To Vaccinate, or Not, in Patients With MS

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Q) Are vaccines safe for patients with multiple sclerosis?

Vaccines are an important component of general disease prevention and are especially useful for patients with chronic illnesses, such as MS, who may be at elevated risk due to disability or medications that alter the immune system. Currently, there are many disease-modifying therapies that attempt to reduce relapses and impact the immune system, MRI activity, and disability. But is it safe for patients with MS to receive vaccines, given the multitude of studies suggesting that infections may increase relapse rate?

In 2002, the American Academy of Neurology published a summary of evidence and recommendations to provide guidance for practitioners.1 The data showed an increased risk for MS relapse during the weeks following infection.2,3 Therefore, preventing infections is beneficial for patients with MS. An analysis of studies in patients with MS who were vaccinated with inactivated vaccines (influenza, hepatitis B, tetanus) found sufficient evidence to support this practice. Studies of patients with MS who were given attenuated vaccines did not find enough evidence to support or reject these vaccines, except in the case of varicella. A study with sufficient follow-up concluded that varicella vaccination was safe for patients with MS who were not immunosuppressed. As a result of this effort, the MS Council for Clinical Practice Guidelines recommends that patients and health care providers follow the CDC’s indications for immunizations (www.cdc.gov/vaccines/schedules/hcp/adult.html).1

On the other hand, administration of the live-virus yellow fever vaccine in patients with clinically relapsing MS was correlated with an increased risk for disease progression in one study.4 The researchers followed disease progression, measured by relapses and MRI activity, in patients taking glatiramer acetate and interferon ß. Relapse rates reached 8.57 within three months after vaccination, compared to a rate of 0.67 the year prior to vaccine administration. Additionally, significant changes were seen on MRI; new or enlarging T2-weighted lesions and gadolinium-enhancing lesions were observed at three months, compared to 12 months prior and nine months after.4 Therefore, the researchers concluded that patients with MS traveling to endemic yellow fever areas should be cautioned regarding the risk for disease progression with vaccination, versus the risk for exposure to yellow fever.

Over the past decade, as newer therapies with different mechanisms of action have become available, concern has risen that patients may not respond to immunizations or may have a higher risk for infection after vaccination. For that reason, several studies have evaluated the ability of patients with MS to mount a normal antibody and cellular immune response after vaccine administration. In 2016, a study by Lin et al determined that patients who received daclizumab were able to mount a normal response after influenza vaccination.5

 

 

 

By contrast, Kappos et al, in a 2015 study, found that patients receiving fingolimod had lower response rates to influenza and tetanus booster vaccines than patients who took a placebo.6 Similarly, in a 2014 study, Olberg et al examined patients receiving interferon ß, glatiramer acetate, natalizumab, and mitoxantrone after receiving influenza and H1N1 vaccinations. The researchers found that those treated with any therapy other than interferon ß had a reduced rate of response and should therefore be considered for vaccine response analysis.7 Bar-Or et al also published data on response rates of patients treated with teriflunomide (7 mg or 14 mg) or interferon ß; rates were reduced with 14-mg teriflunomide compared to the other treatments—but most patients exhibited seroprotection regardless.8 Studying vaccine efficacy in 2013, McCarthy et al evaluated serum antibodies against common viruses before and after treatment with alemtuzumab and found that antibodies remained detectable six months post-alemtuzumab.9

In summary, most specialists agree that vaccines are helpful for patients with MS. However, due to the varied response rates among disease-modifying therapies and the correlation between infection and increased relapse rates, special care should be taken when treating this population. Generally, inactivated vaccines are safe, but seroprotection should be established to determine if a booster is necessary. Attenuated vaccines are generally safe for patients who are not immunosuppressed and can reduce the risk for infection if given prior to immunosuppression. After immunosuppression, attenuated vaccines should not be given until immune recovery has been established. —PP

Patricia Pagnotta, ARNP, MSN, CNRN, MSCN
Neurology Associates, PA
MS Center of Greater Orlando

References

1. Rutschmann OT, McCrory DC, Matchar DB. Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002;59(12):1837-1843.
2. Anderson O, Lygner PE, Bergstrom T, et al. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol. 1993;240(7):417-422.
3. Panitch HS, Bever CT, Katz E, Johnson KP. Upper respiratory tract infections trigger attacks of multiple sclerosis in patients treated with interferon. J Neuroimmunol. 1991; 36:125.
4. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011;68(10):1267-1271.
5. Lin YC, Winokur P, Blake A, et al. Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccine. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):1-10.
6. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology. 2015;84(9):872-879.
7. Olberg HK, Cox RJ, Nostbakken JK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014;20(8):1074-1080.
8. Bar-Or A, Freedman MS, Kremenchutzky M, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552-558.
9. McCarthy CL, Tuohy O, Compston DA, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872-876.

