What happened at ECTRIMS 2016?

Post written by Arman Eshaghi, winner of the ECTRIMS Young Investigator Award 2016

MS researchers from around the globe gathered in London, UK, last week for the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). ECTRIMS is the largest global MS conference, bringing together over 9,000 researchers and health professionals for the latest updates and research findings on treatment, care and management of MS.

During ECTRIMS, we saw significant progress in the field of MS and new studies on progressive MS. Below are some of the highlights.

Positive results for a fingolimod-like drug for people with secondary progressive MS

Siponimod is a similar drug to fingolimod, but it has a more targeted effect on white blood cells and therefore may have fewer side effects compared to fingolimod while maintaining similar beneficial effects.

In a phase III trial called EXPAND (the biggest clinical trial on people with secondary progressive MS with 1,651 people from 31 countries) (Ludwig Kappos et al, abstract 250), participants received either a daily placebo or siponimod tablet. Further results from the trial were presented at ECTRIMS showing that, after 3 and 6 months, people with MS who received siponimod had slower progression as assessed by Expanded-Disability Status Scale (EDSS). Novartis, the producer of siponimod, will apply for the regulatory approval to formally include this drug as a treatment for secondary progressive MS. The results of this study have been submitted for publication. We will report the details as soon as they are published. You can read more about this trial on the International Progressive MS Alliance website.

Negative results for fluoxetine in progressive multiple sclerosis

Fluox-PMS is a multi-centre study performed in Belgium and Netherlands (Melissa Cambron et al, abstract 253). Fluoxetine is mainly used for the treatment of depression, but may be useful to protect brain cells from dying (degeneration). In this study investigators asked whether fluoxetine could slow the progression of MS. This drug trial included both people with primary progressive MS and secondary progressive MS. Participants were divided in two groups of placebo (68 participants) and fluoxetine (69 participants). After 108 weeks, there was no significant difference between the two groups of participants in terms of the rate of progression. Therefore, this study failed to show significant improvement in people with progressive MS who took fluoxetine. Although the trial showed a trend towards a reduction in disability progression, a larger and longer trial would be needed to show if this trend was statistically significant.

MS-SMART: reports on the recruitment phase

Three research abstracts were presented, which reported the recruitment phase for a promising drug trial for people with secondary progressive MS, called MS-SMART (Peter Connick, abstract P1203). MS-SMART stands for Multiple Sclerosis – Secondary progressive Multiple Arm Randomisation Trial. This trial for secondary progressive MS is testing 3 drugs at once:

• amiloride – licensed to treat heart disease
• fluoxetine – licensed to treat depression
• riluzole – licensed to treat motor neurone disease (MND)

This is an ongoing study in 13 different sites across the UK. A total of 440 participants with worsening secondary progressive MS have been recruited in 4 groups: (1) placebo, (2) riluzole, (3) fluoxetine, and (4) amiloride. Investigators plan to follow participants for 96 weeks and assess the effects of each drug on clinical, disability and MRI outcomes. We look forward to seeing the results over the coming years.

Lipoic acid: is it useful for people with secondary progressive MS?

Lipoic acid is a tablet with antioxidant effects. In a study from Portland, Oregon, USA, investigators ran a clinical trial on 54 participants with secondary progressive MS (Rebecca Spain, abstract 222). Participants were divided into two groups who either received placebo or lipoid acid. The results of this trial after 96 weeks of follow up showed that the group who received the lipoic acid treatment had lower rate of brain shrinkage. However, there was no significant effect of the treatment on disability and clinical measures in people who received the treatment. Authors stressed the need for trials with more participants in order to prove the effectiveness of lipoic acid.

ORATORIO trial: New promising information on Ocrelizumab, a treatment for people with primary progressive MS

Last year, Ocrelizumab showed positive results for people with primary progressive MS (ORATORIO trial). The ORATORIO trial is a multi-center and multi-national drug trial. This year several groups presented new data on the trial from around the world (Jerome De Seze et al, poster 720, Gavin Giovannoni et al, poster 746, Jerry Wollinsky et al, poster 1278, Jerome De Seze et al, poster 1279). Ocrelizumab treatment showed consistent positive effects on walking and slowing the disability progression. The most common adverse event was the reaction at the site of infusions.

MS risk factors: smoking, vitamin D and obesity

In a proportion of people with MS, the disease starts without fulfilling all the criteria for MS (clinically isolated syndrome). People with clinically isolated syndrome may (or may not) develop MS over time. The factors that can affect conversion from clinically isolated syndrome to MS are of high interest if they can be modified and reduce the conversion rate to MS.

Investigators from the MS centre of Barcelona (CEMCAT) reported their findings on the relationship between vitamin D and smoking at the time of the diagnosis of clinically isolated syndrome on the risk of developing MS and disability progression in participant, followed for many years (Maria Isabel Zuluaga et al, abstract 252).

Investigators looked the vitamin D levels in 503 people with clinically isolated syndrome. They also looked at a blood marker of smoking (cotinine) in 464 people with clinically isolated syndrome. This study started in 1995 and followed participants for an average of 8 years (up to 15 years). Investigators did not find any significant increase for the conversion to MS in people with low vitamin D or those who were smokers. However, low levels of vitamin D, and cigarette smoking were both significantly associated with development of higher disability in the study participants. Therefore, both these risk factors, if modified, can slow the progression of disability in people with clinically isolated syndrome.

People with relapsing remitting MS are often treated by injectable interferons. A study from the Danish MS centre (Petersen et al, Righospitalet, University of Copenhagen, Denmark, abstract 178) on 1,145 people with relapsing remitting MS showed that smoking has significant effects on the response to treatment with interferon. Investigators observed that people with MS who smoked more, were less likely to respond to interferon treatment.

In another study from University of California in Berkeley and San Francisco (poster 454), Lisa Barcellos and colleagues asked whether body mass index (an index to define normal weights) has any effect on the risk of developing MS. Investigators looked at a huge population of people with MS and healthy volunteers from USA and Sweden (close to 20,000). They found a causal association between abnormal increase in weight (overweight or obese people) and the risk of MS. Authors suggested that this observation might be due to the effect of obesity on the immune system.

Comparing alemtuzumab, natalizumab or fingolimod

Report from MS Research Australia
There was great interest in a presentation by Dr Tomas Kalincik and his colleagues who had conducted a major analysis comparing the clinical data of people receiving alemtuzumab, natalizumab or fingolimod, using the extensive international data gathered in the MSBase database. The results suggest that natalizumab and alemtuzumab are better able to suppress relapses in comparison with fingolimod. Alemtuzumab and natalizumab appear to be similar in suppressing relapses and disability progression, with natalizumab more often showing an early improvement in disability levels. Of course, these effects represent the overall effects across a large population and may vary considerably for each individual. Treatment decisions also need to be based on other factors including general health, family planning, and other work and life related factors for each individual.