Factors Affecting the Decision to Initiate Disease-Modifying Therapy in Patients with Multiple Sclerosis

Speaking at the 65th American Academy of Neurology Annual Meeting “Criteria for Stopping and Starting Multiple Sclerosis Therapy” seminar, Brian Weinshenker, MD, FAAN, Professor of Neurology at the Mayo Clinic, said that current practice regarding treatment of relapsing-remitting multiple sclerosis (RRMS) is to initiate disease-modifying therapy (DMT) as soon as possible after a confirmed diagnosis. This is underlined by a recent National Multiple Sclerosis Society (NMSS) Disease Management Consensus Statement on DMT for multiple sclerosis. Weinshenker said that the specific wording (shown below in italics) in this document should be noted by all clinicians treating patients with MS.

The NMSS recommends that initiation of treatment with interferon beta or glatiramer acetate should be considered as soon as possible following a definite diagnosis of MS with active MS and may also be considered for selected patients with a first attack who are at high risk of MS. However, the tendency in clinical practice is to implement DMT immediately and universally. Weinshenker said this is done because it’s easy and the patients are happy (at least initially). However, DMT often becomes an indefinite treatment because there are no guidelines on when to terminate therapy. Weinshenker also noted that there are no recommendations on when to monitor, clinically and radiologically. He said that because the natural course of MS is mostly subclinical, the concept of cost/benefit assessment, before and after DMT, is controversial.

Assessment of the long-term effectiveness these drugs is also a controversial issue. Weinshenker expanded on the findings of long-term studies cited by Helen Tremlett, PhD, BPharm, in the same seminar. Several of these appeared to show that DMT was beneficial in altering the course of MS. However, some of the studies had design flaws, such as cross-over trials in which patient dropout was a problem in switching from open-label to randomized treatment. Others displayed ascertainment (sampling) bias, immortal time bias, or informed censoring. Weinshenker professed to be very conservative and unconvinced about the long-term benefits of DMT while acknowledging that there is plenty of evidence accumulating.

Weinshenker said, in routine clinical practice, the questions clinicians should be asking are:

• How certain is the diagnosis?
• How active is the disease?
• What are the patient’s preferences (likelihood of compliance)?
• What are the contraindications (eg, pregnancy)?
• What monitoring is required?
• What is the best drug for the patient?

Weinshenker then reviewed case reports from his clinical practice to illustrate a range of presentations of the disease in individual patients and how treatment decisions were arrived at. For example, a young female reported MS symptoms but was asymptomatic on examination. Since MRI features indicated significant demyelinating lesions, she was considered a good candidate for interferon beta-1a. Another female patient discontinued interferon following evidence of venous stenosis and was prescribed natalizumab instead. A third female patient had a small burden of MRI lesions, unremarkable signs on examination, and an indeterminate prognosis. This patient was agreeable to monitoring with “watchful waiting.” Subsequently, the lesions worsened, requiring corticosteroids. After two years, she had a relapse and was then started on fingolimod.

The cases presented by Weinshenker clearly illustrated a comment in the NMSS Consensus Statement that “the Society recognizes the factors that go into a decision to treat (MS) are complex and best analyzed by the individual patient’s neurologist.”