If you are a Healthcare Professional (HCP) and are interested in getting up to speed on some advanced topics around the management of MS please take a look at the programme below. We converted our November meeting to be virtual, which has opened some spaces for more people to attend.
At Barts-MS we spend a lot of time teaching people about MS. It is not only important to generate new information (ideas, testable hypotheses and research), but also to disseminate knowledge (teaching). However, with the COVID-19 pandemic and the resultant social distancing, almost all teaching has gone online and that does not make for very engaging and interesting. Most of us are webinar-ed or Zoomed-out. I wrote a piece on Medium that I titled Zoomed-Out addressing this exact point.
Can we make teaching the next generation of potential MSologists more interesting? I think we can. The following is an example of case-based teaching we are trying out at our first MS Academy Basecamp in a few week’s time. Let’s hope it works and it encourages more junior doctors, nurses, therapists and other allied HCPs to plan a career in multiple sclerosis.
Scenario 1: You are called to see a case with double-vision due to an internuclear ophthalmoplegia (INO) in casualty and an abnormal MRI suggestive of MS.
How are you going to confirm the location of the lesion?
How do you diagnose MS?
What MS mimics do you need to exclude?
How do you profile the patient’s prognosis at baseline?
Is the patient eligible for DMTs?
How do you de-risk the DMTs?
Scenario 2: Your consultant asks you to see a young woman of 26 with her partner. She is coming for a scheduled follow-up appointment after a diagnostic work-up for MS. The consultant tells you she has MS.
How are you going to confirm the diagnosis of MS before seeing her?
How are you going to tell her the diagnosis?
How are you going to counsel her about her future disease course?
She asks if she can have a family. What are you going to tell her?
What is active MS, highly active MS and rapidly evolving severe MS?
What is the difference between maintenance-escalation and immune reconstitution therapies? How are you to explain the difference to them between these two treatment options?
Scenario 3: You are asked to do an MS follow-up clinic for your consultant neurologist?
How are you going to prepare for the clinic?
What information are you going to record in the medical notes?
How are you going to investigate and manage an MS-bladder?
How do you manage MS-related fatigue?
Should you routinely screen for and manage MS-related cognitive impairment?
Scenario 4: You attend your departments, MS Research Day, for patients with MS and are asked to prepare a teaching session for the attendees.
How do you explain the cause of MS to the attendees?
What are the latest treatments available for progressive MS?
A woman attendee asks you about the risks of her children getting MS. What do you tell her?
An attendee asks about stem cell therapy; how are you going to counsel her?
What would you want us to teach the next generation of MSologists and how?
For those who missed our online journal club on radiologically isolated syndrome (RIS) or asymptomatic MS, which was held online this afternoon, you can catch-up with the banter on YouTube.
An interview with Rachel Horne who wrote the extraordinary blog post “The Kingdom of the Sick” (14th July 2020), which in my opinion is almost certainly the most well written and insightful piece on this blog.
CoI: nothing relevant in relation to this blog post
Here we go again. Most readers will have gathered by now that NICE has not recommended Siponimod for treating active SPMS under the NHS. This is a big disappointment for the MS community in the UK particularly for those patients who have active SPMS or worsening SPMS on a DMT who were hoping to be switched to Siponimod.
It is clear that some of the assumptions NICE have made about the treatment of MS don’t represent the reality on the ground, in particular, that most people diagnosed with SPMS do not have any disease-modifying treatment. I would argue that the biggest population of potential ‘siponimod-eligible’ patients with SPMS are those smouldering away on existing DMTs. A straw poll of UK MSologits we did in 2014 indicated that most were reluctant to label their patients as having SPMS because of the implications it has for treatment. Most MSologists don’t necessarily stop existing DMTs in patients with worsening disability because they are concerned about the potential for a rebound in inflammatory disease activity.
1.1 Siponimod is not recommended, within its marketing authorisation, for treating secondary progressive multiple sclerosis with evidence of active disease (that is, relapses or imaging features of inflammatory activity) in adults.
