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March 11 2021
Professor Luisa Klotz
Dr Sharmilee Gnanapavan
This Medical Education program is funded and organized by Merck KGaA, Darmstadt, Germany.
The materials contained on the site are intended for educational purposes only and must not be considered medical advice from a healthcare professional.
This program is intended for healthcare professionals only.
This program is not intended for US healthcare professionals. Merck KGaA, Darmstadt, Germany only sponsors medical education programs for US healthcare
professionals consistent with ACCME guidelines or similar grantors of accreditation, and consistent with US law and guidance. GL-NONNI-00322 | March 2021
Welcome to acadeMe
A knowledge forum for healthcare professionals with a focus on development,
access and exchange of best-in-class knowledge about MS
This live educational programme is initiated, funded and organised by
Merck KGaA, Darmstadt, Germany
Our faculty and their disclosures
Professor Luisa Klotz Dr Sharmilee Gnanapavan
Department of Neurology, University Barts and The London School of Medicine
Hospital Münster, Albert-Schweitzer- and Dentistry, Queen Mary University
Campus, Münster, Germany London, London, UK
Prof. Klotz has received compensation for serving on Dr Gnanapavan reports consulting fees/honoraria:
Scientific Advisory Boards for Alexion, Genzyme, Biogen, Genzyme, Teva, Roche, Merck, Novartis,
Janssen, Merck, Novartis and Roche. She received Neurodiem, Janssen Cilag
speaker honoraria and travel support from Bayer, Travel support: CMSC, Teva, Novartis, Genzyme,
Biogen, Genzyme, Grifols, Merck, Novartis, Roche, Biogen, ECTRIMS, National Multiple Sclerosis
Santhera and Teva. She receives research support Society and MS Research Australia.
from the German Research Foundation, the IZKF Grant support: UK MS Society, National Multiple Sclerosis
Münster, IMF Münster, Biogen, Novartis and Merck Society, NIHR, ECTRIMS, Genzyme, Takeda and Merck
The views expressed here reflect the clinical experience and opinions of the experts and do not
necessarily reflect guideline recommendations or Merck company position.
This presentation was given on March 11 2021, and represents the knowledge base at this time.
Infection risk and the immune system in MS patients
Time
Session Presenter
(CET)
Welcome, introduction, and objectives to the virtual meeting including topics to be
17:00–17:05
discussed and the interactive sessions
17:05–17:15 An update on the overall risk of infection associated with treatment of MS with DMTs
Are patients with MS receiving DMT at more risk of COVID-19 than the healthy Luisa Klotz
17.15−17:35
population? and
An evaluation of the role of vaccination in the routine treatment of MS patients Sharmilee Gnanapavan
17:35−17:55 receiving DMTs and what do we need to know about COVID-19 vaccines when
treating MS patients
17:55–18:00 Summary and close of virtual meeting
The views expressed here reflect the clinical experience and opinions of the experts and do not
necessarily reflect guideline recommendations or Merck company position.
This presentation was given on March 11 2021, and represents the knowledge base at this time.
Learning objectives
To understand the properties of
To understand what the
the immune system and
infection risks are for MS
how it contributes to
patients receiving DMTs
reduce infection
To understand the general
To learn how to reduce
vaccination needs in MS
the impact of the COVID-19
patients and to prepare for
pandemic on MS patients
future COVID-19 vaccines
Risk of infection and the use of DMTs
Considerations for MS practice in the ‘new normal’
Evolution of new models of care in critical times; need to consider the risk to the patient, use of
DMTs during periods of infection and vaccination implications
Risks to the Evaluation of use of Vaccination implications
patient DMTs
DMT, disease modifying therapy.
