Early Implementation of Highly Effective Therapy for Multiple Sclerosis
The ongoing debate about changing the approach to treating relapsing-remitting multiple sclerosis (RRMS) from an escalation strategy to the early implementation of highly effective therapy (HET) is based on the documented high inflammatory activity of the disease in its early stages and the concept of a therapeutic window for its suppression shortly after diagnosis. We bring you a summary of several recent pieces of information about the benefits and safety of HET as an initial treatment for RRMS.
Early Intensive Treatment Strategy with HET
Currently, nearly twenty disease-modifying drugs (DMDs) are registered for the treatment of RRMS, offering a dozen different mechanisms of action. Therefore, there is an active debate on what treatment to start with for a patient with a newly diagnosed disease. Historically, a step-by-step escalation therapy approach was used in these patients, starting with drugs of lower/medium efficacy up to HET. Since neurological damage begins in the early stages of RRMS development, even before the appearance of the first symptoms, early implementation of HET could improve long-term clinical outcomes by minimizing the accumulation of neurological damage.1 However, there is still no consensus on how intensively newly diagnosed RRMS patients should be treated.2
Greater Slowing of Disability Progression with Early HET
One of the studies comparing early HET in RRMS with starting treatment with moderately effective DMDs and then escalating to HET was based on the Italian multiple sclerosis patient registry. It included individuals with at least 5 years of follow-up and at least 3 check-ups after initiating DMDs. The early HET group included patients who had fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, or cladribine as their first DMDs. The escalation group included patients who started HET after ≥ 1 year of using glatiramer acetate, interferons, azathioprine, teriflunomide, or dimethyl fumarate. Propensity scoring was used to create matching patient groups in a 1:1 ratio. From 2702 RRMS patients, 363 pairs were created with a median follow-up of 8.5 years.2
In the escalation group, a statistically significantly higher mean annual increase in disability score (EDSS) was found compared to the early HET group: by 0.1 points after 1 year, by 0.3 points after 5 years, and by 0.67 points after 10 years. The authors of this 2021 study concluded that early implementation of HET after RRMS diagnosis significantly slows the progression of disability compared to the step-by-step escalation treatment strategy.2
Comparison of Efficacy, Safety, and Treatment Costs
This year, a meta-analysis of 7 studies on this topic was published. The authors compared the efficacy, safety, and financial costs of escalation therapy and early HET in RRMS. They conducted a search of the Medline, Embase, and Scopus databases (as of September 2022) and identified studies that compared these 2 treatment strategies for RRMS in adult patients with a follow-up period of at least 5 years.3
The 7 studies included in the analysis comprised a total of 3467 patients. In the early HET group, a 30% lower risk of worsening EDSS was found after 5 years compared to the escalation treatment group (relative risk [RR] 0.7; 95% confidence interval [CI] 0.59−0.83; p < 0.001). An analysis of 2 studies involving 1118 participants assessing safety showed a similar safety profile for both treatment strategies. The results also suggested a possible cost-effectiveness of HET.3
Conclusion
The described studies contribute to the debate on the treatment strategy of RRMS by providing arguments for the early implementation of HET, which, according to their results, is associated with slower progression of disability, has a similar safety profile, and can be cost-effective compared to traditional escalation therapy.
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Sources:
1. Freeman L., Longbrake E. E., Coyle P. K. et al. High-efficacy therapies for treatment-naïve individuals with relapsing-remitting multiple sclerosis. CNS Drugs 2022 Dec; 36 (12): 1285−1299, doi: 10.1007/s40263-022-00965-7.
2. Iaffaldano P., Lucisano G., Caputo F. et al.; Italian MS Register. Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies. Ther Adv Neurol Disord 2021; 14: 17562864211019574, doi: 10.1177/17562864211019574.
3. Pipek L. Z., Mahler J. V., Nascimento R. F. V. et al. Cost, efficacy, and safety comparison between early intensive and escalating strategies for multiple sclerosis: a systematic review and meta-analysis. Mult Scler Relat Disord 2023 Mar; 71: 104581, doi: 10.1016/j.msard.2023.104581.
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