The Evolution of Therapeutic Strategies for Multiple Sclerosis: Balancing Clinical Outcomes With Managed Care

In Friday's afternoon educational symposium, entitled "The Evolution of Multiple Sclerosis Treatment: The Role of the Managed Care Pharmacist," Ronald J. DeBellis, PharmD, FCCP, of the Keck Graduate Institute School of Biopharmacy, started off with his presentation, "Evaluation of the Safety and Efficacy of MS Therapies," which discussed the safety and efficacy profiles of the various new and emerging therapies for multiple sclerosis (MS). The first study DeBellis covered was a 16-year, long-term follow-up study involving interferon (IFN) β-1b. Patients with relapsing-remitting MS who took IFN-β1b demonstrated a sustained reduction of annualized relapse rate (ARR) of up to 40% in comparison to patients who did not receive the drug. Longer exposure to IFN-β1b was correlated with delayed progression to a score of at least 6 on the expanded disability status scale (EDSS). DeBellis reported that there were no new safety concerns and that the side effects associated with treatment decreased over time. In the PRISMS study, a long-term follow-up study with IFN-β1a, disability worsened, with mean EDSS scores increasing from 2.38 to 4.38, and 35% of patients progressed to EDSS score of at least 6.0. In a long-term US trial with glatiramer acetate, which began in 1991 with 124 patients, the ARRs were reduced by over 80%, with 58% of patients maintaining stable EDSS scores or demonstrating improvement. However, patients who withdrew from the trial experienced EDSS score increases 4.5 times that of those who continued receiving treatment. In addition to touching base on fingolimod and teriflunomide, DeBellis noted that natalizumab has been shown by the American Academy of Neurology to have significant benefits in reducing MS disease activity and severity on clinical and MRI measures. In patients with worsening MS receiving standard therapy, natalizumab is considered the drug of choice, and DeBellis added that it is "possibly the most potent agent out there." Concluding his portion of the presentation, DeBellis' key takeaway was that worsening cases of MS may require the use of medications that are effective but have unfavorable toxicity profiles. Furthermore, the MS community should be looking forward to oral agents for monotherapy and combination therapies.

The second panelist to take the podium was Jody Corey-Bloom, MD, PhD, of the University of California, San Diego, whose presentation was titled, "New and Emerging Therapies for MS." She pointed out that in the past 2 decades, the MS community has witnessed substantial therapeutic progress, with 9 FDA-approved agents, 3 agents currently in phase 3 trials, and another 2 agents with completed phase 3 trials. Current treatments for MS utilizes disease-modifying agents, such as IFN-β products, glatiramer acetate, natalizumab, fingolimod, and teriflunomide, all of which have shown success in completed phase 3 trials in relapsing MS. As options for disease management are limited, Corey-Bloom discussed factors to consider for switching therapies. By monitoring outcomes, individuals are able to decide whether or not a switch should occur and when it should occur. Agent- and patient-specific factors help decide how a medication switch should be accomplished. Looking forward, Corey-Bloom noted that monoclonal antibodies, such as daclizumab, alemtuzumab, and ocrelizumab, as well as small molecules, such as laquinimod and fumarate, are on the horizon. When compared with placebo, high-dose daclizumab with IFN-β was associated with more than 3 times less the number of new/enlarged Gd+ lesions. She pointed out that alemtuzumab, while its administration of twice in 2 years is attractive, is a "scary drug" that should be set aside for the experienced, and she expects a very stringent risk evaluation and mitigation strategy (REMS) program to be implemented for the agent due to substantial safety concerns with myelosuppression. She noted that ocrelizumab was an "interesting drug" that is related to rituximab. The small molecules discussion featured laquinimod in the ALLEGRO and BRAVO studies, which reduced ARR by 23% and 21%, respectively. Dimethyl fumarate (BG-12), a convenient oral formulation, was featured in the DEFINE and CONFIRM studies, and has demonstrated substantial benefit with a 49% reduction in ARR at 2 years in comparison to placebo. Risk-benefit discussions should be held with patients considering any new drug therapy.

The last person up to the podium was Kristen Helms, PharmD, an associate clinical professor at the Auburn University Harrison School of Pharmacy. Her presentation, "Improving Patient Adherence to Disease Modifying Therapies," had the learning objectives of identifying patients who are nonadherent to disease-modifying therapies (DMTs), and to discuss strategies to help address common adverse effects and other issues associated with DMTs that may improve patient adherence. Her key messages were that nonadherence is most common early in MS treatment, and that early intervention and patient education could increase the rates of medication adherence. Helms noted that patients who discontinued therapy for MS encountered significantly greater disability at entry, as well as higher rates of relapse and disease progression. Unfortunately, discontinuation rates in the first 6 months of therapy are high, ranging from 9% to 20%, with adherence steadily decreasing over the course of treatment. There are numerous reasons for nonadherence, of which adverse drug reactions are major players. Other contributors may include a perceived lack of efficacy by the patient, cognitive and emotional changes, a fear of injections, and the inconvenience of the medication regimen. The perceived lack of efficacy of a drug regimen, Helms elaborated, is one of the most common reasons for treatment nonadherence, and unrealistic expectations from the patient exacerbates that perception. To combat the many contributing factors for patient nonadherence, Helms made a series of recommendations for pharmacists that included patient education, engaging patients in therapy decisions, and setting realistic expectations for drug efficacy. Other strategies involve warning patients about the side-effect and toxicity profiles associated with specific agents and explaining how to treat those adverse effects symptomatically. Other approaches for pharmacists and providers are to implement prevention and management strategies in advance, and to use REMS programs to optimize patient awareness and education. A combination of all the different strategies with the concerted efforts of the pharmacist, clinician, and patient will help to ensure higher rates of adherence and improved patient outcomes.