Disease Modifying Agents for multiple sclerosis

The main benefits of taking one of the Disease Modifying Agents are:

Fewer relapses
Less severe relapses
Reduce the build-up of disability which can occur if you don’t recover completely from relapses
DMDs work with different parts of the immune system to reduce the inflammation caused by MS to nerve cells in the brain and spinal cord. This helps reduce the number and severity of relapses.

Inflammation does not always result in a relapse or visible symptoms. This silent activity may mean that although you are feeling well, there may still be changes caused by your MS that can only be seen on a brain scan. MRI scans show that taking a DMD can lead to fewer, smaller or no new areas of damage (lesions) in the brain and spinal cord. Treating the visibly active (relapses) as well as the silently active aspects of MS is a new goal that is emerging in MS treatment. This goal is often called no evidence of disease activity (NEDA). The aim is to reach a point where you are free of visible (relapses) and invisible (changes seen only on brain scans) MS disease activity.

Some research suggests that DMDs work best when they are started as soon as possible after diagnosis, effectively before there is any sign of disability, to reduce the build-up of damage to nerve cells.

It may take three to six months from starting treatment for a DMD to become fully effective, so the benefits of treatment may not be immediately obvious.

Most people will continue to have a background of symptoms. DMDs are not able to repair nerve damage already caused by MS so they cannot reverse existing symptoms.

When used to treat clinically isolated syndrome, some of the DMDs have been shown to delay further episodes that would lead to a definite diagnosis of MS.

None of the DMDs is recommended for people with secondary progressive MS who no longer experience relapses or for people with primary progressive MS. Some people with secondary progressive MS who continue to have disabling relapses may benefit from taking one of the DMDs.

Do disease modifying drugs reduce long term disability?

Our understanding of how well DMDs work is mainly based on clinical trials of people receiving treatment for 2-4 years only. A number of studies have looked at long term effectiveness but there have been conflicting results as to whether DMDs slow down disability.  As a result, there is still a lot of debate amongst neurologists and researchers about their long term effects.  Though currently there is a lack of definitive evidence, there are now some studies which are helping to move us closer to a better understanding of the impact of DMDs on disability over time.

The UK Department of Health Risk Sharing Scheme, for example, has been conducting a study to observe more than 5,000 people taking one of the four injectable DMDs (Avonex, Betaferon, Copaxone, and Rebif), following them over 10 years.  Levels of disability are the main focus of the study, not relapse rate.  People with MS included in the study are being monitored for changes in their disability (measured by EDSS), compared to an untreated group.

A recently published paper shows that after six years, the group on treatment have developed lower levels of disability compared to the untreated group.  The researchers conclude that all four drugs are effective in slowing the progress of the disease over the six year time period.

While these results provide encouraging evidence that DMDs slow down the progression of MS, there is currently no evidence that DMDs delay the onset of secondary progressive MS.

What are the risks of taking disease modifying drugs?

All the DMDs can potentially cause side effects – see information on individual drugs for more details.  Some people do not experience any side effects at all, some find they ease after the first month or two as their body adapts to the drug and others may find that side effects persist.  Your MS team will give you advice on how to reduce the impact of side effects.  A few people find side effects cause problems or are intolerable and have to change or stop treatment.

Some of the DMDs are associated with less common but potentially serious and life-changing side effects.  There are mechanisms in place to minimise the risks for people taking one of these drugs, such as advice on warning signs, additional tests and regular check-ups. Your MS team will step in quickly if there is any cause for concern.  However, some people may feel that, despite regular monitoring, they are unwilling to take the risk of developing serious side effects.  Others may feel that the benefits of the drugs outweigh the risks.

How do we know the disease modifying drugs work?

Phase III clinical trials provide the main evidence for the effectiveness of DMDs.

DMD clinical trials recruit hundreds of people and last for about two years.  The main aim of these trials is to compare the number of relapses in people taking the new drug with those taking the standard treatment or placebo.  Trials can include other measures such as the number of lesions seen on MRI scans and changes in disability which last for 3 months or more.  Any side effects the participants report are recorded and monitored.

Comparing one drug with another

Relatively few clinical trials have directly compared one DMD with another.

Comparing the results of one clinical trial with another may not give an accurate picture of which DMD is more effective than another.  One of the main problems is that the groups of people recruited for each of the trials will be different, in terms of average age, gender mix, where they live and how long they have been diagnosed with MS.  For example, the earliest large-scale DMD trials were carried out 25 years ago; it’s likely that, on average, participants in the early studies will have had MS for a longer time than those recruited for more recent clinical trials.

Statistical techniques have been developed which take account of differences in the groups of participants in trials; this approach have been used to compare results from separate clinical trials and provide an indirect comparison of how effective the drugs are at reducing relapse rates.

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