1.2 This recommendation is not intended to affect treatment with siponimod that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS healthcare professional consider it appropriate to stop.
Why the committee made these recommendations
Interferon beta-1b is the only disease-modifying treatment available for people with active secondary progressive multiple sclerosis. However, few people take it.
Most people do not have any disease-modifying treatment. Clinical trial results show that siponimod reduces the number of relapses and slows disability progression compared with placebo. It is uncertain how effective siponimod is compared with interferon beta-1b because there is no evidence directly comparing them.
Because of the limited clinical evidence, the cost-effectiveness estimates are uncertain, and none of the analyses reflect the committee’s preferred assumptions. Therefore, siponimod is not recommended.
The idea that MS is three diseases rather one disease is clearly coming back to haunt the field. I think most people working in MS understand that MS is one disease with superimposed inflammation, i.e. relapses and focal MRI activity, determining the clinical phenotype and being the treatment target for licensed anti-inflammatory agents such as siponimod. The question about whether or not focal inflammation drives all pathology has yet to be answered, but based on the early treatment trials of highly-effective agents this seems likely.
As always we as an MS community are going to have to respond to NICE. But what do we say? I am not sure there is a consensus amongst UK neurologists about how we diagnose and manage SPMS. The following are a series of questions that I think need to be answered when it comes to managing pwMS who are ‘transitioning to’ or have become secondary progressive, which will inform the content and tone of our response to NICE. As always our role as MSologists and MS HCPs is to be patient advocates; I sincerely hope we won’t let you down.
What components of ‘disease activity’ do you think should define active SPMS?
What timeframe should be used to define active SPMS?
Do you actively screen for and diagnose SPMS in patients on DMTs?
Do you actively avoid diagnosing SPMS so that you don’t have to stop their DMT?
Do you generally stop DMTs in patients who have transitioned to becoming secondary progressive?
What concerns you when stopping DMTs in patients who have transitioned to becoming secondary progressive?
Do you think it is appropriate to stop DMTs in patients who have transitioned to becoming secondary progressive to see if they become active?
Do you start or switch patients who you have diagnosed as having active SPMS onto interferon-beta-1b according to NHS England’s or other guidelines?
Do you have any patients under your care who have become secondary progressive on DMTs who are now wheelchair-bound (EDSS>6.5)?
This week I am participating in a debate on how to manage patients with MS on DMTs during the COVID-19 pandemic. Rather than a didactic lecture, I am going to debate several issues with Dr Kerstin Hellwig in relation to two case scenarios (see below), which will highlight the evolving complexities of how to manage MS during these troubling times. If you haven’t registered yet please do so ASAP as places are limited.
Case 1: A 36-year old male has been on ocrelizumab for 2 years; this is his second DMT after having previously received interferon β-1a. He was due his 6th dose of ocrelizumab in March 2020 but this has been postponed indefinitely by his MS centre.
Do you agree with this decision?
What are his chances of getting severe COVID-19 with B-cell depletion?
What about secondary bacterial infections in the event he does get COVID-19?
When will it be safe to resume ocrelizumab treatment?
He is worried that on ocrelizumab therapy he will be unable to show response to an anti-SARS CoV-2 vaccine? Is this a factor to consider when reviewing his treatment?
Would you consider switching his treatment to allow him to be ‘vaccine-ready’ and if yes to what therapy would you switch?
Case 2: A 28-year old woman with highly active RRMS. Previously suffered relapses on dimethyl fumarate in the past. She was treated with oral cladribine in June and July 2019. She is due her second course in late June and July 2020. She had been told be her treating neurologist that she should delay her next course of treatment until after the COVID-19 pandemic is over.
Do you agree with this decision?
How effective is one course of oral cladribine and will it be sufficient to protect her during the current pandemic?
If she received her 2nd year of oral cladribine should she be shielded and for how long?
