REPORT FROM THE EUROPEAN CHARCOT FOUNDATION ANNUAL MEETING – BAVENO, ITALY, NOVEMBER 28-30, 2013 – The optimal strategy for managing patients with an inadequate response to an initial disease-modifying therapy (DMT) was the focus of discussion at a session of the ECF annual meeting and two somewhat different approaches were presented.
At initial presentation, an individual patient’s risk factors for a more aggressive disease course will influence treatment selection, stated Dr. Mark Freedman, Ottawa, Ontario (Freedman M. ECF 2013). High-risk features include multifocal presentation, relapse frequency and severity, and disability. Patients at lower risk of early progression are candidates for an injectable DMT, teriflunomide or dimethyl fumarate. Those at higher risk would be candidates for earlier use of fingolimod or natalizumab.
He recommended 3-4 clinic visits in the first year of treatment and a follow-up MRI with gadolinium at 12 months to assess treatment response. A lateral switch from one first-line therapy to another due to efficacy or tolerability concerns may be appropriate in patients who continue to be at low risk of progression. Escalation to fingolimod or natalizumab should be considered in patients with significant breakthrough disease. The clinician’s level of concern about an inadequate treatment response is guided by relapse, progression and MRI criteria outlined in the recent Canadian treatment optimization recommendations (Freedman et al. Can J Neurol Sci 2013;40:307-323).
Dr. Freedman noted that clinicians should have a Plan B in mind for managing patients with breakthrough disease. An important consideration is that the selection of one therapy may influence subsequent treatment options. For example, early use of an agent with immunosuppressant effects may make the later use of natalizumab a less attractive option.
A more aggressive induction approach was presented by Dr. Giancarlo Comi, Milan, Italy (Comi ECF 2013). He noted that with a gradual escalation strategy, 45% of patients will experience a relapse within the first two years on treatment and about 80% will experience treatment failure within eight years.
DMTs act primarily on the inflammatory component of MS, so they will have a declining impact during the course of disease. So in the risk-benefit assessment, it would be more rational to use a higher-risk therapy earlier in the course when its greater effectiveness may justify the risks, rather than later on when it will offer less benefit but the same higher risks, Dr. Comi argued. He recommended early use of fingolimod or natalizumab, depending on the patient’s JC virus antibody status. Patients with very poor prognostic features or highly aggressive disease at presentation could be considered for alemtuzumab induction, then de-escalated to maintenance therapy with an injectable, teriflunomide or laquinimod.
Reviewer: Dr. Daniel Selchen. Head of Neurology, St. Michael’s Hospital, Toronto, Canada.