Summary: A new study reports intensive therapy during the early stages of MS results in better long term outcomes for the patients.

Source: Cardiff University.

New findings by researchers at Cardiff University suggest that intensive therapy during the early stages of multiple sclerosis (MS) leads to better long-term outcomes for patients, despite it often being viewed as a riskier option than other first line treatments.

Dr Emma Tallantyre, from Cardiff University’s Division of Psychological Medicine and Clinical Neurosciences, said: “Over the last 10-20 years we have seen huge advances in the treatment of relapsing-remitting MS, with over 12 licensed medications having been shown to suppress disease activity.

“However, the medications differ considerably in their efficacy and safety; the drugs with the strongest effect are often associated with the most worrisome risks. As a result, there remains considerable uncertainty amongst clinicians and people with MS in how aggressively to treat the condition in its early stages, with high-efficacy early intensive therapies often reserved for those with rapidly evolving severe MS.

“Our study sought to explore long-term outcomes for people with MS according to their initial treatment strategy – either early intensive therapy, which is associated with a more complex safety profile, or milder medications which can be escalated to stronger drugs in the event of continued disease activity.”

The team looked at data from a cohort of 592 people with MS, treated in south Wales during the last 20 years. The analysis primarily focused on the change in Expanded Disability Status Scale (EDSS), a method of quantifying disability in MS and monitoring changes in the level of disability at five years after starting treatment. Of the 592 people in the study, 104 were prescribed early intensive therapies whilst 488 initially embarked on less risky, moderate-efficacy treatments.

“We found that in this cohort, long-term outcomes were more favourable following early intensive therapy versus first-line disease modifying therapies, suggesting that existing thresholds for this therapeutic approach may be too high, and the delay imposed by escalation strategies may result in lost therapeutic opportunity,” added Dr Tallantyre.

Professor Neil Robertson, Professor of Neurology and co-author of the study, said: “This data shows that in a very complex therapeutic landscape, routine data collected in NHS clinics has huge value in providing real-world evidence that can help to answer the questions that are important to patients.

“Indeed, our findings have contributed to a successful award of over $10 million to fund DELIVER-MS, a multi-centre prospective trial of disease modifying therapy algorithms with participants in the UK and USA.

“In the meantime, there is work to be done in developing adequate procedures for treating patients using the escalation approach. These need to detect where first-line treatments are failing to slow the progression of the disease and respond by moving patients to more effective therapies without people developing permanent disability.”

Dr Susan Kohlhaas, Director of Research at the MS Society, added: “People with MS regularly tell us that treatment decisions are difficult to make. This study could be a game changer because it suggests people who have early intensive treatment have a better long term prognosis. We’re driving research into more and better therapies, and are proud to have funded this work. The next step is to complete the DELIVER-MS trial – a phase 2 study to compare the risks and benefits of this approach to one where treatments escalate in intensity. Once complete we hope this could have really positive implications for people with MS.”

About this neuroscience research article

Source: Cardiff University

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is adapted from the Cardiff University news release.

Original Research: Abstract for “Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis” by Katharine Harding, PhD; Owain Williams, MBBCh; Mark Willis, PhD; James Hrastelj, MBBS; Anthony Rimmer, MBBS; Fady Joseph, MD; Valentina Tomassini, PhD; Mark Wardle, MD; Trevor Pickersgill, MRCP; Neil Robertson, MD; and Emma Tallantyre, PhD in JAMA Neurology. Published February 19 2019.

doi:10.1001/jamaneurol.2018.4905

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Cardiff University”Long Term Benefits From Intensive Therapy in Early Stages of Multiple Sclerosis.” NeuroscienceNews. NeuroscienceNews, 20 February 2019.

<https://neurosciencenews.com/ms-early-therapy-10787/>.[/cbtab][cbtab title=”APA”]Cardiff University(2019, February 20). Long Term Benefits From Intensive Therapy in Early Stages of Multiple Sclerosis. NeuroscienceNews. Retrieved February 20, 2019 from https://neurosciencenews.com/ms-early-therapy-10787/[/cbtab][cbtab title=”Chicago”]Cardiff University”Long Term Benefits From Intensive Therapy in Early Stages of Multiple Sclerosis.” https://neurosciencenews.com/ms-early-therapy-10787/ (accessed February 20, 2019).[/cbtab][/cbtabs]

Abstract

Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis

Importance

Uncertainty remains about how aggressively to treat early multiple sclerosis. High-efficacy disease-modifying therapies (DMTs) are often reserved for individuals expressing poor prognostic features at baseline.

Objective

To analyze long-term outcomes in a population-based cohort according to initial treatment strategy.

Design, Setting and Participants

In this cohort study, data were derived from January 1998 to December 2016, and analysis was performed in January 2017. From a total of 720 patients prescribed a DMT, 592 (82%) were included in analysis. Reasons for exclusion were first treated elsewhere or privately (n = 39), clinical trial participant (n = 25), and insufficient clinical data (n = 45).

Exposures

Patients were classified according to first-line treatment strategy: high-efficacy (early intensive treatment [EIT]) or moderate-efficacy DMT (escalation [ESC]).

Main Outcomes and Measures

Primary outcome was 5-year change in Expanded Disability Status Scale score. Secondary outcome was time to sustained accumulation of disability (SAD). Models were adjusted for sex, age at treatment, year of starting DMT, and escalation to high-efficacy treatment in the ESC group.

Results

Mean (SD) age of 592 patients at symptom onset was 27.0 (9.4) years. Mean (SD) 5-year change in Expanded Disability Status Scale score was lower in the EIT group than the ESC group (0.3 [1.5] vs 1.2 [1.5]); this remained significant after adjustment for relevant covariates (β = −0.85; 95% CI, −1.38 to −0.32; P = .002). Median (95% CI) time to SAD was 6.0 (3.17-9.16) years for EIT and 3.14 (2.77-4.00) years for ESC (P = .05). For those within the ESC group who escalated to high-efficacy DMT as second-line treatment, median (95% CI) time to SAD was 3.3 years (1.8-5.6; compared with EIT group log-rank test P = .08). After adjustment for relevant covariates, there was no difference in hazard of SAD between the groups. However, 60% of those who escalated to high-efficacy DMTs were observed to develop SAD while still receiving initial moderate-efficacy treatment before escalation.

Conclusions and Relevance

In a real-life setting, long-term outcomes were more favorable following early intensive therapy vs first-line moderate-efficacy DMT. Contemporary surveillance strategies and escalation protocols may be insufficiently responsive. This finding is particularly relevant as patients in real-world practice are typically selected for an EIT approach to therapy on the basis of clinical and radiological features predictive of a poor outcome. These data support the need for a prospective randomized clinical trial.

Feel free to share this Neuroscience News.