Conference Coverage
VANCOUVER—When selecting a therapy for a patient with multiple sclerosis (MS), drug adherence, side effects, and the patient’s risk of aggressive disease are among the considerations that may influence treatment choice, said Scott Newsome, DO, Director of Neurology Outpatient Services and the Neurology Infusion Center at Johns Hopkins University School of Medicine in Baltimore. Patients’ risk tolerance, desire to pursue pregnancy, and John Cunningham virus (JCV) antibody status also can affect the treatment decision.
Scott Newsome, DO
“I wish we had a cookbook recipe. I wish we were able to say, … ‘This is what you’re going to go on, this is what we’re going to expect,’ but that’s not the case. Maybe one day it will be the case, but until then we have to look at many different factors in choosing therapies,” Dr. Newsome said at the 68th Annual Meeting of the American Academy of Neurology.
Two Decades of Advances
The FDA first approved an MS therapy, interferon beta-1b, in 1993. Now, more than 10 treatments with various routes of administration and mechanisms of action have FDA approval, including a new injectable agent approved in May. Additional promising therapies are on the horizon.
“The world of MS therapeutics is evolving and becoming more complicated,” and neurologists have an “ongoing need to balance efficacy, safety, and tolerability of therapeutic interventions for each patient,” Dr. Newsome said.
Dr. Newsome hopes that in the future, biomarkers will help clinicians identify which specific treatments are the best options for each patient. In addition, more research is needed to determine the best time to start a new drug after a patient develops lymphopenia on another MS therapy, and to better understand how prior treatment with other agents affects the risk of progressive multifocal leukoencephalopathy (PML) and other adverse outcomes, he said.
With current therapies, “treating early and having a low threshold to escalate therapy is very important,” Dr. Newsome said. Monitoring relapses and MRI activity may be helpful when evaluating the efficacy of a newly initiated therapy. If a patient has subclinical disease activity six to 12 months after starting a therapy, many clinicians switch therapies and consider treatments that have different mechanisms of action. If a patient develops one small T2 lesion a year out from starting a therapy, he or she does not necessarily need to switch therapies, however. “These drugs are not cures, so you have to look at various factors when you’re thinking about switching or escalating,” Dr. Newsome said. If a patient has a definite relapse, poor recovery from a relapse, disability progression, or robust MRI activity, even when the patient is asymptomatic, clinicians should consider switching therapies.
Risk of Aggressive Disease
Recommendations published in 2013 by the Canadian MS Working Group along with other groups have noted that patients who are male or African American, have an older age at MS onset, or have motor, cerebellar, sphincter, or brainstem involvement are more likely to have aggressive MS. Frequent relapses, poor recovery from relapses, high MRI lesion burden at presentation, brain atrophy, and a low level of vitamin D also are associated with more aggressive disease. Thus, if a patient is African American, does not recover well from a transverse myelitis attack, and has 15 lesions on MRI, including many that are gadolinium-enhancing, with a high spinal cord lesion load, the patient is at high risk of aggressive disease. “When I see this demographic, this phenotype, I’m thinking maybe we need to start with a stronger immune therapy,” said Dr. Newsome.
Based on a cross-comparison of results from the drugs’ pivotal trials, newer medications seem more effective. Head-to-head trials are the only way to establish drug equivalence or superiority, however. With newly diagnosed MS, especially aggressive MS, many clinicians first prescribe an oral agent or an IV therapy instead of an earlier injectable therapy, with the aim of preventing future disability, Dr. Newsome said.
Injectable, Oral, and IV Therapies
Injectable agents include interferon agents (IFN beta-1a, PEG IFN beta-1a, and IFN beta-1b) and glatiramer acetate. In phase III trials, the interferon agents and glatiramer acetate reduced relapses by about 30%, compared with placebo. They also affected MRI activity and had a modest effect on 12-week disability progression, as measured by the Expanded Disability Status Scale (EDSS), with reductions in the range of about 30% to 40%, compared with placebo.
More recently approved oral and infusion agents may be good options for patients who develop injection fatigue, which can affect adherence, or who have breakthrough disease activity on injectable therapies, Dr. Newsome said. Fingolimod, the first approved oral therapy, is given once daily. Teriflunomide is administered once daily, and two doses are available. Dimethyl fumarate, the newest oral medication, has a mechanism of action similar to that of glatiramer acetate, but also has a unique mechanism of action in that it activates a transcriptional pathway that may help with oxidative and metabolic stress in MS. It is given twice daily.