Alemtuzumab Update

As promised to all my colleagues in the Middle East and North Africa, who attended my alemtuzumab update webinar this evening, you can view my slides and download them from my SlideShare site.

CoI: multiple

Post-partum relapses after alemtuzumab

One of the problems of immune reconstitution therapies (IRTs), such as HSCT, alemtuzumab and cladribine, is nagging worry that at some time in the future your MS will reactivate. Some people with MS (pwMS) try and avoid potential triggers of disease activity, for example, vaccinations and pregnancy, particularly the post-partum state. Unfortunately, there is some evidence the latter may trigger disease activity, but at quite a low rate.

The following is the data on 122 pregnancies post-alemtuzumab presented earlier this year at ECTRIMS. The annualised relapse rate (ARR) fell to 0.02 during pregnancy, i.e. 2 relapses in 100 years, with 98% of patients being relapse-free. In comparison, in the first year after pregnancy, the ARR was 0.22, i.e. 22 relapses in 100 years of follow-up, with 82% of patients being free of relapse. The ARR was then similar to pre-pregnancy levels in the second and third years after pregnancy (0.12 each year; with 89% and 92% of patients relapse-free in each year, respectively).

One of the reasons for women with MS choosing an IRT is to start or extend their families. Based on this data I would recommend that they do just that and in the unlikely event of post-partum disease activity (1 in 5 chance) it can be dealt with by an additional course of treatment or possibly starting another DMT. What do you think?

We have many patients in our centre who have had children after alemtuzumab in our centre. I refer to them as the alemtuzumab babies because they represent the success of treating MS early and effectively. It was only 20 years ago that the previous generation of neurologists were advising their patients with MS not to have children. How times have changed?

Celius et al. Postpartum relapse after first on-study pregnancy in RRMS patients treated with alemtuzumab in the phase 2 and 3 clinical development program over 8 years. ECTRIMS Online Library. Celius E. Sep 12, 2019; 279136; P776

Introduction: In childbearing women with MS, relapses may increase in frequency and severity during the postpartum period. In phase 2 and 3 clinical trials of alemtuzumab (CAMMS223 [NCT00050778]; CARE-MS I [NCT00530348]; CARE-MS II [NCT00548405]) and their extensions (CAMMS03409 [NCT00930553]; TOPAZ [NCT02255656]), alemtuzumab significantly reduced relapse rates in RRMS patients versus SC IFNB-1a and maintained efficacy over 8 years. Product labelling recommends use of contraception in women of childbearing potential for 4 months after treatment.

Aims: To examine over 8 years relapse rates before, during, and after the first pregnancy in alemtuzumab-treated patients in the CARE-MS and extension trials.

Methods: Contraceptive use was required during core studies, and for 6 months after alemtuzumab administration in the extension studies. The analysis included patients who received alemtuzumab (baseline: 5 days; 12 months later: 3 days) in phase 2 or phase 3 trials or their extension studies and became pregnant after receiving at least one dose of alemtuzumab. Patients could receive other DMT or additional as-needed alemtuzumab (12 mg/day on 3 days; ≥12 months apart) in the extensions. After pregnancy, other DMT was allowed in CAMMS03409; other DMT or further alemtuzumab was allowed in TOPAZ. The analysis only considered a patient’s first pregnancy, regardless of the outcome. Pregnancy had to occur by Month 85 to allow for at least 1-year follow-up post-pregnancy onset.

Results: Over 8 years, 122 pregnancies met inclusion criteria; 72% of pregnancies began >12 months after the last alemtuzumab dose, 18% began >4 to 12 months after the last dose, and 10% began ≤4 months after the last dose. Annualised relapse rate (ARR) in the year prior to study entry was 1.8. Two years and 1 year before pregnancy, ARR was 0.10 and 0.12 respectively, with 91% and 89% of patients free of relapse. ARR fell to 0.02 during pregnancy (98% of patients relapse-free). In the first year after pregnancy, ARR was 0.22, and 82% of patients were free of relapse. ARR was similar to pre-pregnancy levels in the second and third years after pregnancy (0.12 each year; 89% and 92% of patients relapse-free in each year). Safety will be discussed in the presentation.

Conclusion: In the year after the first pregnancy in alemtuzumab-treated patients, an increase in relapse rates was minimal and less than that expected from the literature. Relapse rates returned to pre-pregnancy levels by the second year postpartum.

