Multiple Sclerosis (MS) is a complex autoimmune condition with various treatment options available. This article reviews the current medications for MS and discusses the roles of genetic testing and clinical pharmacy services in optimizing treatment for each individual.

Types of disease-modifying therapies for MS

The primary therapies are various types of disease-modifying drugs (DMDs), also known as disease-modifying therapies (DMTs), that aim to reduce inflammation and slow disease progression. These include monoclonal antibodies such as Tysabri, Ocrevus, and Lemtrada. While biological medications for treating multiple sclerosis (MS) are effective, many patients cannot tolerate biologics or DMDs and prefer oral treatments. Recent oral medications include fingolimod (Gilenya), siponimod (Mayzent), dimethyl fumarate (Tecfidera), and teriflunomide (Aubagio).

Other medications for managing specific symptoms

In addition to DMDs there are several other kinds of medications used for managing specific symptoms. These include:

• Corticosteroids for acute flare-ups,
• Muscle relaxants for spasticity,
• Stimulants to combat fatigue and brain fog,
• Physical and occupational therapy to maintain strength and mobility to support daily activities,
• Cognitive therapy for challenges related to memory and thinking.

Most immunosuppressants cause unpleasant side effects and elevate the risk of severe infections. The choice of therapy depends on the type of MS, the severity and progression rate, comorbidities, medication tolerability, and the preferred method of administration. Regular MRI monitoring and clinical assessments evaluate treatment effectiveness and guide necessary adjustments to the therapeutic approach. These factors can also influence treatment adherence and the risk of relapsing.

Why might S1P receptor modulators be preferred over traditional immunosuppressants?

Oral treatment with sphingosine-1-phosphate receptor modulators may be more convenient for MS patients and can be prescribed alongside other medications to manage various symptoms. The key advantage of S1P modulators is that these drugs offer more targeted action compared to the broad immunosuppression associated with traditional DMDs. S1P modulators specifically influence lymphocyte trafficking rather than general immune suppression, which may result in a lower risk of certain infections. S1P receptor modulators are taken as once-daily pills, making them more convenient for patients compared to injectable or infused DMDs like methotrexate or biologics. This convenience also facilitates adherence to the treatment regimen.

While S1P receptor modulators require monitoring, it is often less intensive than that of some DMDs. After initial cardiac monitoring, routine follow-up is relatively straightforward. No periodic liver biopsy is necessary (unlike for some DMDs). However, there are situations in which DMDs might be preferred:

• Pregnancy planning – DMDs like hydroxychloroquine have better pregnancy safety data
• Cardiac conditions – S1P modulators require cardiac monitoring and may be contraindicated
• Specific disease patterns where DMDs have demonstrated long-term efficacy

How do S1P receptor modulators work?

These medications work by activating S1P receptors, which are vital for lymphocyte trafficking. Lymphocytes typically exit lymph nodes by following an S1P gradient. S1P modulators activate S1P1 receptors on lymphocytes, effectively “trapping” active lymphocytes (T and B cells) within lymph nodes, thus preventing them from circulating and causing inflammation.

Upon discontinuation of the drug, lymphocytes regain their ability to exit lymph nodes. It is important to note that S1P receptors are also found in cardiac tissue, meaning that off-target side effects can affect the heart. Ponesimod and other newer selective agents have shorter recovery times. Due to its longer half-life, fingolimod requires a longer recovery period. This mechanism explains why these drugs necessitate monitoring of lymphocyte counts and highlights the importance of first-dose cardiac monitoring.

Key differences between S1P receptor modulators used in treating multiple sclerosis (MS) and other autoimmune conditions:

These metabolic differences influence:

1. The necessity for pharmacogenetic testing, particularly for siponimod and etrasimod.
2. Interactions between drugs and other supportive medications,
3. The onset time of action and duration of lymphopenia (a lower than normal white blood cell count) following discontinuation,
4. Requirements for dose titration and monitoring needs.

Improving MS therapy safety and tolerability

The tolerability and side effects of many non-biologic drugs are influenced by a person’s DNA, other medications, age, weight, and diet. Clinical pharmacists consider these factors to assess therapy options and offer recommendations to your doctor.

The Pillcheck pharmacogenetic test reports non-biologic immunosuppressants, S1P receptor modulators, and various other medications used for MS therapy that have pharmacogenetic labelling. It also includes a medication review by a clinical pharmacist. By suggesting dosage adjustments or recommending alternative medications, Pillcheck pharmacists can help individuals customize their treatment plans, leading to better tolerability of their medications. This personalized approach also improves adherence to treatment and lowers the risk of relapse.

Furthermore, the Pillcheck service may be eligible for reimbursement through certain health benefit plans. If you have experienced difficulties tolerating MS medications, it’s worth checking if your medications are included in the Pillcheck list.

Furthermore, the Pillcheck service may be eligible for reimbursement through certain health benefits plans. If you have experienced difficulties tolerating MS medications, it’s worth checking if your medications are included in the Pillcheck report.

Summary

• Disease-modifying drugs for MS can pose a risk of long-term complications, such as infections, necessitating careful dosing and monitoring of therapy.
• Oral S1P receptor modulators may provide more convenience than injectable drugs, potentially enhancing therapy compliance.
• The tolerability and side effects of S1P receptor modulators, non-biologic DMDs, and other MS medications are influenced by an individual’s inherited drug metabolic profile.
• Pharmacogenetic testing, combined with a thorough medication review by an expert pharmacist, can assist you and your doctor in evaluating MS therapy options that may be more easily tolerated.

Selected references

Geiger CK et al., Treatment Patterns by Race and Ethnicity in Newly Diagnosed Persons with Multiple Sclerosis. Drugs Real World Outcomes. 2023 Dec;10(4):565-575. doi: 10.1007/s40801-023-00387-x

Kane M. Siponimod Therapy and CYP2C9 Genotype. 2023 Aug 9. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical Genetics Summaries

Liu M et al., Siponimod and CYP2C9 Allele Prevalence Among Blacks. J Clin Pharmacol. 2020 Apr;60(4):429-431. doi: 10.1002/jcph.1546

Gardin A et al., Effect of Fluconazole Coadministration and CYP2C9 Genetic Polymorphism on Siponimod Pharmacokinetics in Healthy Subjects. Clin Pharmacokinet. 2019 Mar;58(3):349-361. doi: 10.1007/s40262-018-0700-3.

Śladowska K et al., Efficacy and safety of disease-modifying therapies in pediatric-onset multiple sclerosis: A systematic review of clinical trials and observational studies. Mult Scler Relat Disord. 2025 Jan 7;94:106263. doi: 10.1016/j.msard.2025.106263