News
ORLANDO – Effective oral therapy has been at the top of the wish list of many multiple sclerosis patients for a long time – and now, seemingly all of a sudden, three approved oral agents are available to choose from.
For patients, the obvious attractions of oral therapy are ease of administration and that it’s less of a reminder that they have a serious chronic illness. But which agent is the right fit for a given patient?
All three oral drugs – fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera) – are "definitely" suitable as first-line therapy in selected newly diagnosed MS patients, Dr. Mariko Kita asserted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
But the three oral drugs are not interchangeable. Each has a different mechanism of action and its own side effect profile, emphasized 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
Today few neurologists – certainly less than 10% – are using any oral agent as first-line therapy. That’s in part due to cost and reimbursement issues, but to a much greater extent it’s because most physicians don’t yet feel comfortable that the safety profiles of the oral agents are fully known. The drugs are still too new, in the eyes of most practitioners. After all, both natalizumab (Tysabri) – considered the most effective of the injectable agents – and fingolimod – the first oral agent to receive marketing approval, back in October 2010 – had to have revisionary cautions added to their labeling shortly after they were introduced.
But provider experience with the orals is expected to grow quickly. And absent any late bombshells regarding side effects, it’s widely anticipated that the use of oral agents for MS will surge within the next few years, with a corresponding decline in popularity of injectable therapies.
Demand for oral therapy will be high all across the patient spectrum: in newly diagnosed patients, in individuals with a lengthy disease history who have tried all the available disease-modifying therapies with less than satisfactory results and have been awaiting something new, in patients intolerant to or experiencing breakthrough disease on a first-line injectable agent, as well as in patients who are stable on their current injectable disease-modifying therapy but are experiencing injection fatigue or growing more concerned about their parenteral therapy’s long-term risks, Dr. Kita predicted.
Choosing between the oral options appropriately requires a focus on patient-specific factors, including comorbid conditions, reproductive status, and consideration of how the oral drug will fit in to the big picture of a long-term, staged therapy plan, she added.
Here’s her personal clinical rundown on the approved oral drugs:
• Fingolimod: This is a drug best reserved for MS patients who are otherwise relatively healthy, in Dr. Kita’s view. Specifically, it’s a less favorable option for patients with diabetes, smokers, and others with reduced pulmonary function, and in individuals at increased risk of infection, including those with a high Expanded Disability Status Scale score.
Fingolimod is a sphingosine-1-phosphate agonist. It sequesters lymphocytes in the lymph nodes so they can’t participate in autoimmune activity. The required testing prior to starting the drug, the need for careful observation during the first dose, and the necessary ongoing monitoring as long as the patient is on fingolimod make this a labor-intensive drug.
Bearing those caveats in mind, she continued, fingolimod is "reasonable" to use as a first-line agent, or as a second-line agent in the setting of intolerance to or breakthrough disease while on prior therapy.
"But I would caution those who are reserving these oral agents as second-line that we need to think about what we can reasonably expect from them. If we’re moving to them as second-line because of tolerability issues with first-line agents, yes, I think that’s most reasonable. But if we’re moving because of breakthrough disease, our experience with these agents in cases of failure with standard first-line therapies is very, very limited. Sure, the differing mechanism of action offers a reasonable alternative option, but the expectation that the oral will be better than a failed injectable has not yet been proven," Dr. Kita said.
• Teriflunomide: This is the active metabolite of leflunomide, a treatment approved by the Food and Drug Administration for rheumatoid arthritis. It was approved for treating relapsing forms of MS last fall. Teriflunomide nonselectively inhibits rapidly dividing cell populations by curbing pyrimidine synthesis via bonding to the enzyme dihydroorotate dehydrogenase.