Category: Archive

Invitation to Future-proofing Healthcare: NeuroSense

I have been invited to speak this Thursday evening at a meeting in London. There are still free places if you want to attend. As usual, I will post my slides online.


People continue to be intrigued by the mysteries of the brain, but many areas of neuroscience remain unexplained. Will we ever be truly able to solve these puzzles? What does the future of neuroscience look like? Which innovations will improve daily life for people living with neurological conditions? Will big data and better brain measurement lead to improved outcomes?


Future-proofing Healthcare: NeuroSense, the second in a series of non-promotional events exploring the answers to these questions, following the launch of the series in November 2017.

To view the full agenda and to book your place, please register here by Monday 2 April as places are limited.

What can I expect if I attend?


Experts, innovators and professors from across the neuroscience space will discuss advances in understanding neurological conditions, the role of technological innovations in improving the lifestyle of people with these conditions and what we can expect from the field of neuroscience.

Speakers include Dr David Reynolds from Alzheimer’s Research UK; Professor Gavin Giovannoni, Chair of Neurology at Barts Health; Neuroscientist & BBC presenter Dr Jack Lewis; innovative University of West England student & founder of Walk to Beat Neha Chaudhry; and leading British neurosurgeon and top-selling author, Henry Marsh. The event will be facilitated by Top 100 UK Scientist Dr Hannah Critchlow.

There will also be the opportunity to view an array of fascinating cutting-edge developments in our exhibition, including: VR experiences that simulates some symptoms of MS and dementia, robotic inventions from cats to walking sticks designed to support individuals living with Alzheimer’s and Parkinson’s, human-centred activity products and games to help people lead active lives, and interactive EEG experiences looking at brain activity through gaming and art.

What & Where?


The event will take place 6:30-9:45pm on Thursday 5 April at Studio Spaces, Warehouse Studio, Unit 2 110 Pennington Street, St Katharine‘s & Wapping, London, E1W 2BB.

Refreshments will be provided as part of the meeting.


For information and to register please click here.

Please note that this event is being sponsored by Roche. 

The MS Establishment

The recent commentary by Alasdair Coles and riposte by Jack Antel has sparked a prickly debate about the role of a relatively small number of academic neurologists, who are also known as KOLs (key opinion leaders), in relation to MS clinical trials and their subsequent publications. 

Coles highlights 25 people in particular as dominating the MS space. I am one of them. Some of the points he raises are valid and are almost identical to ones raised by Owen Jones in his brilliant book ‘The Establishment’. 


I am sure Alasdair Coles and Owen Jones understand that the ‘MS clinical trial fraternity’ and ‘British politics’, respectively, are no different to other networks in that a smallish number of people emerge to take on leadership roles and positions of influence. Nobody plans this, it simply happens; it is a social phenomenon. Contrary to what is implied by Coles and Jones, there is no conspiracy, no secret society. The people who end up forming ‘the establishment’ usually do so because of their skills, for example their knowledge, wisdom, experience, ability to work to together in a group and their communication skills (written and verbal), which in the case of MS clinical trials is their willingness and ability to help disseminate knowledge to regulators, their colleagues, patients and the wider MS community. I am not going to make excuses for being part of the ‘MS Establishment’ and for participating in multiple MS trial steering and writing committees. It is an important part of my role as an academic and, more importantly, part of my commitment to people with MS. Alasdair Coles and Owen Jones are both members of their own ‘Establishments’, they are both elites. In my opinion, due to his contributions to the field of MS, Alasdair Coles is a card-carrying life member of the MS Establishment. 

 It is difficult to respond to the guest author accusation without a full investigation into each author. Speaking for myself; on all the manuscripts reporting phase 2/3 clinical trial results I have been actively engaged as either a trialist, steering committee member or in another role, for example presenting data to the EMA’s scientific advisory group or the Committee for Medicinal Products for Human Use (CHMP). When you see my name on follow-on papers of interesting post-hoc analyses from trials that I have not actively participated in, I have usually made a request to the company concerned to do the specific analyses and have contributed to them in other ways. I have never been asked to join a writing committee as a guest; there has always been a reason why I have been asked. 

 Professor Ian McDonald, one of my mentors, gave me advice just before he retired. He had the insight to see how the field was evolving and that it would be necessary to interact with the Pharmaceutical industry to develop treatments for MS. His advice was that if I was to get involved, or as he put it ‘get into bed’, with Pharma I must make sure I do it with several companies rather than one. He said having multiple conflicts of interest mitigates against the problem of being a ‘one company person’. As an example, he mentioned a specific British academic neurologist who had fallen from grace for representing one company.