CoI: multiple

Unaccountable

The European Union and its Institutions have been heavily criticised as part of the Brexit debate as been undemocratic and unaccountable to the man or woman on the street. However, it is only when their decisions impact on you, or your patients, that you realise that these critics have a valid point.

Last week the European Medicine Agency’s safety committee (PRAC or Pharmacovigilance Risk Assessment Committee) did something that makes me despair. They railroaded through changes to alemtuzumab’s SmPC (summary of product characteristics) against the advice of experts and without data to support their position. Their advice is therefore not evidence-based and as a result, it is likely to deny many pwMS access to one of our most effective DMTs.

The PRAC states “Alemtuzumab should no longer be used in patients …. who have autoimmune disorders other than multiple sclerosis”. There is no evidence to support this statement. PwMS who have a pre-existing autoimmune disease are not at an increased risk of developing complications from alemtuzumab or secondary autoimmune disease when compared to pwMS who don’t have a pre-existing autoimmune disease.

The problem I have is that the PRAC made this decision despite robust evidence to the contrary being presented by Genzyme and advice from experts in the field. I even co-signed a letter that Prof. Alasdair Coles penned to the PRAC, CHMP and MHRA, which clearly fell on deaf ears.

The behaviour of the PRAC reminds me of the Michael Gove interview with Faisal Islam on Sky News that took place on the 3rd June 2016 in the run-up to the Leave-Remain EU referendum:

Gove: I think the people in this country have had enough of experts, with organizations from acronyms, saying—

Faisal Islam: They’ve had enough of experts? The people have had enough of experts? What do you mean by that?

Gove: People from organizations with acronyms saying that they know what is best and getting it consistently wrong.

Faisal Islam: The people of this country have had enough of experts?

Gove: Because these people are the same ones who got consistently wrong what was happening.

Faisal Islam: This is proper Trump politics this, isn’t it?

Gove: No it’s actually a faith in the —

Faisal Islam: It’s Oxbridge Trump.

Gove: It’s a faith, Faisal, in the British people to make the right decision.

Does the EMA expect us to have faith in their decision-making?

As an MSologist looking after pwMS this upsets me and worries me immensely. The implications of ignoring experts is one thing, but what are the implications for my patients? What impact will this PRAC decision have in practice?

I estimate that about a third of pwMS will have a comorbid autoimmune disease and may even be more than a third. The latter depends on how you define autoimmunity. This means many people with MS will be denied access to alemtuzumab because of EU officials who ignored the evidence presented to them and without any transparency around their thought processes and why they made this decision. This is no way for EU officials to be acting when we are trying to argue the case for Britain staying in the EU.

Lack of transparency with the EMA is not new. I have been involved with many EMA-CHMP decisions and it really depends on the whim of rapporteur or co-rapporteur. Unlike the FDA which holds its meetings in the open, with the EMA and its various sub-committees you have no idea of the decision-making processes that go on behind closed doors. I am often asked why the British voted to leave the EU. The elephant in the room is the EU itself and how it functions; its decisions impact the lives of its citizens and this is another example of very, very, poor decision making with many downstream ramifications.

CoI: multiple

Are IRTs ahead of their time?

I am beginning to think that immune reconstitution therapies or IRTs are ahead of their time. Many neurologists, people with MS (pwMS), payers – particularly fee-for-service insurance companies – and the regulators are unable to get their heads around how these agents work. In addition, a few recent review articles, written by colleagues, cast doubt on this treatment strategy and the terminology we use.

IRTs are the only treatments that are addressing the cause of MS and hence have the potential to cure MS. We will know in the near future how many pwMS in very long-term remission post -alemtuzumab, -HSCT or -cladribine are truly MS free. This information is critical to convince a sceptical field of the value of these treatments.

The mortality associated with HSCT makes people shudder. Although the risk of dying from one of the complications of HSCT is quoted as being between one of 1 in 333 (0.3%) to 1 in 50 (2%) many pwMS are taking this risk in the UK or abroad. Despite HSCT being a viable treatment option for pwMS in England and now Scotland many UK MSologists don’t routinely put this option on the table when discussing switching treatments with their patients who are failing other high-efficacy therapies. Why?

Even going to the easy-to-use, easy-to-monitor, oral cladribine option we are seeing slow adoption. Why? I am now convinced HCPs don’t understand IRTs, in particular, the concepts of frontloading of risk and long-term remission.

