You are here:

MS research update - Can people with MS be disease free in the long term? - 5 January 2015

Summary

With the introduction of new, more effective drugs for relapsing remitting multiple sclerosis (RRMS), a new treatment goal is emerging. No evidence of disease activity (NEDA), also referred to as freedom from disease activity, represents a high level of treatment effectiveness, as it suggests that the treatment has resulted in a complete remission of MS. However it is not currently known what proportion of patients with MS can be expected to have NEDA over time, this study aimed to follow 219 people with RRMS over a period of seven years to investigate their disease activity.

The participants were assessed with yearly MRI scans and clinical visits every six months at which relapses and EDSS scores were evaluated. NEDA was defined as no relapses, no sustained increase in EDSS score, and no new or enlarging lesions on annual MRI scans.

The study found that after one year 46% of participants had NEDA but at seven years only 8% of participants were NEDA. However it was also found that those participants who showed NEDA at the two year point, had less disability at the seven year point.

The researchers conclude that the ability of NEDA to predict future disability levels needs to be investigated further and NEDA could also be used to evaluate the effectiveness of new MS drugs in trials.

Background

With the introduction of new, more effective drugs for relapsing remitting multiple sclerosis (RRMS), a shift in what to expect from treatment is beginning to develop, from one of partial response, such as reducing the number of relapses, to one of potential remission. A new treatment goal, no evidence of disease activity (NEDA), also referred to as freedom from disease activity, is the aspiration. It represents a high level of treatment effectiveness, as it suggests that the treatment has resulted in a complete remission of the disease. However it is not currently known what proportion of patients with MS can be expected to have NEDA over time and whether disease activity is more often observed as clinical symptoms or lesions on brain scans that may not necessarily result in symptoms. This study aimed to follow a group of people with RRMS over a period of seven years to investigate their disease activity.

How this study was carried out

219 people who had been diagnosed with clinically isolated syndrome (CIS) or RRMS were included in this study. All were aged between 18 and 65 years old, 174 (80%) were female and at the start of the study the average age of participants was 40 years old. The participants were a mixed group, some took no treatments and some were taking a disease modifying therapy, but not for the whole study period. This study looked at a 'real world' situation, so was looking at what happened to the participants over a period and so was not looking at what happened as a result of treatment with a particular drug.

The participants had been assessed over a period of seven years, with yearly MRI scans and clinical visits every six months at which relapses and EDSS scores were evaluated. The researchers used clinical observations and MRI scans to assess if the participants had any evidence of disease activity.

A relapse was defined as the appearance of new symptoms that lasted more than 24 hours were not caused by infection. Progression was defined as an increase of 1 or more in EDSS score that was still apparent at a subsequent assessment. New MRI scan activity was defined as new or enlarging lesions or gadolinium-enhanced lesions visible on a brain or spinal cord MRI.

The authors defined NEDA as no relapses, no sustained increase in EDSS score, and no new or enlarging lesions on annual MRI.

What was found

The study found that after one year 46% of participants met the criteria for NEDA, 27.5% of participants were still NEDA at two years and only 8% of participants were NEDA after seven years.

Participants were most likely to show disease activity by having a new lesion being visible on an MRI scan, followed by having a relapse. Increases in EDSS score (indicating disease progression) were the least likely to happen, 57% of participants had no evidence of progression after seven years. The study also found that those participants who showed NEDA at the two year point, had less disability at the seven year point.

What does it mean?

The study shows that remaining completely free of disease activity over a long term period is unlikely. However it showed that NEDA status at two years could potentially be used to give a prognosis, as those who were disease free at two years had less disability after seven years. The authors suggest that as the goal of drug therapy in MS is to treat people to prevent disability, it seems logical that treating so there is no evidence of disease activity either clinically or on MRI scans, could be a treatment goal. They conclude that the ability of NEDA to predict future disability levels needs to be investigated further and it could be used to evaluate the effectiveness of new MS drugs in trials.

