- MS Research Days
- Trials and studies
Monday, 27 December 2010
The investigators conclude: "Despite the small sample size, therapeutic trends were observed in favor of combination therapy. An adequately powered controlled trial of mycophenolate in MS appears warranted."
Remington et al. Ther Adv Neurol Disord. 2010 Jan;3(1):3-13.
I couldn't agree more with the investigators; given the current dogma concerning the autoimmune pathogenesis of MS, mycophenolate should be given a chance. The problem is that with the imminent launch of several oral therapies, will it be possible to design an affordable trial to test mycophenolate in RRMS? I suspect not!
Frohman et al. Ther Adv Neurol Disord. 2010 Jan;3(1):15-28.
Is it ethical to do under-powered studies? NO!
Should people with MS who volunteer to participate in treatment trials expect the studies to be appropriately powered? YES!
Wednesday, 22 December 2010
Motl et al. Neuropsychiatr Dis Treat. 2010 Nov 16;6:767-74.
Monday, 20 December 2010
Vollmer et al. Mult Scler. 2010 Dec 6.
* cytokines is a term immunologists use to describe the protein messages that cell send to each other to communicate; not too dissimilar to the role of hormones!
Wang et al. Cochrane Database Syst Rev. 2010 Dec 8;12:CD008386.
Jagannath et al. Cochrane Database Syst Rev. 2010 Dec 8;12:CD008422
Gunnarsson et al. Ann Neurol 2010
Amato et al. Neurology 2010;75:1794-802.
Monday, 6 December 2010
Drugs that target a specific type of retinoid acid receptor (RXR-γ) are a promising target to stimulate remyelination in the damaged central nervous system.
Click here for article by Huang and colleagues, Nature Neuroscience 2010;doi:10.1038/nn.2702
Friday, 3 December 2010
Click here for on-line access to the report
The committee of scientists, convened by the National Academies' Institute of Medicine, doubled the upper level of vitamin D that people that people between the ages of 9 and 50 can safely take in any given day from 2,000 to 4,000 IU.
Please click here to read a commentary in Science News
Wednesday, 1 December 2010
MS is a common, complex neurological disease. Although the precise aetiology of MS is not yet known numerous studies indicate that both genetic and environmental factors are important. It now appears that the environment acts long before MS becomes clinically evident and suggests the existence of a prodromal phase for the disease. The possibility of a prodrome indicates a window of opportunity to potentially reverse early disease processes before clinical disease becomes evident. Studying a prodrome requires techniques other than clinical observation such as monitoring "endophenotypes" that result from associated risk factors. Identifying and studying individuals, for example family members of people with MS, with a high risk of developing the disease provides a powerful opportunity to understand the MS causal cascade and is highly relevant to strategies that are aimed at preventing this debilitating disease.
We are therefore recruiting people with MS who have brothers and/or sisters without MS, and people with MS who are twins (identical and non-identical) to explore the possible cause of MS. Twins will help us understand the cause of disease and the influence of early environmental exposures; identical twins have the same genetic background and twins in general share the same early environment, which can be different when looking at non twins and unrelated individuals.
If you can help please click here for more details
Saturday, 16 October 2010
Monday, 4 October 2010
Critics have poopooed this observation as the study was single-blinded and liable to unblinding; i.e. only the evaluating neurologist is blinded to what the study subject received in the study. Due to infusion reactions from Alemtuzumab it is not possible to do double-blinded studies with the agent; i.e. studies in which the evaluating neurologist and study subjects do no know what they have received.
In an additional analysis of the phase 2 trial data it appears that the participants with no clinical disease activity immediately before treatment, or any clinical or radiological disease activity during the study trial, were noted to improve after Alemtuzumab but not following interferon β treatment. This would suggest that disability improvement after Alemtuzumab may not simply be due to its anti-inflammatory effects.
This statement is subject to the same criticisms levelled at the whole study; but despite these criticisms this would be the first treatment in MS to offer such a benefit. No wonder PwMS are so excited about the prospect of receiving this therapy.