The study below shows that patients failing alemtuzumab in year one after the first course of five infusions, do very well after receiving their second course. Despite these patients having more active disease and early breakthrough activity, they do very well longterm with high chances of being rendered NEDA and experiencing disability improvement and having brain volume loss that slows markedly – into the normal range – after year 2.

DMTs are about protecting the end-organ or brain and keeping it as healthy as possible so that pwMS can live a normal life as possible and have the necessary reserve to deal with ageing when it sets in. Is this message difficulty to communicate? Knowing this brain volume data why wouldn’t we want to at least offer an IRT to all our patients with active disease and I mean first, second or third line? It is clear the sooner you are treated with an IRT the better you do.

I am now planning to do a series of online lectures on IRTs to explain why they should be so appealing as a treatment strategy for pwMS. Would you be interested in watching?

I also have a vested interest in getting IRTs adopted. We want to use them as induction agents in more advanced MS to be followed by maintenance therapies that target the processes within the brain and spinal cord to address smouldering MS.

Van Wijmeersch et al. Efficacy of alemtuzumab over 6 years in relapsing-remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies. Mult Scler. 2019 Nov 1:1352458519881759

BACKGROUND: Alemtuzumab is administered as two annual courses for relapsing-remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen.

OBJECTIVE: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers).

METHODS: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension.

RESULTS: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1-2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: -0.67% (CARE-MS I); -0.47% (CARE-MS II)) declined after Course 2 (Year 6: -0.24%; -0.13%).

CONCLUSION: Early relapsers’ outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit.

CLINICALTRIALS.GOV REGISTRATION NUMBERS: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553.

CoI: multiple

The Phoenix

Like a phoenix rising from the ashes for the third or fourth time, alemtuzumab is given yet another life. I am sure many neurologists and people living with MS will be grateful, but I don’t agree with its positioning.

EMA’s safety committee or PRAC has handcuffed alemtuzumab and is restricting it for adults with relapsing-remitting multiple sclerosis that is highly active despite adequate treatment with at least one DMT or if the disease is worsening rapidly with at least two disabling relapses in a year and brain-imaging showing activity. The new indication is not too dissimilar to that of natalizumab. Just when we are pushing for natalizumab to get a first-line license to address our #AttackMS concept, alemtuzumab gets yoked to natalizumab.

In my opinion, the contraindication handcuff that alemtuzumab must no longer be used in patients who have auto-immune disorders other than MS is not necessarily correct. I am not aware that having another comorbid autoimmune disease puts you at increased risk of developing another autoimmune disease after being treated with alemtuzumab. I have asked Joanne Jones and Alasdair Coles from Cambridge who have the most experience with alemtuzumab, both clinically and scientifically, and they agree. I think we need to appeal this contraindication as it may deny many pwMS access to one of our most effective DMTs. I suspect that Sanofi-Genzyme will have data from their trial programme to help appeal this contraindication.

Looking at this with from a glass-half-full perspective is the good news that at least we still have alemtuzumab as a treatment option for pwMS with more active disease. However, this will deny many pwMS with active MS from being treated with the most effective DMT first-line.

When will regulators come to the realisation that the decision to take on risks should be taken by the person with the disease guided by their HCP and not the regulators? By moving alemtuzumab to a predominantly 2nd-line position means pwMS will now have to wait several years to access the most effective DMT. I am not sure the new positioning of alemtuzumab in the therapeutic hierarchy will stop the more educated and determined people with MS seeking HSCT abroad or in the private sector.

I am curious to know if my letter to the EMA (below) helped. But having alemtuzumab back on the treatment landscape as predominantly 2nd-line therapy means we will at least be able to offer alemtuzumab as a realistic option before, or alongside, HSCT in London. This also means we can go ahead with our head-2-head comparison of alemtuzumab vs. HSCT to assess HSCT’s relative efficacy and safety against a licensed DMT.

