The MS Trust runs a regular search for interesting and relevant research articles relating to multiple sclerosis using Medline, a specialised search engine for medical journals. The original abstracts to each of the articles can be accessed via the links provided.

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MS research update - Can ocrelizumab slow down disability in primary progressive MS - 30 January 2017

Summary

Ocrelizumab is an experimental new treatment which reduces the number of B cells, a type of white blood cell, or lymphocyte thought to be involved in the abnormal immune response that attacks the myelin coating of nerve cells. This study was designed to test whether ocrelizumab could prevent an increase in disability in people with primary progressive MS.

732 people with primary progressive MS took either ocrelizumab or placebo as an iv infusion (drip) every 6 months for at least 2 years.

Fewer people taking ocrelizumab had increased disability, compared to those taking placebo. Comparing the two groups, people taking ocrelizumab were 24% less likely to have an increase in their disability than those taking placebo.

Infusion-related reactions, chest infections and oral herpes were more frequent in the ocrelizumab group. Neoplasms (abnormal growth of tissues which can be benign or malignant) developed in 2.3% of those taking ocrelizumab, which included 4 cases of breast cancer. compared with 0.8% of the placebo group.

The results suggest that ocrelizumab could slow down the progression of MS. The increased number of neoplasms in the ocrelizumab group will need to be monitored closely.

Ocrelizumab is also being developed as a treatment for relapsing remitting MS. Data published in a second paper reported that ocrelizumab reduced the number of relapses by 50% compared to beta interferon.


Background

Promising topline results from the primary progressive MS clinical trial for ocrelizumab have been reported by the manufacturer and at scientific meetings. Full details of the study have now been published.

How this study was carried out

732 people with primary progressive MS with EDSS of 3 to 6.5 were recruited. Participants took ocrelizumab or placebo by intravenous infusion (drip) every 6 months, consisting of two infusions 14 days apart.

The main aim of the study was to see if ocrelizumab could prevent an increase in disability score, in other words, maintain the current level of disability. This was measured by the number of participants with an increased EDSS which was still evident 3 months later. The study also recorded the number of participants with an increased EDSS still evident 6 months later, walking speed over 25 feet and volume of brain and lesions.

What was found

Fewer people taking ocrelizumab had an increase in disability, compared to placebo. An increase in disability which lasted 12 weeks was seen in 32.9% of those taking ocrelizumab and 39.3% of those taking placebo. In addition, increased disability which lasted at least 24 weeks was seen in 29.6% taking ocrelizumab and 35.7% taking placebo. Comparing the two groups, people taking ocrelizumab were 24% less likely to have an increase in their disability than those taking placebo.

After 120 weeks of treatment, walking speed over 25 feet was 39% slower for ocrelizumab compared to 55% slower for placebo. Brain lesion volume decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo. Loss of brain volume was 0.9% for ocrelizumab and 1.09% for placebo.

Infusion-related reactions, chest infections and oral herpes were more frequent in the ocrelizumab group. Neoplasms, an abnormal growth of tissues which can be benign or malignant, developed in 2.3% of those taking ocrelizumab (which included 4 cases of breast cancer) versus 0.8% of the placebo group.

What does it mean?

The study found that, compared to placebo, fewer people taking ocrelizumab experienced an increase in their disability. In other words, the study showed that ocrelizumab was more effective at maintaining the current level of disability. The increased number of neoplasms in the ocrelizumab group will need to be monitored closely.

Ocrelizumab is also being developed as a treatment for relapsing remitting MS. In the same issue of the New England Journal of Medicine, investigators reported that ocrelizumab reduced the number of relapses by 50% compared to beta interferon.

Montalban X, et al.
Ocrelizumab versus placebo in primary progressive multiple sclerosis.
New England Journal of Medicine 2017; 376: 209-220.
Abstract 

Hauser SL, et al.
Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis.
New England Journal of Medicine 2017; 376: 221-234.
Abstract 

Calabresi PA.
B-cell depletion - a frontier in monoclonal antibodies for multiple sclerosis.
New England Journal of Medicine 2017; 376: 280-282.
Abstract 

More about ocrelizumab and other drugs in development for progressive MS

Ocrelizumab is an experimental drug treatment which is being tested in relapsing remitting and primary progressive MS. It reduces the number of B cells, a type of white blood cell, or lymphocyte, which is thought to be involved in the abnormal immune response that attacks the myelin insulation covering nerve cells. Ocrelizumab is taken as an intravenous infusion every 6 months, consisting of two infusions 14 days apart.