Preliminary experiments hint that Alemtuzumab stimulates white blood cells to produce growth factors that promote survival of nerve cells and enhanced oligodendrocyte (cells that produce myelin) function. This data will need to be replicated and shown to be relevant in patients treated with Alemtuzumab.
The implications of this research for PwMS cannot be overemphasised; at last a possible treatment with the potential to promote recovery.
Jones et al Brain. 2010 Aug;133(Pt 8):2232-47. Epub 2010 Jul 21.
Friday, 24 September 2010
In my opinion, long-term safety data can only be obtained from post-marketing surveillance studies and the extension study of the pivotal clinical trial. Unfortunately, there are probably not enough patients in the latter study to answer this question. It is a good thing that the drug is licensed in Russia and Australia.
Click here for press release from Merck-Serono
Click here for Bloomberg's press release
Click here for the abstract of the CLARITY study
Wednesday, 22 September 2010
Click here for Bloomberg's Statement
To see how the drug works please see the following YouTube video:
Click here for YouTube video on Fingolimod's mechanism of action
Wednesday, 8 September 2010
1. We have yet to optimise disease-modifying therapies. Is expecting a cure too much?
2. What about restorative therapies?
3. Symptomatic MS therapies are dismal; too many side effects and limited or suboptimal efficacy.
4. What about prevention? Preventative strategies are just beginning to emerge as potential option.
Without investment in research how are we going to address these needs?
You may find Vince Cable's speech interesting.
Click here for his speech
Sunday, 5 September 2010
The current dogma: inflammation in MS is mediated by either T-helper one (Th1) or T-helper 17 (Th17) cells. In comparison, allergies are due to a T-helper two (Th2) immune response, which may be protective in MS.
A large analysis of all published studies on allergic disease and MS provides no evidence of a positive or negative association between the allergic diseases asthma , allergic rhinitis and eczema.
Implications: this analysis challenges the current dogma and also raises questions about the treatment strategy of trying to stimulate Th2 immunity in PwMS; e.g. by promoting parasitic infections of the gut.
Click here for abstract: Monteiro et al. Acta Neurol Scand. 2010 Apr 29 (Epub ahead of print)
Thursday, 2 September 2010
A study in 80 PwMS was performed to evaluate the effect of 8 weeks of treatment with LDN (4.5mg taken at night). Although LDN was associated with significant improvement in some mental health quality of life measures, the trial was too small to draw definitive conclusions.
Interpretation: this study was too small to be definitive. However, it provides further support for a large definitive study of LDN in MS. Unfortunately, the current "Big Pharma" business model does not support investigating drugs that are off patent. May be "Big Pharma" will now try and develop a follow-on me-to drug to test in PwMS.
Cree et al. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. 2010 Aug;68(2):145-50.
Click here to read article
Click here to read article
Tuesday, 24 August 2010
Click here for article
Please see the following press releases on the significance of this work:
1. The Guardian
2. The Metro
Sunday, 15 August 2010
Twin studies were first proposed over a century ago to separate the relative contributions of nature (genes) and nurture (the environment) in determining a trait/disease. Higher concordance (where both twin pairs are affected) rates between genetically identical (monozygotic, MZ) twins versus non identical (dizygotic, DZ) twins provides evidence for genetic factors determining a disease. In MS, about 30% of MZ twins are concordant as compared to about 5% of DZ twins. More MZ twins being concordant as compared to DZ, suggests that genes are involved in MS, but the fact that MZ twins are not 100% concordant means that the environment also plays a role in the cause of MS.
However, given that the average adult has billions of cells and that when DNA is copied between these cells errors can arise, differences in the DNA sequence of MZ twins have been reported. Furthermore, a relatively new field of genetics, called epigenetics, which refers to modifications of DNA that regulate the function of the genome, has also been shown to differ between MZ twins. MZ twins discordant for a disease could actually therefore be explained by genetic or epigenetic differences between twins, but until recently this has not been examined in detail.
