# Expert opinion on COVID-19 vaccines and cladribine tablets in MS: A plain language summary

Peter Rieckmann, Diego Centonze, Gavin Giovannoni, Le H. Hua, Celia Oreja-Guevara, Daniel Selchen, Per Soelberg Sorensen, Patrick Vermersch, Heinz Wiendl, Hashem Salloukh, et al.

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## To cite this version:

Peter Rieckmann, Diego Centonze, Gavin Giovannoni, Le H. Hua, Celia Oreja-Guevara, et al. Expert opinion on COVID-19 vaccines and cladribine tablets in MS: A plain language summary. Neurodegenerative disease management, 2022, Neurodegenerative disease management, 13, pp.5-13. 10.2217/nmt-2022-0027. hal-04907757

HAL Id: hal-04907757

https://lilloa.hal.science/hal-04907757v1

Submitted on 12 Feb 2025

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# Expert Opinion On COVID-19 Vaccines and Cladribine Tablets in MS: A Plain Language Summary

Peter Rieckmann, Diego Centonze, Gavin Giovannoni, Le H Hua, Celia Oreja-Guevara, Daniel Selchen, Per Soelberg Sørensen, Patrick Vermersch, Heinz Wiendl, Hashem Salloukh & Bassem Yamout

**To cite this article:** Peter Rieckmann, Diego Centonze, Gavin Giovannoni, Le H Hua, Celia Oreja-Guevara, Daniel Selchen, Per Soelberg Sørensen, Patrick Vermersch, Heinz Wiendl, Hashem Salloukh & Bassem Yamout (2023) Expert Opinion On COVID-19 Vaccines and Cladribine Tablets in MS: A Plain Language Summary, Neurodegenerative Disease Management, 13:1, 5-13, DOI: 10.2217/nmt-2022-0027

**To link to this article:** https://doi.org/10.2217/nmt-2022-0027

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Published online: 24 Oct 2022.

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# Expert opinion on COVID-19 vaccines and cladribine tablets in MS: a plain language summary

Peter Rieckmann<fnref n="1" />, Diego Centonze², Gavin Giovannoni³, Le H Hua⁴, Celia Oreja-Guevara⁵, Daniel Selchen⁶, Per Soelberg Sørensen⁷, Patrick Vermersch⁸, Heinz Wiendl⁹, Hashem Salloukh¹⁰ & *Bassem Yamout¹¹

First draft submitted: 11 July 2022; Accepted for publication: 9 September 2022; Published online: 24 October 2022

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## Summary

### What is this summary about?

People with multiple sclerosis (shortened to MS) who are taking **cladribine tablets** may have concerns about whether they can be vaccinated against COVID-19. This summary

details the findings from a previously published article, in which an international committee of 10 MS experts developed recommendations to answer some important questions about COVID-19 vaccines in people with MS (including relapsing-remitting or active secondary progressive disease) taking **cladribine tablets**.

### What were the results?

The committee identified 13 recommendations, which were all agreed upon by at least three-quarters (75%) of the 38 voting MS experts. Generally, they recommended that people with MS taking **cladribine tablets** should be vaccinated for COVID-19 as soon as possible, because the vaccine is thought to be both safe and effective, and vaccine responses were not likely to be affected by **cladribine tablets**.

### What do the results mean?

Overall, people with MS taking **cladribine tablets** should receive the COVID-19 vaccine to protect themselves, unless advised differently by their healthcare provider.

