Author: Gavin Giovannoni

#ClinicSpeak: have you ever used melatonin?

Is melatonin an effective treatment for seasonal affective disorder? #ClinicSpeak

 Summary: This post summarises the biological effects of melatonin and the reviews the literature on its effectiveness as a treatment for depression. Embedded in the post is a short survey to assess melatonin use in people with MS. 

 Yesterday one the commentators enquired about SAD (seasonal affective disorders) in MS. I have done a preliminary search and can’t find any specific research on how common SAD is in MSers, nor on its treatment in MSers. Despite this, there is an increasing trend for patients in my clinic to self-medicate with melatonin to try to improve their sleep, night-time bladder function and mood (including SAD). At present the evidence to support melatonin for these indications is weak. The meta-analysis below of melatonin as a treatment for depression is highlights the lack of evidence, but the authors’ acknowledge problems with the trials, which tended to be underpowered. The solution? Better designed, larger, trials. Are you up for participating in a web-based study? This may be an opportunity for the MS community to study the effective of an intervention on their own.




What is melatonin?

 Melatonin is a hormone that is produced by the pineal gland and regulates sleep and wakefulness. Melatonin synchronizes circadian rhythms including sleep-wake timing, blood pressure regulation, seasonal reproduction, and many others. Its effects are produced through activation of melatonin receptors. As a medicine, it is used for the treatment of insomnia, in particular jet-lag, despite evidence of its effectiveness is very weak. Melatonin is sold over the counter and the web in the United States, Canada and some European countries, but not in the UK. We can prescribe it on a named-patient basis in the UK. I would be interested to know how many of you have used melatonin, for what reason and how have you acquired the medication. 



De Crescenzo et al. Melatonin as a treatment for mood disorders: a systematic review. Acta Psychiatr Scand. 2017 Jun 14.

 OBJECTIVE: Melatonin has been widely studied in the treatment of sleep disorders and evidence is accumulating on a possible role for melatonin influencing mood. Our aim was to determine the efficacy and acceptability of melatonin for mood disorders.


 METHOD: We conducted a comprehensive systematic review of randomized clinical trials on patients with mood disorders, comparing melatonin to placebo.

RESULTS: Eight clinical trials were included; one study in bipolar, three in unipolar depression and four in seasonal affective disorder. We have only a small study on patients with bipolar disorder, while we have more studies testing melatonin as an augmentation strategy for depressive episodes in major depressive disorder and seasonal affective disorder. The acceptability and tolerability were good. We analyzed data from three trials on depressive episodes and found that the evidence for an effect of melatonin in improving mood symptoms is not significant (SMD = 0.37; 95% CI [-0.05, 0.37]; P = 0.09). The small sample size and the differences in methodology of the trials suggest that our results are based on data deriving from investigations occurring early in this field of study.

 CONCLUSION: There is no evidence for an effect of melatonin on mood disorders, but the results are not conclusive and justify further research.

CoI: none

#ResearchSpeak: does HSCT have a chance?

Alemtuzumab 5-year extension data supports flipping the pyramid and hitting MS early and hard. #ResearchSpeak

Summary: The following post summarises the very good 5-year extension data of people with MS treated with alemtuzumab in the pivotal phase 3 trials. In short, the result of very good with most subjects only requiring 2 courses of treatment with a very good outcome. Particularly impressive is the observation of ‘normalised’ brain volume loss in years 3, 4 and 5. 

The following are the 5-year extension study results of the alemtuzumab trial subjects. If you have MS these results are simply the best long-term data we have on any DMT including HSCT (hematopoietic stem cell therapy). 


We have been pushing the treatment paradigm of flipping the pyramid (high-efficacy first-line) for some time now. The CARE-MS 1 study is just this, i.e. these subjects were DMT naive before being treated with alemtuzumab; 68.5% only needed two cycles of treatment in year 1 and 2 with the majority being NEDA in years 3, 4 and 5. The important metric is brain volume loss, a measure of end-organ damage, which was less than or equal to 0.2% per year. This level of brain volume loss is what you see in normal people. 