Ocrelizumab has previously been investigated as a treatment for rheumatoid arthritis but studies were discontinued because of a high incidence of opportunistic infections in participants. Opportunistic infections are infections that do not normally occur in a healthy person but may occur when the immune system is compromised.

Ocrelizumab is currently being assessed for European drug licensing and will then be appraised for cost and effectiveness as an NHS treatment. If these steps are successful, the drug could be available on the NHS by 2018 at the earliest.

Information about ocrelizumab, high-dose biotin, siponimod and other drugs being investigated as treatments for progressive MS can be found through our Drugs in Development webpage.


Research by topic areas...

Causes of MS

Xia Z, Steele SU, Bakshi A, et al.
Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members.
JAMA Neurol. 2017 Jan 17. [Epub ahead of print]
abstract

Backhaus I, Mannocci A, Lemmens PH, et al.
Smoking as a risk factor for developing Multiple Sclerosis: A meta-analysis of observational studies.
Clin Ter. 2016 May-Jun;167(3):82-92.
abstract

Disease modifying drugs

van Kempen ZL, Leurs CE, Vennegoor A, et al.
Natalizumab-associated progressive multifocal leukoencephalopathy is not preceded by elevated drug concentrations.
Mult Scler. 2016 Dec 1:1352458516684023. [Epub ahead of print]
abstract
Read the full text of this paper

Reen GK, Silber E, Langdon DW.
Interventions to support risk and benefit understanding of disease-modifying drugs in Multiple Sclerosis patients: A systematic review.
Patient Educ Couns. 2016 Dec 28. pii: S0738-3991(16)30581-X. [Epub ahead of print]
abstract

Bonnan M, Marasescu R, Demasles S, et al.
No evidence of disease activity (NEDA) in MS should include CSF biology - Towards a 'Disease-Free Status Score'.
Mult Scler Relat Disord. 2017 Jan;11:51-55.
abstract

Willis M, Pearson O, Illes Z, et al.
An observational study of alemtuzumab following fingolimod for multiple sclerosis.
Neurol Neuroimmunol Neuroinflamm. 2017 Jan 10;4(2):e320.
abstract
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García-Ruiz AJ, Izquierdo-Ayuso G, Navarro-Mascarell G, et al.
Efficacy of the Treatments Used in Multiple Sclerosis: From Meta-analysis to Number Needed to Treat.
Clin Neuropharmacol. 2017 Jan/Feb;40(1):37-42.
abstract

Drugs in development

Liu Y, Vollmer T, Havrdova E, et al.
Impact of daclizumab versus interferon beta-1a on patient-reported outcomes in relapsing-remitting multiple sclerosis.
Mult Scler Relat Disord. 2017 Jan;11:18-24.
abstract
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Zeydan B, Rodriguez M, Kantarci OH.
Timing of Future Remyelination Therapies and Their Potential to Stop Multiple Sclerosis Progression.
Adv Exp Med Biol. 2017;958:161-170.
abstract

Other treatments

Miller E, Kostka J, Włodarczyk T, et al.
Whole-body cryostimulation (cryotherapy) provides benefits for fatigue and functional status in multiple sclerosis patients. A case-control study.
Acta Neurol Scand. 2016 Dec;134(6):420-426.
abstract

Physical activity

Sandroff BM, Motl RW, DeLuca J.
The Influence of Cognitive Impairment on the Fitness-Cognition Relationship in MS.
Med Sci Sports Exerc. 2017 Jan 23. [Epub ahead of print]
abstract

Karpatkin HI, Cohen ET, Klein S, et al.
The Effect of Maximal Strength Training on Strength, Walking, and Balance in People with Multiple Sclerosis: A Pilot Study.
Mult Scler Int. 2016;2016:5235971.
abstract
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Dixon-Ibarra A, Nery-Hurwit M, Driver S, et al.
Using health promotion guidelines for persons with disabilities to develop and evaluate a physical activity program for individuals with multiple sclerosis: A feasibility study.
Eval Program Plann. 2016 Dec 13;61:150-159. [Epub ahead of print]
abstract

Straudi S, Basaglia N.
Neuroplasticity-Based Technologies and Interventions for Restoring Motor Functions in Multiple Sclerosis.
Adv Exp Med Biol. 2017;958:171-185.
abstract