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MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.

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MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.

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MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.

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Q) Are vaccines safe for patients with multiple sclerosis?

Vaccines are an important component of general disease prevention and are especially useful for patients with chronic illnesses, such as MS, who may be at elevated risk due to disability or medications that alter the immune system. Currently, there are many disease-modifying therapies that attempt to reduce relapses and impact the immune system, MRI activity, and disability. But is it safe for patients with MS to receive vaccines, given the multitude of studies suggesting that infections may increase relapse rate?

In 2002, the American Academy of Neurology published a summary of evidence and recommendations to provide guidance for practitioners.1 The data showed an increased risk for MS relapse during the weeks following infection.2,3 Therefore, preventing infections is beneficial for patients with MS. An analysis of studies in patients with MS who were vaccinated with inactivated vaccines (influenza, hepatitis B, tetanus) found sufficient evidence to support this practice. Studies of patients with MS who were given attenuated vaccines did not find enough evidence to support or reject these vaccines, except in the case of varicella. A study with sufficient follow-up concluded that varicella vaccination was safe for patients with MS who were not immunosuppressed. As a result of this effort, the MS Council for Clinical Practice Guidelines recommends that patients and health care providers follow the CDC’s indications for immunizations (www.cdc.gov/vaccines/schedules/hcp/adult.html).1

On the other hand, administration of the live-virus yellow fever vaccine in patients with clinically relapsing MS was correlated with an increased risk for disease progression in one study.4 The researchers followed disease progression, measured by relapses and MRI activity, in patients taking glatiramer acetate and interferon ß. Relapse rates reached 8.57 within three months after vaccination, compared to a rate of 0.67 the year prior to vaccine administration. Additionally, significant changes were seen on MRI; new or enlarging T2-weighted lesions and gadolinium-enhancing lesions were observed at three months, compared to 12 months prior and nine months after.4 Therefore, the researchers concluded that patients with MS traveling to endemic yellow fever areas should be cautioned regarding the risk for disease progression with vaccination, versus the risk for exposure to yellow fever.

Over the past decade, as newer therapies with different mechanisms of action have become available, concern has risen that patients may not respond to immunizations or may have a higher risk for infection after vaccination. For that reason, several studies have evaluated the ability of patients with MS to mount a normal antibody and cellular immune response after vaccine administration. In 2016, a study by Lin et al determined that patients who received daclizumab were able to mount a normal response after influenza vaccination.5

 

 

 

By contrast, Kappos et al, in a 2015 study, found that patients receiving fingolimod had lower response rates to influenza and tetanus booster vaccines than patients who took a placebo.6 Similarly, in a 2014 study, Olberg et al examined patients receiving interferon ß, glatiramer acetate, natalizumab, and mitoxantrone after receiving influenza and H1N1 vaccinations. The researchers found that those treated with any therapy other than interferon ß had a reduced rate of response and should therefore be considered for vaccine response analysis.7 Bar-Or et al also published data on response rates of patients treated with teriflunomide (7 mg or 14 mg) or interferon ß; rates were reduced with 14-mg teriflunomide compared to the other treatments—but most patients exhibited seroprotection regardless.8 Studying vaccine efficacy in 2013, McCarthy et al evaluated serum antibodies against common viruses before and after treatment with alemtuzumab and found that antibodies remained detectable six months post-alemtuzumab.9

In summary, most specialists agree that vaccines are helpful for patients with MS. However, due to the varied response rates among disease-modifying therapies and the correlation between infection and increased relapse rates, special care should be taken when treating this population. Generally, inactivated vaccines are safe, but seroprotection should be established to determine if a booster is necessary. Attenuated vaccines are generally safe for patients who are not immunosuppressed and can reduce the risk for infection if given prior to immunosuppression. After immunosuppression, attenuated vaccines should not be given until immune recovery has been established. —PP

Patricia Pagnotta, ARNP, MSN, CNRN, MSCN
Neurology Associates, PA
MS Center of Greater Orlando

 

Q) Are vaccines safe for patients with multiple sclerosis?

Vaccines are an important component of general disease prevention and are especially useful for patients with chronic illnesses, such as MS, who may be at elevated risk due to disability or medications that alter the immune system. Currently, there are many disease-modifying therapies that attempt to reduce relapses and impact the immune system, MRI activity, and disability. But is it safe for patients with MS to receive vaccines, given the multitude of studies suggesting that infections may increase relapse rate?

