This Cochrane Database Systematic Review pooled the data from 44 high quality studies of 11 different disease modifying treatments (DMTs) for MS, including some that are less routinely used. The studies included 17,401 adults with either relapsing-remitting (RRMS) or progressive types of MS who were treated for an average of two years.
They found that there is good evidence that both natalizumab and interferon beta 1a (Rebif) can reduce relapses and disability progression compared to placebo in people with RRMS. However, they highlighted concerns over the risk of PML with natalizumab especially after more than two years of treatment. Other DMTs presented a more complex balance of benefits and risks for people with RRMS, with some being more favourable than others.
In studies on progressive forms of MS, few studies were of high quality and no drug was shown to be effective in preventing disability progression.
Disease modifying treatments (known as DMTs or DMDs) may be prescribed for people who are experiencing relapses as they act on the immune system to calm down the inflammation that causes relapses.
There are currently seven key disease modifying drugs licensed in the UK: Four are different forms of beta interferon called interferon beta 1a (Avonex), interferon beta 1a (Rebif), interferon beta 1b (Betaferon in the UK but Betaseron in the USA), interferon beta 1b (Extavia). The other three DMTs are glatiramer acetate (Copaxone), natalizumab (Tysabri), and fingolimod (Gilenya).
There are other drugs which have been used to modify the disease course in MS but are used less frequently including mitoxantrone (Novantrone), methotrexate (Maxtrex), cyclophosphamide (Endoxana), azathioprine (Imuran), immunoglobulins (IVIg), and long-term corticosteroids.
How this study was carried out
This study was a meta-analysis which means that it combined the results from previous studies as long as they met certain strict criteria. These included:
- The study design was a randomised controlled trial (RCT)
- participants were over 18
- participants met the Poser or McDonald criteria for a diagnosis of MS
- treatment was with interferon beta 1b (Betaferon), interferon beta 1a (Rebif, Avonex), glatiramer acetate, natalizumab, mitoxantrone, methotrexate, cyclophosphamide, azathioprine, immunoglobulins or long-term corticosteroids
- treatment had been compared with placebo or another active agent
- the dose was within the therapeutic range
- the route of administration was subcutaneous injection for interferon beta 1b, interferon beta 1a (Rebif) and glatiramer acetate, intramuscular injection for interferon beta 1a (Avonex), by the intravenous route for natalizumab, mitoxantrone, cyclophosphamide and immunoglobulins, orally for methotrexate and azathioprine or administered intravenously or by the oral route for corticosteroids.
Forty-four studies were included in this review. They included a total of 17,401 adults with either relapsing-remitting (RRMS) or progressive types of MS. The average length of treatment was 24 months.
The study was a Cochrane Database Systematic Review which are highly regarded independent reviews. This review aimed to find out if some treatments worked better than others and if some were more acceptable to people with MS.
You can read more about how this study was carried out here
What was found
For people with relapsing remitting MS (RRMS) :
- there is good evidence that both natalizumab and interferon beta 1a (Rebif) can reduce relapses and disability progression compared to placebo. These treatments are more effective than interferon beta 1a (Avonex) in people with RRMS. However, natalizumab can induce the sometimes serious condition called progressive multifocal leukoencephalopathy (PML), especially after more than two years of treatment
- interferon beta 1b (Betaferon), glatiramer acetate, and mitoxantrone may also prevent relapse and disability progression in people with RRMS. These treatments are associated with possible medium and long-term side effects, and the balance of risk and benefit might be unfavourable
- interferon beta 1a (Avonex), intravenous immunoglobulins, cyclophosphamide, and long-term corticosteroids have an unfavourable risk-benefit balance for people with RRMS
- there is not enough high quality data to say whether there is a favourable risk-benefit balance using azathioprine.
For people with progressive MS:
- nine drugs (interferon beta 1b (Betaferon), interferon beta 1a (Avonex and Rebif), glatiramer acetate, mitoxantrone, methotrexate, cyclophosphamide, intravenous immunoglobulins, and long-term corticosteroids) had been studied in people with progressive MS. However, few studies were of high quality and no drug was shown to be effective in preventing disability progression in people with progressive MS.
What does it mean?
The authors emphasise that the trials included in this study only looked at the risks and benefits of treatment over an average of two years so no conclusion can be drawn about the longer term benefits or risks. Consequently, they suggest that longer term studies are much needed. They also point out that almost three quarters of the studies were sponsored by pharmaceutical companies. The full discussion of the results along with the authors conclusions is available online.
Filippini G, Del Giovane C, Vacchi L A, et al.
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis..
Cochrane Database Syst Rev. 2013 Jun 6;6:CD008933. [Epub ahead of print]
Plain language summary
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Read the full text as a PDF file (137 pages)
More about disease modifying treatments
Not everyone with RRMS will be offered DMTs and the choice of treatments (if any) will depend on the licensing and prescribing criteria within the NHS in the UK as well as the characteristics and activity of that individual's MS. Information on deciding when to begin DMTs is available along with suggestions on weighing up the risks and benefits. Some people decide to switch or stop treatment either because of side effects or because they find that a particular treatment is not working for them.
Some tips about discussing DMTs or other treatments with health professionals and examples of questions you might like to ask are listed here.
The future of DMTs
Finding more effective DMTs, for people with RRMS and with progressive forms of MS, is an active area of research. You can read about some of them here and see how far each one has progressed through the different phases of clinical trials and towards possible licensing and availability through the NHS.
Research by topic areas...
Symptoms and symptom management
Molton I, Hirsh AT, Smith AE, et al.
