Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking disease-modifying drugs.
Methods:
A modified Delphi consensus process (October 2017–June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017.
Results:
Recommendations include the need for an ‘infectious diseases card’ of each patient’s infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received.
Conclusion:
Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
GBD 2016 Neurology Collaborators. Global, regional, and national burden of multiple sclerosis 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol2019; 18(3): 269–285.
2.
MontalbanXGoldRThompsonAJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler2018; 24(2): 96–120.
3.
HardingKWilliamsOWillisM, et al. Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis. JAMA Neurol2019; 76(5): 536–541.
4.
WinkelmannALoebermannMReisingerEC, et al. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol2016; 12(4): 217–233.
5.
FarezMFCorrealeJArmstrongMJ, et al. Practice guideline update: Vaccine-preventable infections and immunization in multiple sclerosis. Neurology2019; 93(13): 584–594.
6.
ZrzavyTKollaritschHRommerPS, et al. Vaccination in multiple sclerosis: Friend or foe?Front Immunol2019; 10: 1883.
Bar-OrACalkwoodJCChognotC, et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology. Epub ahead of print 29 July 2020. DOI: 10.1212/WNL.0000000000010380.
RubinLGLevinMJLjungmanP, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis2014; 58(3): e44–e100.
12.
MoriabadiNFNiewieskSKruseN, et al. Influenza vaccination in MS: Absence of T-cell response against white matter proteins. Neurology2001; 56(7): 938–943.
13.
OlbergHKEideGECoxRJ, et al. Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy. Eur J Neurol2018; 25(3): 527–534.
14.
EpsteinDJDunnJDeresinskiS.Infectious complications of multiple sclerosis therapies: Implications for screening, prophylaxis, and management. Open Forum Infect Dis2018; 5(8): ofy174.
15.
Bar-OrAFreedmanMSKremenchutzkyM, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology2013; 81(6): 552–558.
16.
CoolesFAAndersonAEDraytonT, et al. Immune reconstitution 20 years after treatment with alemtuzumab in a rheumatoid arthritis cohort: Implications for lymphocyte depleting therapies. Arthritis Res Ther2016; 18(1): 302.
17.
McCarthyCLTuohyOCompstonDA, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology2013; 81(10): 872–876.
18.
MehlingMEichinDHafnerP, et al. Avidity of vaccine-induced influenza IgG fails to increase in fingolimod-treated patients with MS. Neurol Neuroimmunol Neuroinflamm2014; 1(3): e28.
19.
MehlingMFritzSHafnerP, et al. Preserved antigen-specific immune response in patients with multiple sclerosis responding to IFNbeta-therapy. PLoS ONE2013; 8(11): e78532.
20.
MehlingMHilbertPFritzS, et al. Antigen-specific adaptive immune responses in fingolimod-treated multiple sclerosis patients. Ann Neurol2011; 69(2): 408–413.
21.
OlbergHKCoxRJNostbakkenJK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: An explorative study. Mult Scler2014; 20(8): 1074–1080.
22.
SchwidSRDeckerMDLopez-BresnahanM, et al. Immune response to influenza vaccine is maintained in patients with multiple sclerosis receiving interferon beta-1a. Neurology2005; 65(12): 1964–1966.
23.
VågbergMKumlinUSvenningssonA.Humoral immune response to influenza vaccine in natalizumab-treated MS patients. Neurol Res2012; 34(7): 730–733.
24.
von HehnCHowardJLiuS, et al. Immune response to vaccines is maintained in patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflamm2018; 5(1): e409.
25.
Bar-OrAWiendlHMillerB, et al. Randomized study of teriflunomide effects on immune responses to neoantigen and recall antigens. Neurol Neuroimmunol Neuroinflamm2015; 2(2): e70.
26.
KapposLMehlingMArroyoR, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology2015; 84(9): 872–879.
27.
KaufmanMPardoGRossmanH, et al. Natalizumab treatment shows no clinically meaningful effects on immunization responses in patients with relapsing-remitting multiple sclerosis. J Neurol Sci2014; 341(1–2): 22–27.
28.
BinghamCO3rdLooneyRJDeodharA, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: Results from a controlled clinical trial. Arthritis Rheum2010; 62(1): 64–74.
29.
van AssenSHolvastABenneCA, et al. Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum2010; 62(1): 75–81.
30.
GelinckLBTengYKRimmelzwaanGF, et al. Poor serological responses upon influenza vaccination in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis2007; 66(10): 1402–1403.
31.
KadoRSandersGMcCuneWJ.Suppression of normal immune responses after treatment with rituximab. Curr Opin Rheumatol2016; 28(3): 251–258.
32.
KimWKimSHHuhSY, et al. Reduced antibody formation after influenza vaccination in patients with neuromyelitis optica spectrum disorder treated with rituximab. Eur J Neurol2013; 20(6): 975–980.
33.
OrenSMandelboimMBraun-MoscoviciY, et al. Vaccination against influenza in patients with rheumatoid arthritis: The effect of rituximab on the humoral response. Ann Rheum Dis2008; 67(7): 937–941.
34.
RahierJFMoutschenMVan GompelA, et al. Vaccinations in patients with immune-mediated inflammatory diseases. Rheumatology2010; 49(10): 1815–1827.
35.
FarezMFCorrealeJ.Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol2011; 68(10): 1267–1271.
36.
RolfesLPawlitzkiMPfeufferS, et al. Fulminant MS reactivation following combined fingolimod cessation and yellow fever vaccination. Int J Mol Sci2019; 20(23): 5985.
37.
MoiolaLBarcellaVBenattiS, et al. The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement. Multiple Sclerosis Journal2020, Submitted.
38.
Di PietroAVisalliGAntonuccioGM, et al. Today’s vaccination policies in Italy: The national plan for vaccine prevention 2017-2019 and the Law 119/2017 on the mandatory vaccinations. Ann Ig2019; 31(2Suppl. 1): 54–64.
39.
GenentechI. RITUXAN® (rituximab) injection, for intravenous use, 2019. Drug data sheet.
40.
Sanofi Belgium. Summary of product characteristics: LEMTRADA 12 mg concentrate for solution for infusion, 2018. Drug data sheet.
41.
MarinMMartiMKambhampatiA, et al. Global varicella vaccine effectiveness: A meta-analysis. Pediatrics2016; 137(3): e20153741.
42.
FanPTYuDTClementsPJ, et al. Effect of corticosteroids on the human immune response: Comparison of one and three daily 1 gm intravenous pulses of methylprednisolone. J Lab Clin Med1978; 91(4): 625–634.
43.
WandingerKPWesselKTrillenbergP, et al. Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients. Acta Neurol Scand1998; 97(6): 359–365.
44.
BonanniPSaccoCDonatoR, et al. Lifelong vaccination as a key disease-prevention strategy. Clin Microbiol Infect2014; 20(Suppl. 5): 32–36.
45.
ChangKP.Vaccination for disease prevention and control: The necessity of renewed emphasis and new approaches. J Immunol Immunotech2014; 1(1): 10.17653/2374-9105.SSe0001.
46.
MailandMTFrederiksenJL.Vaccines and multiple sclerosis: A systematic review. J Neurol2017; 264(6): 1035–1050.
47.
LebrunCVukusicS.Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society. Mult Scler Relat Disord2019; 31: 173–188.
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