Firstly, for completing our #ThinkSocial survey, which was very useful and a good guide of why this campaign is important. And secondly, for the very kind donor who has given us a very generous grant to study whether, or not, targeted public engagement and patient-public involvement activities increase social capital and improve outcomes for people living with MS. By formally studying this we hopefully generate the necessary evidence to help others adopt our approach and to help get their PeS and PPI initiatives funded by the NHS and other relevant payers.
This survey and funding news coincides with the publication of our review on social capital. Well done to Saul and Alison for taking this forward. Saul is funded by an ECTRIMS fellowship and this paper will count towards his outputs.
Social capital (SC) is a broad term that encompasses the many resources derived from social connections. The contemporary study of SC in public health has deep roots in the related fields of sociology, economics, and politics. Its multidisciplinary nature and the varying potential ways it could affect individuals have resulted in different but overlapping models to approach SC in the health field. There are currently no standardized measures of SC, and even more, challenging its impact on health outcomes seems to vary according to the level of analysis. Despite the accumulating evidence that supports a protective effect of SC on mental and physical health, and mortality, not enough attention has been paid to the potential drawbacks of SC. The role of SC in neurological disease is just beginning to be explored. Concerted efforts are needed to ensure that empirical evidence on SC could be properly translated into interventions for health‐promoting purposes. In this paper, we review the current state of scientific knowledge on the subject of SC, with a focus on its application in the field of neurology.
I did a post-ECTRIMS interview with a Portuguese health magazine last week. The interview has helped me reflect and formalise some of my many ideas about secondary progressive MS that have been fermenting in my cortex for some months. I have therefore put pen to paper using a new format the self-interview.
Q: Prof G what was your main highlight at ECTRIMS 2018?
Without a doubt the acceptance by the wider MS community that progressive, or more advanced, MS is modifiable. Until quite recently most people thought that once someone with MS loses the ability to walk it is over for them from a treatment perspective. The two-stage MS hypothesis has been responsible for entrenching this worldview, i.e. an early modifiable inflammatory phase that is then followed by a secondary neurodegenerative phase.
Q: You say MS is #1_not_2_or_3_diseases; how does this position sit with the positive siponimod in secondary progressive (EXPAND) trial results and negative fingolimod in primary progressive (INFORMS) trial results?
Firstly, these were very different studies. The PPMS, or INFORMS, study was much smaller study and hence potentially underpowered for the question it was asking. The INFORMS population had less ‘inflammatory’ activity and was more advanced in terms of the biology of MS than the EXPAND population. More importantly, the SPMS or EXPAND study was event-driven and continued until there were enough events to get a result. I don’t think the discordance of these results supports MS being more than one disease. Another aspect that has been ignored is the obvious fact that fingolimod and siponimod are different drugs and may differ in their mode of actions, i.e. siponimod may have subtle effects within the CNS or potentially off-target effects that explain some of its efficacy.
Q: Do you think the EXPAND trial results are clinically meaningful?
Yes, I do think they are clinically meaningful because if you have SPMS having a drug that will slow down your disease progression is better than having no drug. The unmet need in SPMS is enormous. I agree that the effect on disease progression may seem small in terms of numbers, but this treatment effect will get bigger with time, because of therapeutic lag. It takes time for anti-inflammatory therapies to have an effect in more advanced MS because disease worsening in the next year or two is driven by damage sustained in the past. It takes time for this damage to work through the system, hence switching off inflammation now will take years to manifest as a treatment response.
It is also important to understand that siponimod will become a platform therapy on which we can build more effective combinations. It is clear that an anti-inflammatory therapy on it own is unlikely to make a big difference in more advanced MS. We need to build a therapeutic pyramid and add-on neuroprotectives, remyelination therapies and in the future neurorestoratives therapies. Regulators don’t like combination therapies unless one of them is a licensed product; siponimod could be that licensed product.
Q: What are you going to tell your patients about siponimod?
I am going to spread the hope. The ocrelizumab in PPMS (ORATORIO) and siponimod in SPMS (EXPAND) results are just the beginning of a new treatment era in MS. We need to celebrate the results of these trials and build on them. These trial results have challenged and killed the dogma of MS is a two-stage disease and that once you become disabled you are beyond hope.