The results in the CARE-MS 2 extension study are no less impressive. These subjects had all failed prior DMTs and hence had a longer disease duration and went onto alemtuzumab with greater underlying damage and/or loss of brain reserve; 60% only needed two cycles of treatment (year 1 and 2), the majority were NEDA and brain volume loss in years 3, 4 and 5 were well under 0.2% per year. Please note brain volume loss in year 1 and 2 are high, this is because of therapeutic lag. Brain volume loss in the next 2 years of your disease is primed by previous inflammatory disease activity hence we would not expect alemtuzumab to impact on this previous damage. 

The cons of alemtuzumab are well rehearsed; ~45-50% of subjects will develop secondary autoimmunity over time. The commonest is autoimmune thyroid disease. Alemtuzumab comes with strict monitoring requirements, i.e. monthly blood and urine monitoring for at least 48 months after the last course of treatment. There is also a not so insignificant infection risk in the first few weeks after alemtuzumab infusions. The studies below quote epoch NEDA rates, i.e. NEDA rates per annum. The accumulative rates are lower than this and at 5 years the NEDA rates are less than 50% for both the CARE-MS 1 and 2 studies. The latter is important as this will be the metric we use if and when we do our trial comparing AHSCT to alemtuzumab in the NHS. 

Despite these negatives, there is little doubt that alemtuzumab is the most effective DMT we have available to treat people with active MS. Alemtuzumab is also the most cost effective therapy we have licensed to use under the NHS. NHS England would prefer us to use alemtuzumab to all other licensed DMTs because of this. NICE is not the only HTA (health technology appraisal) to come to this conclusion, the Norwegian HTA has drawn the same conclusion. At an NHS service level, alemtuzumab is causing a pharmacovigilance nightmare for us. To see the scale of the problem imagine you treat 100 patient per year with alemtuzumab and you have to do monthly blood and urine monitoring. After 5 years you will have 500 patients requiring monthly monitoring and 500 patients requiring annual MRI scans. This is an industrial-scale logistics problem; it is something we have to gear up for. This is why other emerging DMTs such as oral cladribine and ocrelizumab will have an advantage over alemtuzumab. The monitoring requirements are so much less with these agents that the incentives for MS services to shift to a less arduous mix of DMTs are obvious. For the individual person with MS I would ask your neurologist what the long-term brain atrophy data is for cladribine and ocrelizumab and how they interpret the results. Then you should ask them if they, or one of their close family members, had MS which agent would they choose? I think you may find their answer quite surprising. 

Havrdova et al. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017 Aug 23.

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348).


METHODS: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs).

RESULTS: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined.

CONCLUSIONS: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses.

Coles et al. Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology. 2017 Aug 23.

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy.


METHODS: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed.

RESULTS: Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3-5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1-5: -0.48%, -0.22%, -0.10%, -0.19%, -0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter.

CONCLUSIONS: Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment.

Alemtuzumab vs. HSCT: who will come out on top?

CoI: multiple, I am a co-author on these papers

#ClinicSpeak & #GuestPost: how much social capital do you have?

Social capital is important in MS; but how important? #ClinicSpeak #GuestPost

Summary: The following post explains the concept of social capital; in essence how socially connected you are. Social capital predicts outcome in many chronic diseases and is closely linked to quality of life (QoL). MS reduces social capital, but by how much? Not enough research has been done on social capital in in the field of MS. 


It’s good to be back for a second post. I have enjoyed reading all your comments on my first post about MS in South America (In case you missed it!). A lot has happened since then. This training programme has pushed me out of my comfort zone and has triggered my interest in and passion for addressing health inequalities. As always, the proof of the pudding is in the eating! Here is my new post on Social Capital.



THE UNEXPLORED ROLE OF SOCIAL CAPITAL IN MS

While previous studies have shown mixed results, emerging evidence suggests that there is an association between higher income inequality and worse health outcomes. Despite global progress in reducing poverty, inequality continues to persist and large disparities remain in health outcomes. Accordingly, researchers have become increasingly interested in exploring the effects of the socio-economic environment on individual and public health. Although the impact of social conditions on health equity is well documented, there is no consensus as to the relative importance of each factor. Many determinants are involved and, among them, social capital has emerged as one of the most interesting old ideas being revisited from a new perspective.