Could measuring her lymphocyte counts assist in management of this patients?
What is a safe lymphocyte count?
Would delaying her second course of oral cladribine affect her ability to be vaccinated with an anti-SARS-CoV-2 vaccine in the next 12-24 months?
Today is World MS Day 2020 and its theme is ‘connections’.
MS Connections are about building community connection, self-connection and connections to quality care. The event is coordinated by the MSIF, who want to challenge social barriers that leave pwMS feeling lonely and socially isolated. Together, they are advocating for better services and are celebrating support networks. Another action the championing of self-care.
For some of you, these objectives may look very soft and fluffy, when all you want is hard science, innovation and new treatments to prevent, stop, reverse and cure MS. However, if you been in the field for decades you realise that science happens slowly and incrementally and even when it does deliver real groundbreaking innovations and results, the field is often not ready to adopt them. Why? Social scientists know the answers to this, which is why I spend more time nowadays reading the social sciences than I do reading the sciences.
For example, the biggest class of innovations to hit the field of MS during my career are the immune reconstitution therapies (IRTs), i.e. alemtuzumab, cladribine and HSCT. Many pwMS who have been treated with IRTs are now in longterm remission and have potentially been cured of their MS. Yes, these individuals may live out their lives with no further attacks. The rate of adoption of IRTs is depressingly low and with COVID-19 and its fallout, they are being abandoned as treatment options by many HCPs.
I think we as a field are making a big mistake by abandoning IRTs. As a class, IRTs have to be the answer to how we will treat MS in the future. I envisage using IRTs as true induction therapies and following them with targeted maintenance treatments (e.g. antivirals) and add-on remyelination and neurorestorative therapies in the future. IRTs are the gateway to really changing the lives of pwMS, yet we seem to be abandoning them.
Please note I personally think anti-CD20 therapies should be used as IRTs; i..e. two years of treatment with a high-dose followed by maintenance therapy. This will also make anti-CD20 therapies safer as a class; their Achille’s heel will always be longterm safety.
Back to World MS Day. The objectives of #MSConnections reminds me of our #ThinkSocial campaign, which is to focus on the social determinants of health (SDoH) and how they impact on MS outcomes.
What are the SDoH?
The SDoH are life-enhancing resources, such as food supply, housing, economic and social relationships, transportation, education and health care, whose distribution across populations effectively determines length and quality of life. As MS is such a disabling disease with poor quality of life it is likely to impact on the SDoH, which in turn will have a negative feedback and make MS outcomes worse. This vicious cycle has to be broken if we want to optimise MS outcomes; i.e. when applying the philosophy of marginal gains we can’t ignore the SDoH when managing someone with MS.
The Swedish study below, which I often quote, is an example of how having MS reduces your earnings. Interestingly, the reduction in earnings even begins before MS diagnosis and clearly increases thereafter. I suspect some people who have prodromal MS have difficulty working, which impacts on the average outcome or earnings. Besides sickness absence and disability pension, educational level and type of occupation are influential determinants of earnings in pwMS. In other words, inequality plays a role in determining your earnings once you have MS. Are you surprised? I am not.
