Multiple Sclerosis: Walking the Walk with Better Therapies

Multiple sclerosis (MS) is an incurable immune-mediated inflammatory disease that produces symptomatic episodes months or years apart in different anatomic locations. It attacks myelinated axons in the central nervous system (CNS), destroying the myelin and the axon to varying degrees. Over time, MS causes significant physical disability; within 20 to 25 years, more than 30% of patients become disabled.^1,2 Table 1^3-6 lists symptoms; note that each patient’s presentation differs.

Approximately 20% of patients present with optic neuritis as their initial demyelinating symptom, while roughly 40% of patients develop this after diagnosis. Patients report loss of vision or color vision in the affected eye(s) and ocular pain, especially when the affected eye moves. Some patients also develop phosphenes (transient light flashes or black squares) before, during, even months after optic neuritis events.^3,4

MS presents in several forms (Table 2^1,3,7,8), reflecting clinical relapses, time to disease progression, and lesion development on magnetic resonance imaging (MRI). Nearly 50% of patients initially diagnosed with relapsing-remitting MS (RRMS) convert to a secondary- progressive pattern within 10 to 15 years. This pattern may not include relapses, but it is characterized by progression over years, with increasing disability. Treatment with disease-modifying therapies (DMTs), however, may slow the progression. Unlike RRMS, secondary-progressive MS without relapses is often refractory to currently available DMTs.^1,3,7,8

Table 2. Types of Multiple Sclerosis

Types of Multiple Sclerosis

Statistics and Important Points

Relapsing remitting MS

• Affects 85% of patients
• Patients experience worsening of preexisting symptoms or onset of new symptoms for periods exceeding 24 hours, without concomitant fever
• Followed by remissions; symptoms disappear partially or completely

Progressive forms of MS

Secondary-progressive MS

• A progression of RRMS
• Before DMTs, 50% of patients progressed to SPMS after 10 years of RRMS; early intervention with DMTs seems to have decreased the incidence

Primary-progressive MS

• Affects ~10% of patients at diagnosis
• Function declines steadily with few flares

Progressive-relapsing MS

• Affects <5% of patients

• Occasional relapses superimposed on clearly progressive disease

Progressive-relapsing benign MS

• Affects <5% of patients
• Diagnosis can only be made in hindsight
• Characterized by minimal disease activity

^{DMT = disease-modifying therapy; RRMS = relapsing-remitting multiple sclerosis; SPMS = secondary-progressive multiple sclerosis.Adapted from references 1, 3, 7, and 8.}

MRI, a nonspecific imaging test, is preferred to confirm MS and monitor disease progression in the brain and the spinal cord. Clinicians also use MRI and the evoked potentials test, which records the timing of CNS responses to specific stimuli, to measure treatment response and evaluate MS.⁷

Treatment

Early aggressive treatment with DMTs may slow disease progression and irreversible neurologic damage. Although efficacy data can be used to determine each agent’s ability to prevent clinical relapses and reduce inflammatory activity detected by MRI, no single biomarker predicts a patient’s response to treatment.^3,9

Treatment teams face several hurdles when caring for patients with MS. Few guidelines, however, address the wide variations in presentation well or cover all approved agents.¹⁰ Pharmacists may find it helpful to group the 13 FDA-approved agents based on their approval and administration routes:

• Self-injectable DMTs (interferon [IFN] beta products, glatiramer acetate [GA], PEGylated IFN beta-1a, and generic GA)^11-16
• DMTs administered by IV infusion (ie, natalizumab, alemtuzumab, and daclizumab)^17-23
• DMTs administered orally (ie, fingolimod, teriflunomide, and dimethyl fumarate)^17-23

Mitoxantrone is also approved for managing MS, but its association with cardiotoxicity and secondary leukemias limits its clinical use.¹⁸ Few head-to-head clinical trials compare the DMTs.⁷ When deciding on a course of treatment, neurologists consider efficacy, safety, tolerability, patient preference, and convenience,²⁴ and share decision making with the patient.⁹

Adherence and MS-Related Problems

All DMTs produce adverse effects that contribute to nonadherence.²⁴ Pharmacists need to counsel patients that it takes time to adjust to medication. Patients who experience intolerable adverse effects or show significant laboratory abnormalities, a poor or dwindling response, evidence of progression, or new activity on MRIs may need to switch therapies.²⁵

Many of the medications used to treat MS are dispensed from specialty pharmacies or administered in physicians’ offices. Therefore, community pharmacists are more likely to deal with patients’ MS-related problems. Table 3^26-29 describes MS’s common symptoms and the medications for treating them.

