.12099
• 10 Huang W, Wang L, Zhang B, Zhou L, Zhang T, Quan C. Effectiveness and tolerability of immunosuppressants and monoclonal antibodies in preventive treatment of neuromyelitis optica spectrum disorders: a systematic review and network meta-analysis. Mult Scler Relat Disord 2019; 35: P246-P252 https://doi.org/10.1016/j.msard.2019.08.009
• 11 Abbas AK, Lichtman AH, Pillai S, Preface. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 10. Elsevier; 2021: 5-7
• 12 Metze C, Winkelmann A, Loebermann M, Hecker M, Schweiger B, Reisinger EC. et al. Immunogenicity and predictors of response to a single dose trivalent seasonal influenza vaccine in multiple sclerosis patients receiving disease-modifying therapies. CNS Neurosci Ther 2019; 25 (02) 245-254 https://doi.org/10.1111/cns.13034
• 13 Morris MA, Gibb DR, Picard F, Brinkmann V, Straume M, Ley K. Transient T cell accumulation in lymph nodes and sustained lymphopenia in mice treated with FTY720. Eur J Immunol 2005; 35 (12) 3570-3580 https://doi.org/10.1002/eji.200526218
• 14 Ricklin ME, Lorscheider J, Waschbisch A, Paroz C, Mehta SK, Pierson DL. et al. T-cell response against varicella-zoster virus in fingolimod-treated MS patients. Neurology 2013; 81 (02) 174-181 https://doi.org/10.1212/WNL.0b013e31829a3311
• 15 Arvin AM, Wolinsky JS, Kappos L, Morris MI, Reder AT, Tornatore C. et al. Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management. JAMA Neurol 2015; 72 (01) 31-39 https://doi.org/10.1001/jamaneurol.2014.3065
• 16 Mikulska M, Lanini S, Gudiol C, Drgona L, Ippolito G, Fernández-Ruiz M. et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid cells surface antigens. Clin Microbiol Infect 2018; 24 (Suppl. 02) S71-S82 https://doi.org/10.1016/j.cmi.2018.02.003
• 17 Redelman-Sidi G, Michielin O, Cervera C, Ribi C, Aguado JM, Fernández-Ruiz M. et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors). Clin Microbiol Infect 2018; Jun 1;24 Suppl 2 S95-107 https://doi.org/10.1016/j.cmi.2018.01.030
• 18 Fine AJ, Sorbello A, Kortepeter C, Scarazzini L. Central nervous system herpes simplex and varicella zoster virus infections in natalizumab-treated patients. Clin Infect Dis 2013; 57 (06) 849-852 https://doi.org/10.1093/cid/cit376
• 19 Evens AM, Jovanovic BD, Su YC, Raisch DW, Ganger D, Belknap SM. et al. Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol 2011; 22 (05) 1170-1180 https://doi.org/10.1093/annonc/mdq583
• 20 Lazdina U, Alheim M, Nyström J, Hultgren C, Borisova G, Sominskaya I. et al. Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent. J Gen Virol 2003; 84 (01) 139-146 https://doi.org/10.1099/vir.0.18678-0
• 21 Ciardi MR, Iannetta M, Zingaropoli MA, Salpini R, Aragri M, Annecca R. et al. Reactivation of hepatitis B virus with immune-escape mutations after ocrelizumab treatment for multiple sclerosi. Open Forum Infect Dis 2018; 6 (01) ofy356-ofy356 https://doi.org/10.1093/ofid/ofy356
• 22 Tsutsumi Y, Yamamoto Y, Ito S, Ohigashi H, Shiratori S, Naruse H. et al. Hepatitis B virus reactivation with a rituximab-containing regimen. World J Hepatol 2015; 7 (21) 2344-2351 https://doi.org/10.4254/wjh.v7.i21.2344
• 23 Triplett J, Kermode AG, Corbett A, Reddel SW. Warts and all: fingolimod and unusual HPV-associated lesions. Mult Scler 2019; 25 (11) 1547-1550 https://doi.org/10.1177/1352458518807088
• 24 Wan KM, Oehler MK. Rapid progression of low-grade cervical dysplasia into invasive cancer during natalizumab treatment for relapsing remitting multiple sclerosis. Case Rep Oncol 2019; 12 (01) 59-62 https://doi.org/10.1159/000496198
• 25 Krammer F. The human antibody response to influenza A virus infection and vaccination. Nat Rev Immunol 2019; 19 (06) 383-397 https://doi.org/10.1038/s41577-019-0143-6
• 26 Bar-Or A, Calkwood JC, Chognot C, Evershed J, Fox EJ, Herman A. et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: the VELOCE study. Neurology 2020; 95 (14) e1999-e2008 https://doi.org/10.1212/WNL.2022s1210000010380
• 27 Kappos L, Mehling M, Arroyo R, Izquierdo G, Selmaj K, Curovic-Perisic V. et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology 2015; 84 (09) 872-879 https://doi.org/10.1212/WNL.2022s1212022s1211302
• 28 Lebrun C, Vukusic S. French Group for Recommendations in Multiple Sclerosis (France4MS) and the Société Francophone de la Sclérose En Plaques (SFSEP). Immunization and multiple sclerosis: recommendations from the French multiple sclerosis society. Mult Scler Relat Disord 2019; 31: 173-188 https://doi.org/10.1016/j.msard.2019.04.004