Baranzini and colleagues sequenced the genome and epigenome from one pair of MZ twins discordant for MS (http://www.nature.com/nature/journal/v464/n7293/full/nature08990.html). Given that the sequence of the first human genome that was released in 2000 represented 15 years of work and $3 billion. This work represents the future of genetic research as technology has vastly improved meaning that a whole genome can be sequenced in 1 week for $10,000.
So what was found? Comparison of the entire genome and some regions of the epigenome did not find any reproducible difference in DNA sequence between twins, suggesting that as previously thought, the environment plays the most significant role in determining twin concordance for MS.
However, genetic and epigenetic differences between twins are not completely ruled out by this study. Whilst the paper represents a huge effort, there are a number of limitations including the fact that only 3% of the epigenome was investigated. The epidemiology of MS (e.g. more females being affected) implies that epigenetics will be important in the cause of the disease and more work is needed to work out which factors are involved.
Watch this space.
Tuesday, 10 August 2010
Monday, 9 August 2010
As it is difficult to get enough vitamin D from diet alone, many are recommending vitamin D supplementation (vitamin D3), and some are pushing for the fortification of foods.
It’s a half-hour show and good food for thought, so have a listen here: http://www.bbc.co.uk/iplayer/episode/b00t66nr/Food_Programme_01_08_2010/
Monday, 26 July 2010
"The potential of stem cell therapies for neurological conditions has been over-hyped by both the basic scientists involved and the media. This is great pity as it raises false expectations of a breakthrough for vulnerable people with disabling conditions.
At present the research is a long way from reaching the clinic with some early exploratory safety studies underway in the UK and elsewhere. The science suggests that mesenchymal stem cells, i.e. those derived from skin, and bone-marrow derived stem cells may work as immunomodulatory therapies rather than as a neuro-restorative therapies; this means that they will be of benefit early in the course of the disease to modify the clinical course. They will not help people who are already disabled.
Embryonic stem cells, which are derived from foetal tissue, are unlikely to be used in humans as they have a propensity to cause primitive tumours because of their ability to differentiate in numerous cell types; there are several reports of this occurring already. In my opinion, routine storage of cord blood cells should therefore be done for altruistic reasons to support research. To do it specifically for an unproven therapy or a potential therapy in the future cannot be recommended at this stage."
Wang et al. Lancet. 2010 Jul 17;376(9736):148-9.
Tuesday, 22 June 2010
What are the implications of these findings for people with MS?
Clearly we need to wait for other studies in this area to clarify the discrepency in the results of these studies. From a clinical perspective we continue to advise against undergoing any interventional therapy until there is clarity on whether or not CCSVI is a real entity or not.
Please click here for an abstract on the study
Click here for press release
The signficance of this license cannot be under estimated; particularly as the registration study will probably set a precedent for how spasticity studies are done in the future. The Ashworth Scale has had its day and is seriously flawed as an outcome measure. This result can also be viewed as a victory for patient-related outcome measures or PROMS.
Wednesday, 12 May 2010
Friday, 30 April 2010
Staples et al. Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis. BMJ 2010;340:c1640.
Sunday, 25 April 2010
Sunday, 18 April 2010
J. William Lindsey, Landon M. Hatfield, Houston, TX
The cellular immune response against EBV is similar in PwMS and controls; with no evidence of cross-reactivity between EBV and brain antigens.
[S31.003] Evaluation of the Incidence of Anti-JCV Antibodies in a Cohort of Natalizumab-Treated MS Patients
Leonid Gorelik, Sarah Bixler, Michaela Lerner, Ewa Wilson, Anne Cheung, Ling Ling Chen, Melissa Berman, Mary Crossman, Ken Simon, Brian Schlain, Susan Goelz, Meena Subramanyam, Cambridge, MA
Classification of MS patients as sero-negative or sero-positive with respect to previous JC virus exposure is possible with a new assay. Thirteen out of 13 patients who developed PML all had evidence of prior infection with JCV, as measured by the presence of anti-JCV antibodies. This assay will help stratify patients into high and low risk groups and modify the risk for individual subjects; those with positive antibodies will have double the risk of getting PML (this is based on the observation that ~54% of subjects in the original natalizumab trial were sero-positive. The corollary to this is that subjects seronegative have a very low risk of getting the disease.
