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MS research update - Natalizumab (Tysabri) helps with fatigue and cognition - 10 May 2012

Natalizumab (Tysabri) is a disease modifying treatment licensed for use in highly active relapsing remitting multiple sclerosis (two or more disabling relapses in one year). Studies have shown natalizumab reduces the occurrence of relapses by around two thirds and significantly reduces the rate of disease progression.

This study investigated whether treatment with natalizumab could help with fatigue and the cognitive problems experienced by 40-60% of people with MS.

Cognitive function was measured before the first infusion of natalizumab and then every 12 months. The tests included ones for memory, attention, concentration, verbal fluency and speed of information processing.

Fatigue and depression were also assessed. The aim was to identify people with fatigue that was severe enough to interfere with their daily activities and those with with mild depression.

100 people who remained on natalizumab treatment for one year and 53 who remained on treatment for two years were included in the analysis. Both groups had a significantly decreased relapse rate and EDSS score. The average score for depression had also decreased.

Before treatment 29% had cognitive problems but this had decreased to 19% after one year. Before treatment 45% of participants had levels of fatigue that interfered with daily activities. After treatment, this had decreased to 29%. The benefits continued in the second year of treatment.

This study shows that natalizumab not only decreases the number of relapses and the rate of disease progression but also improves cognitive performance and fatigue which is helpful for many activities of daily living.

Iaffaldano P, Viterbo RG, Paolicelli D, et al.
Impact of natalizumab on cognitive performances and fatigue in relapsing multiple sclerosis: a prospective, open-label, two years observational study.
PLoS One. 2012;7(4):e35843.

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Neutralising antibodies to beta interferon now less common

Beta interferon, in slightly different forms, is widely used as a disease modifying treatment in MS. It is an effective treatment but the effectiveness can be reduced over time because the body makes neutralising antibodies (known as NAbs). These are proteins produced by the body because it recognises beta interferon as a foreign protein and so mounts an immune response against it. The antibodies bind to the beta interferon and can stop it working. Not everyone makes neutralising antibodies and, in some people, they disappear after a period of time.

Many people using beta interferon are now tested for the presence of neutralising antibodies and, if antibody levels are high and symptoms are getting worse, treatment may be stopped.

This study compared the proportion of people taking beta interferon in 2003-4 who had neutralising antibodies (when testing for neutralising antibodies was rare) with the proportion in 2009-2010.

In 2003-4, 32% of those using beta interferon had neutralising antibodies. In 2009-2010, only 19% of the 1,296 people tested had neutralising antibodies. The change occurred in people on a type of beta interferon called beta interferon 1a (Avonex and Rebif) but not for those on beta interferon 1b (Betaferon). There was also a decrease in the proportion of people with a high titre (concentration) of neutralising antibodies.

The reasons behind these changes may include stricter monitoring of neutralising antibody levels leading to stopping treatment, and the manufacture of less immunogenic forms of beta interferon which the body is better able to tolerate.

Jungedal R, Lundkvist M, Engdahl E, et al.
Prevalence of anti-drug antibodies against interferon beta has decreased since routine analysis of neutralizing antibodies became clinical practice.
Mult Scler. 2012 May 2. [Epub ahead of print]

Research by topic areas...

Symptoms and symptom management

Carvalho S, Alvarenga Filho H, Papais-Alvarenga R, et al.
Is it useful to perform carbon monoxide diffusion capacity and respiratory muscle function tests in patients with multiple sclerosis without disability?
Respirology. 2012 May 7. doi: 10.1111/j.1440-1843.2012.02191.x. [Epub ahead of print]

Laplaud D, Bodiguel E, Bensa C, et al.
Recommendations for the management of multiple sclerosis relapses.
Rev Neurol (Paris). 2012 May 1. [Epub ahead of print]

Disease modifying treatments

Jensen PE, Sellebjerg F, Søndergaard HB, et al.
Correlation between anti-interferon-β binding and neutralizing antibodies in interferon-β-treated multiple sclerosis patients.
Eur J Neurol. 2012 May 5. doi: 10.1111/j.1468-1331.2012.03721.x. [Epub ahead of print]

Drugs in development

Pasternak B, Svanström H, Nielsen NM, et al.
Use of amiloride and multiple sclerosis: registry-based cohort studies.
Pharmacoepidemiol Drug Saf. 2012 May 3. doi: 10.1002/pds.3269. [Epub ahead of print]

Other treatments

Jamshidian A, Gharagozloo M.
Can plasma exchange therapy induce regulatory T lymphocytes in multiple sclerosis patients?
Clin Exp Immunol. 2012 Apr;168(1):75-7.

Shirzadi M, Alvestad S, Hovdal H, et al.
Comparison of carbamazepine rash in multiple sclerosis and epilepsy.
Acta Neurol Scand. 2012 Jan;125(1):60-3


Harbo Poulsen A, Stenager E, Johansen C, et al.
Mobile phones and multiple sclerosis - a nationwide cohort study in Denmark.
PLoS One. 2012;7(4):e34453.

de Sá J, Alcalde-Cabero E, Almazán-Isla J, et al.
Capture-recapture as a potentially useful procedure for assessing prevalence of multiple sclerosis: methodologic exercise using Portuguese data.
Neuroepidemiology. 2012 Apr 27;38(4):209-216. [Epub ahead of print]

Keller JJ, Liang YC, Lin HC.
Association between multiple sclerosis and erectile dysfunction: a nationwide case-control study.
J Sex Med. 2012 Apr 30. doi: 10.1111/j.1743-6109.2012.02746.x. [Epub ahead of print]

Assessment tools

Wang J, Cheng H, Hu YS, et al.
The photopic negative response of the flash electroretinogram in multiple sclerosis.
Invest Ophthalmol Vis Sci. 2012 Mar 9;53(3):1315-23.

Causes of MS

Sternberg Z.
Autonomic dysfunction: A unifying multiple sclerosis theory, linking chronic cerebrospinal venous insufficiency, vitamin D(3), and Epstein-Barr virus.
Autoimmun Rev. 2012 Apr 28. [Epub ahead of print]

Vitamin D

Shaygannejad V, Janghorbani M, Ashtari F, et al.
Effects of adjunct low-dose vitamin D on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial.
Mult Scler Int. 2012;2012:452541.

Psychological aspects

Bodling AM, Denney DR, Lynch SG.
Individual variability in speed of information processing: An index of cognitive impairment in multiple sclerosis.
Neuropsychology. 2012 May;26(3):357-67.

Physical activity

Broekmans T, Gijbels D, Eijnde BO, et al.
The relationship between upper leg muscle strength and walking capacity in persons with multiple sclerosis.
Mult Scler. 2012 May 4. [Epub ahead of print]

Heller BW, Clarke AJ, Good TR, et al.
Automated setup of functional electrical stimulation for drop foot using a novel 64 channel prototype stimulator and electrode array: Results from a gait-lab based study.
Med Eng Phys. 2012 May 3. [Epub ahead of print]

Remelius JG, Jones SL, House JD, et al.
Gait impairments in persons with multiple sclerosis across preferred and fixed walking speeds.
Arch Phys Med Rehabil. 2012 Mar 7. [Epub ahead of print]


Ciccolo JT, Lo A, Jennings EG, et al.
Rationale and design of a clinical trial investigating resistance training as an aid to smoking cessation in persons with multiple sclerosis.
Contemp Clin Trials. 2012 Apr 27. [Epub ahead of print]

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