## How to say

* **Cladribine:** CLAD-ree-BEEN

* **Multiple sclerosis:** MUHL-tuh-pl sklr-OW-suhs

## Where can I find the original article on which this summary is based?

You can read the original article published in the journal *Therapeutic Advances in Neurological Disorders* for free at:
[https://journals.sagepub.com/doi/10.1177/17562864211058298](https://journals.sagepub.com/doi/10.1177/17562864211058298)

<footnote n="1">¹Center for Clinical Neuroplasticity, Medical Park Loip!, Bischofswiesen, Germany, and Department of Neurology, University of Erlangen, Erlangen, Germany; ²Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Pozzilli (IS), Italy; ³Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; ⁴Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA; ⁵Neurology, Hospital Clínico San Carlos, IdISSC, Madrid, Spain, and Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain; ⁶Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada; ⁷Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark; ⁸Univ. Lille, INSERM-U1172, LiINCog, CHU Lille, FHU Precise, Lille, France; ⁹Department of Neurology, Institute of Translational Neurology, University of Münster, Münster, Germany; ¹⁰Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA; ¹¹Neurology Institute, Harley Street Medical Center, Abu Dhabi, UAE, and Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut, Beirut, Lebanon

*Author for correspondence</footnote>
## Who is this article for?

The authors of the original publication developed this summary to help healthcare professionals, people with MS, caregivers, patient advocates, policy makers, and insurance providers understand the recommendations from MS experts specifically focusing on COVID-19 vaccination in people with MS taking **cladribine tablets**.

## What is MS?

MS is a disease where **immune cells** attack the **nerves** in the brain and spinal cord, disrupting communication between the brain and the body.

People with MS may experience many different symptoms, including but not limited to problems with walking, strength, sensation, vision, thinking, speech, fatigue (tiredness), bladder problems, and dizziness.

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**Immune cells (ee-MYOON sells):** Cells that help protect the body against infections. These cells make up the immune system of the body (the body's natural defense system).

**Nerves:** Bundles of fibers that carry messages between the body and the brain.

**Relapsing forms of MS:** Types of MS disease where symptoms are felt and then disappear. Periods where symptoms come back or get worse are called relapses. Relapsing forms of MS include relapsing-remitting MS and active secondary progressive MS.

There are different forms of MS disease. Some are **relapsing forms** of MS where symptoms are felt and then disappear, and some are **progressive forms** where symptoms continually get worse over time.

## What are cladribine tablets?

**Cladribine tablets** are a type of medication taken by mouth (orally). They are approved in over 80 countries (earliest in the European Union in 2017) for treatment of relapsing forms of MS. They are taken for a total of up to 20 days over 2 years, split into 4 to 5 days of treatment in the first and fifth week of each year.

**Cladribine tablets:** Cladribine tablets are a medication available for people with MS, known as MAVENCLAD®. Cladribine tablets are taken by mouth. The dose of cladribine tablets is based on a person's weight.

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In **clinical studies**, **cladribine tablets** improved **disease outcomes** (like reducing the number of MS relapses and number of lesions visible on a magnetic resonance imaging [MRI] scan) for people with relapsing MS.

**Cladribine tablets** are believed to work by influencing certain immune cells (by temporarily reducing their numbers). These immune cells are thought to be involved in the **inflammatory attacks** on the nerves in the brain and spinal cord that lead to MS symptoms. These cells are also involved in fighting off infections and responding to **vaccines**.

* A vaccine response is when the body successfully develops defenses against a virus after a vaccine is given, providing protection in the future

**Clinical study:** A clinical study is a scientific investigation in which participants receive a health-related intervention, such as a medicine, in order to learn about how it works and interacts with the body, or to identify any adverse reactions (side effects) in order to understand the safety of and/or how well the medicine works (efficacy).

**Disease outcomes:** Disease outcomes in MS are measures of how active or severe a person's MS is. These outcomes can include relapses, lesions (damage to the brain seen on MRI), and disease progression (measured by disability worsening), among other measures. Outcomes can be reported by patients or can be measured by a healthcare professional.

**Inflammatory attack:** When immune cells cause damage to the body that leads to MS symptoms.

**Vaccine:** A treatment that helps the immune system learn to fight a virus.

## What is COVID-19?

COVID-19 is a disease caused by a type of coronavirus called SARS-CoV-2. The COVID-19 pandemic has been ongoing since 2020, and people all over the world are at risk of infection by the virus and may experience severe illness as a result.