It is also important to manage expectations in that these treatments are going to slow down and not reverse disability, hence many people with MS may not notice a treatment effect. However, we need these treatments as a platform to add on other therapies I refer to above.
I am definitely going to tell them about the effect siponimod has on cognition. Trial subjects treated with siponimod were more likely to have their cognition stabilise or improve compared to subjects on placebo. I am sure people with secondary progressive MS value their cognition and this bit of information may help them in making a decision about going onto this treatment or not. Please don’t forget MS is a cause of dementia and siponimod is one way of slowing down the development of MS dementia.
Q: In addition to being treated with siponimod is there anything else people with SPMS can do t help?
Yes, there is a lot they can do. This is about the holistic management of MS. If they smoke and they want to stop smoking they should seek professional advice about stopping smoking. The need to optimise their diets, exercise and sleep. The should review their medications and see if any medications that could be making their MS worse can be stopped. They should be screened for comorbidities or other diseases and have these treated. If they are having recurrent infections, particularly urinary tract infections, this should be addressed and treated. There is a lot that can now be done to reduce the risk of bladder infections.
People with MS should use it or lose it. If MS is affecting some function you should seek advice on what you can do to improve or stabilise function in that particular part of the nervous system. Don’t underestimate the value of rehabilitation and focused exercise programmes to help maintain function.
Q: Any final comments?
Don’t shoot the messenger. Although progressive, or more advanced, MS seems to have been neglected for many years these positive studies are catalysing many more studies in progressive MS. We need to reflect and celebrate these successes. Stopping to contemplate where we have come from and were are going to does not mean we have reached the end. One of my favourite poems makes this point very well.
Stopping by Woods on a Snowy Evening
BY ROBERT FROST
Whose woods these are I think I know.
His house is in the village though;
He will not see me stopping here
To watch his woods fill up with snow.
My little horse must think it queer
To stop without a farmhouse near
Between the woods and frozen lake
The darkest evening of the year.
He gives his harness bells a shake
To ask if there is some mistake.
The only other sound’s the sweep
Of easy wind and downy flake.
The woods are lovely, dark and deep,
But I have promises to keep,
And miles to go before I sleep,
And miles to go before I sleep..
CoI: multiple. I am an active steering committee member on both the EXPAND and ORATORIO studies.
How does alemtuzumab cause stroke? It is unlikely to be due to secondary autoimmune disease as it occurs too soon after administration. Could it be due to a mechanism that triggers thrombotic mechanisms, for example via platelet activation? Alemtuzumab causes an early and transient low platelet count (thrombocytopenia), which may be related to thrombosis.
The U.S. Food and Drug Administration (FDA) is warning that rare but serious cases of stroke and tears in the lining of arteries in the head and neck have occurred in patients with multiple sclerosis (MS) shortly after they received alemtuzumab. These problems can lead to permanent disability and even death. As a result, the FDA has added a new warning about these risks to the prescribing information in the drug label and to the patient Medication Guide. They have also added the risk of stroke to the existing Boxed Warning, FDA’s most prominent warning.
The FDA is recommending that patients or their caregivers should seek emergency treatment as soon as possible if the patient experiences signs or symptoms of a stroke or tears in the lining of the head and neck arteries, called arterial dissection, which can include:
Sudden numbness or weakness in the face, arms, or legs, especially if it occurs on only one side of the body
Sudden confusion, trouble speaking, or difficulty understanding speech
Sudden trouble seeing in one or both eyes
Sudden trouble with walking, dizziness, or loss of balance or coordination
Sudden severe headache or neck pain
Most patients taking alemtuzumab who developed stroke or tears in the artery linings developed symptoms within 1 day of receiving alemtuzumab. One patient reported symptoms that occurred 3 days after treatment.
Health care professionals should advise patients at every alemtuzumab infusion to seek immediate emergency medical attention if they experience symptoms of ischemic or hemorrhagic stroke or cervicocephalic arterial dissection. The diagnosis is often complicated because early symptoms such as a headache and neck pain are not specific. Promptly evaluate patients who complain of symptoms consistent with these conditions.