In 2002, the American Academy of Neurology published a summary of evidence and recommendations to provide guidance for practitioners.1 The data showed an increased risk for MS relapse during the weeks following infection.2,3 Therefore, preventing infections is beneficial for patients with MS. An analysis of studies in patients with MS who were vaccinated with inactivated vaccines (influenza, hepatitis B, tetanus) found sufficient evidence to support this practice. Studies of patients with MS who were given attenuated vaccines did not find enough evidence to support or reject these vaccines, except in the case of varicella. A study with sufficient follow-up concluded that varicella vaccination was safe for patients with MS who were not immunosuppressed. As a result of this effort, the MS Council for Clinical Practice Guidelines recommends that patients and health care providers follow the CDC’s indications for immunizations (www.cdc.gov/vaccines/schedules/hcp/adult.html).1

On the other hand, administration of the live-virus yellow fever vaccine in patients with clinically relapsing MS was correlated with an increased risk for disease progression in one study.4 The researchers followed disease progression, measured by relapses and MRI activity, in patients taking glatiramer acetate and interferon ß. Relapse rates reached 8.57 within three months after vaccination, compared to a rate of 0.67 the year prior to vaccine administration. Additionally, significant changes were seen on MRI; new or enlarging T2-weighted lesions and gadolinium-enhancing lesions were observed at three months, compared to 12 months prior and nine months after.4 Therefore, the researchers concluded that patients with MS traveling to endemic yellow fever areas should be cautioned regarding the risk for disease progression with vaccination, versus the risk for exposure to yellow fever.

Over the past decade, as newer therapies with different mechanisms of action have become available, concern has risen that patients may not respond to immunizations or may have a higher risk for infection after vaccination. For that reason, several studies have evaluated the ability of patients with MS to mount a normal antibody and cellular immune response after vaccine administration. In 2016, a study by Lin et al determined that patients who received daclizumab were able to mount a normal response after influenza vaccination.5

 

 

 

By contrast, Kappos et al, in a 2015 study, found that patients receiving fingolimod had lower response rates to influenza and tetanus booster vaccines than patients who took a placebo.6 Similarly, in a 2014 study, Olberg et al examined patients receiving interferon ß, glatiramer acetate, natalizumab, and mitoxantrone after receiving influenza and H1N1 vaccinations. The researchers found that those treated with any therapy other than interferon ß had a reduced rate of response and should therefore be considered for vaccine response analysis.7 Bar-Or et al also published data on response rates of patients treated with teriflunomide (7 mg or 14 mg) or interferon ß; rates were reduced with 14-mg teriflunomide compared to the other treatments—but most patients exhibited seroprotection regardless.8 Studying vaccine efficacy in 2013, McCarthy et al evaluated serum antibodies against common viruses before and after treatment with alemtuzumab and found that antibodies remained detectable six months post-alemtuzumab.9

In summary, most specialists agree that vaccines are helpful for patients with MS. However, due to the varied response rates among disease-modifying therapies and the correlation between infection and increased relapse rates, special care should be taken when treating this population. Generally, inactivated vaccines are safe, but seroprotection should be established to determine if a booster is necessary. Attenuated vaccines are generally safe for patients who are not immunosuppressed and can reduce the risk for infection if given prior to immunosuppression. After immunosuppression, attenuated vaccines should not be given until immune recovery has been established. —PP

Patricia Pagnotta, ARNP, MSN, CNRN, MSCN
Neurology Associates, PA
MS Center of Greater Orlando

References

1. Rutschmann OT, McCrory DC, Matchar DB. Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002;59(12):1837-1843.
2. Anderson O, Lygner PE, Bergstrom T, et al. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol. 1993;240(7):417-422.
3. Panitch HS, Bever CT, Katz E, Johnson KP. Upper respiratory tract infections trigger attacks of multiple sclerosis in patients treated with interferon. J Neuroimmunol. 1991; 36:125.
4. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011;68(10):1267-1271.
5. Lin YC, Winokur P, Blake A, et al. Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccine. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):1-10.
6. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology. 2015;84(9):872-879.
7. Olberg HK, Cox RJ, Nostbakken JK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014;20(8):1074-1080.
8. Bar-Or A, Freedman MS, Kremenchutzky M, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552-558.
9. McCarthy CL, Tuohy O, Compston DA, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872-876.

References

1. Rutschmann OT, McCrory DC, Matchar DB. Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002;59(12):1837-1843.
2. Anderson O, Lygner PE, Bergstrom T, et al. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol. 1993;240(7):417-422.
3. Panitch HS, Bever CT, Katz E, Johnson KP. Upper respiratory tract infections trigger attacks of multiple sclerosis in patients treated with interferon. J Neuroimmunol. 1991; 36:125.
4. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011;68(10):1267-1271.
5. Lin YC, Winokur P, Blake A, et al. Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccine. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):1-10.
6. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology. 2015;84(9):872-879.
7. Olberg HK, Cox RJ, Nostbakken JK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014;20(8):1074-1080.
8. Bar-Or A, Freedman MS, Kremenchutzky M, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552-558.
9. McCarthy CL, Tuohy O, Compston DA, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872-876.

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