Rotstein DL, Healy BC, Malik MT , et al.
Evaluation of No Evidence of Disease Activity in a 7-Year Longitudinal Multiple Sclerosis Cohort..
JAMA Neurol. 2014 Dec 22. [Epub ahead of print]
abstract

More about no evidence of disease activity (NEDA)

In the past, disease modifying treatments for relapsing remitting MS (RRMS), including the beta interferons and glatiramer acetate, have been evaluated on their ability to reduce relapses. On average these drugs reduce relapses by around one third.

With the introduction of new, more effective drugs, there has been a shift in treatment expectations from one of partial response to one of potential remission. The concept of being 'disease free' has been used for several conditions previously, including cancer and rheumatoid arthritis. With rheumatoid arthritis the aim is to now treat people as soon as possible after diagnosis to prevent a build-up of symptoms, rapidly switching to more effective drugs if there is no response to first line treatments. Increasingly, neurologists are advocating a similarly active approach soon after diagnosis of RRMS.

In MS, no evidence of disease activity is defined by a combination of:

  • absence of relapses
  • absence of increased disability which lasts more than three months
  • absence of MRI evidence of MS activity

The concept of NEDA is still evolving and there is debate over additional measures that could or should be included, such as loss of brain volume, which would indicate loss of nerves . As understanding of what causes MS and the underlying causes of the symptoms experienced increases over time, other measures may be added to monitor the effect treatment has on these.

Professor Gavin Giovannoni, a neurologist at Barts and the London School of Medicine and Dentistry, has written and talked extensively on NEDA. At the MS Trust conference in 2013, he likened MS to an iceberg: there could be lots of disease activity occurring early on and 'beneath the surface', as lesions can occur in the brain and spinal cord, which do not result in symptoms. He suggests adopting an aggressive approach to treating MS early could mean people with RRMS could do better when compared to people who have had less active treatment, resulting in less symptoms and less build-up of disability. You can read more of Prof Giovannoni's thoughts on NEDA on his blog, for example in this post about approaches to treatment and this post comparing the current and potential treatment approaches.

Currently the concept of NEDA is still in its infancy and there are many questions still to be answered, including could an earlier and more active approach to treatment prevent the onset of symptoms and could freedom from disease activity delay or even prevent transition to secondary progressive MS?

It is early days and more research is needed to determine the long-term significance of freedom from disease activity for people with MS but we will provide future updates when there is more to report.

Research by topic areas...

Assessment tools

Raggi A, Covelli V, Leonardi M, et al.
Determinants of disability using count-based approaches to icf-based definition of neurological disability.
NeuroRehabilitation. 2014 Dec 29. [Epub ahead of print]
abstract

Bone health

Su S, Liu H.
The association between multiple sclerosis and fracture risk.
Int J Clin Exp Med. 2014;7(11):4327-31.
abstract

Causes of MS

Sorosina M, Esposito F, Guaschino C, et al.
Inverse correlation of genetic risk score with age at onset in bout-onset and progressive-onset multiple sclerosis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Hedström AK, Lima Bomfim I, Hillert J, et al.
Obesity interacts with infectious mononucleosis in risk of multiple sclerosis.
Eur J Neurol. 2014 Dec 20. [Epub ahead of print]
abstract
Read the full text of this paper

Co-existing conditions

Kaya D, Kaya M, Özakbaş S, et al.
Uveitis associated with multiple sclerosis: complications and visual prognosis.
Int J Ophthalmol. 2014;7(6):1010-3.
abstract
Read the full text of this paper

Marrie RA, Elliott L, Marriott J, et al.
Comorbidity increases the risk of hospitalizations in multiple sclerosis.
Neurology. 2014 Dec 24. [Epub ahead of print]
abstract

Marrie RA, Reider N, Stuve O, et al.
The incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in multiple sclerosis: a systematic review.
Mult Scler. 2014 Dec 23. [Epub ahead of print]
abstract