End Note

Patients with MS need early intervention. The Multiple Sclerosis Coalition’s 2014 consensus document (updated in 2016) supports early, wide access to FDA-approved DMTs.³⁰ It is an essential (and free) reference for pharmacists.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.

References

• National Multiple Sclerosis Society. What is MS? NMSS website. nationalmssociety.org/What-is-MS. Accessed January 30, 2017.
• Kim SE. Daclizumab treatment for multiple sclerosis. Pharmacotherapy. 2009;29(2):227-235. doi: 10.1592/phco.29.2.227.
• Bainbridge JL, Miravalle A, Corboy JR. Multiple sclerosis. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. New York, NY: McGraw-Hill; 2014:343-366.
• Saguil A, Kane S, Farnell E. Multiple sclerosis: a primary care perspective. Am Fam Physician. 2014; 90(9):644-652.
• Roodhooft JM. Ocular problems in early stages of multiple sclerosis. Bull Soc Belge Ophtalmol. 2009;(313):65-68.
• Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010;33(8):1061-1067.
• Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria of multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292-302. doi: 10.1002/ana.22366.
• Sayao A-L, Devonshire V, Tremlett H. Longitudinal follow-up of “benign” multiple sclerosis at 20 years. Neurology. 2007;68(7):496-500.
• Wingerchuck DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014; 89(2):225-240. doi: 10.1016/j.mayocp.2013.11.002.
• National Multiple Sclerosis Society. Disease management consensus statement. NMSS website. main.nationalmssociety.org/docs/HOM/Exp_Consensus.pdf. Accessed January 31, 2017.
• Avonex [prescribing information]. Cambridge, MA: Biogen Idec Inc; 2015.
• Copaxone [prescribing information]. Overland Park, KS: Teva Neuroscience, Inc; 2014.
• Extavia [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016.
• Rebif [prescribing information]. Rockland, MA: EMD Serano, Inc; 2015.
• Betaseron [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 2016.
• Plegridy [prescribing information]. Cambridge, MA: Biogen Idec; 2015.
• Lemtrada [prescribing information]. Cambridge, MA: Genzyme Corporation; 2014.
• Novantrone [prescribing information]. Rockland, MA: EMD Serano, Inc; 2008.
• Tysabri [prescribing information]. Cambridge, MA: Biogen, Inc; 2016.
• Tecfidera [prescribing information]. Cambridge, MA: Biogen Inc; 2016.
• Gilenya (fingolimod) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016.
• Aubagio [prescribing information]. Cambridge, MA: Genzyme Corporation; 2016.
• Zinbryta [prescribing information.] Cambridge, MA: Biogen, Inc; 2016.
• Hanson KA, Agashivala N, Wyrwich KW, Raimundo K, Kim E, Brandes DW. Treatment selection and experience in multiple sclerosis: survey of neurologists. Patient Prefer Adherence. 2014;8:415-422. doi: 10.2147/PPA.S53140.
• Coyle PK. Switching therapies in multiple sclerosis. CNS Drugs. 2013;27(4):239-247. doi: 10.1007/s40263-013-0042-5.
• National Multiple Sclerosis Society. Medications. NMSS website. nationalmssociety.org/Treating-MS/Medications. Accessed July 1, 2016.
• Ampyra (dalfampridine) [prescribing information]. Ardsley, NY: Acorda Therapeutics, Inc; 2014.
• Risi O, Cito L, Andretta E, et al. Mirabegron in treatment of neurological overactive bladder in multiple sclerosis patients. International Continence Society website. ics.org/Abstracts/Publish/218/000566.pdf. Accessed July 1, 2016.
• National Multiple Sclerosis Society. MS symptoms. NMSS website. nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Emotional-Changes. Accessed July 1, 2016.
• Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. a consensus paper. The Consortium of Multiple Sclerosis Centers website. http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Accessed January 30, 2017.