Age and the role of restricted activities in adjustment to disability related pain.
J Health Psychol. 2013 May 29. [Epub ahead of print]
Alschuler KN, Ehde DM, Jensen MP.
The co-occurrence of pain and depression in adults with multiple sclerosis.
Rehabil Psychol. 2013 May;58(2):217-21.
Sormani MP, Bruzzi P.
MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials.
Lancet Neurol. 2013 Jun 3. doi:pii: S1474-4422(13)70103-0. 10.1016/S1474-4422(13)70103-0. [Epub ahead of print]
Lienert C, Schawalder G, Findling O, et al.
Tolerance of intravenous methylprednisolone for relapse treatment in demyelinating CNS disease.
Swiss Med Wkly. 2013 May 28;143:0.
Read the full text of this paper
Disease modifying treatments
Shingler S, Swinburn P, Ali S, et al.
A discrete choice experiment to determine patient preferences for injection devices in multiple sclerosis.
J Med Econ. 2013 Jun 4. [Epub ahead of print]
Campbell JD, McQueen RB, Miravalle A, et al.
Comparative effectiveness of early natalizumab treatment in JC virus-negative relapsing-remitting multiple sclerosis.
Am J Manag Care. 2013;19(4):278-85.
Fingolimod for the treatment of relapsing multiple sclerosis.
Expert Rev Neurother. 2013 Jun;13(6):589-602.
Martinelli Boneschi F, Vacchi L, et al.
Mitoxantrone for multiple sclerosis.
Cochrane Database Syst Rev. 2013 May 31;5:CD002127.
Raffel J, Malik O, Nicholas R, et al.
Assessing dalfampridine efficacy in the physician's office.
Mult Scler. 2013 May 31. [Epub ahead of print]
Ray AD, Udhoji S, Mashtare T, et al.
A combined inspiratory and expiratory muscle training program improves respiratory muscle strength and fatigue in multiple sclerosis.
Arch Phys Med Rehabil. 2013 May 25. doi:pii:S0003-9993(13)00400-0. 10.1016/j.apmr.2013.05.005. [Epub ahead of print]
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Characterising aggressive multiple sclerosis.
J Neurol Neurosurg Psychiatry. 2013 Jun 6. [Epub ahead of print]
Fiddes B, Wason J, Kemppinen A, et al.
Confounding underlies the apparent 'month of birth' effect in multiple sclerosis.
Ann Neurol.2013 Jun 6. doi: 10.1002/ana.23925. [Epub ahead of print]
Sleeman KE, Ho YK, Verne J, et al.
Place of death, and its relation with underlying cause of death, in Parkinson's disease, motor neurone disease, and multiple sclerosis: A population-based study.
Palliat Med. 2013 Jun 4. [Epub ahead of print]
Lexell EM, Flansbjer UB, Lexell J, et al.
Self-perceived performance and satisfaction with performance of daily activities in persons with multiple sclerosis following interdisciplinary rehabilitation.
Disabil Rehabil. 2013 Jun 4. [Epub ahead of print]
Ziemssen T, Kempcke R, Eulitz M, et al.
Multiple sclerosis documentation system (MSDS): moving from documentation to management of MS patients.
J Neural Transm. 2013 Jun 1. [Epub ahead of print]
Hughes AJ, Denney DR, Owens EM, et al.
Procedural variations in the Stroop and the symbol digit modalities test: impact on patients with multiple sclerosis.
Arch Clin Neuropsychol. 2013 Jun 4. [Epub ahead of print]
Mazdeh M, Seifirad S, Kazemi N, et al.
Comparison of vitamin D3 serum levels in new diagnosed patients with multiple sclerosis versus their healthy relatives.
Acta Med Iran. 2013 May 30;51(5):289-92.
Schwartz CE, Quaranto BR, Healy BC, et al.
Cognitive reserve and symptom experience in multiple sclerosis: A buffer to disability progression over time?
Arch Phys Med Rehabil. 2013 May 28. doi:pii: S0003-9993(13)00404-8. 10.1016/j.apmr.2013.05.009. [Epub ahead of print]
Feinstein A, Lapshin H, O'Connor P, et al.
Sub-threshold cognitive impairment in multiple sclerosis: the association with cognitive reserve.
J Neurol. 2013 Jun 5. [Epub ahead of print]
Scarpazza C, Braghittoni D, Casale B, et al.
Education protects against cognitive changes associated with multiple sclerosis.
Restor Neurol Neurosci. 2013 Jun 4. [Epub ahead of print]
Wootla B, Watzlawik JO, Denic A, et al.
The road to remyelination in demyelinating diseases: current status and prospects for clinical treatment.
Expert Rev Clin Immunol. 2013 Jun;9(6):535-49.
Pathology and disease mechanisms in different stages of multiple sclerosis.
J Neurol Sci. 2013 Jun 1. doi:pii: S0022-510X(13)00217-7.10.1016/j.jns.2013.05.010. [Epub ahead of print]
Jelinek GA, Hadgkiss EJ, Weiland TJ, et al.
Association of fish consumption and omega 3 supplementation with quality of life, disability and disease activity in an international cohort of people with multiple sclerosis.
Int J Neurosci. 2013 Jun 3. [Epub ahead of print]
Heesen C, Köpke S, Solari A, et al.
Patient autonomy in multiple sclerosis - Possible goals and assessment strategies.
J Neurol Sci. 2013 May 25. doi:pii: S0022-510X(13)00097-X. 10.1016/j.jns.2013.02.018. [Epub ahead of print]