Infection-related health care utilization was increased in
people with MS across all age groups
Percentage of cohort Infection rate (per 10,000 patient years)
0 5 10 15 20 25 0 20 40 60 80
10.9
Overall Urinary tract 76
5
infection 23
12.2
Males
5.2
33
Pneumonia/RTI
10.4 13
Females
5
6.9 22
Age 18-39 Intestinal
3.8 9
9.9
Age 40-49
4.1 Skin and 16
Skin and subcutaneous tissue
subcutaneous tissue 7
13.3
Age 50-59
5.1
14
20.4 Sepsis
Age 60+ 7
10.8
MS population Control MS population Control
Population-based health administrative data from British Columbia, Canada of people with MS who were followed from their first
demyelinating claim until death, emigration, or study end (1996–2013)
MS, multiple sclerosis; RTI, respiratory tract infection. Wijnands JMA, et al Mult Scler J 2017; 23:1506–16
Infection risks with DMTs: comparative summary based on
list of adverse reactions in EU labela,b
NO IDENTIFIED VERY FREQUENCY
UNCOMMON COMMON
RISK COMMON UNKNOWN
IFN β-1a1
IFN β-1b2
No identified risk
Peg-IFN β-1a3
im IFN β-1a4
Glatiramer acetate5 Herpes zoster Bronchitis, herpes simplex Influenza
Influenza, URTI, bronchitis, sinusitis, pharyngitis,
Teriflunomide6
gastroenteritis, oral herpes, laryngitis
Cladribine tablets7 Oral herpes, dermatomal herpes zosterc
Dimethyl fumarate8 Gastroenteritis PML, Herpes zoster
Siponimod9 Herpes zoster
PML
Fingolimod10 Pneumonia Herpes, bronchitis, Tinea versicolor Influenza, sinusitis
Cryptococcal infection
Natalizumab11 PML UTI, Nasopharyngitis
Onychomycosis, gingivitis, fungal skin Listeriosis/listeria
Herpes zoster, LRTI, gastroenteritis, oral and
infection, tonsillitis, acute sinusitis, meningitis
Alemtuzumab12 vulvovaginal candidiasis, influenza, ear infection, URTI, UTI, herpes
cellulitis, pneumonitis, tuberculosis, Epstein-Barr virus
pneumonia, vaginal infection, tooth infection
cytomegalovirus infection reactivation
Sinusitis, bronchitis, oral herpes, gastroenteritis, URTI,
Ocrelizumab13 RTI, viral infection, herpes zoster, nasopharyngitis,
conjunctivitis, cellulitis influenza
aEU labels accessed April 2020; bFrequency: Very common (≥1/10), Common (≥1/100 toPatients with MS are at an increased risk of infections
in real-world populations
Swedish nationwide cohort study of patients with RRMS and treatment with interferon beta and glatiramer
acetate, fingolimod, natalizumab, or rituximab between January 1, 2011, and December 31, 20171
HR=2.34 (1.65–3.33) 300
35
247.1 252.4 Data relating to rituximab
Crude incidence rate
30 250
/1000 patient years
HR=1.53 (0.99–2.35)
207.3 215.6 may have relevance for
25 200
HR=1.81 (1.21–2.71)
19.7 the use of other anti-
20 149.0
150 CD20 therapies in the
HR=0.65 (0.47–0.89) 14.3
15 11.4 treatment of MS
8.9 100
10
5.2
5 50
0 0
Rate of infection Any antibiotic use
General population IFN + GA Fingolimod Natalizumab Rituximab
The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab
was associated with the highest rate of serious infections
Different risk profiles should inform the risk-benefit assessments of these treatments
HR adjusted for age and sex; GA, Glatiramer acetate; HR, hazard ratio; IFN, interferon; RRMS, relapsing remitting multiple sclerosis
1. Luna G et al. JAMA Neurol. 2020;77:184–91DMTs are associated with varying Grade 3–4 lymphopenia
that persist for varying durations
Percentage with grade 3/4 lymphopenia seen in pivotal Time for lymphocyte recovery to within normal range
RCTs following treatment discontinuation
0.0 20.0 40.0 60.0 80.0 100.0
B-cell recovery within 6 months; CD3+ and CD4+ lymphocyte recovery by
Alemtuzumab 99.0 12-months1
Recover to either normal lymphocyte counts or grade 1 lymphopenia 4 weeks post-Tx4
According to CTCAE v5.0 Low lymphocyte counts are maintained with chronic daily dosing. ≥1–2
Fingolimod 18.0
Grade 1 (mild lymphopenia) months post-Tx5
Interferon • ALC < lower limit of normal to 800/mm3
4.3 Resolves on treatment6
Grade 2 (moderate lymphopenia)
Ocrelizumab 1.0 • ALC < 800–500/mm3 After each infusion: B-cell recovery within 72 weeks7
Grade 3 (severe lymphopenia)
Siponimod 1.0 Dose-dependent reduction in peripheral lymphocyte count to 20-30% of
• ALC < 500–200/mm3
baseline values. Normal range in 90% of patients within 10 days8
Grade 4 < 200/mm3
Teriflunomide 0.0 Mild mean reduction in lymphocyte count until the end of the treatment.
