Induction vs. Escalation Treatment: Which Strategy to Choose in the Therapy of Multiple Sclerosis?

Introduction

Therapy for multiple sclerosis is divided into three main categories: acute relapse treatment, disease-modifying therapy (DMT), and symptomatic treatment. Within DMT, there are two primary approaches, known as induction and escalation therapy.

In induction DMT, patients are initially given highly effective drugs with a risky safety profile, requiring monitoring and administration in a healthcare facility. These include monoclonal antibodies such as alemtuzumab and natalizumab. Due to the increased risk of side effects, induction therapy is currently reserved mainly for patients at the greatest risk of impairment and high disease aggressiveness.

In contrast, escalation therapy begins with safer but less effective drugs, such as beta interferons (IFN-β) or glatiramer acetate. If these are insufficiently effective, the treatment is escalated to more effective substances. According to new findings, escalation strategies can lead to missed therapeutic opportunities. Therefore, it is crucial to timely recognize the failure of first-line treatment so that highly effective drugs are not administered too late. Continuous monitoring of MS progression is very important.

Analyzed Data and Studied Population

The prospective cohort study, published in 2019 in the journal JAMA Neurology, aimed to compare the induction and escalation approaches in terms of long-term benefits in controlling disability progression. From a cohort of patients diagnosed with multiple sclerosis, for whom clinical data were collected by physicians between 1998 and 2016, 592 were included in the analysis. Patients were divided according to the type of DMT strategy. Patients in the first group (EIT − early intensive treatment) were treated with highly effective drugs from the outset. This group included 104 patients, 67% of whom used alemtuzumab and 33% natalizumab. The second group (ESC − escalation) began therapy with moderately effective drugs: IFN-β, glatiramer acetate, dimethyl fumarate, fingolimod, or teriflunomide. In 58 of the 488 patients in the ESC group, therapy was escalated to highly effective monoclonal antibodies.

The primary objective of the study was to record changes in the EDSS scale (Expanded Disability Status Scale) after 5 years of DMT. Another monitored data point was the time needed to develop sustained accumulation of disability (SAD), defined by the authors as an increase in EDSS score lasting at least 6 months, precisely determined from the baseline EDSS value. When assessing the results, they considered age, sex, age at the initiation of DMT, and possible escalation to highly effective medications in the ESC group.

Results

The average change in the EDSS scale after 5 years of DMT was significantly lower in the EIT group compared to the ESC group (0.3 vs. 1.2). This result remained significant even after accounting for relevant variables. The average time needed to achieve SAD was almost twice as long in the EIT group compared to the ESC group (6.0 years vs. 3.14 years). Among patients in the ESC group whose treatment was escalated to highly effective DMT, the average time to achieve SAD was 3.3 years, and 60% developed SAD during the initial phase of moderately effective therapy. After adjusting results for relevant variables, no significant difference in the risk of achieving SAD persisted between the groups. 

Conclusion and Discussion

The study's evaluation indicates that patients with multiple sclerosis, for whom DMT is induced by highly effective drugs, achieve more favorable long-term results in the progression of neurological impairment than those undergoing escalation therapy. According to current knowledge, escalation therapy may have insufficient effects on preventing disability development. The acquired data have practical significance; however, due to the limitations inherent in cohort studies, it would be advisable to conduct a clinical randomized study to compare the effectiveness of induction and escalation strategies.

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Sources:
1. Harding K., Williams O., Willis M. et al. Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis. JAMA Neurol 2019 May; 76 (5): 536–541, doi: 10.1001/jamaneurol.2018.4905.
2. Doshi A., Chataway J. Multiple sclerosis, a treatable disease. Clinical Medicine (Lond) 2016; 16 (Suppl. 6): s53–s59, doi: 10.7861/clinmedicine.16-6s-s53.