The social capital concept emerged in sociology early in the past century. Social capital refers to the resources derived from the cooperation between individuals and groups. It has been hypothesized to partially explain how social conditions influence health and mortality. More recently, the concept of social capital has become the subject of intense discussion, as it may represent a pathway by which public health interventions lead to health improvement. The exact nature and magnitude of these effects remain controversial as there is no standardized method to measure social capital. However, there are several tools that attempt to address its multidimensional nature.


Many types of social capital are theoretically possible, but an important distinction that should be made is between its cognitive and structural components. The structural dimension is derived from the “visible” forms of social capital and consists of networks, relationships, associations, institutions and organizations that link individuals and communities. On the other hand, the cognitive component refers to the quality of those social structures in terms of peoples’ perceptions of trust, sharing and reciprocity. The different dimensions of social capital are not necessarily mutually exclusive; they are all immersed within a multi-level analytical framework. As many social aspects are encompassed under the same concept, oversimplification and overstandardization are both equally dangerous for social capital research.

Neurological disorders represent a large burden on worldwide health. Patients with neurological conditions are embedded in social networks that may affect their outcomes. This effect has been postulated to modify the risk of dementia and the long-term prognosis in patients with stroke. Regardless of the growing recognition of the role of social capital in chronic diseases, not enough attention has been paid to its potential impact on other disabling neurological conditions such as MS.

A few researchers have explored the relationship between social support and quality of life in patients with MS. However, and to the best of our knowledge, only one study has specifically focused on social capital. The results of this study showed that in patients with MS, quality of life and social capital are somehow related. This study only evaluated one potential target. Many questions remain to be explored in our understanding of how social capital may lead to either positive or negative consequences for patients with MS.

Addressing health inequality matters! Addressing social capital matters too!!

This paper is for those who want to read further, and perhaps more deeply, about this fascinating area: https://goo.gl/GwVajR

References

1. Carpentier CL, Kozul-Wright R, Passos FD. Goal 10 – Why Addressing Inequality Matters. UN Chronicle. 2015;LI,4. https://unchronicle.un.org/article/goal-10-why-addressing-inequality-matters. Accessed 10 August 2017.

2. Bourdieu P. Forms of Capital. In: Richardson JG, ed. Handbook of theory for the sociology of education. Westport, CT: Greenwood Publisher, 1986:241-58. 


3. Nyqvist F, Pape B, Pellfolk T, et al. Structural and cognitive aspects of social capital and all-cause mortality: a meta-analysis of cohort studies. Soc Indic Res 2013;116:545-66.

4. Eriksson M. Social capital and health – implications for health promotion. Glob Health Action 2011;4:1-11.

5. Dhand A, Luke DA, Lang CE, et al. Social networks and neurological illness. Nat Rev Neurol 2016;12(10):605-12.

6. Rimaz S, Mohammad K, Dastoorpoor M, et al. Investigation of Relationship Between Social Capital and Quality of Life in Multiple Sclerosis Patients. Global Journal of Health Science. 2014;6(6):261-272.

7. Harpham T, Grant E, Thomas E. Measuring social capital within health surveys: key issues. Health Policy and Planning 2002,17(1):106-111.

#ClinicSpeak & #ResearchSpeak: what dose of vitamin D?

What dose of vitamin D supplementation do I recommend? #ResearchSpeak #ClinicSpeak


Summary: This blog post makes the case for using an initial dose of vD supplementation (5,000U/day) and then to test blood levels of vD after approximately 6 weeks to adjust the dose accordingly. I use evolutionary medicine to define a treatment target of blood vD levels.


The study below has shown that moderate vitamin D (vD) supplementation (10,400 IU/day) was safe in pwMS and had favourable effects on the immune system. The immunological changes on moderate dose vD are congruent with the effects we would want to see if MS was an ‘autoimmune disease’; e.g. they found a reduction in the proportion of interleukin-17+ve-CD4+ T cells so-called putative autoreactive T cells in MS.


Why do I say moderate dose vD supplementation rather than high-dose? This is because 10,400IU per day is physiological vD supplementation. If you go into the mid-summer sunlight with your upper body exposed for ~20-30 minutes your skin will produce this sort of dose of vD; therefore 10,400IU is not high-dose. The good news is that this study confirms other studies that moderate dose vD supplementation is safe and not associated with any toxicity or adverse events.