Open letter the EMA sent on the 20th August 2019

European Medicines Agency
Amsterdam

Dear Sir/Madam

Alemtuzumab has transformed the MS treatment landscape. It not only provides superior short term efficacy, but a significant number of patients treated with alemtuzumab note improvement in disability. However, its main advantage over other DMTs is that a large proportion of patients go into longterm remission and normalise the rate of their brain volume loss. In regard to the latter, this is unprecedented in comparison to other licensed MS disease-modifying therapies, with the possible exception of haemopoietic stem cell transplantation (HSCT), which is not licensed and hence not widely available to treat patients with MS in Europe. Alemtuzumab, therefore, is the only realistic alternative to HSCT, which has become a very popular treatment choice amongst people with multiple sclerosis, in particular, ‘digital natives’ who get their information online. As with all DMTs the earlier you use them the more effective they are and the greater the benefit to the individual patient. Alemtuzumab is, therefore, an important treatment option for people with MS; being able to offer alemtuzumab early as a treatment option is an important factor in my clinical practice to dissuade many Britsih patients from travelling abroad for HSCT.

At our centre, Barts Health NHS Trust, we have now treated over 250 patients with alemtuzumab with over 40% being treated with alemtuzumab first-line. Patients receiving alemtuzumab first-line tend to have more active disease and less favourable baseline prognostic profile. Despite its side effect profile and the need for monthly monitoring, many patients are willing to take on the risks and the burden of monitoring to be treated with the most effective licensed DMT first-line. All our patients are extensively counselled about the risks and benefits of alemtuzumab treatment and sign an informed consent and a patient contract agreeing to the mandatory monitoring programme. We feel the use of alemtuzumab in the correct environment is relatively safe and the adverse events manageable. Not having alemtuzumab for use in early active disease would mean patients having to wait to fail several other, less effective, licensed DMTs prior to accessing alemtuzumab. I firmly believe in the concept that ‘time is brain and spinal cord’ in MS and delaying access to the most effective treatment would limit our ability to optimise the management of MS in patients with more active disease and in those with a poor prognostic profile. In addition, shifting the use of alemtuzumab to a population of patients with more advanced disease would unfavourably change the benefit-risk profile of alemtuzumab and make it less appealing as a treatment option.

The real-life data of alemtuzumab clearly supports it as being the most effective DMT on the market and its other attributes in relation to its posology make it a very appealing therapy; for example in women wanting to start or extend their families.

In summary, limiting alemtuzumab to a third-line, last resort DMT, will severely limit our treatment options for managing this devastating disease. Alemtuzumab offers many patients with MS a real hope of living as normal a life as possible, however, this option does depend on using alemtuzumab early in the course of the disease. I, therefore, appeal to the MS community and the European Medicine Agency to consider these factors when reviewing the benefits and risks of alemtuzumab as a treatment for MS.

Yours faithfully

GAVIN GIOVANNONI

CoI: multiple

Short- or long-sighted

I saw three patients 9-and-half-years after starting treatment with alemtuzumab as first-line therapy, yesterday. It was a remarkable experience. Only one of the three patients had needed a third cycle of alemtuzumab. All are in long-term remission; i.e. flat-lining on the EDSS, relapse-free and with no MRI activity (NEDA-3). Their EDSS scores yesterday were 1.0, 1.5 and 2.0. All of them are fully functional, with no physical and cognitive restrictions and described themselves as being well. One patient suggested to me she doesn’t have MS anymore. One patient has had ITP and recovered from it. All three patients have normally functioning immune systems with normal total lymphocyte counts. None of them is concerned about infections, travel, vaccinations or secondary malignancies. This is why treating MS with an immune reconstitution therapy, such as alemtuzumab, is so appealing.

I have a dream that this will be the new normal and all people with MS in future will have similar experiences. I sincerely hope the EMA allows people with MS to be treated and managed the same way as these three patients of mine have. I still have had no response from the EMA to my letter below. Maybe they don’t care?

Can anybody tell me from testing their vision if they are short- or long-sighted?

Open letter the EMA sent on the 20th August 2019

European Medicines Agency
Amsterdam

Yours faithfully

GAVIN GIOVANNONI

CoI: multiple

Real Life

After my #1 highlight #ECTRIMS2019 post, I was sent an email by Antoinio Scalafari, a like-minded colleague, to remind me of their real-life data at Imperial College on alemtuzumab in clinical practice. It mirrors the trial experience and needs a platform for discussion (see below).

In parallel, I heard via the MS grapevine that the MS community does not appreciate me questioning the ethics of the DELIVER-MS and TREAT-MS Trials. Why not? These are pragmatic trials to compare escalation therapy with the strategy of flipping the pyramid (high-efficacy therapy first-line).

Giovannoni. Do we have equipoise when it comes to how we treat active multiple sclerosis? Lancet Neurol. 2019 Jul 30. pii: S1474-4422(19)30227-3. doi: 10.1016/S1474-4422(19)30227-3.

