ORLANDO – The burgeoning treatment options for multiple sclerosis are increasingly pushing the disease beyond the comfort zone of general neurologists, according to Dr. Mariko Kita.
"MS has become a very, very active area. We’re diagnosing this condition now earlier than ever before. We are initiating treatments at the earliest sign of this condition. We’re going to be seeing, if we haven’t already, a greater influx of patients into MS centers to try to tease apart which disease-modifying therapy might be best for them. And it’s possible that the general neurologists who aren’t referring patients to us at MS centers are going to limit their discussion. They’re going to stick to their go-to drugs: They’ll say, ‘I’ve got one go-to injectable and one go-to oral, and those are the things I’m going to talk about,’ " predicted Dr. Kita, director of the Virginia Mason MS Center, Seattle, and director of the MS clinical trials unit at Virginia Mason’s Benaroya Research Institute.
Dr. Mariko Kita
There are currently nine Food and Drug Administration–approved disease-modifying therapies for MS, including three recently approved oral agents. Plenty of additional medications are advancing through the developmental pipeline.
"All of these new treatments have definitely had an impact on our clinical practice. They’ve increased our burden in a number of ways," Dr. Kita said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
For one, patient education regarding treatment options has become quite time consuming.
"The discussion of the educational component of the injectables has already been fairly complicated, and now we’re adding to it agents that have a very wide spectrum of mechanisms of action," the neurologist said. "So the question is, how much detail do you go into? What information do you share? And if you’re not in an MS center, do you have help from a nurse educator or others to do this education?"
And then there is the numbing challenge of securing insurance authorization for treatment. "This is perhaps the single biggest unreimbursed burden on my clinic and clinic staff. This is really a major deal for MS centers," Dr. Kita said.
Requisite patient monitoring is also increasingly elaborate. This may include testing prior to putting a patient on an agent, first-dose monitoring, and ongoing monitoring for treatment adherence and the possible emergence of serious side effects.
Take, for example, fingolimod (Gilenya), approved in September 2010 as the first disease-modifying oral agent for MS, and thus the oral drug with which physicians have the most experience.
"The start-up, let’s face it, is labor intensive," Dr. Kita said.
Her personal practice before placing a patient on fingolimod is to order an electrocardiogram, pulmonary function tests, a retinal optical coherence tomography (OCT) scan, a dermatologic evaluation, and a check of varicella titers, with vaccination if appropriate. Then comes the supervised, 6-hour, first-dose observation period.
"We do that in the clinic. We have the patient bring in a companion. They take up an exam room and are not under continuous surveillance, so if issues should arise, we want a companion on hand to call for help. Plus, a medical assistant goes in every hour. And the prescribing physician checks in before the first dose and at the end of the day," she explained.
If patients are taking a medication that prolongs the QT interval, however, as many do in order to control their chronic pain, they should be hospitalized for the first dose of fingolimod, Dr. Kita added.
Monitoring needs to be done on an ongoing basis, although as yet there are no clear guidelines as to the specifics. She recommended an annual brain MRI, an ECG, pulmonary function tests, a dermatologic evaluation, and an OCT, because cases of macular edema have occurred 2 years into treatment.
"That’s not necessarily everyone’s standard practice, but it’s what we do," she continued.
And then there is the issue of monitoring circulating CD4 cell counts. Fingolimod’s mechanism of action involves sequestration of lymphocytes in lymph nodes so they can’t contribute to autoimmunity. As a result, patients maintained on fingolimod experience abnormally low levels of circulating CD4 cells, the clinical significance of which remains unclear.
"I think the immunocompromise issue hasn’t really been resolved. I know of practitioners who say, ‘I don’t want to check CD4 counts because it makes me nervous,’ and I’m not sure that’s the best practice. Having said that, it’s hard to know what to do with those exceedingly low CD4 counts," Dr. Kita said.