Escalation vs. Early Intense Therapy in Multiple Sclerosis

Abstract

The treatment strategy of multiple sclerosis (MS) is a highly controversial debate. Currently, there are up to 19 drugs approved. However, there is no clear evidence to guide fundamental decisions such as what treatment should be chosen in first place, when treatment failure or suboptimal response should be considered, or what treatment should be considered in these cases. The “escalation strategy” consists of starting treatment with drugs of low side-effect profile and low efficacy, and “escalating” to drugs of higher efficacy—with more potential side-effects—if necessary. This strategy has prevailed over the years. However, the evidence supporting this strategy is based on short-term studies, in hope that the benefits will stand in the long term. These studies usually do not consider the heterogeneity of the disease and the limited effect that relapses have on the long-term. On the other hand, “early intense therapy” strategy refers to starting treatment with drugs of higher efficacy from the beginning, despite having a less favorable side-effect profile. This approach takes advantage of the so-called “window of opportunity” in hope to maximize the clinical benefits in the long-term. At present, the debate remains open. In this review, we will critically review both strategies. We provide a summary of the current evidence for each strategy without aiming to reach a definite conclusion.

The Place of Immune Reconstitution Therapy in the Management of Relapsing Multiple Sclerosis in France: An Expert Consensus

“…By definition, the “early high efficacy” strategy involves immediate prescription of a high-efficacy DMT (as far as this can be defined, see above) rather than DMTs usually described as first-line or platform agents [ 5 – 7 ]. In practice, the candidate DMTs for this approach act via continuously prescribed immunosuppression or as IRTs [ 3 , 54 ].…”

“…Most DMTs can be considered to be immunomodulators or immunosuppressants that must be administered continuously [ 3 ]. DMTs are usually prescribed using an escalation approach, where “first-line” or “platform” DMTs are prescribed initially, with a switch to a high-efficacy DMT [ 4 ] in the event of unacceptable breakthrough MS disease [ 5 ]. Alternatively, the “early high efficacy” approach has gained increasing attention in recent years, where high-efficacy DMTs are used immediately [ 5 – 7 ].…”

“…DMTs are usually prescribed using an escalation approach, where “first-line” or “platform” DMTs are prescribed initially, with a switch to a high-efficacy DMT [ 4 ] in the event of unacceptable breakthrough MS disease [ 5 ]. Alternatively, the “early high efficacy” approach has gained increasing attention in recent years, where high-efficacy DMTs are used immediately [ 5 – 7 ]. However, MS is a lifelong condition: longer exposure to the immunosuppressive effects of a continuously applied high-efficacy DMT may bring additional risk of serious adverse safety outcomes, such as serious infections or malignancy [ 7 ].…”

Volumetric Brain Parameters in Association with Cognitive functions in a Sample of Egyptian Multiple Sclerosis Patients

“…They can be categorized into platform therapy and high efficacy therapy (19). Escalation, induction, and lateral shifting are the strategies used to control disease activity according to factors such as the expanded disability status score (EDSS), MRI lesion burden, and the course of progression (20). The high efficacy disease modifying therapy was proven to decrease brain volume loss in patients with multiple sclerosis compared with platform therapies (21).…”

Personalized Diagnosis and Therapy for Multiple Sclerosis

“…Currently there are up to 19 drugs approved to avoid the onset of relapses but there is no clear evidence to guide fundamental decisions such as what treatment should be chosen in the first place. This issue contributes a critical narrative review of the evidence on this still unresolved important issue, whether it is better to offer our patients Escalation Therapy or Early Intense Therapy [ 2 ] to prevent long-term outcomes.…”