Vaccines have been developed against COVID-19 to protect people from severe illness. These vaccines work by displaying a small piece of the virus to the immune system so that the immune system can learn to protect the body against the real virus.

Live vaccines contain live virus (similar to the virus that can infect people) or weakened virus (virus that is weaker than the normal virus people could be infected with).

Non-live vaccines do not contain any live or weakened virus, only pieces of the virus.

Most of the SARS-CoV-2 vaccines currently approved (mRNA and viral vector vaccines) are non-live vaccines.

Despite the high effectiveness in preventing severe illness and the acceptable safety profile of the COVID-19 vaccines in the general population, some people with MS remain hesitant to receive the vaccine because:

* Some treatments for MS, including **cladribine tablets**, target the immune system to temporarily reduce the number of immune cells. It was unclear whether these treatments might also reduce the effectiveness of COVID-19 vaccines

* The COVID-19 vaccines are relatively new, so there is limited guidance on whether to recommend COVID-19 vaccines to people with MS taking **cladribine tablets**, or when during the **cladribine tablets** treatment schedule it is appropriate to give the vaccine
## Why was the study carried out?

There are still many questions about whether COVID-19 vaccines will be safe and effective in people with MS taking **cladribine tablets**.

Therefore, a group of MS expert neurologists from around the world used their experiences and available knowledge about the COVID-19 vaccines and **cladribine tablets** to create a set of **consensus-based recommendations** about giving COVID-19 vaccines to people with MS taking **cladribine tablets**.

**Consensus-based recommendations:**

Guidelines or suggestions created and agreed upon by experts in the field to help other healthcare professionals know how best to treat their patients. In this study, the guidelines were developed by MS experts to help physicians treat people with MS.

## Who took part in the study and how was the analysis carried out?

This study took place between February and May 2021.

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A committee of **10 MS experts** from around the world came up with **7 important questions** about COVID-19 vaccination in people with MS taking **cladribine tablets**.

These questions addressed important topics like:

* Who should be vaccinated

* The best timing for vaccination

* How well the vaccines work

* How safe vaccination is in those taking **cladribine tablets**

To answer these questions, the committee reviewed and discussed currently available scientific research publications and made **13 recommendations**. Then they invited other MS experts to vote on how strongly they agreed with the recommendations.

* A total of **28 MS experts** from **19 different countries** joined the original 10 committee members to vote (total of 38 experts who voted).

10 international
MS experts

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Committee
members create
questions

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7 questions

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Committee searches
scientific publications
for evidence to answer
each question

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13 recommendations

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Committee finalizes the
questions, reviews the
evidence, and makes
recommendations

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38 experts who voted
Scale of 1-9

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Committee
members (10
experts) and invited
members (28
experts) vote on
recommendations*

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<footnote>*Some recommendations only had votes from 36 MS experts, because 2 experts had technical issues while voting.</footnote>
What were the recommendations from the MS experts?

The MS experts agreed to all **13 recommendations** (statements) about giving COVID-19 vaccines to people with MS currently taking or about to start **cladribine tablets**. This means that at least 75% of experts gave an agreement score of 7, 8, or 9 for each particular recommendation (statement). The majority of recommendations (12) were agreed upon by more than 90% of experts, and the last recommendation was agreed upon by 83.3% of experts.

1

General questions

First, the committee looked at whether people with MS who are taking **cladribine tablets** should receive the COVID-19 vaccine. The experts agreed on the following:

Question 1: Should people with MS taking cladribine tablets be vaccinated against COVID-19?

People with MS taking cladribine tablets should receive the COVID-19 vaccine as soon as possible, unless their treating physician believes there is a particular risk for them.

People with MS are not more likely to be infected with SARS-CoV-2 (the virus that causes COVID-19) or experience severe COVID-19 symptoms, regardless of whether they are taking cladribine tablets.