Marrie RA, Reider N, Cohen J, et al.
A systematic review of the incidence and prevalence of cancer in multiple sclerosis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Marrie RA, Reider N, Cohen J, et al.
A systematic review of the incidence and prevalence of sleep disorders and seizure disorders in multiple sclerosis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Marrie RA, Reider N, Cohen J, et al.
A systematic review of the incidence and prevalence of cardiac, cerebrovascular, and peripheral vascular disease in multiple sclerosis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Marrie RA, Reider N, Cohen J, et al.
A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Diagnosis

Etemadifar M, Janghorbani M, Koushki MM, et al.
Conversion from radiologically isolated syndrome to multiple sclerosis.
Int J Prev Med. 2014 Nov;5(11):1379-86.
abstract
Read the full text of this paper

Disease modifying treatments

Arnold DL, Calabresi PA, Kieseier BC, et al.
Effect of peginterferon beta-1a on MRI measures and achieving no evidence of disease activity: results from a randomized controlled trial in relapsing-remitting multiple sclerosis.
BMC Neurol. 2014 Dec 31;14(1):1058. [Epub ahead of print]
abstract
Read the full text of this paper (PDF)

La Mantia L, Di Pietrantonj C, Rovaris M, et al.
Comparative efficacy of interferon β versus glatiramer acetate for relapsing-remitting multiple sclerosis.
J Neurol Neurosurg Psychiatry. 2014 Dec 30. [Epub ahead of print]
abstract

Kalincik T, Horakova D, Spelman T, et al.
Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.
Ann Neurol. 2014 Dec 27. [Epub ahead of print]
abstract

Meng X, Chin PS, Hashmonay R, et al.
Effect of switching from intramuscular interferon β-1a to oral fingolimod on time to relapse in patients with relapsing-remitting multiple sclerosis enrolled in a 1-year extension of TRANSFORMS.
Contemp Clin Trials. 2014 Dec 26. [Epub ahead of print]
abstract

Zivadinov R, Dwyer M, Barkay H, et al.
Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.
J Neurol. 2014 Dec 27. [Epub ahead of print]
abstract

Sormani MP, Bruzzi P.
Can we measure long-term treatment effects in multiple sclerosis?
Nat Rev Neurol. 2014 Dec 23. [Epub ahead of print]
abstract

Falls

Sosnoff JJ, Moon Y, Wajda DA, et al.
Fall risk and incidence reduction in high risk individuals with multiple sclerosis: A pilot randomized control trial.
Clin Rehabil. 2014 Dec 23. [Epub ahead of print]
abstract

Hormones and MS

Christianson MS, Mensah VA, Shen W.
Multiple sclerosis at menopause: potential neuroprotective effects of estrogen.
Maturitas. 2014 Nov 27. [Epub ahead of print]
abstract
Read the full text of this paper

Gholipour T, Ghazizadeh T, Babapour S, et al.
Decreased urinary level of melatonin as a marker of disease severity in patients with multiple sclerosis.
Iran J Allergy Asthma Immunol. 2015 Feb;14(1):91-7.
abstract

Other treatments

Pryce G, Riddall DR, Selwood DL, et al.
Neuroprotection in experimental autoimmune encephalomyelitis and progressive multiple sclerosis by cannabis-based cannabinoids.
J Neuroimmune Pharmacol. 2014 Dec 24. [Epub ahead of print]
abstract

Paediatric MS

Hinton D, Kirk S.
Paediatric multiple sclerosis: a qualitative study of families' diagnosis experiences.
Arch Dis Child. 2014 Dec 31. [Epub ahead of print]
abstract

Parrish JB, Farooq O, Weinstock-Guttman B.
Cognitive deficits in pediatric-onset multiple sclerosis: what does the future hold?
Neurodegener Dis Manag. 2014;4(2):137-46.
abstract

