Interferons beta |
No change in humoral response when compared to healthy individuals. Tested for influenza, meningococcal, pneumococcal and DT88. Ciotti JR, Valtcheva MV, Cross AH. Effects of MS disease-modifying therapies on responses to vaccinations: a review. Mult Scler Relat Disord. 2020 Oct 1;45:102439. https://doi.org/10.1016/j.msard.2020.102439 https://doi.org/10.1016/j.msard.2020.102...
,1111. 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 Sep 24;93(13):584-94. https://doi.org/10.1212/WNL.000000000000815 https://doi.org/10.1212/WNL.000000000000...
,1616. Bar-Or A, Freedman MS, Kremenchutzky M, Menguy-Vacheron F, Bauer D, Jodl S, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013 Aug 6;81(6):552-8. https://doi.org/10.1212/WNL.0b013e31829e6fbf https://doi.org/10.1212/WNL.0b013e31829e...
,1717. Olberg HK, Eide GE, Cox RJ, Jul-Larsen Å, Lartey SL, Vedeler CA, et al. Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy. Eur J Neurol. 2018 Mar;25(3):527-34. https://doi.org/10.1111/ene.13537 https://doi.org/10.1111/ene.13537...
. Level III evidence American Academy of Neurology (AAN); or 3 Centre for Evidence-Based Medicine - University of Oxford (CEBM) |
Glatiramer |
Possible slight reduction in seroprotection in response to influenza vaccinations, when compared to healthy individuals or those using beta-interferons88. Ciotti JR, Valtcheva MV, Cross AH. Effects of MS disease-modifying therapies on responses to vaccinations: a review. Mult Scler Relat Disord. 2020 Oct 1;45:102439. https://doi.org/10.1016/j.msard.2020.102439 https://doi.org/10.1016/j.msard.2020.102...
,1111. 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 Sep 24;93(13):584-94. https://doi.org/10.1212/WNL.000000000000815 https://doi.org/10.1212/WNL.000000000000...
,1717. Olberg HK, Eide GE, Cox RJ, Jul-Larsen Å, Lartey SL, Vedeler CA, et al. Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy. Eur J Neurol. 2018 Mar;25(3):527-34. https://doi.org/10.1111/ene.13537 https://doi.org/10.1111/ene.13537...
. Level III evidence (AAN); or 3 (CEBM) |
Teriflunomide |
Studies with small sample sizes have shown a slight reduction in immune response after vaccination against influenza and rabies1616. Bar-Or A, Freedman MS, Kremenchutzky M, Menguy-Vacheron F, Bauer D, Jodl S, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013 Aug 6;81(6):552-8. https://doi.org/10.1212/WNL.0b013e31829e6fbf https://doi.org/10.1212/WNL.0b013e31829e...
,1818. Bar-Or A, Wiendl H, Miller B, Benamor M, Truffinet P, Church M, et al. Randomized study of teriflunomide effects on immune responses to neoantigen and recall antigens. Neurol Neuroimmunol Neuroinflammation. 2015 Feb 12;2(2):e70. https://doi.org/10.1212/NXI.0000000000000070 https://doi.org/10.1212/NXI.000000000000...
. Level III evidence (AAN); or 2 (CEBM) The AAN recommendation is to not use live attenuated virus during treatment, or immediately before and up to 6 months after stopping treatment. Screening for tuberculosis (TB) and Varicella. Vaccinate for varicella (immune susceptible). |
Dimethyl fumarate |
A small sample study showed no difference in humoral response to vaccination, when compared to individuals using beta-interferons (DT, meningococcal and pneumococcal)1919. Von Hehn C, Howard J, Liu S, Meka V, Pultz J, Mehta D, et al. Immune response to vaccines is maintained in patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflammation. 2017 Nov 15;5(1):e409. https://doi.org/10.1212/NXI.0000000000000409 https://doi.org/10.1212/NXI.000000000000...
