Commentary: The Multiple Sclerosis Controversy: Is It Escalation or Induction High Efficacy?
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COMMENTARY
Commentary: The Multiple Sclerosis Controversy: Is It Escalation or Induction High Efficacy? Patricia K. Coyle 1
# The American Society for Experimental NeuroTherapeutics, Inc. 2020
Multiple sclerosis (MS) is the major acquired central nervous system (CNS) disease of young adults [1, 2]. It causes organspecific immune-mediated pathology characterized by inflammation, demyelination, and neurodegeneration. MS shows a 3:1 female predominance and great variability in disease expression. Particularly in untreated individuals, there are ongoing accumulating macroscopic and microscopic damages to the CNS. MS is a poster child for a success story in the clinical neurosciences. This major disease has moved from untreatable to quite manageable, with a wide array of disease-modifying therapies (DMTs) [3]. In the USA, the FDA has approved 23 distinct agents covering 10 mechanisms of action, all focused on manipulating the immune system. One of the major current debates in MS involves the optimal choice of the very first DMT. This treatment debate is couched in terms of taking an escalation approach or a highefficacy induction approach [4]. Should a very safe but modestly effective DMT be chosen routinely, or would most patients do better if they were started on a high-efficacy agent from the beginning, even if it carried more risk? Induction, also referred to as immune reconstitution therapy, involves using a potent immunosuppressive for a limited time, because it produces a long-lasting effect on the host immune system [5]. Its use may be followed by a prolonged drug-free period or the institution of a milder maintenance agent. Because MS is so variable and most people present with relatively mild disease, high-efficacy, higher-risk DMTs are generally reserved for very active MS individuals with a poor prognostic profile. The MS DMTs can be divided into injectable immunomodulators, oral agents, and high-efficacy monoclonal or infusible agents. There is accumulating data * Patricia K. Coyle [email protected] 1
Department of Neurology, Stony Brook University Medical Center, Stony Brook, NY 11794, USA
for a therapeutic window of opportunity early on in MS, to maximize long-term therapeutic benefits [6]. The argument has been that a highly effective agent will quickly shut down the immune attack against the CNS, perhaps resetting the severity of the disease and minimizing epitope spread. Virtually, every study has noted MS patients treated early do better than those in whom treatment is delayed. But does the potency of the DMT truly matter? In a recent retrospective observational study from the Global MSBase Registry and the Swedish MS Registry, relapsing patients, who started a highefficacy DMT (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, natalizumab) within 2 years of disease onset (early treatment; N = 213), were matched to those who started these therapies after 4 to 6 years (late treatment; N = 253) [7]. The outcome was development of long-term disability, 6– 10 years later. MS pati
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