In the nearly 5 years since FDA approved alemtuzumab in 2014 to treat relapsing forms of MS, the FDA have identified 13 worldwide cases of ischemic and hemorrhagic stroke or arterial dissection that occurred shortly after the patient received alemtuzumab (see Data Summary). This number includes only reports submitted to FDA,* so additional cases that they are unaware of may have occurred. Twelve of these cases reported symptoms within 1 day of receiving alemtuzumab. As a result, the FDA has added a new warning about this risk in the Warnings and Precautions section of the prescribing information in the drug label. They have also added the risk of stroke to the existing Boxed Warning, FDA’s most prominent warning.
To help FDA track safety issues with medicines, they are urging health care professionals to report side effects from Alemtuzumab or other medicines to the FDA MedWatch program.
I have been taken to task and chastised for neglecting the blog and my patients. I realise that the blog is part of our #ThinkSocial campaign. To help understand the need for social prescribing I would appreciate it if you could please complete the following survey.
We are launching a new campaign called #ThinkSocial. Why?
About a year ago Barts-MS was criticised for pandering to the informed rich. More than half the patients we treat are out-of-area and when it comes to our alemtuzumab-treated patients more than two-thirds are out-of-area; i.e. in an ideal world they should be treated and managed by their local team. The problem we have is that informed patients seek out and find centres who offer them highly-effective treatments.
The implications of this stinging criticism are that we are neglecting the patients on our own patch to look after these other patients. In response to this, we did an audit and showed that our patients (Tower Hamlets, Hackney and Newham) are as likely to be on high-efficacy second-line therapies as patients from other boroughs. Our patients are not being disadvantaged. At about the same time as this criticism, I became aware of the massive variance in the NHS when it comes to DMT prescribing and access to MS services, which prompted us to hold our Variance meeting last month.
In addition to this Barts-MS has been very proactive in promoting their off-label essential DMT list to address under treated MS in resource-poor environments. This has subsequently led to the MS International Federation (MSIF) taking up the challenge and leading on an application to the WHO to get a few highly selected DMTs on the Essential Medicines List (EML).
Independent of this I noticed that patients engaging with our PPI (patient-public involvement) programme seemed to do better than patients who didn’t engage. I suspect this is because PPI increases social capital, i.e. support networks, that helps people with MS. Social capital is well studied in other disease areas, but not MS. As a result of this, we have started to explore social capital as a treatment for MS and are actively studying it. The concept of social prescribing to address the social determinants of health is not new. However, it seems to be gaining traction as a mainstream topic.
On my flight back from MENACTRIMS in Dubai, I was catching up on some of my reading and read the following two articles that are of the moment. You know that when both the NEJM and the BMJ simultaneously review and discuss social medicine something is afoot.
Excerpt: …. In this issue, the Journal launches Case Studies in Social Medicine, a series of Perspective articles, to highlight the importance of social concepts and social context in clinical medicine. The series will use discussions of real clinical cases to translate these tools into terms that can readily be used in medical education, clinical practice, and health system planning….
Excerpt: ….. “Dance lessons for the lonely on NHS,” led the Daily Mail in October. “GPs should prescribe hobbies like ballroom dancing, gardening and art classes to millions of people because it is often better than drugs,” said the Telegraph. This “social prescribing” is being touted widely as a panacea, including for loneliness, obesity, depression, and osteoarthritis. The health and social care secretary, Matt Hancock, is a fan: he wants social prescribing to relieve pressure on the NHS and improve patients’ outcomes…..
I have little doubt that social prescribing will make a massive difference to the way we manage MS. MS not only shreds the brain it shreds social networks. PwMS are frequently depressed, combine this with unemployment, divorce, poverty and reduced benefits and social isolation is not far away for a lot of pwMS. This is why we need to think differently about the holistic management of MS. The difficulty we have as healthcare professionals is to tackle this problem sensitively and with compassion. It is vital that we are not patronising when taking a social history and addressing social problems. A lot of pwMS think this not part of the neurology teams remit.
If you have any ideas on how about social prescribing in the MS space we would be interested to hear about them. Maybe you have examples of things that are working already.
Some of you may recall our readers’ response to the post on the BBC Radio 4 dramatisation of ‘An Instinct for Kindness’. Allyson the main character of the play is an example of someone who may have benefited from social prescribing. Do you agree?
Sometimes you want to say something unrelated to the thread or ask a clinical question or some other MS-related question that has not been answered in past. This is the place for you.