 My criticism of both Coles’ and Antel’s commentaries is that they missed the elephant in the room, i.e. the very small number of women on these papers. As a father of two daughters, I am horrified at how few women have made it up the greasy pole of academic neurology, in particular in the field of MS. The current MS Establishment mainly consists of ageing white men. This is shameful. My wife has recently made a career change and has taken up a senior post in girls’ education. She is adamant that nothing is going to change regarding gender inequality unless men start to engage and actively promote women in their spheres of influence. Who am I to argue?

I have recently been asked to be the PI or principal investigator on a major international MS trial. In view of Coles’ commentary should I turn the offer down? I haven’t and won’t for several reasons. One of them is women. I have made a request to the company concerned to please identify the next generation of KOLs in particular women for the steering committee. I even provided them with a list to this effect. We need diversity, new blood and new ideas. We need at least 50% of the MS Establishment to be women. Now isn’t this the real issue? Isn’t this the real story that should be debated? We need women to shake-up the MS Establishment.  


Alasdair Coles. Authorship of phase 3 trials in multiple sclerosis. First published: 8 March 2018. https://doi.org/10.1002/ana.25203

Jack Antel. The reality of “ghosts” in authorship of clinical trials in multiple sclerosis. First published: 13 March 2018. https://doi.org/10.1002/ana.25199


 http://multiple-sclerosis-research.blogspot.com/2018/03/guest-authors-alternative-view.html. 

ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







Trying to emulate the Cleveland Clinic at Barts-MS

I have just spent two days attending the 2018 or third Cleveland Clinic Neurological Institute MS Summit on ‘MS Treatment Strategies’. I had to give a talk on composite outcomes in trials and clinical practice. I am not sure why I was asked to cover this topic as I would not rate myself as being an expert on MS-related outcome measures.



 As promised I have made my slides available.

The objective of the meeting was to stimulate discussion and get consensus on going beyond typical treatment guidelines for managing people with MS. Can we push the envelope to improve MS outcomes? I am sure we can we just need to change our treatment target beyond what we are prepared to accept today. Despite this, I get the impression that most neurologists seem to target short-term goals, i.e. NEDA over the next year or two. I personally think we should be ‘maximizing brain health’ over the life of our patients. It is our responsibility to make sure we prevent end-organ damage so that our patients get to old age with as much brain as possible to age normally. What do you think? 

 I had the opportunity of visiting the Mellen MS Centre, which provides quite an exceptional MS service. I was bowled over by how many resources are at hand at the Centre; we could only dream of having similar resources in ‘austerity NHS’. For example, there are full-time technicians who assess patients at each visit using a standardised battery of outcome measures. The results of these outcomes with their MRI scans are immediately uploaded into the electronic medical record so that they can impact on decisions there and then; i.e. at the same clinic visit. In comparison, within the NHS there is a neuro-radiology backlog that means that it typically takes weeks to get our MRI reports back. The latter is not the fault of neuroradiology; there is simply not enough neuroradiology consultants. 


We are in the process of implementing an asynchronous system where our patients will come up about a month before their annual clinic appointment to have an MS MOT*; i.e. to have all their outcome measures done, including their MRI, blood monitoring and possibly a lumbar puncture for CSF neurofilament levels. They will then come back for the follow-up appointment with all the data ready for assessment. This will helpfully standardise the annual follow-up assessments. In addition to this, we are designing a programme for our patients to prepare for this annual assessment. They will need to come to the clinic with a list of objectives and what they want the appointment to achieve.

 It is becoming clear that standardising MS management is one way of reducing the variation in the way we manage MS across the UK.

 * MOT = The MOT test (Ministry of Transport, or simply MOT) is an annual test of vehicle safety, roadworthiness aspects and exhaust emissions required in the United Kingdom for most vehicles over three years old used on any way defined as a road in the Road Traffic Act 1988.

ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







News Update: positive GNbAC1 phase 2 results

Has the black swan arrived? Could MS be due to a viral infection? Is the #CharcotProject alive and kicking?




ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







The Phoenix has risen: the era of disease modification in progressive MS has truly arrived

The EXPAND study is the first positive study in people with secondary progressive MS and marks a new landmark in the treatment of MS.



