Category: Archive

More about ageing and MS; this time about the development of progressive MS. 

The main message below is that most pwMS who are destined to develop progressive MS do so before age 75 and the onset of this phase of the disease is more dependent on age than the duration of MS.

Does this mean you are all destined to develop progressive MS? No in this study only 38% people with RRMS went onto develop progressive MS by age 75. Why some RRMSers don’t develop progressive MS is probably due to biological factors and DMTs.

So the message in this post is mixed, i.e. the onset of the progressive phase of MS is age-dependent and not all pwRRMS become progressive.

This is no consolation for PPMSers. However, with the licensing of ocrelizumab for treating early-active PPMS we now have a DMT that can modify the course of PPMS, despite the treatment response to ocrelizumab being age-related. As with RRMS is better to treat PPMS as soon as possible after the onset of the disease; there is no point in waiting to lose reserve and neurological function and the advantage of youth before starting ocrelizumab.

The important question from a biological perspective is how is age modifying the course of MS and is there anything we can do to slow down or stop the ravages of ageing? I would start with a Brain Healthy Lifestyle. However, ageing is a biological programme and I have little doubt that scientists will crack the code and identify pathways that are modifiable. One hurdle still exists, however, society still considers ageing a normal phenomenon. Until we redefine ageing as a disease and healthcare payers agree to pay for anti-ageing treatments the incentive for Pharma to invest in ageing research won’t materialise anytime soon.

We have had this debate before on the blog. Do you agree that ageing is a disease? 

Last week DrK and I joined an esteemed panel of academic neurologists (all male, unfortunately*) to discuss issues around the sequencing of DMTs.

*We need more women on platforms such this and other MS-related committees. The gender divide is very large in the field of MS. It is very embarrassing to me as a father and husband; my daughters and my wife are card-carrying feminists and every bit as capable as their male peers.  


The following is my presentation that many of you requested. You can download it from SlideShare.

Sequencing of DMTs is a very hot topic and increasingly relevant to how we select DMTs today. What factors do we need to consider when choosing DMTs to make sure it is safe to transition patients onto in the future? 

When making a choice of DMT have you asked your neurologist what drug x does do your future DMT choices? This is something that is becoming increasingly important when selecting DMTs. 

Please stop to think and to ask questions. 

Getting it right the first time is more important than you realise. 

ProfG    
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Did you know that if you have MS and are older than 53 years of age you are unlikely to respond to DMTs?

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You will have noticed over the last 5 months that we have been trying to get more guest bloggers engaged with our blog. We would love to increase the volume of guest posts to increase the diversity of opinions and topics on all things MS. Variety is the spice of life and a lot of what we have to say is repetition. 

It is clear that the incidence and prevalence of MS are increasing globally. We are in the throes of an MS pandemic. The one region that is documenting and seeing this change in MS epidemiology is the Middle East and North Africa. 


In response to the unmet need, Barts-MS have been invited by the Alfaisal University and Global Academy for Health Sciences (GAHS) to run an MS teaching course in Dubai on the 30^th & 31^st March 2018. You may be interested in attending.

ProfG    
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I have just heard the tragic news that one of my patients, who was admitted to intensive care over the weekend with pneumonia as a complication of influenza,  sadly passed away last night. I called the patient’s partner to express my sympathy and was surprised to hear that she had not had this season’s flu jab. This is a problem. 

ProfG    
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The elephant in the room is comorbidities such as hypertension, diabetes, obesity, metabolic syndrome and smoking. How can we get pwMS to take their general health seriously? 

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As you are probably aware NICE, true to past form, chose the Christmas period to toss a small grenade into the MS space. I assume they thought that by tossing it on Wednesday 20 December when most people were either away, or about to go away, on Christmas holidays the perceived explosion would be smaller than expected and the shrapnel would cause no collateral damage. NICE was wrong. They are wrong for several reasons.

At present the NICE ‘appraisal consultation document’ on the use of beta interferons and glatiramer acetate for treating MS in the NHS in England recommends that of these two classes of treatment that only Extavia is used to treat people with relapsing MS. Astonginglishly the appraisal states that Copaxone, Avonex, Betaferon, Plegridy and Rebif are not recommended. This proposed ruling only effects new patients; anyone already taking one of these drugs will not be affected by this guidance and can continue without change until they and their neurologist consider it appropriate to stop.

Shared-decision making

What about patient-engagement, shared-decision making, etc. The NHS has, or at least had, a policy of shared-decision making called concordance. This appraisal makes a mockery of shared decision-making. Extavia uses old technology. Of the interferon-beta preparations available it has the least friendly autoinjector and Novartis who market this product have not invested heavily in a support programme for patients starting Extavia. Our nurse specialists and pharmacists simply don’t consider Extavia a treatment option and would opt for one of the other preparations.

Immunogenicity

We know from many earlier studies that interferon-beta-1b (Betaferon & Extavia) is more immunogenic than the other interferons. Over 30% of patients treated with IFNbeta-1b develop neutralizing antibodies (NABs) that stop the drug working. Why would anyone prescribe a more immunogenic biologic when there are less immunogenic alternatives?

Innovation

This appraisal flies in the face of innovation. In fact is a kick in the teeth for innovation. Please note Avonex and Rebif have both been reformulated over their life cycles to improve their tolerability and immunogenicity. Plegridy is actually a new product; it uses pegylation to extend its circulating half-life. Plegridy investment and many years to be developed and licensed. What kind of message does this send to Pharma and academia about innovation? I thought NICE was meant to include innovation as one the variables they took into account when they made their decisions. In fact, why is Plegridy being considered part of this MTA (multi-technology appraisal)? Surely it deserves its own STA (single technology appraisal)?

On the cheap

Ever since the NICE turned down interferon-beta and GA as part of the initial tranche of single technology appraisals they have not changed the threshold for approving drugs. In other words, the cost per QALY that NICE deem cost-effective has been static for 15 years. Healthcare inflation has gradually reduced the actual cost per QALY that the NHS is prepared to pay for MS drugs. In addition, they have yet to incorporate indirect, in particular social, costs into their modelling. This explains why the NHS pays so little for MS DMTs. Is this fair? Patients in the USA are paying more than 5x the price for DMTs that we are. 

ProfG    
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The latest data from Canada indicates that the prevalence and incidence of MS continues to increase; this is a trend across the world. Importantly, Canada may have just surpassed Scotland as the highest prevalence region of the world. Why is this happening? Why has MS become a pandemic? Is there anything we can do about this?

Mokry et al. Obesity and Multiple Sclerosis: A Mendelian Randomization Study. PLoS Med. 2016 Jun 28;13(6):e1002053.

Gianfrancesco et al. Causal Effect of Genetic Variants Associated With Body Mass Index on Multiple Sclerosis Susceptibility. Am J Epidemiol. 2017 Feb 1;185(3):162-171.

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The HSCT zealots would want you to believe that HSCT is the solution to MS and that we the neurologists are preventing you from accessing this curative treatment. Are they correct? Or do we need evidence from randomised trials?

ProfG    
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