Recovery from Grade 1/2 lymphopenia 10.6–16.6 weeks post-Tx9,10
ALC, absolute lymphocyte count; CTCAE, Common Terminology Criteria for Adverse Events; DMF, Dimethyl fumarate; DMT, disease-modifying drug; RCT, randomized clinical trial; Tx, treatment.
1. Lemtrada® EU SmPC, July 2020; 2. MAVENCLAD® SmPC, January 2020; 3. Fox, RJ et al. Neurol Clin Pract 2016;6:220–9; 4. Tecfidera® EU SmPC, January 2020; 5. Gilenya® EU SmPC, December
2019; 6. Rebif® EU SmPC, January 2020; 7. Ocrevus® EU SmPC, June 2020; 8. Mayzent® EU SmPC, 2020; 9. Aubagio® EU SmPC, February 2020; 10. Schweitzer F, et al. J Neurol 2020; eb 8. doi:
10.1007/s00415-019-09690-6.Long-term immunosuppression seen with DMT
Treatment with fingolimod Ocrelizumab decreases Natalizumab causes
leads to persistent reduction CD19+ cells to negligible reductions in B cells and T Dimethyl fumarate causes
in peripheral lymphocyte levels by week 2, with cells in the CSF that persist Lowerchronic reductions
in
Limit of Normal
counts, with recovery upon return to LLN more than 1 for up to 6 months after lymphocytes4
cessation1 year after cessation2 treatment cessation3In CLARITY, cladribine tablets exert differential effects on
specific lymphocyte subsets1
• Lymphocyte recovery began soon after treatment in each of years 1 and 2
• Median lymphocyte counts (all) recovered to the normal range and CD19+ B cells recovered to threshold values by week 84, approximately 30
weeks after the last dose of cladribine tablets in year 2
• Median CD4+ T cell counts recovered to threshold values by week 96 (~43 weeks after the last dose of cladribine tablets in year 2)
• Median CD8+ cell counts never dropped below the threshold value
CD19+ B lymphocytes CD4+ T lymphocytes CD8+ T lymphocytes
0.40 1.2
0.6
Median (Q1–Q3) CD19+ (109/L)
Median (Q1–Q3) CD8+ (109/L)
Median (Q1–Q3) CD4+ (109/L)
1.0
0.35
0.9 0.5
0.30 0.8
0.25 0.7 0.4
0.6
0.20 0.3
0.5
0.15 0.4
0.2
0.10 0.3 LLN: 0.35 x 109/L LLN: 0.2 x 109/L
LLN: 0.1 x 109/L 0.2
0.05 0.1
0.1
0 0 0
0 24 48 72 96 120 144 168 192 216 240 0 24 48 72 96 120 144 168 192 216 240 0 24 48 72 96 120 144 168 192 216 240
Weeks Weeks Weeks
Threshold counts were defined as 0.10 × 109 , 0.35 × 109, and 0.20 × 109 cells/L for CD19+ B cells, and CD4+ and CD8+ T cells, respectively.