Please note that I am a co-author on this paper and I sit on the trial steering committee. I am clearly conflicted and therefore you may not want to read or hear what I have to say about the trial’s findings. 

Siponimod is the second-in-class of the so-called sphingosine-1-phosphate modulators; the first being fingolimod. The EXPAND phase 3 trial published in today’s Lancet is a landmark study in that this is the first positive study in ‘non-relapsing SPMS’. Why was this study positive when so many others have failed? It was very large with 1651 subjects included in the study and was a so-called event-driven study, i.e. it went on for a long as necessary to accumulate enough disability progression events to answer the question of whether of not Siponimod can modify the course of SPMS. 


I am aware that many people have and will continue, to pooh-pooh the results as not being meaningful, i.e. the treatment effect is too small. This same pooh-pooh phenomenon occurred with the original interferon-beta studies in RRMS and more recently the ocrelizumab in PPMS study. I must point out that most of the patients in the EXPAND trial required walking aids, hence there was not much reserve in the motor pathway to the legs to see a treatment effect. This also means that therapeutic lag has to be taken into account; therefore, it takes time to see a treatment effect. So a small difference over 3-4 years may translate into big differences over 5 to 10 years. 

Interestingly Siponimod did not have an impact on the 9HPT nor the T25W. It looks as if these two outcome measures were very noisy in this study. This is something that needs to be explored as it challenges our length-dependent axonopathy hypothesis. 

 Despite this Siponimod had a very strong effect on focal MRI lesions and brain volume loss. I, therefore, have little doubt about the robustness of these trial results. It is also clear that the SPMSers who were less disabled and younger benefited most. This means that when we treat ‘SPMS’ we will need to treat as early as possible. I can hear the naysayer saying that you are simply treating relapsing-remitting MS. I would say so what. The pathological processes driving RRMS and SPMS are probably the same and Siponimod will be effective in both the relapsing and more advanced stages of the disease. 

I suspect the EXPAND or Siponimod trial results will rekindle the debate about when SPMS begins and when can SPMS is diagnosed. I personally think that the pathology that drives SPMS is there from the start and that we need to be aware of potential disease worsening/progression even if we don’t see a change in physical disability. George Ebers and colleagues used to diagnose SPMS with a median EDSS of 2.0. Their diagnosis was based on a history of clinical worsening in the presence of an abnormal neurological examination. For example, someone may report that their left foot gets weak and drags after 30 minutes walking. They then come back a year later and now report dragging after just 10 minutes. Provided they have abnormal neurological signs in the legs on examination they could be diagnosed as having SPMS. Neurologists, however, have shifted the goalposts and now diagnose SPMS when the patients have an EDSS of 4.0 or higher. Why? Simply because once you label someone with SPMS it excludes them from DMTs that are licensed for relapsing MS and it also tells them they a form of the disease that is not modifiable. The latter is something neurologists have wanted to avoid and patients have wanted to avoid it as well. Why would someone want to be labelled as having a progressive untreatable disease? These results change that for; SPMS is now a modifiable disease and there is now a treatment for this phase of the disease. 

I know people with progressive MS would like a treatment that doesn’t just slow down the rate of their worsening disability. They want a treatment that reverses their disability. However, Siponimod can only do what it can do, i.e. as it is an anti-inflammatory it can only stop new focal MS lesions from forming and prevent new damage. Siponimod can’t repair existing damage and it can’t reverse existing disability. However, it can form the base of the pyramid for add-on therapies for the future, i.e. neuroprotectives, remylienators and neurorestoratives. I would, therefore, urge you all to focus on the positives and to celebrate these results as a milestone in the treatment of MS, i.e. progressive, or as I prefer advanced, MS. 


Why the Phoenix? I couldn’t use the eagle, ocrelizumab claimed that bird. We have had so many false starts and hopes dashed in the past in relation to DMTs for SPMS. To me Spinoimod represents the Phoenix rising from the fire of failed SPMS trials to finally offer people with SPMS some hope. We now know how to adequately power and perform SPMS trials. I sincerely hope this trial will act as a catalyst for new SPMS trials. There is no lack of ideas or compounds when it comes to future SPMS trials. We at Barts-MS are pushing forward with our Chariot-MS study and are actively discussing several potential trials in SPMS with Pharmaceutical companies.


Kappos et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet March 2018 https://doi.org/10.1016/S0140-6736(18)30475-6

Background:  No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor1,5 modulator, on disability progression in patients with SPMS.

Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144.

Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups.

Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS.


ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







Is it not time to extend the diagnosis of MS into the asymptomatic phase?

At a continuing medical education (CME) meeting I co-chaired in Vienna, a concept emerged that is silently gnawing away at my consciousness and has changed my thinking.


The concept concerns how we deal with the problem of the radiologically isolated syndrome (RIS) or asymptomatic MS.





I have openly criticised the New McDonald criteria for not allowing us to make a diagnosis of asymptomatic MS. Why? Because if we buy into the concept of time is brain and our treatment aim is to maximise lifelong brain health then we really need to be able to treat RIS. Why? People diagnosed with RIS, currently a pre-disease state, already have evidence of end-organ damage. People with RIS have smaller brains than age- and sex-matched healthy controls. When you interrogate RISers, about 25% of them already have significant cognitive impairment in at least two domains. In other words, the biological processes that drive MS (‘The Shredder’) are present in the asymptomatic stage. What we then have to rely on is that one of their next lesions occurs in an eloquent pathway to cause an attack so that MS can be diagnosed and only then treated, or not. I say possibly because in many countries early MS, or clinically isolated syndromes (CIS), can’t be treated and the person has to wait to have a second attack. Possibly, a more worrying statistic is that about 10% of people with RIS, who are diagnosed with MS, go onto present with primary progressive MS. This proportion is similar to the proportion of PPMSers in the wider MS population. As you know PPMS is more advanced and less modifiable than MS in the early or so-called relapsing phase (RRMS). I hypothesise that if we treated RIS we may be able to prevent, or at least delay, a proportion of them presenting later with PPMS.


The debate we had at the weekend meeting is that if you have someone with RIS and you offer them a formal neuropsychological assessment and they come back with cognitive deficits can you count this as a sentinel event, or an attack, and diagnose them as having MS? We all agreed that we would still need to show dissemination in time and space, which could now be done using MRI and/or CSF analysis (presence of locally synthesised oligoclonal IgG bands).


I will now argue for using cognition as one of the neurological domains for defining MS. Some of my colleagues disagreed with me, but a lot nodded their heads in agreement. We need consensus on this. Clearly, the implications of #ThinkingCognition are enormous and it will allow one to make a diagnosis of MS in a proportion of patients in the so-called prodromal or asymptomatic phase of MS. The implications of this proposal are to change our diagnostic criteria for MS.


As we start to have this debate in MS our colleagues in Alzheimer’s and Parkinson’s disease have stolen a march on us. They have been disappointed time and again with failed DMT trials. By the time you are diagnosed with Alzheimer’s disease or Parkinson’s disease, it is too late to modify the disease; i.e. you have lost too much brain. Therefore there is a strong move to try and diagnose people with AD and PD before they present clinically. The principle is now so entrenched in the neurodegenerative disease space that most AD trials currently recruiting are recruiting high-risk cohorts with early pathological biomarkers of disease (amyloid-beta imaging and/or positive ApoE4 carrier status).


Up until now, we in the field of MS have been so far ahead of our colleagues working in AD and PD in terms of disease-modification. They have learnt from us that early is better. I am therefore surprised that we are letting them steal our thunder. I am aware that some of you would argue that as MS is not such a disabling disease we can afford to wait. Tell that to the 50% of unemployed MSers with an EDSS of 3.0 or less and also tell that to the 10% of RISers who present with PPMS a few years down the line.


We as a community need to take the ‘Time Matters MS’ mantra seriously and walk the talk. I, therefore, propose that we include cognitive impairment as part of our assessment of someone with RIS and if we find cognitive impairment we use that as evidence of an attack (cognitive relapse) and if they then fulfil McDonald criteria for dissemination in time and space, and other conditions are excluded, they have MS.


If you don’t agree with me let’s start a debate.


Please have your say and complete this short survey.




Thompson et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173.


The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.


Kantarci et al. Primary Progressive Multiple Sclerosis Evolving From Radiologically Isolated Syndrome. Ann Neurol. 2016 Feb;79(2):288-94.


OBJECTIVE: The aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS).



METHODS: A multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome[CIS] or relapsing-remitting MS) and were also compared to two other population- and clinic-based PPMS cohorts.


RESULTS: Of the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow-up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± standard deviation; 49.1 ± 12.1) in the RIS group were comparable to other PPMS populations (p > 0.05). Median time to PPMS was 3.5 years (range, 1.6-5.4). RIS evolved to PPMS more commonly in men (p = 0.005) and at an older age (p < 0.001) when compared to CIS/MS, independent of follow-up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution than those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow-up period (P = 0.005). Other MRI characteristics in the preprogressive phase of PPMS were indistinguishable from CIS/MS.

