One of the Hot Topics under discussion during the recent 9th Joint ECTRIMS-ACTRIMS Meeting, #MSMilan2023, was the risk of infectious diseases in individuals with MS receiving disease-modifying therapies (DMTs). The challenges that underlie the understanding of treatment-associated risks have long been recognised by clinicians and there is a need to look forward to minimise risk, while ensuring the overall wellbeing of patients with MS.
DMTs and the risk of infection
In recent years, there has been a rapid evolution in the treatment armamentarium for individuals with MS, with a large number of DMTs now available. The majority of DMTs act to modulate the immune system, thereby introducing a degree of immune impairment that can increase the susceptibility of the individual to infection. As part of the 9th Joint ECTRIMS-ACTRIMS Meeting, Krzysztof Selmaj [1] highlighted the increased risk of infection in individuals with MS treated with immunomodulatory, immunosuppressant or cell-depleting therapies. The complexity of the immune system means that any alteration in the initiation, continuation or termination of an immune response is likely to be problematic, with the differing characteristics and mechanisms of action of different DMTs adding a further layer of complexity.
Vaccination and the prevention of infection
Vaccination can offer one of the most effective means to prevent infectious diseases. Given the potential impact of DMTs upon the immune system of individuals with MS, and the increased risk of infection, there is a need for careful consideration of vaccinations as part of the holistic approach to patient management. However, DMTs may also alter vaccine effectiveness, so it is important to consider the optimal timing of vaccination to ensure maximum benefit whenever possible and prevent future delays in therapy initiation. In July 2023, the first European consensus on vaccination [2] in individuals with MS was published and included recommendations intended to guide the best care based on currently available evidence.
During the recent SARS-CoV-2 pandemic, a wealth of research was undertaken to assess response to vaccines in individuals with MS together with the impact of DMTs upon vaccine response, the safety of the SARS-CoV-2 vaccine in individuals with MS, and the clinical impact of loss of vaccine effectiveness. As part of the Hot Topics session, Susana Otero-Romero [3] raised the value of vaccination for primary prevention of infection, and discussed a move towards an individualised vaccination strategy tailored to each patient’s individual requirements. There is a potential decrease in immunogenicity when vaccines are administered alongside certain DMTs, specifically anti-CD20 and sphingosine-1-phosphate (S1P) therapies, as confirmed with the extensive use of the COVID-19 vaccine. However, some evidence, provided by Muriel Schraad [4], stated that repetitive vaccination increases titre, especially so under non-selective S1P, whilst selective S1P enact only little influence on immunogenicity from the start of treatment on. The widely accepted strategy is therefore to prioritise immunization before initiating treatment and/or to identify the optimal vaccination window. Moreover, live attenuated vaccines are contraindicated with immunosuppressive treatments, leaving MS patients vulnerable to infections with significant consequences, such as varicella or yellow fever where vaccination is not performed prior to treatment initiation. Moreover, use of certain DMTs may warrant the use of prophylactic antibiotics in cases where vaccination alone may not be sufficient to prevent infections. Recent emerging data suggest that the use of live attenuated vaccines after stem cell transplantation may be safe and effective in selected patients, suggesting the possibility of their use in carefully selected individuals with MS after a risk-benefit assessment.
Infection risk with DMTs
There is also a need to consider latent or chronic infections and the risk of re-activation with DMTs, as highlighted during the Hot Topics session by Lucia Moiola [5]. The risk of DMT-associated infections is a major factor in the treatment decision-making process and there is a need for risk reduction and management strategies for infections to be included, both at diagnosis and before starting a new DMT. This should include consideration of possible latent or chronic infections with appropriate treatment and collection of vaccination history. Moreover, it should be noted that the risk-benefit relationship between DMTs and infection will alter over time, due to immunosenescence and the increased risk of infection as individuals with MS age.
Opportunistic infections may also occur during treatment with DMTs due to their immunosuppressive or immunomodulatory effects. These include herpes and cryptococcal infections, candidiasis and listeriosis, progressive multifocal leukoencephalopathy, human papillomavirus and urinary tract infections, respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections, with some of these emerging as a consequence of long-term treatment with immune suppressing therapies. Therefore, during treatment with DMT there is a need to adopt surveillance strategies to ensure the early identification and diagnosis of infections. This strategy permits early treatment of any infection, thus avoiding complications and/or the need to stop current DMT.
Promoting continued advances in research
The MS scientific community continually carries out a wealth of research, with the overall aim of improving patient outcomes and quality of life. Such research deepens our understanding of the disease, which will ultimately enable us to take a step closer to the provision of personalised care, with the potential to halt disease progression without jeopardising patient health. The exchanges of skills and information that occur between healthcare professionals at events such as the 9th Joint ECTRIMS/ACTRIMS Congress in Milan, Italy are invaluable, and can only serve to further improve our knowledge of MS and how best to manage patients.
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ECTRIMS Insights articles are produced with the intent of being a neutral source of information sharing and objective analysis for the MS and neuroscience community. Unless otherwise stated, cited information in our articles does equivocate official endorsement from ECTRIMS.
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REFERENCES
[1] Selmaj K, et al. The risk of infections due to the use of immunomodulatory/ immunosuppressant/ cell depleting therapies. 9th Joint ECTRIMS-ACTRIMS Meeting. 2023.
[2] Otero-Romero S, et al. Mult Scler. 2023;29(8):904-925.
[3] Otero-Romero S, et al. Primary prevention: towards an individualised vaccination strategy. 9th Joint ECTRIMS-ACTRIMS Meeting. 2023.
[4] Schraad M, et al. Long-term observation of SARS-CoV-2 vaccination response in multiple sclerosis in a real world scenario. 9th Joint ECTRIMS-ACTRIMS Meeting. 2023.
[5] Moiola L, et al. Secondary prevention: the importance to investigate for latent/ chronic infections and how to handle infections during DMT. 9th Joint ECTRIMS-ACTRIMS Meeting. 2023.