To remind you it is our policy to advise all our patients to ensure they are vD replete; we aim for a plasma level of 25OH-vD3 of greater than 100 nmol/L and less than 250 nmol/L. I start by recommending 5,000IU/day and testing blood levels about 12 weeks later. If levels are still low and the patient has been adherent then we increase the dose to 10,000 IU/day and if too high we reduce the dose to between 2,000-4,000IU/day. It is clear that plasma levels of vD are highly variable and are affected by dietary and multiple genetic factors. I never tell my patients that this will improve or help their MS; we say it may do but the real reason for being vD replete is to improve, or maintain, your bone health. Please note we do not recommend calcium supplementation in parallel with vD supplementation. As far as we are concerned there is no reason for pwMS to take calcium supplements unless they have thin bones (osteopenia or osteoporosis). If you are taking moderate or high-dose vD and calcium supplements together you will need to have your calcium levels monitored (please discuss this with your doctor).


Who’s advice am I giving? We tend to favour the Vitamin D Council’s advice regarding the initial dose of supplementation. With regard to our target level of plasma vD levels; I have adopted the evolutionary medicine approach espoused by Reinhold Veith (see old slide show below). This theory is based on what your vD levels would be if you worked outdoors with skin exposed (lifeguards & farm labourers) and what vD levels are in hunter-gatherer societies. Using a reference population gets around the likely problem that modern societies are vD deficient and hence you can use population mean vD levels to establish a normal range of plasma vD levels.


The problem I have with vD supplementation is adherence; pwMS simply forget to take their supplements and don’t take our advice when it comes to getting their relatives on supplements as well.



Sotirchos  et al. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology. 2015 Dec 30. pii: 10.1212/WNL.0000000000002316.

 OBJECTIVE: To study the safety profile and characterize the immunologic effects of high- vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS).


 METHODS: In this double-blind, single-center randomized pilot study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months. 

 RESULTS: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0-44.7 ng/mL) than in the low-dose group (6.9 ng/mL; 95% CI 1.0-13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17+CD4+ T cells (p = 0.016), CD161+CD4+ T cells (p = 0.03), and effector memory CD4+ T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4+ T cells (p = 0.018) and naive CD4+ T cells (p = 0.04). These effects were not observed in the low-dose group. 

 CONCLUSIONS: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD4+ T cells and decreased proportion of effector memory CD4+ T cells with concomitant increase in central memory CD4+ T cells and naive CD4+ T cells.

 CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects.

#NewsSpeak: Results from CHANGE-MS Phase 2b Study

Are HERVs in the final common pathway that leads to demyelination in MS? #NewsSpeak #ResearchSpeak


It is very difficult for me to comment on these results without seeing the data firsthand. However, as there is no difference at 6-months between active- and placebo-treated subjects this trial must be interpreted as being negative. Please note that GNbAC1 targets the envelope protein of probably one human endogenous retrovirus or HERV.  GNbAC1 is a monoclonal antibody and is not an antiviral agent, hence this study does not exclude a role of HERVs in the pathogenesis or molecular pathway of MS. 

Press release: BusinessWire. GeNeuro and Servier Announce Six-Month Results from CHANGE-MS Phase 2b Study in Multiple Sclerosis. August 28, 2017 01:30 AM Eastern Daylight Time


GeNeuro and Servier announced their 6-month results from the 12-month CHANGE-MS Phase 2b study of three doses of GNbAC1 for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The data showed that GNbAC1 is well tolerated and that there is no statistical difference at 6-months between GNbAC1 and placebo in the study’s primary endpoint of reducing the number of cerebral Gad-enhancing lesions as measured by MRI, nor on the other MRI measures of neuroinflammation. Relapses in the overall population decreased by over 50% relative to the year prior to study but there was no significant difference at 6 months between treated and placebo groups. Based on the unique mechanism of action and pharmacokinetics of GNbAC1, the study will continue, as planned, exploring potential benefits of the drug on MRI and clinical measures, including remyelination properties, with final results from the full 12-month expected in the first quarter of 2018.