Very few HCPs routinely screen for the SDoH during consultations. I think we are making a mistake by not. The following is a shortlist of some of the SDoH that may impact on MS outcomes:
1. Level of education and health literacy 2. Poverty (absolute or relative) 3. Employment / unemployment 4. Access to social services (personal independent payments, etc.) 5. Home environment (heating, cleanliness, amenities, etc.) 6. Local environment (safety, green spaces, amenities, etc.) 7. Food poverty (absolute or relative) 8. Transport (access and costs) 9. Childcare (access and costs) 10. Social isolation (social networks, access to the internet, mobile phone, data, etc.) 11. Lifestyle factors (sedentary vs. active, smoking, alcohol and other addictions) 12. Need to be looked after by a child (childcarer) or ageing parents or other family members (aged carers) 13. Cognitive impairment and hidden psychiatric comorbidities (depression and anxiety) 14. Physical and emotional abuse
How do we address these issues during a consultation without upsetting pwMS by being too overbearing? Some solutions to improving or at least addressing the SDoH could include:
1. Provide information about IT solutions to help pwMS. 2. A high-risk register of patients within the MS service; patients on this list would need to be seen and contacted more frequently, ideally on pre-planned and regular basis. 3. Selective home visit programme. 4. Making sure patients know that they can get hospital transport so they don’t go out of pocket or reimburse their travel costs. 5. Convert were possible physical face-2-face visits with telemedicine options (COVID-19 has turbocharged this change). 6. To do a complex needs assessment similar to what is done in other disease areas to identify high-risk or vulnerable patients. 7. Encourage the government to waive prescription costs for pwMS and other disabilities. 8. Encourage the government to create a healthy food voucher system for pwMS and other disabilities. 9. Encourage the government to improve social services for pwMS and other disabilities. 10. Engage pwMS and include them in your service; for example, using an MS Health Champions model. 11. Explore social prescribing to increase social capital. 12. Enrol all patients into a lifestyle and wellness programme.
On World MS Day do you have any suggestions we can add to the list? I co-chair the SDoH workstream on our Raising the bar initiative so any workable ideas may get implemented in the NHS or as part of social services.
OBJECTIVES: To investigate earnings among people with multiple sclerosis (PwMS) before and after MS diagnosis compared with people without MS, and if identified differences were associated with educational levels and types of occupations. Furthermore, to assess the proportions on sickness absence (SA) and disability pension (DP) in both groups.
DESIGN: Population-based longitudinal cohort study, 10 years before until 5 years after MS diagnosis.
SETTING: Working-age population using microdata linked from nationwide Swedish registers.
PARTICIPANTS: Residents in Sweden in 2004 aged 30-54 years with MS diagnosed in 2003-2006 (n=2553), and references without MS (n=7584) randomly selected by stratified matching.
OUTCOME MEASURES: Quartiles of earnings were calculated for each study year prior to and following the MS diagnosis. Mean earnings, by educational level and type of occupation, before and after diagnosis were compared using t-tests. Tobit regressions investigated the associations of earnings with individual characteristics. The proportions on SA and/or DP, by educational level and type of occupation, for the diagnosis year and 5 years later were compared.
RESULTS: Differences in earnings between PwMS and references were observed beginning 1 year before diagnosis, and increased thereafter. PwMS had lower mean earnings for the diagnosis year (difference=SEK 28 000, p<0.05), and 5 years after diagnosis, this difference had more than doubled (p<0.05). These differences remained after including educational level and type of occupation. Overall, the earnings of PwMS with university education and/or more qualified occupations were most like their reference peers. The proportions on SA and DP were higher among PwMS than the references.
CONCLUSIONS: The results suggest that the PwMS’ earnings are lower than the references’ beginning shortly before MS diagnosis, with this gap increasing thereafter. Besides SA and DP, the results indicate that educational level and type of occupation are influential determinants of the large heterogeneity of PwMS’ earnings.
COVID-19 impact has extended to East Africa. Instead of a face-to-face meeting, the East African Neurologists have moved their CPD (continuing professional development) online in the form or regular webinars. In the past, I would probably have had to travel to East Africa to give a guest lecture at their annual meeting. Post-COVID-19 I can now do this online, which is a much cheaper and greener option for the environment and much more time-efficient for all concerned.
The other advantage of webinars is that the CPD event doesn’t have to be geographically limited in that people can register and log-in from all over the world. This is taking the democratisation of knowledge and learning to the next level and is one of the reasons that motivated me to start triMS.online.
So if you are not from East Africa and you want to attend the webinar below please do not hesitate to register online and log-in tomorrow. Places are limited.