People with MS taking cladribine tablets should receive the COVID-19 vaccine, even if they were already infected and have recovered.

Average score from MS experts

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Percentage of MS experts who agreed*

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38 of 38
MS experts

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36 of 38
MS experts

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35 of 38
MS experts

Evidence for the recommendations:

There is a lot of evidence showing that COVID-19 vaccines are effective in the general population, helping to reduce severe illness, deaths, and in some cases, infections.

As of January 2021, 272 people with MS taking **cladribine tablets** who were infected with SARS-CoV-2 (the virus that causes COVID-19) were assessed, and it was found that taking **cladribine tablets** did not result in more severe COVID-19 illness.

* These data came from the Merck KGaA Global Patient Safety Database.

<footnote>*An MS expert was said to agree with the recommendation if they gave a score of 7, 8, or 9.</footnote>
## 2 Timing questions

Second, the committee looked at whether people with MS taking **cladribine tablets** should be prioritized to receive the COVID-19 vaccine, and whether they should receive the vaccine as soon as possible. They also looked at when people with MS should be vaccinated: before or during treatment with **cladribine tablets**. The experts agreed on the following:

**Question 2: Should people with MS taking cladribine tablets be prioritized to receive the COVID-19 vaccine?**

People with MS should only be prioritized to receive the vaccine if they have other risk factors (like other health problems) that make them more likely to experience severe COVID-19 illness. This also depends on whether the person is about to start treatment with cladribine tablets.

**Average score from MS experts**

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**Percentage of MS experts who agreed***

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**Question 3: Should everyone with MS taking cladribine tablets receive the COVID-19 vaccine as soon as possible?**

The risks from contracting COVID-19 are higher than the risks of receiving the vaccine in people with MS taking cladribine tablets.

**Average score from MS experts**

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**Percentage of MS experts who agreed***

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Taking cladribine tablets is unlikely to impact the effectiveness of the COVID-19 vaccine in people with MS.

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It's currently uncertain how long the COVID-19 vaccine will provide protection for, so people with MS should get booster shots if needed based on local guidelines.

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**Question 4: When should a person with MS receive the COVID-19 vaccine if they are planning to start taking cladribine tablets?**

Worsening of MS is a bigger risk than infection with SARS-CoV-2 (the virus that causes COVID-19). People with MS should focus on controlling their MS symptoms, and then receive the COVID-19 vaccine if able. However, treating physicians should balance local rates of infection and the risk for each person with MS.

**Average score from MS experts**

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**Percentage of MS experts who agreed***

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Depending on their current symptoms, people with MS should usually wait to take cladribine tablets until 2-4 weeks after they receive the COVID-19 vaccine.

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<footnote>*An MS expert was said to agree with the recommendation if they gave a score of 7, 8, or 9.</footnote>

<footnote>*An MS expert was said to agree with the recommendation if they gave a score of 7, 8, or 9.</footnote>

<footnote>*An MS expert was said to agree with the recommendation if they gave a score of 7, 8, or 9.</footnote>
**Question 5: If a person with MS is already being treated with cladribine tablets, when should they receive the COVID-19 vaccine?**

People with MS should receive the COVID-19 vaccine as soon as it is recommended for them, regardless of when their next dose of cladribine tablets is.

**Average score from MS experts**

**Percentage of MS experts who agreed***

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**Evidence for the recommendations:**

Data from several studies showed that people with MS taking **cladribine tablets** are not more likely to have severe COVID-19 illness.

Other factors like age, disability level, obesity, heart diseases, and treatment with other MS treatments can affect a person's risk of getting severe COVID-19.

Data from a small number of people with MS taking **cladribine tablets** in the **MAGNIFY-MS** study showed that treatment with **cladribine tablets** did not reduce the response to seasonal flu or chicken pox vaccines.

However, more studies are needed to confirm that **cladribine tablets** do not impact responses to COVID-19 vaccines.