Physical activity

Kindred JH, Ketelhut NB, Rudroff T.
Glucose uptake heterogeneity of the leg muscles is similar between patients with multiple sclerosis and healthy controls during walking.
Clin Biomech (Bristol, Avon). 2014 Dec 17. [Epub ahead of print]
abstract

Azimzadeh E, Hosseini MA, Nourozi K, et al.
Effect of Tai Chi Chuan on balance in women with multiple sclerosis.
Complement Ther Clin Pract. 2014 Nov 27. [Epub ahead of print]
abstract
Read the full text of this paper

Pregnancy and childbirth

Masera S, Cavalla P, Prosperini L, et al.
Parity is associated with a longer time to reach irreversible disability milestones in women with multiple sclerosis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Prognosis

Le Teuff G, Abrahamowicz M, Wynant W, et al.
Flexible modeling of disease activity measures improved prognosis of disability progression in relapsing-remitting multiple sclerosis.
J Clin Epidemiol. 2014 Nov 24. [Epub ahead of print]
abstract

Provision of care

Levin MC, Jackson WC.
Developing a therapeutic plan for treating MS: evidence for new treatments.
J Clin Psychiatry. 2014 Dec;75(12):e34.
abstract

Gibson JC, Fakis A, Phillips MF, et al.
A questionnaire survey comparing the educational priorities of patients and medical students in the management of multiple sclerosis.
JRSM Open. 2014 Dec;5(12):2054270414558656.
abstract
Read the full text of this paper

Psychological aspects

Askari F, Ghajarzadeh M, Mohammadifar M, et al.
Anxiety in patients with multiple sclerosis: association with disability, depression, disease type and sex.
Acta Med Iran. 2014 Dec;52(12):889-92.
abstract

Quality of life

Fernández-Jiménez E, Arnett PA.
Impact of neurological impairment, depression, cognitive function and coping on quality of life of people with multiple sclerosis: a relative importance analysis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Rehabilitation

Rusu L, Neamtu M, Rosulescu E, et al.
Analysis of foot and ankle disorders and prediction of gait in multiple sclerosis rehabilitation.
Eur J Med Res. 2014 Dec 24;19(1):2. [Epub ahead of print]
abstract
Read the full text of this paper (PDF)

Taylor M, Griffin M.
The use of gaming technology for rehabilitation in people with multiple sclerosis.
Mult Scler. 2014 Dec 22. [Epub ahead of print]
abstract

Stem cells

Nash RA, Hutton GJ, Racke MK, et al.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report.
JAMA Neurol. 2014 Dec 29. [Epub ahead of print]
abstract

Symptoms and symptom management

Motl RW, Learmonth YC.
Neurological disability and its association with walking impairment in multiple sclerosis: brief review.
Neurodegener Dis Manag. 2014 Dec;4(6):491-500.
abstract

Vermersch P.
MObility ImproVEment with spasticity in multiple sclerosis in Europe: the MOVE 1 EU study.
Neurodegener Dis Manag. 2014 Dec;4(6):407-15.
abstract

Vitamin D

Thouvenot E, Orsini M, Daures J, et al.
Vitamin D is associated with degree of disability in patients with fully ambulatory relapsing-remitting multiple sclerosis.
Eur J Neurol. 2014 Dec 20. [Epub ahead of print]
abstract

Year: 2016

December 2016

November 2016

July 2016

May 2016

April 2016

March 2016

February 2016

January 2016

Year: 2015

December 2015

November 2015

October 2015

May 2015

April 2015

March 2015

February 2015

January 2015

Year: 2014

December 2014

November 2014

October 2014

September 2014

August 2014

July 2014

June 2014

May 2014

April 2014

March 2014

February 2014

January 2014

Year: 2013

December 2013

November 2013

October 2013

September 2013

August 2013

July 2013

June 2013

May 2013

April 2013

March 2013

February 2013

January 2013

Year: 2012

December 2012

November 2012

October 2012

September 2012

August 2012

July 2012

June 2012

May 2012

April 2012

March 2012

February 2012

January 2012

Print this page