GNbAC1 is the result of more than 25 years of research into human endogenous retroviruses (HERVs), including 15 years at Institut Mérieux and INSERM, a French national medical research institute. Found in the human genome, certain HERVs have been linked to various autoimmune and neurodegenerative diseases. Researchers have demonstrated that the retroviral envelope protein encoded by a HERV-W family human endogenous retrovirus (pHERV-W), which has been identified in brain lesions of patients with MS, particularly in active lesions, stimulated inflammatory processes through an interaction with the TLR4 receptor of innate immunity and inhibited neuron remyelination. pHERV-W env has also been identified in the pancreas of Type 1 diabetes (T1D) patients. By neutralizing pHERV-W env, GNbAC1 could at the same time block these pathological inflammatory processes and restore remyelination in MS patients and maintain insulin production in T1D patients. As pHERV-W env has no known physiological function, GNbAC1 is expected to have a good safety profile, without directly affecting the patient’s immune system, as observed in all clinical trials to date.

CoI: multiple

#ClinicSpeak & #DietSpeak: could diet be the next DMT?

Are you what you eat? How healthy is your diet? #ClinicSpeak #DietSpeak

 Whilst on holiday I spent several days with a very good friend of mine, from South Africa, who now lives in the US. His wife is a card-carrying dietician, who runs her own consulting business that helps athletes, companies and individuals improve their health and wellness through diet and exercise. After listening to her and seeing her methods in action, it became clear to me that my approach of leaving dietary and exercise interventions up to you and your general practitioners to implement is wrong; it doesn’t work. As part of ‘the holistic management’ of multiple sclerosis, we need to engage with lifestyle and wellness interventions more proactively. I am convinced they should be promoted as part of our disease-modifying therapy offering. 

 The saying ‘you are what you eat’ may be overused, but it captures the essence of what you need to do to optimise your health and wellness. We are aware from a recent dietary audit of patients attending Bart-MS that the average diet of pwMS living in London is very poor. Our interpretation of the audit results was that it is not MS specific, but simply reflects the poor diet of the general population of London, and presumably the whole country. Despite ongoing public health campaigns and wide media coverage on healthy eating, it is clear that most people either don’t listen, ignore the advice or don’t feel it is necessary to change their behaviour. I am aware that the issues around healthy eating are complex and that the food landscape is mired in politics and is heavily influenced by big business with vested interests. 


From ‘Viva: You are what you eat‘


We have tended to shy away from promoting any specific diet for the management of MS. Saying this I have done several posts on diet and its effect on MS; two particular posts, one on ketogenic diets (5th-Jan-2016) and the other on intermittent fasting (30th-May-2016) generated interest and quite a lot of discussion. There is emerging evidence of that intermittent ketosis and fasting may have general health benefits, which include potential benefits for pwMS. I, therefore, plan to do a series of posts on diet and nutrition in relation to MS over the next few months. These will be general posts about diet and nutrition and will give advice on what you can do to optimise your own diet to improve your general health and wellness. The aim of this exercise is to generate content to produce a #ClinicSpeak tool to help you manage your diet as part of the holistic self-management of MS. 

 Please note a themed series of posts in relation to one topic, that is not specifically related to research or a political campaign, is something we have not done before. Is this something you would find useful going forward? We could, for example, do a series on bladder management, DMT monitoring, etc. This content could then be migrated onto a curated site such as ClinicSpeak to make navigation easier. Thoughts? 

 CoI: nil in relation to this post

#NewsSpeak & #ThinkSpeak: blog rejuvenation

We need your help to rejuvenate the blog #NewsSpeak #ThinkSpeak #MSBlog

Just back from my family holiday and for the first time in a long time I feel well, have a manageable workload and have a list of things to do in the new academic year that will refocus our research and educational agenda on the things we do best. Whilst away I had a complete break from academic activities including the blog, which is why I probably feel so well. I read some very stimulating books, unrelated to MS and neurology, that have provided me with food for thought. 



High on the ToDo list to do is to review our blogging activity and to improve our offering. From discussions with numerous pwMS, comments on the blog and emails (thank you) we are aware that we have lost our core readership and that most of you now have problems understanding our posts. We are aware, from our web analytics, that the number of people who read the blog regularly has fallen and the number of times you come back for information is decreasing. 