[P05.047] The Kinetics of CSF Lymphocyte Recovery after Cessation of Natalizumab in Patients with Multiple Sclerosis
Adil Javed, Chicago, IL, Howard Rossman, Farmington Hills, MI, Anthony Reder, Chicago, IL
After stopping natalizumab treatment CSF lymphocytes counts may recover within 3 months. This implies that immune surveillance is restored shortly after cessation of natalizumab therapy and coincides with observation that IRIS in the setting of natalizumab-associated PML also occurs at this time-point unless hastened by plasma exchange.
[S31.002] Effects of Natalizumab Treatment on the Presence of JC Virus DNA in Blood or Urine in Multiple Sclerosis Patients
Richard Rudick, Solon, OH, Paul O'Connor, Toronto, ON, Canada, Chris Polman, Amsterdam, The Netherlands, Andrew Goodman, Rochester, NY, Soma S. Ray, Stephanie Jurgensen, Cambridge, MA, Susan Goelz, Portland, OR, Fiona Forrestal, Maidenhead, Berkshire, United Kingdom, Leonid Gorelik, Alfred Sandrock, Cambridge, MA
Cross-sectional and longitudinal testing in a large cohort of MS patients demonstrates that there is no substantial change in the presence of JCV DNA in the plasma, whole blood or urine with natalizumab treatment. Less than 1% (4 out of 1397) patients had JCV DNA in their blood, which did not predict the occurrence of PML. In addition, in cases that developed PML plasma samples were negative prior to diagnosis. This study and other recent studies seriously calls into question the validity of the results of other smaller studies suggesting that natalizumab increases peripheral blood and urine JCV detection rates. From a practical perspective we cannot use plasma, peripheral blood or urine JCV DNA detection to predict PML risk in natalizumab-treated patients. Will this study end the debate? Please watch this space.
[P05.036] Long-Term Follow-Up of Immune Thrombocytopenia after Treatment of Multiple Sclerosis Patients with Alemtuzumab in CAMMS223
Edward Fox, Round Rock, TX, N. A. on Behalf of the CAMMS223 Study Group
Cutaneous symptoms of ITP went unrecognized in the 1st case until onset of a fatal cerebral haemorrhage. Five other cases were subsequently diagnosed with ITP with onset between 1.5 and 16 months after alemtuzumab. In one case ITP resolved without treatment. In 2 cases, remission was achieved with corticosteroid treatment alone and in the other 2 patients following treatment with rituximab cycle. On balance these results suggest that ITP is a manageable side effect of alemtuzumab provided it is detected and treated early.
[P04.213] Alemtuzumab Reduces Disease Progression in RRMS: Long-Term Results of the CAMMS223 Trial
Omar Khan, Detroit, MI, N. A. on Behalf of the CAMMS223 Study Group
At year 4: (1) 77% of alemtuzumab-treated patients were relapse–free compared to 49% of IFNB-1a-treated patients; (2) 91% of alemtuzumab-treated patients were disease progression free vs. 68% of IFNB-1a patients (p<0.001); (3) 71% of alemtuzumab patients were clinically disease-free v. 35% for IFNB-1a at year 4 (p<0.001). A treatment effect at year 4 in patients who only completed 2 annual cycles of alemtuzumab during the first 12 months supports the strategy of aggressive induction therapy in early MS. No wonder PwMS want this drug.