. Level III evidence (AAN); or 3 (CEBM) Post-hoc analysis of a subgroup of patients showed no relationship between lymphocyte count and response to vaccination1919. Von Hehn C, Howard J, Liu S, Meka V, Pultz J, Mehta D, et al. Immune response to vaccines is maintained in patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflammation. 2017 Nov 15;5(1):e409. https://doi.org/10.1212/NXI.0000000000000409 https://doi.org/10.1212/NXI.000000000000...
. Level IV evidence (AAN); or 4 (CEBM) |
Fingolimod |
Reduced immune response against influenza (A and B) and tetanus vaccines, when compared to patients using beta-interferons or healthy individuals1717. Olberg HK, Eide GE, Cox RJ, Jul-Larsen Å, Lartey SL, Vedeler CA, et al. Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy. Eur J Neurol. 2018 Mar;25(3):527-34. https://doi.org/10.1111/ene.13537 https://doi.org/10.1111/ene.13537...
,2020. 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 Mar 3;84(9):872-9. https://doi.org/10.1212/WNL.0000000000001302 https://doi.org/10.1212/WNL.000000000000...
-2222. Mehling M, Hilbert P, Fritz S, Durovic B, Eichin D, Gasser O, et al. Antigen-specific adaptive immune responses in fingolimod-treated multiple sclerosis patients. Ann Neurol. 2011 Feb;69(2):408-13. https://doi.org/10.1002/ana.22352 https://doi.org/10.1002/ana.22352...
. Level I/II evidence (AAN); or 2 (CEBM) Screening for hepatitis B. Vaccinate for varicella (immune susceptible). There may be a reduction in antibody titers produced by the vaccine after initiation of treatment with fingolimod2323. Signoriello E, Bonavita S, Sinisi L, Russo CV, Maniscalco GT, Casertano S, et al. Is antibody titer useful to verify the immunization after VZV vaccine in MS patients treated with fingolimod? A case series. Mult Scler Relat Disord. 2020 May;40:101963. https://doi.org/10.1016/j.msard.2020.101963 https://doi.org/10.1016/j.msard.2020.101...
. Level III evidence (AAN); or 3 (CEBM). |
Natalizumab |
Some studies suggest a reduced immune response against influenza and tetanus vaccines in a percentage of patients using natalizumab, when compared to those using beta-interferons or healthy individuals1717. Olberg HK, Eide GE, Cox RJ, Jul-Larsen Å, Lartey SL, Vedeler CA, et al. Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy. Eur J Neurol. 2018 Mar;25(3):527-34. https://doi.org/10.1111/ene.13537 https://doi.org/10.1111/ene.13537...
,2121. 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 Feb;25(2):245-54. https://doi.org/10.1111/cns.13034 https://doi.org/10.1111/cns.13034...
,2424. Kaufman M, Pardo G, Rossman H, Sweetser MT, Forrestal F, Duda P. Natalizumab treatment shows no clinically meaningful effects on immunization responses in patients with relapsing-remitting multiple sclerosis. J Neurol Sci. 2014 Jun 15;341(1-2):P22-7. https://doi.org/10.1016/j.jns.2014.03.035 https://doi.org/10.1016/j.jns.2014.03.03...
,2525. Olberg HK, Cox RJ, Nostbakken JK, Aarseth JH, Vedeler CA, Myhr KM. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014 Jul 1;20(8):1074-80. https://doi.org/10.1177/1352458513513970 https://doi.org/10.1177/1352458513513970...
. Level III evidence (AAN); or 3 (CEBM) |
Ocrelizumab |
The VELOCE study showed a reduction in immune response and seroconversion rate in patients treated with ocrelizumab compared to patients using beta-interferons or without treatment (tetanus, pneumococcal, meningococcal and influenza vaccines were evaluated)2626. 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 Oct;95(14):e1999-2008. https://doi.org/10.1212/WNL.0000000000010380 https://doi.org/10.1212/WNL.000000000001...
