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MS research update – What effect do disease modifying drugs have on disability progression? – 14 December 2015

Summary

The disease modifying drugs work by interacting with different parts of the immune system to treat the inflammation caused by MS, reducing the number and severity of relapses. There is also some evidence that the DMDs can reduce disability progression (the build-up disability over time).

This study was a review which pooled the previous research into the DMDs to investigate the effect of DMDs on disability progression. The review found that overall people taking a DMD are less likely to see an increase in their disability. Although the analysis does have several limitations, including not looking at other indicators of MS disease activity which might also be important to levels of disability and how someone’s MS may develop over time.

Background

Disease modifying drugs (DMDs) are a group of treatments for people with relapsing multiple sclerosis. They work with different parts of the immune system to reduce the inflammation caused by MS to nerve cells in the brain and spinal cord. The main benefits of taking one of the DMDs are fewer relapses and any relapses experienced should be less severe. There is also some evidence that the DMDs can reduce disability progression (the build-up disability over time).

This study reviewed the previous research to investigate the effect of DMDs on disability progression.

How this study was carried out

This study was a review which pooled the previous research into the DMDs. To be included in the review and analysis the studies needed to be:

13 studies, lasting between one and three years, including a total of 9,788 participants met these criteria and were included in the analysis. The studies assessed change in disability over a three month period. That is a change in EDSS score, of at least 0.5 point, that lasted (was sustained) at least over a period of three months.

The researchers looked at the pooled study results to see if all DMDs could have an effect on disability progression and also if there were any differences depending if the drug was used as a “first line” (tried first) or “second line” (only used after another DMD had been tried and had not worked) therapy or if there were differences depending on how the drug was taken, injected into muscle, injected under the skin or taken as a pill.

What was found

The review found that overall the DMDs reduce the risk of increasing disability compared to participants taking a placebo. Further analysis revealed that there were no differences in the effect on disability regardless of how the drug was taken or whether it was used as first or second line.

What does it mean?

Although this study shows people taking a DMD are less likely to see an increase in their disability, the analysis does have several limitations. Firstly, the researchers only looked at the effect of disability worsening using the EDSS and did not look at other indicators of MS disease activity which might also be important to levels of disability and how someone’s MS may develop over time. Secondly, some studies on DMDs were excluded from this review as they did not have the relevant data included in the paper, so this review does not include all DMD studies. Finally there may be bias in the results, potentially due to the funders of the studies that were included, which is often the manufacturer of the drug, but also due to the number of participants that dropped out of the studies, so the study results were not necessarily complete.

Comment

As outlined in this review our understanding of how well DMDs work is mainly based on clinical trials of people receiving treatment for up to three years only. The effect of DMDs over the much longer term is currently still being investigated. A number of studies have looked at longer term effectiveness but there have been conflicting results as to whether DMDs slow down disability. As many of the DMDs have only been available for a few years it will be a while yet before we have definitive evidence of their long terms effects and if there are different effects with each of the different DMDs.

Tsivgoulis G, Katsanos AH, Grigoriadis N, et al.
The effect of disease modifying therapies on disease progression in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.
PLoS One. 2015 Dec 7;10(12):e0144538. eCollection 2015.
Abstract
Read the full text of this paper

More about disease modifying drugs

Disease modifying drugs (DMDs) work with different parts of the immune system to prevent the inflammation caused by MS. This helps reduce the number and severity of relapses. Inflammation in MS can also lead to permanent damage to the nerves in the brain and spinal cord. Reducing this inflammation may help to reduce the build-up of disability over time.

In the UK, there are now 11 DMDs that have been approved for use in the NHS for people with relapsing MS. Each drug offers a different combination of benefits and risks. Choosing which DMD to try is a complex decision and although the neurologist and MS specialist nurse can advise on eligibility and suitability for treatments, often people with MS are faced with a choice between two or more drugs.

You can learn more about the disease modifying drugs in MS Decisions, our independent online guide to the DMDs or in our book Disease modifying drugs a guide to treatments for relapsing MS which can be read online, downloaded as a pdf or ordered as a printed version.

Research by topic areas...

Assessment tools

Motl RW, Learmonth YC, Wójcicki TR, et al.
Preliminary validation of the short physical performance battery in older adults with multiple sclerosis: secondary data analysis.
BMC Geriatr. 2015 Dec 3;15:157.
Abstract
Read the full text of this paper

Disease modifying drugs

Lo Re M, Capobianco M, Ragonese P, et al.
Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.
Neurol Ther. 2015 Dec 8. [Epub ahead of print]
Abstract
Read the full text of this paper

Kappos L, Radue EW, Chin P, et al.
Onset of clinical and MRI efficacy occurs early after fingolimod treatment initiation in relapsing multiple sclerosis.
J Neurol. 2015 Dec 8. [Epub ahead of print]
Abstract
Read the full text of this paper

Braune S, Lang M, Bergmann A; NeuroTransData Study Group.
Efficacy of fingolimod is superior to injectable disease modifying therapies in second-line therapy of relapsing remitting multiple sclerosis.
J Neurol. 2015 Dec 8. [Epub ahead of print]
Abstract
Read the full text of this paper

Voskuhl RR, Wang H, Wu TC, et al.
Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial.
Lancet Neurol. 2015 Nov 24. [Epub ahead of print]
Abstract

Pathophysiology

Steenwijk MD, Geurts JJ, Daams M, et al.
Cortical atrophy patterns in multiple sclerosis are non-random and clinically relevant.
Brain. 2015 Dec 4. [Epub ahead of print]
Abstract

Physical activity

Manca A, Cabboi MP, Ortu E, et al.
The Effect of Contralateral Strength Training on Muscle Weakness in People With Multiple Sclerosis: A Proof-of-Concept Case Series.
Phys Ther. 2015 Dec 4. [Epub ahead of print]
Abstract

Psychological aspects

Grech LB, Kiropoulos LA, Kirby KM, et al.
Coping Mediates and Moderates the Relationship Between Executive Functions and Psychological Adjustment in Multiple Sclerosis .
Neuropsychology. 2015 Nov 30. [Epub ahead of print]
Abstract

Relapses

Laura A, Mirko P, Tommaso C, et al.
Effects of particulate matter exposure on multiple sclerosis hospital admission in Lombardy region, Italy.
Environ Res. 2015 Nov 25;145:68-73. [Epub ahead of print]
Abstract

Symptoms and symptom management

Chalah MA, Riachi N, Ahdab R, et al.
Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation.
Front Cell Neurosci. 2015;9:460. Review.
Abstract
Read the full text of this paper

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