Many of my colleagues have criticised and reprimanded me for being over-enthusiastic in stating that immunosuppressive MS DMTs are relatively safe for pwMS if they happen to develop COVID-19 whilst on treatment. However, the issue has been asymmetry of knowledge. I have known that patients on DMTs who get COVID-19 are doing well. This is based on knowledge acquired from multiple sources albeit confidentially. I have been trying to encourage my colleagues to put this information into the public domain, but clearly it is not happening soon enough. The delays in getting this information out to you the MS community has been far too slow. Do you agree? The good news is there are now platforms to speed up the dissemination of data; let’s hope it changes behaviour.
At last, the Italian COVID-19 and MS pilot data has been published in a peer-reviewed journal. They report on the first 232 patients with MS who developed COVID-19. I actually commented on this data on the blog on the 10th April and it was only published yesterday. There is nothing new to report. This delay is simply unacceptable as HCPs and pwMS need this type of information to challenge current treatment guidelines with evidence and more importantly, pwMS need this information to make potentially life-threatening decisions about their MS care. The number of patients on each individual DMTs is probably too small to make a definitive judgement, but sufficient to be reassuring.
So if any of my colleagues are reading this post please put your data out in the public domain ASAP and in a form that is accessible to all. There are several platforms for doing this including the weekly iWiMS webinars (see below) and the MSIFs Global Data Sharing Initiative. The latest data presented in the most recent iWiMS webinar is in line with the Italian data and remains very reassuring. It clearly supports the need to update treatment guidelines and develop an exit plan. At the moment I am still on version 4 of my DMT table.
So what are the wider consequences of asymmetric knowledge? To understand this you need to become an economics scholar. Asymmetric knowledge is an economic construct to explain the consequences of what happens where one party has more or better information than the other in a transaction. It creates an imbalance and can sometimes cause market failure, in this case, a potential moral hazard for pwMS and the wider MS community. Other, examples of this problem are adverse selection and monopolies of knowledge. I abhor the latter and it is particularly important that we try and fight it.
In addition to me falling out with several of my colleagues over this issue, many wars have been caused by asymmetric information. If you are interested in reading more about this topic I would recommend Joseph Stiglitz’s work; he won and shared the Nobel prize for economics in 2002 for “analyses of markets with asymmetric information”.
On March 14, 2020, we sent the case report form to more than 200 Italian neurologists from about 90 multiple sclerosis centres across Italy. As of April 7, 2020, we have collected data on 232 patients from 38 centres, 57 of whom tested positive for COVID-19 and 175 of whom had suspected COVID-19 symptoms but did not have a positive test (appendix p 1). Mean follow-up was 12·6 days (SD 7·4). The severity of COVID-19 infection in 232 patients was classified as mild (no pneumonia or mild pneumonia) in 223 (96%), severe (shortness of breath, respiratory rates ≥30 breaths per min, blood oxygen saturation ≤93%, PaO₂:FiO₂ <300 mmHg/%, and an increase in lung infiltrates of >50% within 24–48 h) in four (2%), and critical (respiratory failure, septic shock, and multiple organ dysfunction or failure) in six (3%). Of the six critical patients, one recovered and five died; all had a positive swab (appendix p 2). 21 patients had undergone a 5-day course of methylprednisolone within 3 months before the onset of COVID-19.
triMSx-online is hosting a webinar next Thursday, 30th April on the topic of managing MS during the COVID-19 pandemic. Things are moving so fast in terms of what is happening that we need some formal teaching course to keep everyone abreast with how to manage MS in these troubling times.
Our MS services have been transformed by the pandemic and the way we use DMTs has also changed. Advice on how to use DMTs seems to change on a weekly basis as new data emerges on the biology of SARS-CoV-2/COVID-19 and how patients with MS who get COVID-19 are doing. The programme (see below) has been designed to upskill you rapidly with developments across the globe and how these can potentially impact on your MS service. There will also be time to ask questions and discuss specific issues. Even if you can’t make the live event the presentations will be put online for later viewing and we will have a post-event Q&A session asynchronously.