Thresholds for CD19+ B cells and CD8+ T cells were chosen based on values used in previous studies of disease modifying therapies for multiple sclerosis and the threshold for CD4+ T cells was chosen
based on the value used for initiating antiretroviral therapy in patients with HIV below which there is an increased risk of infection
1. Comi G et al Mult Scler Relat Disord. 2019;29:168–74.Reported incidence of respiratory-related infections
according to grade of lymphopeniaa,b
Adj-AE per 100 PY
0 2 4 6 8 10 12 14 16
Nasopharyngitis 5.24
13.48
Upper RTI 3.41
9.67
Pharyngitis 0.73
4.51
Influenza 2.75
3.35
Bronchitis 1.72
2.23
Viral upper RTI 0.64
2.23
Lower RTI 0
1.12
RTI bacterial 0
1.11
Sinusitis 0.95
1.11
Tonsilitis 0.27
1.11
Tracheitis 0.12
1.16
Tonsilitis streptococcal 0
1.11
Tuberculosis 0
1.11 During Grade 2 or less During Grade 3 or 4
aAllstudies that used Cladribine tablets monotherapy, matching the recommended dose: CLARITY, CLARITY EXT and ORACLE-MS + follow-up in PREMIERE;
bDefined as the onset of the Grade 3 or 4 lymphopenia to first Grade 2 or lower plus 2 weeks.
Adj-AE per 100 PY, adjusted AE incidences per 100 patient-years; RTI, respiratory tract infection.
Cook S et al. Mult Scler Relat Disord 2019;29:157–67 (suppl.).French COVISEP registry: Neurological disability, age and
obesity were risk factors for severe COVID-19 infection
Multivariate analysis of factors influencing risk of severe COVID-19 defined by
a severity scorea of 3 or more
Lower risk of Higher risk of
Group OR (95% CI) severe outcome severe outcome
Had a COVID-19 Age per 10 years 1.85 (1.39–2.46)
MS patients severity score >3a Male 1.61 (0.83–3.11)
Obesity 2.99 (1.03–8.70)
Cardiac comorbidity 2.68 (0.97–7.40)
EDSS 3), obesity and older age were at highest risk of severe COVID-19 infection
aCOVID-19 severity was assessed on a 7-point ordinal scale (ranging from 1=not hospitalized with no limitations on activities to 7=death) with a cut-off at 3 (hospitalized and not requiring supplemental
oxygen).
CI, confidence interval; COVID-19, coronavirus disease 2019; DMT, disease-modifying drug; EDSS, expanded disability status scale; OR, odds ratio.
Louapre C, et al. JAMA Neurol 2020;77:1079–88.MS Global Data Sharing Initiative: Anti-CD20 DMTs
were associated with worse COVID-19 outcomes
Aim: To analyse the risk of severe COVID-19 in patients with MS treated with
anti-CD20 DMTs vs other DMTs
n=343 patients using anti-CD20 DMTs,
n=492 patients using other DMTs
• x1.5 hospital admission, x2.6 ICU admission and x3.1 ventilation use was more frequent with anti-CD20 use
• There was no significant difference in death between anti-CD20 use vs other DMTs
COVID-19, coronavirus disease 2019; DMT, disease-modifying therapy; ICU, intensive care unit; MS, multiple sclerosis.
Simpson-Yap S. et al. ACTRIMS-ECTRIMS 2020.What is required for an adequate vaccination
immune response?
1. Phagocytosis by
innate immune cells1,2 2. Adaptive immune cell activation
and antibody production1,2 3. Generation of memory cells for
rapid response to virus1,2
• Innate immune cells • Phagocytes present antigens to B • Memory cells enable the body to mount
digest pathogens and T cells, which become activated a rapid response upon re-exposure to
present viral antigens • B cells produce large quantities of the virus
antigen-specific antibodies • Upon re-exposure to the virus, memory
B cells can quickly produce virus-
specific antibodies
> > M
B cells can
recognize
free antigens
directly
Antibodies, produced by B cells, are the primary vaccine-induced immune effectors;
Long-term vaccine protection requires the persistence of the ability to generate
vaccine-induced antibodies and other immune responses against a specific viral antigen3
M, memory.