Wednesday, 14 April 2010
Brennan R, et al. Strains of Epstein-Barr virus infecting multiple sclerosis patients. Mult Scler. 2010 Mar 29. [Epub ahead of print]
Opinion: a deeper look is required before abandoning the possibility that a specific strain may cause the disease. The million dollar question is how and where to look?
Tuesday, 13 April 2010
"I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone" Hippocratic Oath
Sunday, 11 April 2010
The issue of causation theory has come up recently in relation to our posts on CCSVI. If you are interested in reading more about causation and causation theory, specifically in relation to MS, I would recommend the following articles as a starter:
Giovannoni G, et al. Infectious causes of multiple sclerosis. Lancet Neurol. 2006 Oct;5(10):887-94.
Giovannoni G, Ebers G. Multiple sclerosis: the environment and causation. Curr Opin Neurol. 2007 Jun;20(3):261-8.
Saturday, 10 April 2010
Click here for: Khan et al. Ann Neurol. 2010 Mar;67(3):286-90.
These findings indicate that asymptomatic or sub-clinical nerve fibre (or axonal loss) occurs in the visual pathways in MS.
1. If these findings can be confirmed it will add credence to the claims that MS is a primary neurodegenerative disease. "I hope not."
2. This study supports the use of OCT as a method to evaluate the effectiveness of neuroprotective agents in MS; we will need to show that drugs or combinations of drugs stop or at least slow down this loss of nerve fibres to accept that they are "neuroprotective".
Click here: Talman et al. Longitudinal study of vision and retinal nerve fiber layer thickness in MS. Ann Neurol 2010; in press.
Thursday, 8 April 2010
Wednesday, 31 March 2010
Saturday, 27 March 2010
Treating spasticity in MS is a big problem; it is very common and the current drugs we use are too sedating and tend to have a negative impact on cognition, which limits their use early on in the course of the disease.
This study compares Sativex (the active ingredient in cannabis) with placebo in a 15-week study. The design of this study is interesting for two reasons: (1) it used an enrichment phase to select responders before randomising them to blinded active comparator stage of the trial; and (2) it used a numeric rating scale (NRS) as the primary outcome rather than the Ashworth scale (the traditional outcome measure in spasticity trials). In summary the change in NRS score and responder-status (defined as a greater than or equal to 30% improvement from baseline) were both significantly superior for Sativex, compared with placebo. Importantly, Sativex appears to be well tolerated in this group of patients with quite advanced MS.
It will be interesting to see if Sativex gets a license based on the results of this trial. The availability of Sativex will allow us to "spread the hope" and offer something to patients in whom our current medications are not enough to control their spasticity.
Tuesday, 23 March 2010
Among 110 North American paediatric CIS/MS subjects, every 10 ng/mL increase in the adjusted 25 hydroxyvitamin D3 level was associated with a 34% decrease in the rate of subsequent relapses.
This study adds compelling evidence in support of a role for vitamin D in reducing MS relapse rates as initially seen in smaller studies in adult MS cohorts (Wingerchuk et al, JNNP 2005; Soilu-Hänninen et al, JNNP, 2008). As vitamin D deficiency/insufficiency is endemic worldwide (Holick, NEJM, 2007), further studies of vitamin D as a treatment measure in MS are warranted.
Clifford DB, et al. Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurol. 2010 Apr;9(4):438-446.
Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010 Apr;9(4):425-437.
These developments underpin the urgent efforts to implement an appropriate risk-stratification strategy to lower the risks of developing PML for people with MS receiving Natalizumab.
Please watch this space for an update.
