Conference Coverage
INDIANAPOLIS—Disease-modifying therapies approved for relapsing-remitting multiple sclerosis (MS) do not slow clinical worsening in progressive MS, according to research reviewed at the 2015 CMSC Annual Meeting. These anti-inflammatory medicines can decrease the risk of relapses and the formation of new T2 lesions, however. They therefore may benefit patients with active progressive MS.
Mitoxantrone is the only medicine that is FDA-approved for the treatment of secondary progressive MS. Few neurologists recommend this chemotherapy drug because it has limited efficacy in progressive MS, is highly cardiotoxic, and increases the risk of leukemia, said Dennis Bourdette, MD, Roy and Eulalia Swank Family Research Professor and Chairman of the Department of Neurology at Oregon Health & Science University School of Medicine in Portland.
Dennis Bourdette, MD
No Effect on EDSS Worsening
Researchers have studied the efficacy of several therapies for relapsing-remitting MS among patients with secondary progressive MS. A European trial found that interferon beta-1b delayed worsening of Expanded Disability Status Scale (EDSS) score in people with progressive disease. A subsequent North American trial had opposite results, although investigators observed that the drug decreased relapses and the formation of new T2 lesions.
In another study, researchers administered 60 µg of intramuscular interferon beta-1a once per week to patients with secondary progressive MS. The standard dose of interferon beta-1a for treating relapsing-remitting MS is 30 µg. Although the treatment delayed worsening on the MS Functional Composite, it did not delay worsening of EDSS score, and the FDA did not approve it for secondary progressive MS. Interferon beta-1a decreased relapses and the formation of new T2 lesions in patients with secondary progressive MS, however.
Trials of medicines approved for relapsing-remitting MS in patients with primary progressive MS have yielded similar results. Studies suggest that glatiramer acetate, rituximab, and fingolimod do not delay worsening of EDSS score among these patients, but do decrease the number of new T2 lesions.
Researchers are examining several other therapies, including natalizumab and ibudilast, in patients with progressive MS. “I’m not particularly optimistic that agents such as natalizumab that are anti-inflammatory therapies are going to be effective in altering the progressive component of MS,” said Dr. Bourdette.
A Joint Decision Between Doctors and Patients
Despite the failures of these medicines in progressive MS in clinical trials, neurologists should not give their patients the impression that nothing can be done, he continued. Much can be done with symptomatic therapies to improve the quality of life of patients with progressive MS. In addition, current disease-modifying therapies might be appropriate for some patients with progressive MS, but physicians must counsel these patients about the pros and cons of taking a disease-modifying therapy.
Some patients begin treatment after receiving a diagnosis of relapsing-remitting MS and later present with evidence of progressive myelopathy. These patients no longer have relapses or new T2 lesions and have developed secondary progressive MS. “We don’t have strong evidence to guide us about whether we should continue the therapy or not” for these patients, said Dr. Bourdette. One small study suggested that some of these patients do well after they stop taking their current therapies, but “we need better evidence.”
Neurologists should discuss openly with patients with secondary progressive MS the advantages and disadvantages of stopping therapy. Although cessation of treatment may have advantages, it could reveal a previously hidden relapsing component of the disease. A decision about treatment should be made jointly after a discussion of the patient’s goals and concerns, said Dr. Bourdette. If the decision is to stop treatment, the neurologist should develop a monitoring plan that includes periodic MRIs.
Rather than treatment cessation, some patients may ask about escalation. Clinical experience and current clinical trial evidence, however, suggest that more aggressive immunosuppression only increases these patients’ risk of complications without providing benefit. “I don’t think escalation without any evidence of active inflammatory disease is a good idea,” said Dr. Bourdette.
Other patients present with progressive MS and evidence of active inflammatory disease, such as a history of recent relapses or gadolinium-enhancing lesions, but are not receiving any therapy. Such patients should be strongly encouraged to participate in a clinical trial if they are eligible. “It’s important to try to help enroll in those studies,” said Dr. Bourdette.
The patient cannot make an informed decision about treatment unless he or she understands that the goal of the therapy would be to prevent relapses and the formation of new lesions, not to stop disease progression. For some patients, an occasional small gadolinium-enhancing lesion without relapses would not justify the initiation of a therapy. If the neurologist and patient decide to begin treatment, the neurologist should recommend the safest medicine available, most likely one of the injectable drugs, said Dr. Bourdette.