I would like to thank all our readers for persevering. Tomorrow is the launch of the first triMS-online virtual conference. The ideas underpinning this meeting arose from suggestions on this blog.
The driving principles underlying triMS-online are:
High-quality, short, themed meetings that are of the moment; too often the larger conventional meetings are planned months and years in advance and don’t necessarily have the flexibility to present topical subjects. triMS-online wants to be different.
Access to international experts using a shorter format than that is traditionally used at conventional conferences; we don’t want viewer’s drifting off because the talks are too long. All presenters are being trained to give punchy well-timed talks. We know human attention span, particularly online, is short.
A more diverse group of presenters, i.e. younger presenters, with a more international flavour and with gender equality in mind.
Synchronous and asynchronous attendance; you can log-in and watch the meeting live or come in after the meeting is over and watch the talks at a time that suits you.
Access; online meetings will allow people from all over the world to access high-quality online content. This is particularly relevant to people living in resource-poor countries who don’t necessarily have the finances to travel to International meetings in expensive cities.
Environmentally friendly; we hope that by attendees not needing to travel we can help reduce the environmental footprint of meetings.
Create a platform and format that can be used locally or regionally. We anticipate creating a triMS-online X platform in the near future, which will allow others to host regional meetings; these could be different languages and addressing specific topics of interest to specific countries.
The following is the first triMS-online programme; it is not too late to register. We would encourage young academics, in particular, those who are disadvantaged and from under-represented groups to submit ideas and posters for the next meeting. CoI: multiple
The MS Academy held our first #MSVariance meeting on 1st and 2nd of November in Birmingham. We were oversubscribed, which would indicate that there is an appetite for change in the way we practice MSology in the UK. I learnt a lot from the meeting and had several of my assumptions challenged.
Lesson 1: Be more proactive about including women and other under-represented groups in the meeting from the beginning. Our apologies for not including women on the steering committee; it was my mistake. The steering committee self-selected each other based on a discussion we had about #MSVariance following a debate on this topic at the ABN earlier this year in Birmingham. We have already made amends and have approached some women to help taking things forward so that this initiative gains momentum.
Lesson 2: Variance does not imply inequality. I thought variance, in the context of MS services, as being a euphemism for inequality. It is not. The variance in MS services and their provision may arise at the top due to improvements in access and the rapid adoption of innovations. This then could act as a stimulus or other centres and individuals to up their game and to improve things. In other words, variance acts like an evolutionary selection pressure; i.e as a driver for improvement. The question is that we need to make this variation transparent so all can see it and respond to it. For this to happen we are going to need to set-up a rolling national audit.
Lesson 3: Don’t be too hard on ourselves and celebrate the successes. We were very fortunate to have Stephen Bleach a Times Editor and Journalist who has MS attend and speak at the meeting. He had written a personal account of having MS in the preceding week’s Sunday Times. He compared his journey with the disease to that of his late father’s. His father developed MS in the pre-DMT era when MS services were poorly developed and he tragically had a very poor outcome. At the end of the meeting he got up and reminded us to celebrate his success; his MS was diagnosed and treated rapidly and he is now doing very well and working full time. His future with MS may still be uncertain, but it promises to be a much better future than what his father had at the same stage. Stephen’s perspective is important, but his experience is what we need to replicate across the country. Time is brain and there are simply too many people with MS outside the system, with unacceptable delays getting into the system to be assessed for treatment. In addition, access to MS services is highly variable with some people having to travel long distances to be assessed.
Lesson 4: Don’t reinvent the wheel. There are a lot of initiatives that are currently running to address some of the issues that underpin #MSVariance. NHSE are reviewing the configuration and implementation of neuroscience services, which includes MS. GIRFT (get it right the first time) is also looking into what it can do to raise neurological standards across the country. What we clearly need are well-defined channels to disseminate information accurately and timely. It is clear that there are pockets of excellence across the country and that we need to celebrate these and get them to share best practice. The MS Trust has a mechanism to do this, with several cases studies that have been published on the MS Trust’s website. There is clearly an appetite for centres to be able to access each other’s protocols and this is something we can do relatively easily and effectively using the MS Academy.