INTERPRETATION: Subjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age-dependent manner. Besides age, unequivocal presence of spinal cord lesions and being male predicted evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum.

ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







Is it the B-cell and/or the T-cell? Prof G eats his hat.

At Barts-MS we have been pushing the B-cell hypothesis based on circumstantial evidence when a lot of genomic, and other data, make it clear that T-cells are also involved in the pathogenesis of MS. Now that the first non-depleting BTKi (Bruton Tyrosine Kinase Inhibitor) is effective in MS does this change our central hypothesis? 



Yes, I am eating my hat. I predicted that unless a BTKi was depleting it would not work in MS. Why? 

I am convinced that EBV causes MS and that the only way to control MS was to deplete the peripheral blood and lymph nodes of B cells, in particular, memory B cells, to reduce the EBV viral load. 

 EBV lives in memory B cells and provides these cells with a survival advantage by stimulating a signaling or messaging pathway, which is independent of antigen stimulation. The B cell needs this EBV-induced signal stay alive and proliferate.

Another pathway to keep B cells alive is via antigen stimulation. For the antigen stimulation to work, the B cell needs Bruton tyrosine kinase (BTK) activation, which plays a crucial role in B cell maturation. Mutations in the BTK gene cause a rare primary immunodeficiency syndrome that is X-linked (the gene is on the X-chromosome) called agammaglobulinemia or Bruton’s agammaglobulinemia. 

 Patients with this type of agammaglobulinemia have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation. Based on this genetic disorder many Pharma companies have been targeting BTK as a treatment for lymphoma and autoimmune disease. 


There is a licensed BTKi called Ibrutinib that is licensed for B cell lymphomas. About 2-years ago the Mouse Doctor and I had quite detailed conversations with Abbvie about doing an investigator-led, proof of concept study, to test Ibrutinib in MS. Abbvie were very supportive of this, but Janssen who co-developed Ibrutinib had cold feet, so our proposal never got off the ground. I made the argument that Ibrutinib, a depleting BTKi, would be superior to the non-depleting BTKi in development.

Therefore, I was somewhat surprised to see the press release from Merck last week confirming that the evobrutinib phase 2b study was positive in MS. This is telling us that you don’t need to deplete B cells to get a therapeutic effect and that B-cell antigen signalling and presentation are back on the cards. This puts T-cells back on the agenda, possibly downstream of B cells. I personally can’t wait to see how effective evobrutinib is at suppressing MS disease activity. It will need to be as good as anti-CD20 therapy to have a chance in the marketplace. Let’s hope we get to hear the results of the trial at ECTRIMS. I am also aware of at least two other Pharma companies with their own BTKi about to go into clinical trials in MS. It is quite amazing how Pharma seems to get things much quicker than the wider MS community in terms of therapeutic targets; c’est la vie! 




Now will Merck develop evobrutinib as a monotherapy or will they leverage the mode of action of oral cladribine (Mavenclad)? Cladribine is currently being used as a SIRT (selective immune reconstitution therapy). However, most pwMS will relapse or have a recrudescence of disease activity at sometime after receiving cladribine. Could cladribine be turned into a true induction treatment followed by evobrutinib as a maintenance therapy? 


We have shown that cladribine has a profound effect on B cells, in particular, memory B cells. Could evobrutinib post-cladribine maintain the remission very, very long term? This is how I would develop at least one of the trials in the phase 3 programme. 


What about evobrutinib post-alemtuzumab? With alemtuzumab, I would use a BTKi in parallel. A BTKi may not only be effective in preventing recrudescence of MS disease activity it could possibly prevent the secondary autoimmunity post-alemtuzumab. Maybe this is the logic behind Genzyme’s recent licensing agreement with Principia Biopharma to develop PRN2246 a BTKi in MS.

Biogen also has a BTKi (BIIB068) that is currently being tested in lupus. Will they let Merck and Genzyme steal a march on them? As the dominant pharma company in MS, I suspect they won’t. 

Evobrutinib appears to have triggered a BTKi Lemming Syndrome (a psychological quasi-condition in which the afflicted person/pharma-company becomes subject to the whims of a portion of popular culture, and bends his/her entire persona/company to conform to the norms dictated by the media-moguls/other pharma companies in charge of a said trend ;-).