Alison Thomson (designer) and Beki Aldam (writer), our public engagement gurus, have reviewed our content and blogging activity and have compared it to well-described attributes of successful blogs and have identified several issues. Alison and Beki are confident that we can reverse our decline and are planning to take us back to basics. As part of our rejuvenation, they will be re-training us in the art of writing for a lay audience. Their aim is to improve the quality and reduce the quantity, of our offering so that the majority of our readers will understand what we are writing about – ‘less is more’. 

If you have any suggestions to help us please feel free to comment on the blog or send Alison and Beki an email (bartsmsblog@gmail.com). For example, one potential option is to change very little, but provide you with tools to curate our content. What do you think? 

#NeuroSpeak: what do when you have failed a IRT?

Sequencing of DMTs will become increasingly complex. #NeuroSpeak

 Somebody asked over the weekend what I would do if someone failed alemtuzumab and had a persistent lymphopaenia. In short it depends on individual factors. 


I have had three patients like this already.

#1: One patient had 5 courses of alemtuzumab and had developed anti-alemtuzumab antibodies and had very little depletion after her last round of treatment. Her disease remained active on MRI (multiple enhancing lesions). Her lymphocyte counts were around 0.9. I recommended rituximab, but as she was hoping to start a family she opted for de-escalation therapy and chose glatiramer acetate. Her neurologist tells me she is doing well on GA. This case illustrates that you don’t always have to go upwards in terms of efficacy, you can de-escalate and use a platform therapy after an IRT (immune reconstitution therapy).

#2: The second case failed alemtuzumab therapy at month 17 into her two years of treatment. Interestingly she repopulated rapidly after her second course, i.e. her lymphocyte counts were 0.8 at month 1 and were 0.9 the week before she started her second course of alemtuzumab. I suspect she may be another case of anti-alemtuzumab antibodies. She had previously failed glatiramer acetate. As she was JCV-seronegative she elected to be treated with natalizumab. This patient was offered HSCT, but turned it down when she realised there would be a good chance of her not being able to have children. The haematologist had given her 45-50% chance of going into the premature menopause. She had the option of egg banking, but as her MS active she was not prepared to wait 2 months and go through the relatively stressful, and invasive procedures, of ovarian stimulation and egg harvesting. Then there is the cost of storage.

#3: The third case who I saw last week with her second relapse after her second course of alemtuzumab (month 19). Interestingly, despite having just started natalizumab she still had a relapse. Her lymphocyte count was 0.8. when she started natalizumab. This last relapse came on just 2 weeks after her first infusion of natalizumab. This shows you that almost all DMTs take time to start working and that a relapse takes weeks to evolve. In other words, if you are destined to have a relapse in the next week or two natalizumab will not prevent it from occurring. This patient was also offered daclizumab, but after the recent death due to fulminant hepatotoxicity on daclizumab, she decided to go with natalizumab. Interestingly, this patient has also just developed Graves disease (thyrotoxicosis) so she was hit with a secondary autoimmune complication of alemtuzumab without deriving the long-term benefit of its efficacy. This particular patient would have chosen ocrelizumab, over natalizumab, if it was available. The option of rituximab is not on the table as in the first case as NHS England have stopped us using rituximab to treat MS.

I am hoping to create a ClinicSpeak App that deals with all the issues raised about the sequencing of treatments. The purpose of the App is to help people understand issues such as the ones raised in these case vignettes.

CoI:multiple

#GuestPost & #ClinicSpeak: An MSer’s perspective

What does an MS’er look for in their HCP team?


A few weeks ago I was speaking about living with MS to a group of healthcare professionals (HCPs), mostly trainee neurologists and MS nurses. It gave me the opportunity to speak to them about what I look for in an HCP, as a patient who is living with MS. ProfG was in attendance and he asked if I could turn what I said into a guest blog post. So here it is!
*Disclaimer: These are my personal views and I’m fully aware that everyone deals with their diagnosis differently so may look for different things from their HCPs*

Be approachable
It sounds obvious, but the worst thing is to feel that your HCP team aren’t approachable and you’re on your own. Small things like smiling, not clock watching, asking how someone is outside of their MS… they all go towards putting us at ease and building a good relationship. I don’t mind that my neurologist’s clinic often runs late because I know that once I’m in there, he gives me all the time that I need. What would really annoy me is being “pushed out of the door” when my 15 minutes is up regardless of whether I’ve discussed everything I need to discuss.
On the subject of time, remember to give patients time to ask questions. The last thing you need is someone to go home after an appointment and consult Dr. Google. I personally know someone who was given a likely diagnosis of MS, wasn’t told what it is, went home and googled it and managed to convince himself he was dying. Really not helpful for the patient or you!

