What Pharmacists Should Know About Multiple Sclerosis

Approximately 1 million individuals are living with multiple sclerosis (MS) in the United States, according to the National MS Society.¹ The condition is caused by the immune system attacking the protective sheath (myelin) that covers nerve fibers and can result in a wide range of symptoms such as the inability to walk.² Most patients with MS experience a relapsing-remitting disease course, which involves periods of new symptoms or relapses that occur over days or weeks and usually improves partially or completely.² There is no cure for MS, so treatment usually involves therapies that improve recovery from attacks, slow disease progression, and manage symptoms.

Treatment Options and Recommendations

Treatments for MS include pharmacotherapy and physical therapy. Corticosteroids can help to treat MS attacks by reducing nerve inflammation. Adverse effects include increased blood pressure and blood glucose, mood changes, and fluid retention.²  The American Academy of Neurology (AAN) recommends a careful evaluation of the risks/benefits of disease-modifying therapies (DMTs).³ The DMTs can help to slow the disease process and assist with keeping the condition stable by decreasing the number of new lesions that can form, preventing existing ones from becoming larger, and decreasing the number of relapses.⁴

Treatment options include injectable medications, oral treatments, and infusions. Beta interferons, such as interferon beta-1a (Avonex), are injectable treatments, and common adverse effects include flu-like symptoms and pain at the injection site. Glatiramer acetate (Copaxone, Glatopa) is a subcutaneous injection, and adverse effects may include injection site reactions.⁴

Three new oral medications were approved for MS in 2019: cladribine (Mavenclad), siponimod (Mayzent), and diroximel fumarate (Vumerity).⁴ The dose of cladribine is a cumulative dosage of 3.5 mg/kg orally divided into 2 yearly treatment courses, and the drug carries a Boxed Warning for an increased risk of cancer and fetal harm. Siponimod dosing is determined by genotype testing and is either 1 mg or 2 mg orally once daily. Adverse effects may include headache, bradycardia, increased blood pressure, and increases in liver function tests. The starting dose of diroximel fumarate is 231 mg twice a day orally for 7 days followed by a maintenance dose of 462 mg (two 231 mg capsules) twice per day. Diroximel fumarate can cause liver problems and a rare brain infection known as progressive multifocal leukoencephalopathy, which has also been reported in patients taking a similar drug called dimethyl fumarate (Tecfidera). Evidence suggests that diroximel fumarate may cause less gastrointestinal adverse effects than dimethyl fumarate.⁴

Individuals with MS receiving immunosuppressive therapies are at a higher risk of developing vaccine-preventable infections.⁵ Pharmacists should ensure that patients are up-to-date on their immunizations and recommend that individuals receive an influenza vaccine annually. The AAN recommends that patients needing live vaccines receive them at least 4 to 6 weeks before initiating treatment with immunosuppressive medications.⁵ Individuals currently receiving immunosuppressive therapies or have recently discontinued them should not receive live vaccines unless the risk of infection is high.

Pipeline Drugs on the Horizon

Celgene has submitted a New Drug Application (NDA) for ozanimod, an oral sphingosine 1-phosphate receptor modulator, with an anticipated approval date of March 25, 2020.^6,7 The NDA is based on positive results from the SUNBEAM and RADIANCE trials demonstrating that ozanimod was effective at preventing MS relapses.^6,7 Ponesimod is an investigational drug being studied by Janssen for relapsing MS.⁸ The phase 3 OPTIMUM head-to-head study showed that ponesimod was superior to the FDA-approved MS drug teriflunomide (Aubagio) for the primary endpoint of preventing relapses.⁸

References:

1. National MS Society.  How Many People Live with MS.  National MS Society website.   https://www.nationalmssociety.org/What-is-MS/How-Many-People.  Accessed January 30, 2020.
2. Mayo Clinic. Multiple Sclerosis. Mayo Clinic website.  https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/diagnosis-treatment/drc-20350274. Last updated April 19, 2019. Accessed January 30, 2020.
3. Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline: disease-modifying therapies for adults with multiple sclerosis report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology. 2019;92(2):112. doi: 10.1212/WNL.0000000000006722.
4. National MS Society. Disease-Modifying Therapies for MS. National MS Society website.  https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-The-MS-Disease-Modifying-Medications.pdf. Last updated November 2019.  Accessed February 2, 2020.
5. Farez MF, Correale J, Armstrong MJ. Practice guideline update summary: vaccine-preventable infections and immunization in multiple sclerosis report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology;93(13):584-594. doi: 10.1212/WNL.0000000000008157.
6. Comi G, Kappos L, Selmaj KW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicenter, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009-1020. doi: 10.1016/S1474-4422(19)30239-X.
7. US FDA and EMA accept applications for ozanimod for the treatment of relapsing forms of multiple sclerosis [news release]. Summit, NJ. June 6, 2019: Celgene website.  https://ir.celgene.com/press-releases-archive/press-release-details/2019/US-FDA-and-EMA-Accept-Applications-for-Ozanimod-for-the-Treatment-of-Relapsing-Forms-of-Multiple-Sclerosis/default.aspx. Accessed February 2, 2020.
8. New head-to-head phase 3 study data showed ponesimod superiority versus Aubagio (teriflunomide) 14 mg in adults with relapsing multiple sclerosis (MS) [news release].  Stockholm, Sweden; September 11, 2019: Johnson & Johnson website.  https://ir.celgene.com/press-releases-archive/press-release-details/2019/US-FDA-and-EMA-Accept-Applications-for-Ozanimod-for-the-Treatment-of-Relapsing-Forms-of-Multiple-Sclerosis/default.aspx. Accessed February 2, 2020.