Evobrutinib


Who said it wasn’t an interesting time to be in MS? We clearly in a new era where we are unpacking the pathogenesis of MS and autoimmunity, in general, using new biological targets. 


Roll on ECTRIMS the evobrutinib results are going to be one of the highlights, if not the highlight of this year’s meeting. 


MERCK KGaA
DARMSTADT, Germany, March 7, 2018 /PRNewswire/ — Primary endpoint met for evobrutinib (Bruton’s Tyrosine Kinase Inhibitor – BTK) in relapsing multiple sclerosis (MS)  First proof of concept for BTK inhibitor in MS.

Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced positive results from its Phase IIb study of evobrutinib (Bruton’s Tyrosine Kinase Inhibitor – BTK) in relapsing multiple sclerosis (MS). The study has met its primary endpoint, demonstrating that evobrutinib resulted in a clinically meaningful reduction of gadolinium enhancing T1 lesions measured at weeks 12, 16, 20 and 24 in comparison to patients receiving placebo.

“We are encouraged by these early positive results of evobrutinib in relapsing MS,” said Luciano Rossetti, Head of Global Research & Development at the Biopharma business of Merck KGaA, Darmstadt, Germany. “The trial will continue so as to further inform our clinical development strategy for evobrutinib in MS.”

Details of this clinical study can be found on ClinicalTrials.gov.

Evobrutinib, discovered by Merck KGaA, Darmstadt, Germany, is also in Phase IIb studies in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

About evobrutinib

Evobrutinib (M2951) is in clinical development to investigate its potential as a treatment for multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is an oral, highly selective inhibitor of Bruton’s Tyrosine Kinase (BTK) which is important in the development and functioning of various immune cells including B lymphocytes and macrophages. Evobrutinib is designed to inhibit primary B cell responses such as proliferation and antibody and cytokine release, without directly affecting T cells. BTK inhibition is thought to suppress autoantibody-producing cells, which preclinical research suggests may be therapeutically useful in certain autoimmune diseases. Evobrutinib is currently under clinical investigation and not approved for any use anywhere in the world.


SANOFI-GENZYME

Sanofi, Principia agree to develop multiple sclerosis drug candidate

• Clinical-stage oral drug candidate (PRN2246) with the potential to treat multiple sclerosis
• Principia to receive $40 million upfront payment, future milestone payments could total $765 million

Thursday, November 9, 2017 7:48 am EST, Paris, France and South San Francisco, Calif

Sanofi will develop Principia Biopharma Inc.’s experimental oral treatment that shows promise in multiple sclerosis (MS) and, potentially, other central nervous system (CNS) diseases.

Under the license agreement signed this week, Sanofi will develop Principia’s Bruton’s tyrosine kinase (BTK) inhibitor (PRN2246), which was designed to access the brain and spinal cord by crossing the blood-brain barrier and impact immune cell and brain cell signalling. This may help treat MS and other CNS diseases. PRN2246 is currently in clinical development.

“Our agreement with Principia is an example of Sanofi’s strategic commitment to build our drug discovery and development pipeline in MS and neurological diseases,” says Rita Balice-Gordon, PhD, Global Head of MS/Neuroscience Therapeutic Research Area at Sanofi. “Complementing our own internal R&D expertise, external relationships like this may accelerate delivery of new treatments to patients living with these serious diseases.”

“Sanofi is an ideal partner for PRN2246. The agreement allows Principia to maximize the BTK opportunity in neurology with a strong partner for PRN2246 while focusing internal resources on our lead BTK inhibitor in another therapeutic area.” said Martin Babler, Chief Executive Officer of Principia Biopharma. “PRN2246 is a blood brain barrier crossing, highly potent BTK inhibitor, that we believe is especially well suited for the treatment of MS and other neurological disorders.”


BIOGEN


Biogen sneaks previously unknown lupus drug into the clinic

by Ben Adams Jul 13, 2016 10:49am

…… Analysts at Jefferies have found that Biogen ($BIIB) has quietly sneaked a lupus candidate into the lab for initial testing, coming as it does after the Big Biotech has in recent months cut its lupus research programs.

…… But in a note to clients posted today, Jefferies said that the company has now put forward a Bruton’s tyrosine kinase (Btk) inhibitor, known as BIIB068, into the clinic.

…… According to clinicaltrials.gov, the experimental candidate is targeting systemic lupus erythematosus (SLE) in a Phase I trial of 52 patients, which is expected to enroll by December.