1. Warrington R et al. Allergy Asthma Clin Immunol 2011;7(Suppl 1); 2. Clem AS. J Glob Infect Dis 2011;3:73–8; 3. Siegrist CA. Vaccine Immunology, Elsevier. Available at:
https://www.who.int/immunization/documents/Elsevier_Vaccine_immunology.pdf.Effect of ocrelizumab on vaccine responses in patients with
multiple sclerosis (The VELOCE study)
Proportion of patients with ≥4-fold increase Influenza vaccine response:
in tetanus antibody titre pre-vaccination/post-vaccination GMTs
0.0 100.0 200.0 300.0 400.0
127.0
24.4
54.5 A/Hong Kong/4801/2014 121.3
8 weeks 52.8
23.9 143.6
Treatment difference 36.7
B/Brisbane/60/2008
of −30.7% 49.4
33.7
324.0
26.1
A/Switzerland/9715293/2013
60.6 86.7
4 weeks 65.7
24.2 Control (IFN or no DMT) 189.2
OCR 27.1
B/Phuket/3073/2013 71.3
49.3
390.8
0 20 40 60 80 39.6
A/California/7/2009
Proportion of Patients (%) 66.3
115.3
Positive response rate to TT vaccine at 8 weeks was 23.9% in Control (IFN or no DMT) GMT-post Control (IFN or no DMT) GMT-pre
the OCR vs 54.5% in the control group. Ocrelizumab GMT-post Ocrelizumab GMT-pre
Peripherally B-cell depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines.
Use of standard, non-live, vaccines while on OCR treatment remains a consideration.
102 patients were randomized 2:1 to ocrelizumab versus placebo and were drawn from 19 centers in the United States and 2 centers in Canada between October 2015 and August 2016.
GMT, geometric mean titres; IFN, interferon; OCR, ocrelizumab; TT, tetanus toxoid
Bar-Or A et al. Neurology 2020;95:e1999-e2008Fingolimod: Immune responses to influenza vaccine in
patients with MS
Seasonal influenza Tetanus toxoid Randomized, multi-centre, placebo-controlled
OR: 0.62
study evaluating immune responses in
100 OR: 0.21 OR: 0.25 OR: 0.43
(95% CI: 0.08, 0.54) (95% CI: 0.11, 0.57) (95% CI: 0.20, 0.92) (95% CI: 0.29, 1.33) fingolimod-treated patients with MS
85
• 138 randomized patients (fingolimod 95, placebo
Percentage responder rate
80 75 43), 136 completed the study
61
60 54
49 Fingolimod-treated patients with MS were able
43
40 38 to mount immune responses against antigens
40
• Majority met regulatory criteria indicating
seroprotection
20
• Response rates were reduced compared with
placebo-treated patients and this should be
0 considered when vaccinating patients on
Week 3 Week 6 Week 3 Week 6
fingolimod
Fingolimod (0.5 mg) Placebo
Randomized, multicentre, placebo-controlled study evaluating immune responses in fingolimod-treated patients with MS. Influenza vaccine contained antigens of California, Perth, and Brisbane virus strains
1. Kappos L, et al. Neurology. 2015;84:872–9.MAGNIFY-MS: Seasonal influenza vaccine response in
relation to lymphopenia status and vaccination timing
In a small retrospective investigation of the MAGNIFY-MS study, antibody titres were measured in patients who were
vaccinated with a seasonal influenza vaccine at different time points during treatment with Cladribine tablets (n=12)
Lymphopenia status:
4x titre increase Grade 2 (n=5)
Grade 1 (n=2)
Normal (n=5)
2x titre increase
Cladribine tablets
treatment course†
Seroprotection
maintained*
No seroprotection
Month 0 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5
Year 1 Year 2
*Seroprotection was defined as HAI titres ≥40.
†4–5 days of at-home oral treatment: Cladribine tablets are administered as 2 courses separated by 1 year, each course consisting of 2 treatment weeks (a maximum of 20 days of treatment). On treatment
days, patient receives 1 or 2 tablets as a single daily dose, depending on body weight. Treatment with Cladribine tablets must be initiated and supervised by a physician experienced in the treatment of MS.