Lesson 5: This initiative goes beyond DMTs. At the start of the meeting, there was some discussion about the focus of the initiative. Many attendees felt strongly that it should not only be about reducing variation in the prescribing of DMTs, but it should include the needs of all MSers, in particular, those with more advanced or progressive MS. I couldn’t agree more.
Lesson 6: Expanding the brief to look at the social determinants of health. These are clearly important for health in general and almost certainly play a role in MS outcomes. However, data presented on this specific topic show that more research is needed. On a similar note, there was some discussion about social capital and lifestyle and wellness. Therefore, we will need to think carefully about how we incorporate these components into any metrics we develop and specific programmes to improve social capital and wellness.
Lesson 7: Chief Energy Officer. As I left for the meeting on the first morning of the meeting my wife mentioned to me that the main role of a CEO is being changed to that Chief Energy Officer. She said that my role at the meeting was to create the necessary energy and to inspire people to make change happen and to take control. In fact, Ben Bridgewater, one of the external speakers, implored us to #TakeControl and #ToMakeItHappen. If we didn’t make it happen then no one else would. I must admit my energy levels have been rather low; too MSed out, which is why I have taken so long to pen this post. However, I am just back from a very special holiday and feel rested and energised.
Lesson 8: Patient Activation. There is a difference between ‘patient engagement’ and ‘patient activation’. George Pepper, from shift.ms, gave a brilliant talk on what true patient activation should look like. It was clear that we need to define it and to make it happen. Patients who are actively engaged in their care are the true change agents. What we need now need to do it create the environment both inside and outside the NHS. In fact, we are planning to do this for our #BrainHealth #TimeMatters initiative and the following is a draft programme to train MSers to become #MSActivists. Please note this initiative is global, but will also include MSers from the UK. If you have any ideas to add to the programme below please do not hesitate to contact me.
Draft BrainHealth Training Course for People with MS
(2-day course)
Pre-reading and online content review, a needs analysis (online survey) and to prepare a short 2 min presentation on who you are and what delegates want to achieve as a Brain Health Champion / Ambassador
Introduction – Gavin Giovannoni
What is the MS Brain Health initiative and why is it important for people with MS?
Introductions – each person does a 2-minute presentation
Objectives of the BrainHealth Champions Programme – Gavin Giovannoni
Why do we need Brain Health champions?
How can you help?
What is your role locally, nationally and internationally?
Patient activation and empowerment – TBA
This component will define what we mean about patient activation and how to empower yourself with knowledge. This will cover the essential components of what should be in a patient bill of rights and/or patient charter. It will also cover shared decision-making and what constitutes best practice in terms of shared-decision making.
Health Policy and how it applies to the treatment of MS – External Speaker who is an expert on policy
In this section, you will learn about health policy and how to use it to promote better MS services and ultimately better outcomes for people with MS.
Personal branding, how to create an online profile and to use social media effectively – External Speaker who is an expert on branding and social media
This will component of the training programme will cover (1) personal branding, (2) your online presence, (3) how to use social media and (4) how to use tools to automate your online activity.
Brain Health Tools – OHPF
This component will review the available Brain Health tools, patient check-list and future plans
Breakout sessions to come up with new ideas for tools and initiatives to drive innovation and its adoption.
Social Capital – TBA
How important are the social determinants on MS outcomes?
How to measure social capital?
How to create or expand social capital?
Review of the competitive space
Lessons from other disease areas, e.g. dementia, type 1 diabetes
Partnerships: setting-up partnerships with other groups
How to share best practice
Projects and mentoring scheme
A session on potential projects to kick-start Brain Health initiatives locally
How to get funding for projects
Buddy up with a national mentor to help participants implement their Brain Health projects
Follow-up webinars to review projects
This will include online presentations of the specific Brain Health projects
Conclusion
Certificate of attendance and confirmation of being a Brain Health Champion
As we all are aware, there is an increasing number of organisations developing and providing digital services to help make life easier for people with MS.
Salford Royal has partnered with Shift.ms and Clever Together, a Healthcare Advisory Group, to understand the value of digital services from the viewpoint of people with MS.
Clever Together are specialists in involving people in the process. Using Clever Together’s online workshop software, the plan is to host a discussion for two weeks from Monday 12th November to understand the value of digital services from the viewpoint of MSers.