Human leukocyte antigen-DR15, low infant sibling exposure and multiple sclerosis: Gene-environment interaction
The cause of multiple sclerosis (MS) is not yet conclusively known but both genes and the environment are important. A region on chromosome 6, the HLA class II, exerts the single strongest genetic effect but the involvement of the environment is also inescapable and is no better illustrated than by the geographical distribution of the disease. The identity of the environmental factors involved in MS is not known unequivocally but there are a few leading candidates, namely, Epstein-Barr virus, vitamin D and smoking. It has been suggested that low sibling infant exposure (classed as having no older siblings and any younger siblings having an age difference of at least 5 years) increases MS risk (Ponsonby et al, JAMA, 2005). Genetic and environmental factors are not independent. In an intriguing study, van der Mei and colleagues observed that HLA-DRB1*15 (a form of the gene involved in MS on chromosome 6) interacted with low sibling infant exposure to increase MS risk. This result could thus be of importance in disease aetiology but requires replication. Other groups have been unable to support an effect of low infant sibling exposure on the risk of MS (Sadovnick et al, Lancet Neurol, 2005; Bager et al, Am J Epidemiol, 2006) so the gene-environment interaction uncovered by van der Mei and others may be specific to Australia; this will require confirmation.
Dr Sreeram Ramagopalan
Tuesday, 16 March 2010
Conclusion: My take on this is that we need to focus on active and preactive MS lesions; I suspect that is where the action will be. Although the score at the moment is strongly against overt CNS EBV infection being a direct factor in MS pathogenesis we need to keep an open mind to the contrary. Post-mortem tissue studies are not necessarily the best means of investigating the link between active EBV infection within the central nervous system and MS.
Thursday, 4 March 2010
Jaquiéry E, et al. Intrathecal immune responses to EBV in early MS. Eur J Immunol. 2009 Dec 16;40(3):878-887. [Click here]
Tuesday, 23 February 2010
Friday, 12 February 2010
We remain sceptical about this theory; venous outflow obstruction does not explain the epidemiology of MS and falls down short on many other observations.
The interventions required to relieve venous obstruction are not without risks. The 'blood blockage theory' remains a theory and any involvement with the theory should be via ethically approved research studies.
Wednesday, 10 February 2010
Meredith Wadman. Drug ads move online, creating a web of regulatory challenges. Nat Med 2010;16:22. or http://www.nature.com/nm/journal/v16/n1/full/nm0110-22.html
I interpret this as a show of confidence by the companies that we can overcome the PML problem; there are now 31 confirmed cases of post-marketing PML in patients with MS receiving natalizumab.
Sunday, 7 February 2010
Please send this link to as many people with multiple sclerosis that you know.
".... if you have little UVB exposure, my advice is as follows: healthy children under the age of 1 years should take 1,000 IU per day—over the age of 1, 1,000 IU per every 25 pounds of body weight per day. Well adults and adolescents should take 5,000 IU per day....."
Before starting vD supplementation at this level we would urge you to see your doctor to discuss things formally; ideally this should be done in conjunction with blood monitoring.
Saturday, 6 February 2010
What do you think?
I responded as follows:
“Yes, there are several ethical considerations that need to be taken into account in relation to placebo-controlled MS trials; this issue has been extensively debated and discussed in the literature and there are International guidelines on the conduct of placebo-controlled trials.
In the UK, ethics committees make us insert a statement in the patient information sheet stating that there are licensed therapies and that by participating in a particular study people with MS could be denying themselves active treatment. In addition, we have to reconsent study participants after each relapse and/or confirmed disease progression. In addition, contemporary placebo-controlled trials have rescue arms, which allow study subjects active treatment within a study if their disease becomes active.
It is important to recognise that despite there being licensed therapies some patients don’t want to go onto them because they are injectables; if we did all trials with an active comparator, i.e. an injectable, we would exclude these patients from participating. People with needle phobia and those that have failed injectables because of side effects make up the majority of patients volunteering for placebo-controlled trials. I suspect, however, that once oral therapies are licensed for MS it will become very difficult to recruit subjects for placebo-controlled trials.
The issue of placebo-controlled trials should also be viewed on the background of the limited efficacy of the current injectables and the fact that we still don’t have data on whether or not they impact on the long-term prognosis of the disease.
