Multiple sclerosis therapy consensus group (MSTCG): answers to the discussion questions

Abstract

Question 1: when should disease-modifying immunotherapy be initiated? Before or after the onset of disability? Already with CIS (e.g., isolated optic neuritis)? An explicit goal of multiple sclerosis (MS) therapy is the “best possible disease control”, including the “best possible quality of life” of the patient, with the option to use highly effective therapeutics early or as early as possible in response to disease activity. Specifically, the appropriate disease-modifying therapy (DMT) is selected based on the individual patient, and incorporates a situation and prognostic analysis that includes disease activity, disease severity, balancing therapy safety and risks, and considering the patient’s age, gender, and living situation. From the perspective of the MSTCG (Multiple Sclerosis Therapy Consensus Group) and supported by several large observational and registry studies, modern MS therapy can and should prevent the accumulation of disability and, thus, possible neurodegeneration. The MSTCG recommends classifying MS as mild/ moderate or active/highly active (see Fig. 1). The classification is based on i) relapse frequency, ii) MRI findings (lesion load, lesion localization), and iii) regression of relapse(s), disease activity, and disease severity (measured by clinical as well as radiological parameters); also, the patient’s age and comorbidities have to be considered. Activity is determined based on clinical relapses (severity of clinical symptoms/duration/tendency to regress) and/or MRI activity (contrast-enhancing lesions; new or enlarged T2 lesions). Progression is determined by an annual or more frequent examination, including a careful clinical assessment. In addition to the EDSS, standardized instruments for assessing clinical function in patients with MS include the Multiple Sclerosis Functional Composite (MSFC), the Brief International Cognitive Assessment for MS (BICAMS), the 6and 2-min walk tests, or the timed 25-ft walk test. Notably, the MS classifications are not categorical and rigid: they require continuous review and close follow-up. It is generally agreed that DMTs have a better effect early in the course of MS. Recent registry data indicate that later initiation of DMT leads to more extensive disability in the longer term [1–3]. In addition to preventing acute episodes of the disease, prophylactic therapy may reduce the risk of long-term neurologic deterioration or secondary progression [4]. The long-term therapeutic benefits strongly depend on how early DMT is started. Due to the great heterogeneity of the clinical MS course, the further individual patient’s course is extremely difficult to predict. Although the term “benign MS” has been abandoned eventually, there may be courses that do not lead to any (significant) disability after 30 years – even without therapy. While in overall analyses up to 15–20% of patients may not accumulate measurable disability in the longer term, there are no reliable or accepted predictors for a course without substantial disability. Hence, DMT in MS must be started as early as possible after diagnosis to avoid further/future disability. In individual cases, a wait-and-see approach with regular neurological and imaging checks may also be considered in patients with very low lesion burden and complete remission of mild clinical symptoms. In the context of a clinically isolated syndrome (CIS) suggestive of central nervous system demyelination, defined as a monofocal or multifocal clinical