My prevention hat

About three years ago I started wearing another hat; a preventive medicine hat.

We started the Preventive Neurology Unit within our medical school focusing on MS, Parkison’s Disease and all-cause dementia. The unit is growing rapidly and gaining momentum. It was with great pride that I was able to attend and speak at first symposium. I have uploaded my slides for anyone who wants to download them for personal use. 

It is clear that we have an obligation to the next generation of pwMS. The study below shows that young people with MS take a massive cognitive hit. The study shows that at a presentation about a quarter of young people with MS have cognitive impairment at baseline and ~15% had a measurable decline over the next 2 years. In a world where our self-worth is largely defined by our cognition, these figures are scary. The observation that MS is a dementing disease is not new and goes back many decades. 

The willingness of the MS community to accept this is worrying; they say calling MS a dementing disease is stigmatising. Yes and no. Yes, if you want to put your head in the sand and no if you want the MS community to do something about it. It is clear that the dementia is preventable; i.e. the less brain damage that you allow to accumulate the less cognitively impaired the pwMS will become. This is the message behind our treat-early treat-effectively campaign and why we need to flip the pyramid. Access to the most effective treatments early on is the only way to really prevent end-organ damage. 

More importantly, is the observation that MS is preventable. We estimate that by tackling childhood and adolescent obesity and smoking may reduce the incidence of my MS by ~25%. Vitamin D supplementation may reduce the incidence by a further 40%. Preventing EBV infection with a vaccine strategy may prevent the majority of people developing MS. May be admitting how bad MS is at a personal and population-level will get funders to put more money and resources into prevention. 

I think we should call a spade a spade and forget the rose-tinted world most people like to live in. We need to take MS prevention seriously; we owe it the next generation of people who are destined to develop MS. Wouldn’t it be nice if they didn’t get MS? 

Wallach et al. Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline. Mult Scler. 2019 Nov 28:1352458519891984.

BACKGROUND: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS.

OBJECTIVE: To screen for cognitive impairment early in the course of POMS and analyze predictive factors.

METHODS: Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free.

RESULTS: At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing (n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT.

CONCLUSION: Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.

CoI: multiple

Paediatric-onset MS

As you are aware approximately 3% of people with multiple sclerosis develop their first symptoms in childhood and adolescence. As the incidence and prevalence of MS are increasing we are seeing more children and adolescents with the disease. Why?

Relative to MS in adults, most neurologists and other healthcare professionals are unfamiliar with the diagnostic evaluation, clinical course, outcome, and management of MS in children.

To remedy some of these deficiencies we are running a dedicated triMS.online meeting on Paediatric MS on Tuesday 11th, June 2019. We have an exciting programme of international speakers. As with all triMS.online meetings you don’t necessarily have to watch them live, but can log-in after the event and watch the content in your own time. You can also ask questions, which the speakers will respond to for up to 4 weeks after the event.

www.trimsonlineconference.com

Don’t forget to register and please forward the invitation to your colleagues.

CoI: multiple

Extinction-Rebellion

If you live in London you may have had your life interrupted over the last two weeks by the Extinction Rebellion protests. This is a serious environmental movement that wants us to act now to save the planet from environmental catastrophe.

As part of the protest, my daughters have been giving me a hard time about my carbon footprint. They want to know if I am offsetting my air miles, which I do occasionally, that is when I personally book my flights. But in general, I am sure that most of my air miles are not offset. However, there is one initiative I am proud of that is addressing climate change and that is TriMS.online.

triMS-online is a virtual online conference for people interested in MS. The original idea of triMS-online came from this blog; thank you.  

The aims of triMS-online are multiple. The objective is to do punchy, short, themed MS-related conferences online that can be viewed as a live event, or asynchronously, i.e. when you have the time. This is particularly useful for people who can’t travel for family reasons, for example, you may have young children or you are a carer. Or you simply don’t have the time and/or resources to travel to large international meetings.

triMS-online is environmentally friendly; imagine how many air miles we are avoiding by not having to fly people to conferences?

The other advantage of triMS-online is that it takes high-quality MS research and education to resource-poor environments across the globe. We want a new generation of MS researchers and HCPs to have access to the latest MS research and teaching.

As founding chair of the scientific committee of triMS-online, I wanted to use the opportunity to shake things up a bit. When you go to ECTRIMS it is generally the same-old faces and KoLs on the platforms; the English refer to this as the ‘Old Farts’ syndrome, which includes me. We, therefore, invited a diverse group of ‘young’  MS academics from across the globe to run triMS-online and we made a strategic decision of having at least an equal number of women on the steering committee; in fact, 6 out of 10 of members are women.

The following is our second triMS-online programme, which addresses paediatric MS. We plan to run about 2-3 triMS.online conferences a year and have many ambitious plans for the triMS-online platform going forward. One idea is to host regional meetings on the platform, for example, a Latin American meeting in Spanish. Why not one in Polish or for that matter any other language?

I urge you to register for the next meeting and to submit posters. The platform is like a real conference with meeting rooms, social events and exhibition spaces.

We will be need feedback, including suggestions for future meetings. Don’t be shy and join the revolution, even though it may not be a rebellion.

We would encourage young academics, in particular, those who are from under-represented groups to submit posters for this next meeting.

CoI: multiple

Old but good news: children and adolescents get their first licensed DMT in Europe

I personally want to thank all those involved in getting fingolimod licensed as the first disease-modifying therapy for children and adolescents with MS. Getting this trial done was a ‘mission impossible’. Novartis, the steering committee, investigators and all study participants must be congratulated on getting past the finish line. History will judge this as an important milestone for MSers and the wider MS community.


However, I am very disappointed that the EMA (CHMP) only licensed this for highly-active or rapidly-evolving severe MS. Why the restrictive label? When will the EMA beging to trust neurologist, MSers and their families to do the right thing? The way the EMA treat us is insulting and does not put MSers’ interests first. 

Surely it is time to change fingolimod’s label? We need fingolimod to be first-line. Why can’t we be trusted to use fingolimod wisely in the interests of our patients with active MS? Surely it is safer than alemtuzumab? Possibly safer than ocrelizumab? Can someone explain the thinking and logic behind the latest pair of EMA handcuffs?

The following is verbatim from the EMA’s website:

On 20 September 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product Gilenya. The marketing authorisation holder for this medicinal product is Novartis Europharm Limited.

The CHMP adopted an extension to the existing indication as follows:

“Gilenya is indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis for the following groups of adult patients and paediatric patients aged 10 years and older:


Patients with highly active disease despite a full and adequate course of treatment with at least one disease-modifying therapy (for exceptions and information about washout periods see sections 4.4 and 5.1).

or


Patients with rapidly evolving severe relapsing-remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.”

Detailed recommendations for the use of this product will be described in the updated summary of product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.


The timing of this is fortuitous as the study has recently been published in the NEJM:

Chitnis et al. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis. N Engl J Med. 2018 Sep 13;379(11):1017-1027.


BACKGROUND: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.


METHODS: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.

RESULTS: Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).

CONCLUSIONS: Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .).

Comment inTherapy in Multiple Sclerosis – Coming of Age. [N Engl J Med. 2018].


CoI: Multiple; in addition Prof G is a member of the PARADIGMS trial steering committee