Aggressive multiple sclerosis: proposed definition and treatment algorithm

Abstract

Multiple sclerosis (MS) is a CNS disorder characterized by inflammation, demyelination and neurodegeneration, and is the most common cause of acquired nontraumatic neurological disability in young adults. The course of the disease varies between individuals: some patients accumulate minimal disability over their lives, whereas others experience a rapidly disabling disease course. This latter subset of patients, whose MS is marked by the rampant progression of disability over a short time period, is often referred to as having 'aggressive' MS. Treatment of patients with aggressive MS is challenging, and optimal strategies have yet to be defined. It is important to identify patients who are at risk of aggressive MS as early as possible and implement an effective treatment strategy. Early intervention might protect patients from irreversible damage and disability, and prevent the development of a secondary progressive course, which thus far lacks effective therapy.

Disease modifying therapies for relapsing multiple sclerosis

“…146 147 In relapsing multiple sclerosis, early attack rate is associated with long term outcomes. 38 140 Several definitions of "highly active" or "aggressive" disease have been proposed for clinical use, [143][144][145][146][147][148][149] or to facilitate subgroup analyses of RCT data, [150][151][152] typically using a combination of two or more clinical relapses together with one or more of relapse severity, presence of multiple gadolinium enhancing MRI lesions, significant T2 lesion burden, or increase in EDSS score within the preceding year.…”

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis

“…Therefore, the classification as first line and second line is being questioned more and more, and some recommend a classification for mild/moderate and active/ highly active disease courses. There is no universal definition of Bhighly active^MS, though, but taking into account the labeling of the substances, it is generally defined by the occurrence of 2 relapses in the past year with disability progression and a significant increase of T2 lesions at critical locations (e.g., brainstem, cerebellum) on MRI [102]. In this setting, special attention must be paid to assessing the therapeutic risk in light of the expected efficacy of a drug [103].…”

Induction treatment strategy in multiple sclerosis: a review of past experiences and future perspectives

“…Lately, treatment-related mortality rates decreased from 7.3% for the period 1995-2000 to 1.3% during the period 2001-2007 [30] . This might be seen as a consequence of better selection of patients who were not inexorably disabled and who had less-advanced disease, as well as to general advances in post-transplant care [12]. Different transplant procedures are currently in use, but given a lack of comparative studies no evidence exists for one regimen being superior to another.…”

“…Longterm natural history studies [11] provide precious information about negative prognostic factor presenting early at onset or during follow-up and infer that late disability can be predicted on the basis these factor, though helping in identify patients at risk of a more aggressive disease course [12] (Table 1). An epidemiological study assessed on a database of 5891 patients with MS, the proportion of patients that could be defined as affected by "aggressive MS" according to an Expanded Disability Status Scale (EDSS) of 6 (reached in 5 years or before the age of 40) or development of secondary progressive MS (SPMS).…”