…… Jefferies noted that while lupus “remains a challenging condition,” some Btk inhibitors have shown “signals of promise” in early trials………

ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







Reflections on ‘An Instinct for Kindness’

The BBC Radio 4 dramatisation on the assisted suicide of a person with advanced SPMS has generated some heated exchanges. I have now listened to the dramatisation and have reflected on the story. It is a very touching story and I would recommend it to all people with an interest in MS. 
This is my personal take on the story. You may or may not want to hear what I have to say.

Although this is a very sad story about someone with MS, it is filled with love and compassion. The people involved cared. The story also teaches one not to be afraid to face one’s own mortality.

Allyson, the lovely lady with MS in this story, missed out on DMTs and had over the decades became very disabled. She was essentially bed-bound with bladder and bowel involvement, spasticity and pain. She needed carers up to four times per day and had a hoist to transfer her in and out of bed. The story does not mention pressure or bed sores, but she would have been at high risk of pressure sores. She had recurrent urinary tract infections. She end-up living in a downstairs flat with a view of a car park. She missed the beautiful views of Yorkshire that she had had in her previous flat. She had been forced to move to a ground floor flat because of her disabilities.

It is clear that Allyson had become socially isolated and avoided going out. This was because she was worried about being incontinent in public. She was concerned that she wouldn’t be able to get to the toilet on time. She was having intermittent enemas to keep her bowels open. I am sure a lot more could have been done to address her bowel anxiety. I would have switched her to a daily rectal irrigation regime. This allows pwMS, and many like her, to have confidence in their bowel function and with time allows them to overcome their anxiety and regain their confidence about going out. This is how many Paralympians manage their bowels.

She had spasms and pain in her legs and back. She mentioned taking clonazepam. It is clear from the narrative that her spasticity management hadn’t been optimised. There is a lot she could have done to reduce her spasm and control her pain. Was she offered other add-on anti-spasticity agents, e.g. Sativex? Was she a candidate for intrathecal baclofen? In the modern era, you should not be in pain from spasticity. The pain would almost certainly have added to a downward spiral that led to her becoming depressed.

Based on her unwillingness to go out and interact with family and friends I suspect Allyson was depressed. Had she been assessed for depression and treated? Had she been offered CBT and mindfulness therapy? Was she a candidate for an anti-depressant? Dare I ask if she had been asked about suicidal ideation? It is clear Allyson was angry and possibly in denial. I think a lot could have been done to help her.

Social isolation is a massive problem and was probably the primary driver of Allyson eventually taking up the option of assisted suicide. Allyson would have benefitted from social prescribing, i.e. being prescribed activities that would have added meaning to her life. She needed someone to tell her every day that she was loved, needed and had a role to play in society. She was an actress and a teacher. Could she have remained active? She may have been able to stay connected to an amateur dramatic society. Why didn’t she go out to local plays? Why didn’t she engage? Could she have remained active as a teacher; possibly part-time as a tutor? The latter does not need to be done face-to-face; there are technology solutions to allow disabled people to work.

It is clear she suffered from MS-related fatigue. Why was she fatigued? Did she have ongoing MS disease activity? Was she sleep deprived as a result of night-time bladder problems? Was she drinking too much caffeine? Too much alcohol? What other medications was she taking that could have been optimised or stopped to improve her alertness and reduce her fatigue levels? Did she have a sleep disorder?

I think Allyson may have been let down by the NHS, her family and friends, and society. She didn’t need assisted suicide as the final treatment option for her problems. What she needed was love, care and responsive health-care and social systems to optimise her quality of life. 


It sounds as if her son was also in denial. He wasn’t around. I suspect he could have helped his mother. Had he been counselled and taught about MS? He was against his mother’s suicide and I suspect if he had had a more active relationship with his mother it may have prevented her suicide. However, I cannot be sure about the latter as it was not covered in detail in the dramatisation. 

At a personal level I am for assisted suicide; as a libertarian, it is about choice. However, as a doctor and neurologist, I am against assisted suicide. How can I, on the one hand, be trying to do my best to treat my patients, to make their lives easier and better and on the other hand offering assisted suicide? I would hope that if I was looking after Allyson she would have not needed this drastic solution.

