Way Ahead 2009;13(3):2-4
- AAN Highlights
- Fingolimod and cladribine
- Alemtuzumab (Campath)
- Stem cells
- Natalizumab (Tysabri)
- Interferon beta-1a (Avonex)
- Combination therapy
- Economic impact of early mobility impairment
- British MRI expert receives major award
- Rehabilitation in MS (RIMS)
- Other research news
The 61st annual meeting of the American Academy of Neurology took place in Seattle - April 25 to May 2. This annual meeting, a showcase for the latest developments in scientific research, was attended by more than 10,000 of the world's leading researchers and neurologists. Multiple sclerosis was the subject of more than 380 presentations. A summary of the conference highlights follows.
New oral treatments for relapsing remitting MS
Fingolimod and cladribine
Data was presented on the two drugs contending to be the first oral treatment for multiple sclerosis. A one-year phase III study of the investigational oral drug fingolimod showed a significant reduction in annualised relapse rate compared with treatment with an injectable interferon beta-1a. Results of a two-year phase III study comparing cladribine against placebo indicated that cladribine significantly reduces relapse rates in people with relapsing remitting MS.
The manufacturers of these two drugs plan to submit them for licensing in 2009 and NICE has already announced that it may include fingolimod and cladribine in its next round of appraisals.
Other new, experimental treatments
Researchers announced further analysis of data from the phase II CAMS223 study which compared interferon beta-1a (Rebif) with two dose levels of alemtuzumab in early, active relapsing remitting MS. Sustained reduction in disability, defined as a decrease in EDSS of one point or more for more than six months, was twice as likely in those taking alemtuzumab as those taking interferon beta-1a. The researchers suggest that alemtuzumab may halt progression of disability and potentially reverse pre-existing neurological
impairment, but further study is needed to confirm this. A further presentation reported that the improvements seen after two annual cycles of alemtuzumab were still present 2 years after the last dose.
Stem cellsCanadian researchers reported data from 1-8 years of follow-up for 16 people with an aggressive form of MS who had received autologous stem cells (recipients receive their own stem cells) following suppression of their immune system. 6 people improved, 3 worsened and 7 remained unchanged. The degree of improvement varied widely between those treated, but was related to how long they had had MS, those who had had MS for longer took longer to show any perceived benefit.
New data for existing treatments
Natalizumab (Tysabri)The drug manufacturers presented findings of a study that demonstrated the drug may promote remyelination.
A further study suggested that the risk of developing progressive multifocal leukoencephalopathy (PML) is lower than previously thought. Following clinical trials, the risk of developing PML had been calculated as 1 in 1,000 but data from general use suggest a risk closer to 1.2 in 10,000.
MitoxantroneSafety data showed that the risk of developing leukaemia for people with multiple sclerosis who take mitoxantrone for at least a year is close to three times higher than previously thought.
Interferon beta-1a (Avonex)A ten-year follow up study showed that people treated immediately after their first episode of MS symptoms had significantly less chance of experiencing a second attack compared to those with delayed treatment.
Combination therapyTwo new studies suggested that the addition of oral methylprednisolone (MP) to standard therapy with interferon beta-1a is more effective at reducing relapses than interferon beta therapy alone.
One study showed 38% reduction of relapses in those receiving combination therapy compared with interferon beta plus placebo. A second study showed a 62% reduction in relapse rates in people with breakthrough disease who were treated with monthly cycles of MP in addition to weekly treatment with interferon beta-1a.
Economic impact of early mobility impairmentResearchers used data from a registry of more than 8,000 North Americans with MS to assess the impact of impaired mobility on employment and income. As might be expected, mobility correlated significantly with employment; furthermore even minor mobility impairment experienced at otherwise low disability level appeared to contribute to the loss of productivity and income. The greatest changes in income levels occurred when people with MS went from normal mobility to minimal mobility impairment.
British MRI expert receives major award
At the recent American Academy of Neurology (AAN) meeting in Seattle, Professor David Miller of the Institute of Neurology in London was awarded the John Dystel Prize for Multiple Sclerosis Research for his pioneering work using MRI and imaging techniques.
Professor Miller has worked in this area and published widely on MS since the early 1980s. In awarding the prize, Dr Henry McFarland, Chief of the Neuroimmunology Branch at the National Institute of Neurological Disorders and Stroke, said "Much of our understanding of MS through the use of MRI has its roots in David's laboratory." The Dystel Prize is given jointly by the AAN and the American National MS Society.
Rehabilitation in MS (RIMS) Genoa, Italy, 23-25 April 2009
Emma Greenfield, MS Specialist Physiotherapist, Bradford, West Yorkshire and Roz Richardson, Superintendant Neurophysiotherapist, West Sussex.
The 14th Annual Conference of RIMS (Rehabilitaion in Multiple Sclerosis), was recently held in Genoa, Italy. The theme for this year's conference was 'Research Challenges in Multiple Sclerosis Rehabilitation'. The MS Trust bursary winners, Emma Greenfield and Roz Edwards report on the conference.
