Multiple sclerosis (MS) drugs can affect the immune system in various ways, and many of them do weaken it to some extent, especially with long-term use. This weakening is often intentional because MS is an autoimmune disease where the immune system mistakenly attacks the nervous system. The goal of many MS treatments is to reduce or modify this immune attack, but this can also reduce the immune system’s ability to fight infections and respond to vaccines.
To understand how MS drugs impact the immune system long term, it helps to look at the different types of medications and their mechanisms:
**1. B-cell Depleting Therapies (e.g., Ocrevus):**
Ocrevus works by rapidly depleting B-cells, a type of immune cell involved in the autoimmune attack in MS. This depletion happens quickly after treatment starts. Over time, Ocrevus also changes the behavior of T-cells, another immune cell type, reducing their inflammatory activity and increasing regulatory T-cell function, which helps control immune responses. These changes develop gradually over months and contribute to the drug’s long-term effectiveness. However, because B-cells are important for normal immune defense, their depletion can weaken the immune system’s ability to respond to infections and vaccines. Patients on Ocrevus are advised to update vaccinations before starting treatment, as live vaccines may be less effective or unsafe during therapy. There is also a small increased risk of serious infections and rare brain infections like PML (progressive multifocal leukoencephalopathy) in some cases, especially if patients have used other immunosuppressive drugs before[1][4].
**2. Immune Cell Modulators and Suppressors (e.g., Mavenclad):**
Mavenclad reduces the number of lymphocytes, which are white blood cells crucial for immune defense. This reduction is dose-dependent and can be significant, with the lowest lymphocyte counts occurring a few months after treatment starts. Because lymphocytes are essential for fighting infections, this can increase the risk of infections such as herpes zoster and fungal infections. Patients on Mavenclad require regular blood monitoring to check lymphocyte levels and may need to delay treatment if counts become too low. The drug’s immune-suppressing effects can be additive if combined with other immunosuppressive medications[2].
**3. Sphingosine 1-Phosphate Receptor Modulators (e.g., Fingolimod):**
Fingolimod traps certain immune cells in lymph nodes, preventing them from reaching the central nervous system and causing damage. This mechanism reduces the number of circulating lymphocytes, weakening the immune system’s ability to respond to infections. Fingolimod users are at increased risk of infections, including serious ones like meningitis and PML. Vaccinations are complicated during treatment because the immune response may be blunted, and live vaccines are generally avoided. After stopping fingolimod, there can be a rebound effect where the immune system becomes hyperactive, sometimes causing inflammatory syndromes[5].
**4. Other Immune-Modulating Approaches:**
Some experimental or adjunctive therapies, like mesenchymal stem cells (MSCs), are being studied for their ability to modulate immune responses in MS. However, the immune-modulatory capacity of MSCs from MS patients may be reduced compared to healthy donors, possibly limiting their effectiveness. These therapies aim to balance immune suppression with neuroprotection but are not yet standard treatments[3].
**Long-Term Immune System Impact:**
The long-term weakening of the immune system by MS drugs is a trade-off. On one hand, suppressing or modulating immune activity helps prevent MS relapses and slows disease progression. On the other hand, it can increase vulnerability to infections, reduce vaccine effectiveness, and in rare cases, lead to serious complications like PML or cancer. The degree and duration of immune suppression vary by drug type, dos
