Table 1.
UK-licensed disease-modifying treatments (DMTs) for relapsing remitting MS11,27–30
| Treatment | Mode and frequency | Side effects | Indication | Notes |
|---|---|---|---|---|
| Interferon beta 1a (Avonex) | Intramuscular injection 30 μg once per week | >1:100: flu-like, injection site reactions, headache, lymphopaenia, insomnia, diarrhoea, nausea and vomiting, depression, hair loss, liver function derangement, thyroid disease | First-line: active RRMS with ≥2 relapses, or 1 relapse and new MRI lesions as per McDonald 2010 criteria in ≤2 years EDSS<6.5 (able to walk 20 m) | Fridge storage Caution if depression/suicidal ideation |
| Pegylated interferon beta 1a (Plegridy) | Subcutaneous injectionStart with a dose of 63 μg on day 1, followed by 94 μg on day 15, then 125 μg on day 29 and once every 2 weeks thereafter | Caution re: neutralising antibodies with interferon beta 1b in up to 46% of patients. Monitor antibody titres | CIS and at high risk of developing MS with MRI T2 lesions | Fridge storage Keep out of sunlight |
| Interferon beta 1a (Rebif) | Subcutaneous injection Start at 22 μg three times weekly and escalate over 4 weeks to 44 μg three times weekly. | SPMS with ≥2 relapses in ≤2 years and EDSS progression ≤2 points over 2 years | Fridge storage | |
| Interferon beta 1b (Betaferon) | Subcutaneous injection Alternate days Escalate to 250 μg over 3–6 weeks |
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| Interferon beta 1b (Extavia) | ||||
| Glatiramer acetate (Copaxone) | Subcutaneous injection 20 mg once daily or 40 mg three times per week. | >1:100: injection site reactions including lipoatrophy, headache, depression, anxiety and nausea. Also IPIR with flushing, palpitations, dyspnoea and chest pain lasting 15–30 minutes | First-line: active RRMS with ≥2 relapses, or 1 relapse and new MRI lesions, as per McDonald 2010 criteria, in ≤2 years. Able to walk more than 100 m without aids CIS and at high risk of developing MS with MRI T2 lesions SPMS with ≥2 relapses in ≤2 years and EDSS progression ≤2 points over 2 years |
If IPIR lasts longer than 30 minutes then patients should seek urgent medical attention |
| Teriflunamide (Aubagio) | Oral 7 or 14 mg once daily | >1:100: liver function derangement, diarrhoea, nausea, hair thinning and loss | First-line: active RRMS with ≥2 relapses, or 1 relapse and new MRI lesions in ≤2 years | |
| Dimethyl fumarate (Tecfidera) | Oral Initially 120 mg twice daily, then increase after 7 days to 240 mg twice daily |
>1:100: flushing, gastrointestinal upset, lymphopaenia, rash, ketonuria, proteinuria, liver function derangement Very rare cases of PML reported |
First-line: active RRMS with ≥2 relapses, or 1 relapse and new MRI lesions in ≤2 years | Taking oral doses with food may reduce the incidence of flushing and gastrointestinal effects |
| Fingolimod (Gilenya) | Oral 0.5 mg once daily | >1:100: cough, headache, back pain, diarrhoea, infections, liver function derangement, lymphopaenia. <1:100: macular oedema Very rare cases of PML reported |
Second-line: highly active RRMS only with relapses despite treatment with beta interferon for at least 1 year or relapses on glatiramer acetate or tecfidera RRMS on natalizumab at high risk of PML (2014 post-NICE approval) First-line: across UK, ABN guidance suggests fingolimod can be used if highly active RRMS with 2 or more disabling relapses in 1 year and new MRI lesions |
Note: bradycardia and atrioventricular conduction slowing can occur while taking the first dose of fingolimod, therefore the first dose is taken under medical supervision and cardiac monitoring for 6 hours |
| Natalizumab (Tysabri) | Intravenous infusion 300 mg once every 4 weeks | >1:100: headache, dizziness, pruritic rash, infections Clear risk gradient of PML. |
First-line: RES RRMS with ≥2 relapses ≤1 year and no previous DMT and either ≥1 gadolinium-enhancing MRI lesion(s) or ≥9 T2-hyperintense MRI brain lesions, if MRI available Second-line: RES RRMS with ≥1 relapses ≤1 year and previous beta interferon not meeting stopping criteria and either ≥1 gadolinium-enhancing MRI lesion or ≥9 T2-hyperintense MRI brain lesions, if MRI available |
|
| Alemtuzumab (Lemtrada) | Intravenous infusion Initially, 12 mg daily for 5 consecutive days to a total dose of 60 mg Second course: 12 months post initial dose, 12 mg daily for 3 consecutive days to a total dose of 36 mg |
>1:100: acute cytokine release syndrome (headaches, rash, fever, nausea, diarrhoea, hypotension), infections including herpes virus, endocrinopathy (especially thryoid) | First-line: active RRMS with ≥2 relapses in ≤2 years, or 1 relapse and new MRI lesions Second-line: highly active RRMS on DMT and relapse within the last year and new MRI lesions |
Pre-medications: oral or intravenous corticosteroid, oral antihistamine and analgesic to prevent cytokine release syndrome Oral prophylaxis with aciclovir for herpes infection and continued for 1 month |
NHS England has taken on the commissioning of drugs since 2013 and advises that patients must be under the care of a designated MS centre that is registered to take part in the national risk sharing scheme involving the three beta interferon products and glatiramer acetate. The Association of British Neurologists (ABN) advises an annual review while on DMTs that will need to be conducted by the MS specialist neurologist who is also best placed to determine whether MRI scanning is required.
CIS = clinically isolated syndrome; DMT = disease-modifying treatment; EDSS = Expanded Disability Status Scale; IPIR = immediate post-injection reaction; MRI = magnetic resonance imaging; MS = multiple sclerosis; NICE = National Institute for Health and Care Excellence; PML = progressive multifocal leucoencephalopathy; RES = rapidly evolving severe; SPMS = secondary progressive multiple sclerosis; RRMS = relapsing remitting multiple sclerosis.