Be available – keep lines of communication open in a “non-invasive” way
I want to be able to contact my neurology team if I have a concern, especially as I know they’re the experts and not my GP. However, I also know they’re very busy. Rather than taking up a valuable appointment, which might not be necessary, I like having an email contact or mobile number that I can use to speak to my neuro team. Sending an email, text or voicemail means I know I’ll get a response when it’s convenient for them, without feeling like I’m “bothering” a very busy team. Just please remember to respond!

Encourage the expert patient, don’t be afraid of them, especially with shared decision making
Gone are the days when the doctor sits there and tells the patient what to do and the patient just does it, no questions asked. Expert patients are on the increase. I’m one of them. Don’t be afraid of us! We’re not going anywhere and we could make your life easier. I’m able to tell pretty well when something might be my MS or not. That means I contact my neuro team directly, not my GP. That’s more efficient use of time and resources for everyone. Shared-decision making is also much better when a patient is informed. So I’d say encourage patients to be informed and help them to become informed. That way, you can have the confidence that they’re fully aware of the impact of decisions being made about their healthcare.

Be inclusive
An MS patient is often not just one person. It’s a network of people. So, encourage carers, family members and those who have a significant role in the patient’s life to engage with you if necessary. Make the patient aware that they can attend clinic appointments with these people if they’d like.

Mind your language!
Again, it sounds obvious, but I’ve had people contact me after coming out of appointments and ask me to “translate” what their neurologist has told them, especially when it comes to test results. Please use plain language, especially at the time of diagnosis.

Look to your peers – the ones who have patient support, the ones who are leading the way and being innovative.
In the interests of protecting my personal information, I won’t say who my neurologist is, however, when I mention him to other people who have MS their reaction is often “WOW! I wish he was my neurologist. You’re so lucky! That HCP team is fantastic!” These are the HCPs you can learn from. Ask yourself why do their patients like them so much? What are they doing that is setting them apart?

Signpost, signpost, signpost!
You don’t have to know everything and you don’t need to have the time to convey every single bit of information a patient might need to know. But make yourself aware of where they can go for further, reliable information if necessary. The MS Society, MS Trust and MS-UK websites are always good places to start. However, you’d be surprised the number of MS patients I talk to who tell me their neurologist has never mentioned any of these organisations to them. It takes some of the pressure off you so why wouldn’t you do it?!

It’s a consumer market…..
Be aware that as patients we talk to each other, especially with the rise in social media. It’s a consumer market out there. I’ll be honest, if someone isn’t happy with their healthcare team they’ll go onto social media and ask around as to who WILL give them the type of care they want. Then they’ll move to a team that they’re happier with. So if you have patients consistently asking for things that others are getting elsewhere, maybe explore why and how their requests can be fulfilled.

AND FINALLY… Don’t take it personally if you just don’t click with a patient
I want to know that my neurologist is on the same page as me and has the same approach to my healthcare that I do. We’re in this together for the foreseeable future so I want to feel like we’re headed in the same direction. Sometimes there’s just a clash. Don’t take it personally. Life would be boring if we all thought the same, right?


Trishna Bharadia is a multi-award winning advocate for people with multiple sclerosis and chronic illness. Diagnosed with RRMS in 2008, aged 28, she’s used her experiences to raise awareness and improve support for people affected by MS and other chronic illnesses. A full-time Spanish-English translator, in her spare time she collaborates with organisations in the UK and abroad, including charities, pharmaceutical firms and nonprofits, to help improve patient experience and engagement. She’s a writer, blogger, vlogger and inspirational/expert patient speaker, as well as advising on projects, research proposals, and diversity strategies, and is a regular contributor in the media for issues relating to MS, chronic illness and disability. She’s a patron/ambassador for several MS/disability charities and is currently a member of “The Ozone” virtual round table for key opinion leaders across healthcare specialties. You can follow her on Twitter @TrishnaBharadia and Facebook www.facebook.com/trishnabharadia2015