## 3 Safety questions

Finally, the committee looked at whether COVID-19 vaccines are safe for people with MS receiving **cladribine tablets**.

**Question 6: Based on current data, are COVID-19 vaccines safe for people with MS taking cladribine tablets?**

Any approved COVID-19 vaccine that doesn't contain active virus is safe for people with MS taking cladribine tablets.

**Average score from MS experts**

**Percentage of MS experts who agreed***

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Once people with MS taking cladribine tablets receive the vaccine, they should still follow social distancing and other COVID-19 guidelines.

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**Question 7: Will receiving the COVID-19 vaccine make MS symptoms worse or cause a relapse in people taking cladribine tablets?**

According to current data, the COVID-19 vaccine shouldn't cause relapses or make MS symptoms worse permanently. People with MS may temporarily see worsened symptoms, because worsened MS symptoms can be associated with some general side effects of vaccines, like fever.

**Average score from MS experts**

**Percentage of MS experts who agreed***

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<footnote>*An MS expert was said to agree with the recommendation if they gave a score of 7, 8, or 9.</footnote>

<footnote>*An MS expert was said to agree with the recommendation if they gave a score of 7, 8, or 9.</footnote>

<footnote>*An MS expert was said to agree with the recommendation if they gave a score of 7, 8, or 9.</footnote>
**Evidence for the recommendations:**

Studies have shown that COVID-19 vaccines are largely safe and well-tolerated in the general population.
There is currently no evidence that COVID-19 vaccines will cause MS relapses or complications in people with MS.

Please note, the wording of these questions and recommendations has been simplified. To see the original wording, please see the original publication, linked at the end of this article.

**What do these recommendations mean for people with MS?**

These recommendations cover the most important concerns about COVID-19 vaccination in people with MS taking **cladribine tablets**, based on what the experts knew in 2021.

In general, the experts recommended that people with MS taking **cladribine tablets** should be vaccinated for COVID-19 as soon as possible, because studies have shown vaccination to be both safe and effective.

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13 of 13 recommendations
(statements)

In general, the experts agreed that **cladribine tablets** should not impact people's responses to the COVID-19 vaccine.

One limitation of the consensus is that many of the recommendations were made despite limited data. However, since the statements were voted on and the paper was published, more studies have been done that support the recommendations described here.

**These findings only represent the results of one study. Information should be discussed with a healthcare professional.**
Where can readers find more information on this study?

This is a summary of an article called "Expert opinion on COVID-19 vaccination and the use of cladribine tablets in clinical practice," which was published in the journal *Therapeutic Advances in Neurological Disorders*. To read the original article being summarized, for free, please visit: https://journals.sagepub.com/doi/full/10.1177/17562864211058298

This article also has a correction, which can be found here: https://journals.sagepub.com/doi/10.1177/17562864221103037

Original publication citation:

Rieckmann P, Centonze D, Giovannoni G, Hua LH, Oreja-Guevara C, Selchen D, Sørensen PS, Vermersch P, Wiendl H, Salloukh H, Yamout B. Expert opinion on COVID-19 vaccination and the use of cladribine tablets in clinical practice. *Ther Adv Neurol Disord.* 2021;14:17562864211058298.

For more information on MS: National Multiple Sclerosis Society or Multiple Sclerosis Trust

For more information on cladribine tablets (trade name MAVENCLAD®): Cladribine tablets

Acknowledgments

The authors would like to thank everyone who took part in the survey. Plain language summary writing and editing support were provided by R Harris, PhD, and D McWain of Ashfield MedComms (New York, NY, USA), an Inizio company, and was funded by EMD Serono Inc., (Rockland, MA, USA), an affiliate of Merck KGaA (CrossRef Funder ID: 10.13039/100004755). The authors had full control of this summary and provided their final approval of all content.

Who sponsored this study?

This study was sponsored by Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Financial & competing interests disclosure

Full author disclosure information for the authors can be found in the original article.