HAI, haemagglutination inhibition; Roy S, Boschert U. ACTRIMS Forum 2021 [P059].MS vaccination guidelines and consensus statements
Nat Rev Neurol 2012 Mult Scler Relat Disord 2019
Nat Rev Neurol 2012
Neurology 2019
Mult Scler J 2021
Pract Neurol 2020
Loebermann M, et al. Nat Rev Neurol. 2012;8:143–51; Farez MF, et al. Neurology. 2019;93:584–94; Reyes S, et al. Pract Neurology 2020; 20:435–45;
Lebrun C, et al. Mult Scler Relat Disord 2019;31:173–88; Riva A, et al. Mult Scler J 2021;27:347–59.Recommendations for MS patients1
Diphtheria, tetanus, Single im dose
pertussis and between weeks Pregnant women
inactivated polio 16 and 32
im dose at People with MS ≤25 years who are partially immunized or
HPV months 0, 2 & 6 unimmunized against HPV
Trivalent inactivated vaccine to patients ≥65
Single dose
Influenza years. Quadrivalent inactivated vaccine to
annually
patients 65 years.
Pneumococcal polysaccharide Patients with anticipated immunosuppression (long-term),
vaccine compromised pulmonary function, high EDSS score (≥7)
No evidence that hepatitis B, HPV, influenza, tetanus, diphtheria, pertussis, polio, BCG, typhoid, TBE or MMR
vaccinations increase the risk of developing MS
BCG, Bacillus Calmette–Guérin vaccine; HPV, human papilloma virus; im, intramuscular administration; MMR, measles, mumps, rubella; Sc, subcutaneous administration; TBE, tick-borne encephalitis;
VZV, varicella zoster virus
1. Adapted from Reyes S, et al. Pract Neurology 2020; 20:435–45Recommendations for MS patients1
MMR vaccines im/sc dose given Patients with MS who are susceptible to MMR
(Live-attenuated vaccine) 4 weeks apart infections
Different doses according to vaccine
• Varilax – 2 sc doses • People with MS who are susceptible to primary
given 6 weeks apart VZV infection
VZV/Zoster vaccines
• Varivax – 2 im/sc doses • People with MS who are susceptible to primary
(Live-attenuated – Varilix,
Varivax, Zostavaxa, or given 4–8 weeks apart VZV infection
recombinant vaccine – • Zostavax – 1 im/sc dose • Prevention of herpes zoster and post-herpetic
Shingrix)
neuralgia in people with MS aged 70–79 yearsb
• Shingrix – 2 im doses • Prevention of herpes zoster and post-herpetic
separated by 2–6 months neuralgia in people with MS aged ≥50 years
Live-attenuated virus vaccines such as MMR, VZV and yellow fever vaccines are generally not recommended in
people with MS. DMT therapy should not be initiated within 4 to 6 weeks after vaccination with live
or live-attenuated vaccines because of a risk of active vaccine infection
alive-attenuated vaccine not to be given to patients already receiving IRT therapy
bZostavax is licensed for immunization of people aged ≥50 years and can be used outside of the national immunization program based on clinical discretion
im, intramuscular administration; MMR, measles, mumps, rubella; Sc, subcutaneous administration; VZV, varicella zoster virus
1. Adapted from Reyes S, et al. Pract Neurology 2020; 20:435–45Vaccination and DMT1
Maintenance immunomodulatory Maintenance immunosuppression
Inactivated neoantigens/recall antigens generate
immune response. MMR screening before starting
Well-tolerated and effective Live vaccines should not be given to patients treatment*.
IFN treated with DMF unless, in exceptional cases, VZV screening** is also advisable
DMF given the potential risk of persistent
this potential risk is considered to be outweighed
by the risk to the individual of not vaccinating lymphopenia (Vaccination and DMT1
Immune-reconstitution therapy
Vaccination is one of
Immune responses to inactivated neoantigens/recall antigens are preserved after Az the most effective and
treatment but vaccination within 6 months of treatment may result in fewer responders.
cost-efficient methods
Az Immunization with live viral vaccines following alemtuzumab has not been studied in MMR* and VZV** screening before starting treatment
controlled clinical trials in MS and should not be administered to MS patients who have for protecting people
recently received treatment with MS from
Treatment should not be initiated within 4–6 weeks after vaccination with live or infections
attenuated vaccines because of risk of active vaccine infection.