. Level II evidence (AAN); or 2 (CEBM). Vaccinate with live attenuated virus vaccine at least 4 weeks before starting treatment and 2 weeks before for other vaccines. If the patient is already using ocrelizumab, the vaccine should ideally be applied between the 3rd and 5th month after the last infusion, so that induction of immune memory is more effective. In the event that additional doses are required, it is recommended that both or at least one of them be performed in this time window (expert opinion). Level 5 evidence (CEBM). The AAN recommendation is not to use a live attenuated virus vaccine during treatment, or immediately before and up to 6 months after stopping treatment. Screening for hepatitis B. |
Ofatumumab |
Insufficient data. Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). Live attenuated virus vaccines generally contraindicated. In the absence of specific studies for ofatumumab, the authors recommend observing the same recommendations made for ocrelizumab (expert opinion). |
Alemtuzumab |
Insufficient data on medication interference in the humoral response after vaccination. A small study suggests that humoral responses to vaccination performed prior to treatment are maintained2727. McCarthy CL, Tuohy O, Compston DAS, Kumararatne DS, Coles AJ, Jones JL. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013 Sep 3;81(10):872-6. https://doi.org/10.1212/WNL.0b013e3182a35215 https://doi.org/10.1212/WNL.0b013e3182a3...
. Level IV evidence (AAN); or 4 (CEBM) Prophylaxis for herpes at the start of treatment for up to 2 months or until lymphocyte > 200. Screening for TB and varicella, vaccination for varicella before starting treatment. Immunization should be performed at least 4 to 6 weeks before infusion of alemtuzumab. If the patient has already used the medication, wait at least 3 months, and if possible 6 months, to perform the vaccination (expert opinion). The AAN recommendation is to not use live attenuated virus vaccine during treatment or immediately before, and up to 6 months after stopping treatment |
Cladribine |
Insufficient data. A recent small study showed that MS patients treated with cladribine achieved seroprotection levels after influenza vaccination, but only 33% met seroconversion criteria2828. Roy S, Boschert U. P059 - Analysis of influenza and varicella zoster virus vaccine antibody titers in patients with relapsing multiple sclerosis treated with cladribine tablets [Internet]. ACTRIMS Forum Virtual. 2021 [cited 2021 May 15]. Available from: Available from: https://www.abstractsonline.com/pp8/#!/9245/presentation/160 https://www.abstractsonline.com/pp8/#!/9...
. Level IV evidence (AAN); or 4 (CEBM) Consider immunization schedule for immunocompromised patients (expert opinion). Live attenuated virus vaccines generally contraindicated. Immunization should be performed at least 4 to 6 weeks before administration of cladribine. If patient has already used the medication, wait a minimum of at least 3 months, and if possible 6 months from the last dose before carrying out vaccination (expert opinion). Level 5 evidence (CEBM) |
Cyclophosphamide |
Insufficient data. Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). |
Rituximab |
The use of rituximab in studies of patients with rheumatoid arthritis has been associated with a reduction in humoral response and seroconversion rate to influenza and pneumococcal vaccines2929. Bingham CO, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010 Jan;62(1):64-74. https://doi.org/10.1002/art.2503 https://doi.org/10.1002/art.2503...
-3131. Eisenberg RA, Jawad AF, Boyer J, Maurer K, McDonald K, Prak ETL, et al. Rituximab-treated patients have a poor response to influenza vaccination. J Clin Immunol. 2013 Feb;33(2):388-96. https://doi.org/10.1007/s10875-012-9813-x https://doi.org/10.1007/s10875-012-9813-...
. Level III evidence (AAN); or 3 (CEBM) A study of patients with NMOSD showed similar data to the influenza vaccine3232. Kim W, Kim S-H, Huh S-Y, Kong S-Y, Choi YJ, Cheong HJ, et al. Reduced antibody formation after influenza vaccination in patients with neuromyelitis optica spectrum disorder treated with rituximab. Eur J Neurol. 2013 Jun;20(6):975-80. https://doi.org/10.1111/ene.12132 https://doi.org/10.1111/ene.12132...