Since we have been running our MS Research Days, PPI (public-patient involvement) programme and MS Advisory Groups I have seen how engaging with patients, connecting them to us and with other people with MS, changes their worldview. I am more convinced than ever that part of our role as MSologists is to expand our patients social capital or social network. By doing this we would hopefully prevent more people in a similar predicament to Allyson from needing assisted suicide. We are social animals; we need to interact, to be loved and cared for.  Loneliness was the killer here, not MS. 

 Prevent loneliness, prevent social isolation, and the need for assisted suicide as a treatment option for MS will go away.

 Despite these views, I will always respect an informed decision of one of my patients to have an assisted suicide. It is not my role to judge, or withhold, this option. This is why I haven’t refused to write medical reports for Dignitas when requested. Fortunately, to date, none of my patients who have requested these reports has taken up the option of travelling to Switzerland for an assisted suicide. Maybe I should count myself as lucky? On the other hand, I did take the modern Hippocratic oath when I was a final year medical student. At times like this, it is worth reminding oneself of your vows and practising medicine to the best of your abilities.  

 The following is a modern version of the Hippocratic oath; written in 1964 by Dr. Louis Lasagna:

I swear to fulfil, to the best of my ability and judgment, this covenant:

I will respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow.

I will apply, for the benefit of the sick, all measures [that] are required, avoiding those twin traps of overtreatment and therapeutic nihilism.

I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon’s knife or the chemist’s drug.

I will not be ashamed to say “I know not”, nor will I fail to call in my colleagues when the skills of another are needed for a patient’s recovery.

I will respect the privacy of my patients, for their problems are not disclosed to me that the world may know. Most especially must I tread with care in matters of life and death. If it is given to me to save a life, all thanks. But it may also be within my power to take a life; this awesome responsibility must be faced with great humbleness and awareness of my own frailty. Above all, I must not play at God.

I will remember that I do not treat a fever chart, a cancerous growth, but a sick human being, whose illness may affect the person’s family and economic stability. My responsibility includes these related problems if I am to care adequately for the sick.

I will prevent disease whenever I can, for prevention is preferable to cure.

I will remember that I remain a member of society with special obligations to all my fellow human beings, those sound of mind and body as well as the infirm.

If I do not violate this oath, may I enjoy life and art, respected while I live and remembered with affection thereafter. May I always act so as to preserve the finest traditions of my calling and may I long experience the joy of healing those who seek my help.


 Here is the programme

ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







News: British & Irish MSologists are spoilt for choice

The following are two MS-related meetings happening this week. If you had a choice which one would you choose to attend?





ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}







Urgent News Update: daclizumab is withdrawn from the market

The EMA has just announced that Biogen and Abbvie are pulling daclizumab from the market. Why?


On a recent trip to Goettingen in Germany, I was shown a handful of cases with eosinophilic encephalitis occurring shortly after starting daclizumab. The number of cases at that time was just 5, but it was sufficient for me to state that this must be the final nail in the coffin for daclizumab. Daclizumab has taught us a tremendous amount about the pathogenesis of MS, but with a large number of other DMTs on the market, it would be difficult to justify its use with its current, and emerging, safety profile. What daclizumab has taught us is the T-regs are probably not involved in the pathogenesis of MS and that the memory B cell is king. 

ProfG    
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}

.fa:hover {
opacity: 0.7;
}

.fa-facebook {
background: #3B5998;
color: white;
}

.fa-twitter {
background: #55ACEE;
color: white;
}

.fa-google {
background: #dd4b39;
color: white;
}

.fa-linkedin {
background: #007bb5;
color: white;
}

.fa-youtube {
background: #bb0000;
color: white;
}

.fa-instagram {
background: #125688;
color: white;
}

.fa-pinterest {
background: #cb2027;
color: white;
}

.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}

.fa-skype {
background: #00aff0;
color: white;
}

.fa-android {
background: #a4c639;
color: white;
}

.fa-dribbble {
background: #ea4c89;
color: white;
}

.fa-medium {
background: #000000;
color: white;
}

.fa-tumblr {
background: #2c4762;
color: white;
}

.fa-vine {
background: #00b489;
color: white;
}

.fa-foursquare {
background: #45bbff;
color: white;
}

.fa-stumbleupon {
background: #eb4924;
color: white;
}

.fa-flickr {
background: #f40083;
color: white;
}

.fa-yahoo {
background: #430297;
color: white;
}

.fa-soundcloud {
background: #ff5500;
color: white;
}

.fa-reddit {
background: #ff5700;
color: white;
}

.fa-rss {
background: #ff6600;
color: white;
}