• 29 Farez MF, Correale J, Armstrong MJ, Rae-Grant A, Gloss D, Donley D. et al. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology 2019; 93 (13) 584-594 https://doi.org/10.1212/WNL.2022s1212022s1218157
• 30 Apostolos-Pereira SL, Ferreira LC, Boaventura M, Sousa NAC, Martins GJ, d'Almeida JA. et al. Clinical features of COVID-19 on patients with neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm 2021; 8 (06) e1060 https://doi.org/10.1212/NXI.2022s1212022s1211060
• 31 Apóstolos-Pereira SL, Silva GD, Disserol CCD, Feo LB, Matos AMB, Schoeps VA. et al. Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach. Arq Neuropsiquiatr 2020; 78 (07) 430-49. https://doi.org/10.1590/0004-282X20200056
• 32 Campana IG, Silva GD, Apóstolos-Pereira SL, Callegaro D. Successful treatment with 5-day oral 1 g/day methylprednisolone of optic neuritis and myelitis in AQP4 positive Neuromyelitis Optica: a report of two cases. Neuroimmunol Rep 2021; 1: 100045 https://doi.org/10.1016/j.nerep.2021.100045
• 33 Lund FE, Randall TD. Effector and regulatory B cells: modulators of CD4+ T cell immunity. Nat Rev Immunol 2010; 10 (04) 236-247 https://doi.org/10.1038/nri2729
• 34 Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G. et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med 2017; 376 (03) 209-220 https://doi.org/10.1056/NEJMoa1606468
• 35 Moulis G, Lapeyre-Mestre M, Palmaro A, Sailler L. Infections in non-splenectomized persistent or chronic primary immune thrombocytopenia adults: risk factors and vaccination effect. J Thromb Haemost 2017; 15 (04) 785-791 https://doi.org/10.1111/jth.13622
• 36 Principi N, Esposito S. Development of pneumococcal vaccines over the last 10 years. Expert Opin Biol Ther 2018; 18 (01) 7-17 https://doi.org/10.1080/14712598.2018.1384462
• 37 Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J. et al. Eculizumab in Aquaporin-4-Positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019; 381 (07) 614-625 https://doi.org/10.1056/NEJMoa1900866
• 38 Winthrop KL, Mariette X, Silva JT, Benamu E, Calabrese LH, Dumusc A. et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).. Clin Microbiol Infect 2018; 24 (Suppl. 02) S21-S40 https://doi.org/10.1016/j.cmi.2018.02.002
• 39 Avasarala J, Sokola BS, Mullins S. Eculizumab package insert recommendations for meningococcal vaccinations: call for clarity and a targeted approach for use of the drug in neuromyelitis optica spectrum disorder. CNS Spectr 2021; 26 (03) 185-187 https://doi.org/10.1017/S1092852919001627
• 40 Pittock SJ, Weitz I, Howard JF, Sabatella G, Mehta S, Franklin J. Response to: eculizumab package insert recommendations for meningococcal vaccinations: call for clarity and a targeted approach for use of the drug in neuromyelitis optica spectrum disorder. CNS Spectr 2021; 26 (03) 195-196 https://doi.org/10.1017/S1092852920001625
• 41 DeStefano F, Verstraeten T, Jackson LA, Okoro CA, Benson P, Black SB. et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003; 60 (04) 504-509 https://doi.org/10.1001/archneur.60.4.504
• 42 Mouchet J, Salvo F, Raschi E, Poluzzi E, Antonazzo IC, De Ponti F. et al. Hepatitis B vaccination and the putative risk of central demyelinating diseases - a systematic review and meta-analysis. Vaccine 2018; 36 (12) 1548-1555 https://doi.org/10.1016/j.vaccine.2018.02.036
• 43 Mouchet J, Salvo F, Raschi E, Poluzzi E, Antonazzo IC, De Ponti F. et al. Human papillomavirus vaccine and demyelinating diseases-A systematic review and meta-analysis. Pharmacol Res 2018; 132: 108-118 https://doi.org/10.1016/j.phrs.2018.04.007
• 44 Achiron A, Dolev M, Menascu S, Zohar DN, Dreyer-Alster S, Miron S. et al. COVID-19 vaccination in patients with multiple sclerosis: What we have learnt by February 2021. Mult Scler 2021; 27 (06) 864-870 https://doi.org/10.1177/13524585211003476
• 45 Mealy MA, Cook LJ, Pache F, Velez DL, Borisow N, Becker D. et al. Vaccines and the association with relapses in patients with neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2018; 23: 78-82 https://doi.org/10.1016/j.msard.2018.05.003
• 46 Croce E, Hatz C, Jonker EF, Visser LG, Jaeger VK, Bühler S. Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation - a systematic review of randomized trials, observational studies and case reports. Vaccine 2017; 35 (09) 1216-1226 https://doi.org/10.1016/j.vaccine.2017.01.048
• 47 Garjani A, Patel S, Bharkhada D, Rashid W, Coles A, Law GR. et al. Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England. Mult Scler Relat Disord 2022; 57: 103458-103458 https://doi.org/10.1016/j.msard.2021.103458