The insight is expected to broadly focus on exploring the following ‘exam questions’:
What is the state of the art when it comes to digital support for MS patients, as determined by them?
How do people with MS currently use digital to manage their MS?
How would people with MS like to use digital support in the future?
What are the barriers / potential enablers?
What value do people with MS place on information received from different sources? (e.g. from healthcare providers, charities and the experience of other people with MS)
In what format and through what channels do people with MS prefer to receive information? (e.g. written, printed, video, audio)
We note that these are not necessarily the questions that we will ask directly, but rather the questions to drive the development of the engagement within the online workshop and its subsequent analyses.
I have been espousing the message that time is Brain in the treatment of MS, but the NHS makes it difficult to practice what you preach. MS services in the NHS are not configured at present to react quickly in terms of new referrals and as a result, MSers pay the price. In the last few months, two MSers have lost brain and spinal cord because of how long it has taken them to get into the Barts-MS system. This upsets me and leaves me feeling very dissatisfied with my NHS practice.
The first is a patient with quite advanced MS who was reasonably well controlled on fingolimod. She moved to London to join her husband from a European country. She, unfortunately, ran out of fingolimod tablets before seeing me and by the time she arrived in our service she had rebound disease activity with severe brainstem and spinal cord disease activity. She was off her feet with the loss of bowel and bladder function.
The second case was also a European who has been living in the UK for 10 years. His first attack was a brainstem attack that occurred almost 2 years ago. He was initially seen in accident and emergency department of a district hospital. It took him almost a year to see a neurologist and then 6 months for a diagnostic workup to be completed before being referred to me. It took me just shy of 3 months to see him in my new patient MS clinic. By the time I saw him it was 21 months since he had his initial attack. His EDSS was 4.5. He now has bladder and bowel problems, unsteadiness of gait, double vision, weakness in his legs, incoordination in his limbs and depression. He has also lost his job and is unlikely to be able to resume work. His MRI is a full house of poor prognostic factors; high lesion load, Gd-enhancing lesions, posterior fossa and spinal cord lesions, black holes on T1 imaging and some early brain atrophy.
What did we do? We have put both these patients on natalizumab as part of our #BrainAttack paradigm, i.e. to get on top of the MS disease activity before we even have their JCV serostatus back. If they turn out to be JCV positive we can derisk their PML risk, by switching their treatment or offering them extended interval dosing (EID).
All MSologists have patients who have had catastrophic relapses whilst waiting for a diagnostic workup and/or DMTs. We also know that MS activity tends to be clustered, i.e. one of the best predictors of a relapse is a recent relapse. Instead of putting patients with possible early symptomatic MS at risk from having to wait why don’t we to treat them all with natalizumab to protect their brains and spinal cords? This is analogous to treating stroke.
Why natalizumab? It is one of our most effective DMTs, it works very quickly, it is given as an IV infusion, hence there is no problem with adherence and is very safe for up to 12 months. It is also relatively safe in pregnancy. During this 12 month period, the neurologist and the patient can then decide what strategy they want to pursue in the long-term. This could be to continue natalizumab long-term or to switch to another DMT, or in the case of an alternative diagnosis the drug can be stopped.
At Barts-MS we want to promote the #BrainAttack strategy and to potentially do a trial. Please note that if you adopt the #BrainAttack paradigm you need to commit to at least 6 months, and potentially 12 months, of natalizumab treatment, to prevent patients from developing anti-natalizumab or anti-drug antibodies. We rely on the continued administration of natalizumab to trigger high-zone tolerance and to switch off NAB development. We learnt about this when natalizumab was initially pulled from the market in the US after the initial PML scare. Those patients have 1, 2, 3 or 4 infusions were much more likely to become persistently NAB-positive and if this occurs they can never be treated with natalizumab again.
Please note that another issue with these two MSers is that they were both foreigners who grew up outside the UK and simply did not know how to navigate the NHS systems. I think everyone who lives in the UK knows how to navigate the NHS and to be more demanding. I am sure if these MSers had been native to the UK they would have found a way to expedite their appointments. This is no excuse. The tragedy for me is that both these MSers have acquired significant disabilities as a result of NHS systems. I now going to explore the possibility of setting-up an urgent DMT assessment clinic to try an avoid this from happening again.