Don’t I have a right to an opinion? I finish my commentary with a simple question for the trialists: ‘The real litmus test for the investigators of the DELIVER-MS and TREAT-MS trials is the question they should all ask themselves: “If I had multiple sclerosis, how would I want to be treated?” Given the evidence, patients deserve the choice of being treated with a high-efficacy DMT first-line’.

Why shouldn’t MSers with active MS not have the option of being treated with alemtuzumab, or for that matter HSCT?

CoI: multiple

Open letter to the EMA

Just back from ECTRIMS 2019 in Stockholm. My highlight was the alemtuzumab 8-year longterm extension data; the brain volume data is quite extraordinary (figure 5). In short, apart from HSCT, there is nothing that comes close to alemtuzumab in radically slowing-down or preventing end-organ damage.

Comi et al. Alemtuzumab improves clinical and MRI disease activity outcomes, including slowing of brain volume loss, in RRMS patients over 8 years: CARE-MS I follow-up (TOPAZ study). ECTRIMS 2019, P1235.

I was also disappointed to hear the rumour that the EMA’s article 20 procedure was not triggered by an EU member country, but by the EMA itself. A colleague told me that the adverse events reporting from Genzyme were so poor that the EMA could not establish whether or not the new adverse events were causally related to alemtuzumab. So to get some clarity on the new adverse events the EMA triggered their own article 20 procedure to simply get Genzyme to do the work they should have done in the first place.

If this is the case it saddens me that people with MS may not be able to access alemtuzumab early in the course of their disease due to poor internal procedures at Genzyme.

If I had MS I would want to have the option of being treated with alemtuzumab. This is why I wrote the following open letter to the European Medicine Agency. I sincerely hope they listened. I have yet to receive a response from them, but I hope someone at the EMA has MS or has a friend or family with MS and understands why treating MS early and effectively is so important.

Open letter the EMA sent on the 20th August 2019

European Medicines Agency
Amsterdam

Yours faithfully

GAVIN GIOVANNONI

CoI: multiple

Jetlag

Just arrived back from the AAN 2019 in Philadelphia. Jetlagged, which is why I am writing this at 2 am in the morning.

As always the AAN is more a meeting of meetings or networking in academic lingo. These meetings have allowed us to progress several of our ideas including (1) DrK’s #MSAttack study with natalizumab, (2) to think more deeply about our proposed ADIOS Trial (adaptive dosing ocrelizumab study), (3) support for our plasma cell and (4) social capital hypotheses and to (5) to gain a deeper understanding of the emerging new ’safety’ issues surrounding alemtuzumab.

Alemtuzumab is getting an unnecessarily rough ride. I had an opportunity to review all of the vascular events and AEs that led to the EMA triggering article 20. These are all rare events. The intracranial haemorrhages appear to be related to transient hypertension and may relate to the amount of hydration the US infusion centres use when administering alemtuzumab. It is clear that MSers develop a transient rise in blood pressure when receiving alemtuzumab, which means this rare complication can be derisked with anti-hypertensives.

When it comes to the cases of arterial dissections and arterial thromboses on alemtuzumab I was not convinced alemtuzumab is to blame. The majority of the cases had comorbidities or had had procedures that are a more likely explanation for the ischaemic events. In many of the cases, the events were poorly characterised and it was not clear if they had occurred at all; this is particularly in relation to the so-called myocardial infarctions.

It is clear that most if not all of the ‘vascular cases’ have arisen in the USA. Why? I suspect it is because alemtuzumab is being used in a much riskier and older population compared to the other parts of the world. Herein lies the problem. The fact that the EMA has now copied the FDA and made alemtuzumab a 3rd-line DMT will shift the use of alemtuzumab into a riskier older population and thereby increase the likelihood of us seeing these vascular AEs in Europe.

To be honest I am not convinced that the risk-benefit profile of alemtuzumab has changed at all. I would, therefore, appeal to the EMA to include the new AEs in the SmPC, but not to change alemtuzumab’s label. We need to be able to offer alemtuzumab to MSer with early MS when they have the most to gain from the treatment. I am sure MSers are in the best position to weigh up the risks and benefits of alemtuzumab. My big fear is that restricting access to alemtuzumab will simply increase HSCT tourism abroad.