. Level III evidence (AAN); or 3 (CEBM) Live attenuated virus vaccines are generally contraindicated. In the absence of specific studies for rituximab, the authors recommend observing the same recommendations made for ocrelizumab (expert opinion). |
Azathioprine |
Studies in patients with inflammatory bowel disease suggest that patients treated with azathioprine have a normal response to pneumococcal, tetanus and Haemophilus influenzae type B vaccines, but may have a reduced response to the hepatitis B vaccine3333. Dotan I, Werner L, Vigodman S, Agarwal S, Pfeffer J, Horowitz N, et al. Normal response to vaccines in inflammatory bowel disease patients treated with thiopurines. Inflamm Bowel Dis. 2012 Feb 1;18(2):261-8. https://doi.org/10.1002/ibd.21688 https://doi.org/10.1002/ibd.21688...
,3434. Andrade P, Santos-Antunes J, Rodrigues S, Lopes S, Macedo G. Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patients. J Gastroenterol Hepatol. 2015 Nov;30(11):1591-5. https://doi.org/10.1111/jgh.13001 https://doi.org/10.1111/jgh.13001...
. Level III evidence (AAN); or 3 (CEBM) Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). Live attenuated virus vaccines generally contraindicated. |
Mycophenolate mofetil |
Studies in kidney transplant patients with mycophenolate use suggest a reduction in humoral response and seroconversion rate for influenza vaccine (Mulley WR et al Kidney Int 2012; Tsujimura K et al Transplant Proc 2018). Level III evidence (AAN); or 3 (CEBM) Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). Live attenuated virus vaccines generally contraindicated. |
Methotrexate |
Some articles show a reduction in humoral response and seroconversion to influenza and pneumococcal viruses in patients with rheumatoid arthritis3535. McMahan ZH, Bingham CO 3rd. Effects of biological and non-biological immunomodulatory therapies on the immunogenicity of vaccines in patients with rheumatic diseases. Arthritis Res Ther. 2014 Dec 23;16(6):506. https://doi.org/10.1186/s13075-014-0506-0 https://doi.org/10.1186/s13075-014-0506-...
-3737. van Aalst M, Langedijk AC, Spijker R, de Bree GJ, Grobusch MP, Goorhuis A. The effect of immunosuppressive agents on immunogenicity of pneumococcal vaccination: a systematic review and meta-analysis. Vaccine. 2018 Sep 18;36(39):5832-45. https://doi.org/10.1016/j.vaccine.2018.07.039 https://doi.org/10.1016/j.vaccine.2018.0...
. Level III evidence (AAN); or 3 (CEBM) Discontinuation of treatment for 2 weeks can improve response to the influenza vaccine3838. Park JK, Lee YJ, Shin K, Ha Y-J, Lee EY, Song YW, et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018 Jun;77(6):898-904. http://doi.org/10.1136/annrheumdis-2018-213222 http://doi.org/10.1136/annrheumdis-2018-...
. Level II evidence (AAN); or 2 (CEBM) Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). Live attenuated virus vaccines generally contraindicated. |
Corticosteroids |
Live attenuated virus vaccines are contraindicated within 3 months after treatment discontinuation for adults using 20mg/day or children using 2mg/kg/day for more than 2 weeks. If the patient has used corticosteroids in high doses, there should be a gap of at least 15 days before carrying out the vaccination (expert opinion). Level 5 evidence (CEBM). |
Eculizumab |
Insufficient data. Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). Live attenuated virus vaccines generally contraindicated. Patients need to receive vaccines for meningococcus at least 2 weeks before starting treatment. If medication needs to be started sooner than this, prophylactic treatment should be given for 2 weeks |
Inebilizumab |
Insufficient data. Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). Live attenuated virus vaccines generally contraindicated. In the absence of specific studies for inebilizumab, the authors recommend observing the same recommendations made for ocrelizumab (expert opinion) |
Satralizumab |
Insufficient data. Consider immunization schedule for immunocompromised patients (expert opinion). Level 5 evidence (CEBM). Live attenuated virus vaccines generally contraindicated |