When to Switch Therapies in Multiple Sclerosis?

Speaking at the “Criteria for Stopping and Starting Multiple Sclerosis Therapy” educational seminar at the American Academy of Neurology (AAN) 2013 Annual meeting, Mark Keegan, MD, Associate Professor of Neurology at the Mayo Clinic, summarized the systematic approaches to successful treatment of multiple sclerosis (MS). First, an unequivocal diagnosis must be made by clearly identifying the cardinal features of MS in each patient and the clinical course of the disease. Keegan listed the various confirmatory procedures such as neurological examination, MRI scans of brain and spinal cord, CSF protein (immunologic) abnormalities, and evoked potential electrophysiology. Clinicians must also rule out the possibility of disorders that mimic MS clinical features. These findings should be evaluated using the revised McDonald criteria.

Keegan said that about 85% of patients have relapsing-remitting multiple sclerosis (RRMS) characterized by relative clinical stability. Secondary progressive MS (SPSS) is more progressive than RRMS and, typically, a spastic gait is seen between, or in the absence of, attacks. The rarer primary progressive MS (PPMS) is characterized by the lack of prior attacks with resolution. Therapeutic goals in MS include reducing clinical relapses, ameliorating the underlying inflammatory processes, and reversing brain and spinal cord atrophy. Achievement of these goals is shown by an improvement in relapse rate, improved or stable neurological signs, improved or stable MRI features, and a reduction in inflammation.

Like his Mayo Clinic colleague, Brian Weinshenker, Keegan illustrated his talking points with case reports. For example, a 43-year-old woman developed gait ataxia, numbness, and MRI lesions typical of MS. On assessment, her side effects due to interferon therapy led to a switch to glatiramer acetate. The patient became clinically and radiologically stable, with some inflammatory changes, and was mobile but developed abdominal lipoatrophy at the injection site. This was resolved by changing the injection site. While some patients did well on interferon beta, others did not tolerate it, whether by subcutaneous or intramuscular injections. One of Keegan’s patients, when switched to glatiramer acetate, had anaphylaxis. A brain MRI showed all sorts of inflammatory activity and lesions and, following assessment, the patient was recommended natalizumab treatment after counseling regarding the risks, including progressive multifocal leucoencephalopathy (PML), a rare virally-induced complication of this therapy.

Keegan discussed other patients for whom one or other first-line therapies were unsuitable due to lack of efficacy or adverse reactions. He went over different approaches to treating inflammation in MS, depending on the clinical history and the severity, with one patient requiring cyclophosphamide before transitioning to interferon beta-1a. Another patient could not tolerate either interferon beta or glatiramer acetate and was recommended fingolimod by Keegan, but the patient’s primary care provider was very against this so teriflunomide is now being discussed. One of Keegan’s patients even discontinued MS therapy because of her face-lift surgery!

Keegan’s clinical examples strikingly underscore the point made in an Expert Opinion Paper published by the National Multiple Sclerosis Society (NMSS) (also discussed here) that “the factors that go into a decision to treat (MS) are complex and best analyzed by the individual patient’s neurologist.”