CT MMR* and VZV** screening before starting treatment
Live or attenuated vaccines should be avoided during and after cladribine treatment as Concerns that vaccines
long as patient's white blood cell counts are not within normal limits (SmPC)
may exacerbate the
Inactivated influenza vaccine may be less effective. disease and/or that
MTx Live-attenuated vaccines are not recommended earlier than 3 months after the last dose MMR* and VZV** screening before starting treatment some DMTs may
of chemotherapy and/or until immune reconstitution has occurred
prevent immune
No evidence that inactivated vaccines trigger or response to
Inactivated vaccines after HSCT are safe and specific revaccination worsen graft-versus-host disease. immunizations should
Donor immunization with live-attenuated vaccines is
programs have been recommended by the ECIL group. be discussed
HSCT contraindicated 4 weeks before donation.
Live-attenuated vaccines are not recommended earlier than 24 months after the Close contacts of HSCT recipients should be with patients
transplant and should only be considered in patients with no graft vs host disease and no immunized according to the national recommendations
ongoing immunosuppression and special considerations apply when using live-
attenuated vaccines†
Patients with MS with impaired immune systems or being considered for immunotherapy need their vaccination
history assessed and to have a vaccination plan1
AZ, alemtuzumab; CT, Cladribine Tablets; ECIL, European Conference on Infections in Leukaemia; HSCT, haematopoetic stem cell transplantation; MMR, measles, mumps, rubella; MTZ, mitoxantrone;
VZV, varicella zoster virus. *People with MS without a reliable history of appropriate immunization (i.e. having received two doses of MMR) should be tested for measles and rubella antibodies.
**People with MS without a confirmed history of chickenpox or without documentation of a full course of vaccination against VZV should be tested for VZV antibodies.
†Close contacts who need VZV or MMR live-attenuated vaccines should be temporarily separated from HSCT recipient.
1. Adapted from Reyes S, et al. Pract Neurology 2020; 20:435–45.Different approaches are used in modern vaccines
Inactivated Subunit Conjugate Toxoid Attenuated Nucleic acid Viral vector
Influenza (im) PPSV23 HiB Tetanus MMR
HBV PCV13 Diphtheria Varicella Effects of MS DMTs on immune
responses to viral vector and
Polio (im) HPV MCV4 Influenza (nasal) nucleic acid vaccine types have
Polio (po) not yet been reported
COVID-19 vaccine candidates in
Yellow fever
their various development stages
Current candidates for a SARS-CoV-2 vaccine include inactivated,
subunit, live-attenuated, viral vector and nucleic acid vaccines
In EU vaccination using RNA based vaccines from Moderna and Pfizer/BioNTech and using
viral vector based vaccine from Astra Zeneca started in December 2020
In UK, as of 11 March 2021
• 22.81 M people have been vaccinated (first dose)
• Mainly people >65 years of age, residents of care homes, and frontline healthcare workers
170+ 20 25 21 3 Still too early to get information on efficacy and safety of vaccination
Pre-clinical Phase I Phase II Phase III Approved in MS patients
DMT, disease modifying therapy; HiB, haemophilus influenzae type B; HBV, hepatitis B virus; HPV, human papilloma virus; im, intramuscular; MMR, measles/mumps/rubella; MS, multiple sclerosis; po,
oral; MCV4, meningococcal conjugate; PCV13, 23-valent pneumococcal polysaccharide.
Ciotti JR, et al. Mult Scler Relat Disord 2020; 45:102439.Summary
Infection-related health care utilization was increased in people with MS across all age groups
Infections such as UTIs and RTIs remain significant risks in real world populations
DMT use is associated with increased risk of infection and is not uniform across DMTs
Prolonged immunosuppression is associated with increased risk of infection
Information gained from RCTs and real-world experience indicates the risk of opportunistic
infections needs to be managed in patients
COVID-19 has brought unique problems to the management of patients and current evidence
suggests patients receiving anti-CD20 therapy may be more at risk of serious disease
Vaccination offers protection against many infections for patients, but evidence-based guidelines regarding
the use of vaccines in MS patients are lacking
Some DMTs, due to mechanism of action, cause B-cell depletion and treatment brings a risk of decreased
immune responses
Roll out of vaccines preventing serious COVID-19 infections have started in many countries but it is still too
early to know the impact on MS patientsYou can also read