One of the highlights of the meeting was a thought-provoking session led by Susan Bennett on difficult to treat symptoms. She explored the health professionals' approach to new information and evidence-based practice and proposed that when research does not conclusively direct clinicians in their treatment options, experience, combined with knowledge, should underpin patient management and treatment choices.
The first day concluded with a number of presentations about recent research in MS. Of particular interest was a presentation on the positive effects of a Nintendo Wii programme on balance.
The second day opened with a lively and informative lecture by Professor Alan Thompson, Director of the Institute of Neurology, London, who asked the question: "Can MRI scanning be used to predict the prognosis of a patient diagnosed with primary progressive MS?" He cited 2 extensive studies carried out over 5 and 10 years. Results of both studies indicated that, with more sophisticated scanning techniques, it may be possible to predict outcomes and improve understanding of the mechanisms of cell damage in MS. Professor Thompson concluded that further studies are needed with a specific focus on the relationship between abnormalities in grey and white matter.
To round up the conference, Irene Higginson gave an inspirational delivery of a 3-month pilot study that compared the outcomes of patients seen by a fast track palliative care team and those who were offered standard support services. Unsurprisingly, patients under the care of the fast track team fared better both physically and psychologically, but there was also a significant reduction in the cost to health and social care services as a result of fewer hospital admissions and less reliance on social services by those in the trial.
All in all, the conference provided an opportunity to hear about advancements and current research in the world of MS. We are grateful to the MS Trust for the opportunity to visit Genoa, meet other professionals with an interest in MS, and improve our awareness of the vast amounts of research underway - both towards treatments and with rehabilitation.
Other research news
New MS therapies and opportunistic infections
In recent years a number of newer therapies for the treatment of MS have shown promise. But while some of these treatments have proven more effective than the standard self-administered disease modifying drugs many of them carry the risk of much more serious side effects. A recent paper has reviewed the different opportunistic infections and other risks that are associated with some of these newer treatments, stresses the importance of clinical vigilance and careful postmarketing surveillance.
Berger JR, Houf S.
Opportunistic infections and other risks with newer multiple sclerosis therapies.
Ann Neurol 2009; 65(4): 367-377.
Benefit-risk treatment preferences
A recent study investigated the willingness of people with MS to accept life-threatening adverse event risks in exchange for improvements in their MS related health outcomes. 651 Study participants completed a survey questionnaire that asked them to choose hypothetical treatments from pairs of treatment alternatives with varying levels of clinical efficacy and associated risks. Delay in years to disability progression was the most important factor in treatment preferences. In exchange for a reduction in yearly relapse rates from 4 to 1 and an increased delay to progression from 3 to 5 years, participants were willing to accept a 0.38% annual risk of death or disability from PML, a 0.39% risk of death from liver failure, or a 0.48% annual risk of death from leukaemia.
The study highlights the willingness of people with MS to accept risks in exchange for treatments with the potential to improve the course of their MS. Evaluating the risks of treatments against the benefits is a key factor in the decisions that are made in relation to drug treatment in MS.
Johnson FR, Van Houtven G, Ozedmir S et al.
Multiple sclerosis patients' benefit-risk preferences: serious adverse event risk versus treatment efficacy.
J Neurol 2009; 256(4): 554-562.
Identifying and managing breakthrough disease in MS
Breakthrough disease is commonly seen in people with MS despite treatment with disease modifying drug therapy. Yet there is currently no consensus or proven strategy for identifying and managing people who present with breakthrough disease. A review recently published in the Lancet Neurology assesses the current evidence and proposes a number of monitoring strategies including regular follow-up visits planned in advance, regular assessment of compliance with treatment, discussion and management of adverse events, and monitoring of relapses, disability, and MRI measures. The article also highlights opportunities for future research associated with managing patients with MS receiving disease modifying drugs.
Rudick RA, Polman CH.
Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis.
Lancet Neurol 2009; 8: 545-559.
Qualitative data important in determining patient satisfaction
Last year, the MS Trust and Royal College of Physicians conducted an audit of services for people with MS. As part of the audit the MS Trust surveyed 1,300 people with MS. The survey questions were based on guidelines for managing the condition issued by the National Institute for Health and Clinical Excellence (NICE). At the end of each question a free text box allowed people to add additional information or further explanation relating to the question or answer.
The audit revealed inconsistency in individuals' responses to different types of questions. A subsequent study has therefore analysed the qualitative data gathered as part of the audit to investigate the disparity between the global expressions of satisfaction and the negative, and at times heart wrenching, free text comments made. 336 people with MS who completed the study had made free text comments. This qualitative data was analysed using content analysis by grouping content into positive and negative comments and then into more detailed categories and sub-categories. It was found that people with MS who gave conflicting reports of satisfaction with services were more likely to give negative comments regarding the provision of service rather than the quality of service. This study indicates that simple, single questions on satisfaction with services do not offer a valid measure of patient experience whilst highlighting the value of qualitative research in the area of patient satisfaction.
Jones D, Turner M, Singleton C, et al.
A study analysing inconsistent responses from people with multiple sclerosis in a recent national audit.
Disabil Rehabil 2009; May 21:1-9.