What a treatment has to do

Seven aims

MSFrontier sorts every treatment idea by what it aims to do. The same seven aims are used across the Research and Data sections.

• Prevent or delay MS, in people at high risk or with a first episode.
• Stop inflammation: fewer relapses and new lesions.
• Slow progression: less disability worsening over time.
• Protect nerves: keep nerve fibres and nerve cells alive.
• Repair myelin.
• Restore function: improve a symptom or ability such as walking.
• Reset the immune system, so that the disease stops without continuous treatment.

Success at one aim does not imply success at another. Most medicines that prevent relapses have done little against progression without relapses (lesson 4.2).

Three kinds of treatment

Disease-modifying medicines are taken for months or years to change the course of MS. Relapse treatment, usually a short course of high-dose steroids, speeds recovery from an attack without changing the long-term course (lesson "Treating relapses and symptoms"). Symptom treatment and rehabilitation ease the effects of damage that has already happened, such as stiffness, fatigue or bladder problems.

From an aim to a measure

Each aim needs its own measure, and the measure decides how long a trial takes and how many people it needs. Relapse trials count relapses per person per year. Phase 2 trials count new lesions on MRI, which respond within months. Progression trials count confirmed disability worsening on the EDSS, which needs hundreds of people over two years or more. Repair trials use measures of myelin such as evoked potential latency, and symptom trials measure the function itself, such as walking speed (lessons 7.1 to 7.3).

How big is the effect?

Trial results are often reported as relative reductions, which can sound larger than the change for any one person. In the AFFIRM trial, natalizumab reduced the relapse rate by 68 per cent. Over two years, disability progression was confirmed in 17 per cent of people on natalizumab and 29 per cent on placebo. That is a relative reduction of 42 per cent, and an absolute difference of 12 percentage points: about 12 fewer people with progression for every 100 treated for two years.[1] Both ways of reporting are correct, and both are needed to judge a result.

Benefit against risk

The most effective medicines act broadly on the immune system, so their risks matter as much as their benefits. Natalizumab can allow progressive multifocal leukoencephalopathy, a rare brain infection, and the risk depends on antibodies to the JC virus, previous immunosuppressive treatment and the length of treatment, which is why it is measured before and during treatment.[2] B-cell depletion lowers responses to vaccines and increases some infections. Choosing a medicine means weighing its expected benefit against its risks for a particular person.

Why timing matters

Disability that has built up is hard to reverse, so the timing of treatment matters. In a large pooled analysis of trial data, disease-modifying treatment delayed the point at which walking becomes limited (EDSS 4) by about three and a half years, and the need for a walking aid (EDSS 6) by about three years.[3] Trials now running test whether starting with a highly effective medicine, rather than escalating later, improves the long-term course.

Every medicine is a test of an idea

A medicine that works is evidence for the idea behind it, and one that fails is evidence against it, provided the trial was designed to answer the question. Interferon beta was tried partly because MS was once thought to be caused by a virus. Natalizumab came from the idea that damage depends on immune cells entering the brain. Rituximab was tested because some researchers suspected that B cells mattered more than was believed, and its success changed how MS is understood (lesson 11.6). This is why MSFrontier tracks treatment ideas as hypotheses, each judged by its trials.