Prognosis

D'hooghe MB, Haentjens P, Van Remoortel A, et al.
Self-reported levels of education and disability progression in multiple sclerosis.
Acta Neurol Scand. 2016 Dec;134(6):414-419.
abstract

Psychological aspects

Fragoso YD, Going LC, Lourido AM, et al.
Aggressive Traits in People with Multiple Sclerosis-A Case-Control Study.
Arch Clin Neuropsychol. 2017 Feb;32(1):94-97.
abstract

Wilski M, Tasiemski T.
Meaning of Self in Multiple Sclerosis: Implications for Treatment and Rehabilitation.
Adv Exp Med Biol. 2017;958:43-55.
abstract

Jongen PJ, Heerings M, Ruimschotel R, et al.
Intensive social cognitive treatment (can do treatment) with participation of support partners in persons with relapsing remitting multiple sclerosis: observation of improved self-efficacy, quality of life, anxiety and depression 1 year later.
BMC Res Notes. 2016 Jul 29;9:375.
abstract
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Razazian N, Yavari Z, Farnia V, et al.
Exercising Impacts on Fatigue, Depression, and Paresthesia in Female Patients with Multiple Sclerosis.
Med Sci Sports Exerc. 2016 May;48(5):796-803.
abstract

Symptoms and symptom management

Korsen M, Kunz R, Schminke U, et al.
Dalfampridine effects on cognition, fatigue, and dexterity.
Brain Behav. 2016 Nov 11;7(1):e00559.
abstract
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Shamout S, Biardeau X, Corcos J, et al.
Outcome comparison of different approaches to self-intermittent catheterization in neurogenic patients: a systematic review.
Spinal Cord. 2017 Jan 24. [Epub ahead of print]
abstract

Campbell J, Langdon D, Cercignani M, et al.
A Randomised Controlled Trial of Efficacy of Cognitive Rehabilitation in Multiple Sclerosis: A Cognitive, Behavioural, and MRI Study.
Neural Plast. 2016;2016:4292585.
abstract
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Uecker FC, Olze H, Kunte H, et al.
Longitudinal Testing of Olfactory and Gustatory Function in Patients with Multiple Sclerosis.
PLoS One. 2017 Jan 20;12(1):e0170492.
abstract
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Patel VP, Walker LA, Feinstein A.
Processing speed and distractibility in multiple sclerosis: the role of sleep.
Mult Scler Relat Disord. 2017 Jan;11:40-42.
abstract

Morrow SA, Rosehart H, Johnson AM.
The effect of Fampridine-SR on cognitive fatigue in a randomized double-blind crossover trial in patients with MS.
Mult Scler Relat Disord. 2017 Jan;11:4-9.
abstract

Hughes AJ, Parmenter BA, Haselkorn JK, et al.
Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis.
J Sleep Res. 2017 Jan 17. [Epub ahead of print]
abstract

Simpson S Jr, Tan H, Otahal P, et al.
Anxiety, depression and fatigue at 5-year review following CNS demyelination.
Acta Neurol Scand. 2016 Dec;134(6):403-413.
abstract

Mückschel M, Beste C, Ziemssen T.
Immunomodulatory treatments and cognition in MS.
Acta Neurol Scand. 2016 Sep;134 Suppl 200:55-9.
abstract
Read the full text of this paper

Brenner P, Piehl F.
Fatigue and depression in multiple sclerosis: pharmacological and non-pharmacological interventions.
Acta Neurol Scand. 2016 Sep;134 Suppl 200:47-54.
abstract
Read the full text of this paper

Penner IK.
Evaluation of cognition and fatigue in multiple sclerosis: daily practice and future directions.
Acta Neurol Scand. 2016 Sep;134 Suppl 200:19-23.
abstract
Read the full text of this paper

Portaccio E.
Differential diagnosis, discerning depression from cognition.
Acta Neurol Scand. 2016 Sep;134 Suppl 200:14-8.
abstract
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Hämäläinen P, Rosti-Otajärvi E.
Cognitive impairment in MS: rehabilitation approaches.
Acta Neurol Scand. 2016 Sep;134 Suppl 200:8-13.
abstract
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Vitamin D

Ashtari F, Toghianifar N, Zarkesh-Esfahani SH, et al.
High dose Vitamin D intake and quality of life in relapsing-remitting multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial.
Neurol Res. 2016 Oct;38(10):888-92.
abstract