If I needed proof that our blog is read it was in abundance at the AAN. Several people were interested in our ADIOS trial and were thinking of doing versions of their own. The one caveat was new data that Stephen Hauser presented showing that the efficacy of ocrelizumab may be linked to the level of B-cell depletion, i.e. the greater the peripheral B-cell depletion the greater the treatment effect of ocrelizumab on disability progression. There was no dose-related signal on MRI or relapses because these have a floor effect, i.e. virtually all patients are NEDA 1&2 and hence it is impossible to use these outcomes to assess a dose-effect. The one caveat is the dose effect on disability was confounded by body weight; i.e. the larger the patients the less B-cell depletion. As you know MSers with an increased BMI (body mass index) are at increased risk of comorbidities, which may explain why they do less well on ocrelizumab and the observation has nothing to do with the level of peripheral blood B-cell depletion.

The peripheral B-cell depletion data, however, needs to be taken further and tissue and CNS B-cell depletion kinetics need to be studied further. I am convinced the ADIOS trial will be a good place to start with some of these studies. Clearly, it is time to get our grant writing hats on. We need to do this study in the UK.

DrK and I had several meetings with key stakeholders in Biogen about our #MSAttack study. There is little doubt about the efficacy of natalizumab in MS, its safety even in JCV-positive MSers when used for short periods, its rapid onset of action (weeks) and it reversibility (washout) that make it the only suitable DMT for this study. We have changed our trial design slightly, but hopefully, we will be able to get this study funded in the near future. If the #MSAttack study is successful it will change the way we treat and think about active MS and may help natalizumab obtain a first-line indication, which many MSers and CISers deserve; particularly if you want to save brain and spinal cord.

NeuroDoc Gnanapavan got very excited when she saw some posters supporting the use of proteasome inhibitors as a treatment for autoimmune disease. This supports our new SIZOMUS trial (Safety of IxaZOmib targeting plasma cells in Multiple Sclerosis) to try and scrub the brain clean of plasma cells. We will be letting you know much more about this trial in the next few weeks now that we have ethics and MHRA approvals. We will be needing volunteers for this study.

Saul, or Dr Reyes to some, is now one of the pioneers in studying social capital and MS outcomes. His poster on the topic was well received. It is clear that the social determinants of health outcome are very important and have not been systematically studied in MS. Dr Reyes will be changing all that and has many activities planned as part of his ECTRIMS fellowship The poster he presented at the AAN is self-explanatory, but if you have any queries please don’t hesitate to ask.

I have a new hero or heroine; Dr Riley Bove, from UCSF. Riley has developed a telemedicine service to help people with neurological problems in resource-poor areas. The service is provided for free by the USCF residents and staff and is linked to an educational course to train the staff in these countries. The whole service is run using Zoom an online teleconferencing service. Well done Riley; if you lived in the UK I would be putting your name forward for an honours award from our Queen. And if I had more bandwidth I would join and contribute to your service; maybe something for my retirement? Could this platform be expanded to help diagnose and manage MS in resource-poor settings?

It is now 4:10 am and I am beginning to feel a bit groggy. So I will signoff now but will come back with some more AAN highlights in the week.

CoI: multiple

Yellow Fever Vaccine Alert

In the past, I have made the claim that vaccinations, including vaccination with live attenuated viruses such as yellow fever, are relatively safe post-IRTs (immune reconstitution therapies) such as alemtuzumab, cladribine and HSCT.

I even have two Alemtuzumabers on my books who have both had yellow fever vaccines before travelling to Ecuador and the Galapagos Islands. who I frequently mention in talks who had no problems with the vaccine. I will have to retract that advice. HCPs have just been sent the following warning from the MHRA (Medicines and Healthcare products Regulatory Agency).

Yellow fever vaccine (Stamaril) and fatal adverse reactions: extreme caution needed in people who may be immunosuppressed and those 60 years and older

“We have recently received 2 reports of fatal adverse reactions to the yellow fever vaccine (Stamaril). Due to an increased risk of life-threatening reactions, the vaccine must not be given to anyone with a medical history of thymus dysfunction or who is immunosuppressed. In addition, extreme caution must be used and a careful risk assessment conducted before vaccination of people aged 60 years and older due to a substantially increased risk of such adverse reactions in this age group.”

This is particularly relevant to Alemtuzumabers in that there is recent data that has been presented that it damages the thymus. If you are HCP who works with MSers please read the advice on the MHRA’s website.