Managing and Treating Multiple Sclerosis

St. Louis—Multiple sclerosis (MS), the most common chronic disease affecting the central nervous system in young adults, presents a series of health- and cost-related threats but can be treated with several therapies that were described at a satellite symposium at the AMCP meeting titled Challenges and Opportunities for Managed Care Pharmacists in Managing Multiple Sclerosis. Robert J. Lipsy, PharmD, BCPS, FASHP, provided an overview of the disease and described how it is commonly treated. There are approximately 400,000 cases of MS in the United States and 2.5 million worldwide. The chance of developing MS is 1:1000, with the highest incidence occurring in Caucasians, a >2:1 incidence in women compared with men, and three quarters of cases occurring in people between 15 and 45 years of age. MS is the leading cause of disability in young women and the second leading cause of disability in young men in the United States. The total cost of the disease in the United States is $16 billion per year, or a health-related cost of $35,000 per patient per year. The typical approach to therapy involves treating acute exacerbations, modifying disease progression, and managing disease signs and symptoms. There are 7 disease-modifying therapies (DMTs) approved by the US Food and Drug Administration (FDA): intramuscular interferon (IFN) beta-1a, subcutaneous (SC) IFN beta-1a, SC IFN beta-1b, glatiramer acetate, and fingolimod (all first line-therapies), as well as natalizumab (a second-line therapy), and mitoxantrone (for worsening/progressive disease). Adherence is a problem with MS patients, according to Dr. Lipsy, because the disease poses unusual challenges, such as needle phobia, new daily routines, side effects and tolerability issues, and perceived lack of efficacy. Studies have shown many MS patients display new or increased depression within 6 months of treatment initiation, which leads to decreased adherence. Most treatment withdrawals occur within the first year of treatment, with 1 study indicating between 17% and 40% of patients stopped taking DMTs within 1 year. To improve adherence, Dr. Lipsy suggested establishing realistic expectations and telling patients DMTs have been shown to reduce relapses and magnetic resonance imaging activity and attenuate disease activity. However, he also said patients must be aware that DMTs do not cure MS, may not eliminate symptoms, cannot eliminate future disease activity, and only work if patients take them. He provided data showing 51% to 80% of patients are relapse-free at 1 year, 30% to 80% have a relative decrease in annual relapse rate, 31% to 42% have a relative decrease in sustained progression, and 9% to 18% is the absolute rate of disease progression. Common Issues Patients with MS face several potential medical issues, according to Jacquelyn L. Bainbridge, PharmD, FCCP, departments of clinical pharmacy and neurology at the University of Colorado-Denver. Approximately 50% develop cognitive dysfunction, which affects their ability to think, reason, concentrate, and remember, and 5% to 10% suffer from moderate-to-severe cognitive impairment. Cognitive impairment could negatively impact adherence, so Dr. Bainbridge suggested pharmacists should simplify drug regimens if possible by recommending medications taken once daily, monotherapy options, and drugs that could be used for >1 use. Typical treatment includes behavioral coping strategies, which sometimes are combined with cholinesterase inhibitors. Studies have shown approximately 50% of MS patients suffer from depression, although Dr. Bainbridge said, “50% may be a small number.” The cause of depression is not known, but some experts believe it is a psychological reaction to a chronic illness, a part of the grieving process, and may be related to the neuropathology of MS. Treatment for depression varies widely but may include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, bupropion, tricyclic antidepressants, and mirtazapine. Dr. Bainbridge said comorbidities such as insomnia, neuropathy, sexual dysfunction, fatigue, cognition/balance, and incontinence should be considered, too, when selecting treatment options for MS patients with depression. She also added that benefits may take 6 to 8 weeks, treatment duration varies, treatment failure is anticipated, and medication should be monitored in low doses at first to limit side effects before escalating to the maximum tolerated dose. Bladder dysfunction is also common in MS patients, most notably hyperreflexive disorder, which can lead to urinary tract infections as well as urosepsis. Pharmacologic treatments for hyperreflexive disorder include anticholinergic agents (oxybutynin or tolterodine) with or without low-dose imipramine. Patients taking anticholinergic agents may have dry mouth and constipation, especially when administered immediate-release formulations. More Issues Ellen Guthrie, PharmD, clinical assistant professor at the University of Georgia College of Pharmacy, next discussed more issues affecting MS patients. Spasticity, a leading cause of disability, is found in 70% of MS patients and primarily affects the lower limbs, potentially leading to pain, stiffness, tremor, clonus, impaired balance, and spasms. When treating spasticity, the goal is reducing symptoms to improve comfort and function rather than eliminating the spasticity. In fact, a degree of spasticity can help patients because it offers limb stabilization. Dr. Guthrie said patients should receive nonpharmacologic treatments before pharmacologic treatments, with oral baclofen the most common pharmacologic drug. Second-line agents typically used with oral baclofen include tizanidine, diazepam, clonazepam, dantrolene, and clonidine. MS patients also typically have gait disturbances and walking/mobility issues, which are often helped by nonpharmacologic treatments such as exercise, physical therapy, gait training, and assistive devices. Recently, though, dalfampridine became the first FDA-approved treatment for improved walking in MS patients. Studies of MS patients have found 60% to 97% suffer from fatigue, with 15% to 40% indicating fatigue is their worst disease symptom. However, when evaluating fatigue, Dr. Guthrie said physical conditioning, pain management, sleeping patterns, and mood disorders should be taken into consideration to rule out other causes of fatigue. Managing fatigue requires physical therapy, psychology, neurology, and psychiatry, with common pharmacologic treatments including modafinil, 4-aminopyridine, selective serotonin reuptake inhibitors, and amantadine. Meanwhile, sexual dysfunction affects approximately 75% of MS patients and is common in males and females. Sexual dysfunction can be caused by depression, fatigue, neurologic impairment, pain, concurrent medications, alcohol, beta-blockers, monoamine oxidase inhibitors, tricyclic antidepressants, and antidepressants such as fluoxetine, paroxetine, and sertraline. Males normally take phosphodiesterase inhibitors as first-line therapies and alprostadil injections, amantadine, or penile prosthetic devices as second-line therapy. However, sexual dysfunction in females is not easily treated with pharmacologic agents.—Tim Casey