In summary, I don’t think it is unethical to do placebo-controlled trials. However, you have to do them with carefully designed trials and informed consent. People with MS are perfectly capable of making an informed decision about not taking up the option of going on to a moderately effective first-line therapy and volunteering for a placebo-controlled trial of a new agent. At the end of the day we need to be pragmatic; without clinical trials we won’t advance the field and people living with MS are very aware of this. “
Please have your say if you agree or disagree with this stance!
Monday, 1 February 2010
Please see previous posting below discussing the concerns with dalfampridine.
Sunday, 24 January 2010
Ascherio et al. Primary EBV infection and MS. Ann Neurol 2010; in press.
"In this study all EBV-negative subjects (10 out of 10) who developed MS became EBV positive before MS onset. In contrast, only 36% (10 of the 28) controls subjects who were EBV-negative became EBV-positive with follow-up. Ascherio and colleagues conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection."
Interpretation: This study is very important with regard to pinning down whether or not EBV causes MS. It ticks one of the criteria for causation; i.e. the correct temporal sequence. You need to get infected with EBV prior to MS onset.
1. If and when these agents get licensed and the conditions of licensing; i.e. a first- or second-line indication.
2. The price and more importantly the cost-effectiveness of the agents; NICE will dictate the conditions of use in the UK.
3. Level of disease activity; inactive vs. active vs. highly-active disease.
4. Perceived long-term risk; infections and possible risk of malignancy.
5. Local infrastructure to start the orals.
6. Requirements and intensity of monitoring whilst on medication.
7. Fertility issues.
8. Previous use of other disease-modifying agents.
9. Underlying medical problems.
10. Etc, etc.
It is clear from the above that the decisions about which agent to use will be personalised and will depend largely on patient choice. It is important to ensure that patients have choice and that the choice is an informed one.
2010-01-21 18:28:09.776 GMT
21 January 2010; EMA/37607/2010: Press Office
European Medicines Agency recommends additional measures to better manage risk of progressive multifocal leukoencephalopathy (PML) with Tysabri. The risk of PML increases after two years, but benefits of Tysabri continue to outweigh risks for patients with highly active relapsing-remitting multiple sclerosis.
The European Medicines Agency has finalised a review of Tysabri (natalizumab) and the risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by the JC virus. The Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that the risk of developing PML increases after two years of use of Tysabri although this risk remains low. However, the benefits of the medicine continue to outweigh its risks for patients with highly active relapsing-remitting multiple sclerosis, for whom there are few treatment options available.
Because it is important that PML is detected early, the Committee recommended that a number of measures be put in place to ensure that patients and doctors are fully aware of the risks of PML. These include:
* an update of the product information to add information about the increase in the risk of PML after two years of treatment and additional advice on how to manage patients who show signs of PML;
* forms to be signed by patients at the beginning of treatment with Tysabri, and again after two years of treatment, after in-depth discussions about the risk of PML with their doctor.
Measures to minimise the risk of PML were part of the initial marketing authorisation for Tysabri, issued in June 2006. Since then, they have been continuously updated and strengthened to increase awareness of the risk of PML.
The new measures are designed to complement the existing recommendations that patients, and their carers, partners and families should be made aware of the symptoms of PML and that patients should be closely monitored throughout treatment.
1. Tysabri, from Elan Pharma International Ltd, is used to treat relapsing-remitting multiple sclerosis in patients with high disease activity despite treatment with a beta-interferon or whose disease is severe and progressing rapidly.
2. More information about the review of Tysabri is available in a
question-and-answer document. http://www.ema.europa.eu/humandocs/PDFs/EPAR/tysabri/Tysabri_A20-29_Q&A.pdf
3. More information about Tysabri is available in the European Public Assessment Report: http://www.ema.europa.eu/humandocs/Humans/EPAR/tysabri/tysabri.htm
4. This press release, together with other information on the work of the European Medicines Agency, can be found on the Agency's website: www.ema.europa.eu
Tuesday, 5 January 2010
You can download an invitation and preliminary programme from the following link:
We look forward to seeing you on the 30th.