Drug Management of Multiple Sclerosis

This can be divided into relapse management, symptom control and disease modification.

Any episode of sudden increase ( i.e. over 12-24 hours) in distressing symptoms or an increased limitation on activities should be promptly assessed and referred for oral or intravenous methylprednisolone treatment. A urinary tract infection should be excluded as the cause of the exacerbation of symptoms before steroids are considered. The course should be started as soon as possible after onset of the relapse.¹

• Usual dose is 500mg methylprednisolone for 5 days. This is given as a day case treatment, but admission may be arranged if required by the patient.
• Intravenous infusion is given over 4 hours. Oral medication ( as 100mg tablets) is also available.
• Patients often notice an unpleasant metallic taste with this treatment.
• It is no longer considered necessary to taper doses down after this course.
• Gastric protection should be provided by ranitidine 150mg bd, or omeprazole 20mg daily.

The use of steroids on more than three occasions per year, or for longer than three weeks on any one occasion, should be avoided.¹

Fatigue

• First consider and treat any underlying causes e.g. depression, disturbed sleep, chronic pain and poor nutrition.
• Medication should also be reviewed; some medications e.g. beta-interferon, have fatigue as a side-effect.
• General advice, including aerobic exercise.
• Several studies have shown some benefit with amantadine,² although a recent Cochrane review was equivocal about its benefit and tolerability.³

Pain

• This may be of neuropathic origin, or from musculoskeletal problems, secondary to reduced mobility.
• It may need suitable analgesia and, if still a problem, transcutaneous electrical nerve stimulation (TENS) or antidepressant medication.
• Neuropathic pain can be treated using anticonvulsants such as carbamazepine or gabapentin, or using antidepressants such as amitriptyline.

Visual and communication

If nystagmus is causing reduced visual acuity or other visual symptoms, offer a trial of treatment with oral gabapentin (initiated and monitored in a specialist clinic).

Spasticity and spasms

• Baclofen or gabapentin are usually prescribed as first-line. However, other drugs, including tizanidine, clonazepam, or dantrolene can also be used if treatment is unsuccessful or side effects are intolerable.
• There is only poor quality data regarding the comparative efficacy and tolerability of anti-spasticity agents and a Cochrane review concluded that no recommendations could be made to guide prescribing.⁴
• Troublesome spasticity and spasms should be assessed by a specialist team. Intramuscular botulinum toxin can be considered for relatively localised hypertonia or spasticity that is not responding to other treatments.

Urgency or urge incontinence

• Anticholinergics e.g. oxybutynin, tolterodine⁵
• Desmopressin may be used for night problems, or to control urinary frequency during the day, but should never be used more than once in 24 hours.

Bowel problems

Constipation may require the routine use of suppositories or enemas.

Swallowing difficulties

These may need further assessment e.g. by videofluoroscopy, and possibly short-term nutritional support via nasogastric tube or percutaneous endoscopic gastrostomy (PEG) tubes.

Emotional lability

Antidepressant medication or cognitive behavioural therapy should be considered as part of an overall programme. Anxiety may required psychologically based treatment, or medication such as antidepressants or very short term benzodiazepines.

Sexual dysfunction

Male sexual dysfunction; erectile dysfunction needs full assessment of possible causes such as anxiety and medication. Sildenafil may be used.⁵

• People with MS should be offered immunisation against influenza.
• Infections may be associated with a worsening of disability and may trigger a relapse.

Complementary therapies

• There is anecdotal evidence of patient perceived benefit from some complementary therapies e.g. reflexology and massage.⁶
• People with MS should be advised that linoleic acid 17-23 g/day may reduce progression of disability. A recent Cochrane review found only slight decreases in relapse rate and relapse severity associated with omega-6 fatty acids in some small studies.⁷ These findings were limited by the quality of the studies.

NICE does not recommend either interferon beta or glatiramer acetate,⁸ but the Department of Health, the National Assembly for Wales, the Scottish Executive, the Northern Ireland Department of Health, Social Services & Public Safety, and the manufacturers have reached agreement on a risk-sharing scheme for the NHS supply of interferon beta and glatiramer acetate for multiple sclerosis.⁹

Interferon beta

• Interferon beta is licensed for use in patients with relapsing, remitting multiple sclerosis (characterised by at least two attacks of neurological dysfunction over the previous 2 or 3 years, followed by complete or incomplete recovery) who are able to walk 100m unaided. Not all patients respond and a deterioration in the bouts has been observed in some.
• Interferon beta-1b is also licensed for use in patients with secondary progressive multiple sclerosis but its role in this condition has not been confirmed.
• It is given by subcutaneous (Rebif® and Betaseron®) or intramuscular (Avonex®) injection. Preparations vary but can be alternate days (Betaferon®), three times per week (Rebif®) or weekly (Avonex®).
• Most commonly reported side-effect is a flu-like ague for 24 hours after the injection, which is effectively treated with ibuprofen. This lessens over time. Injection site reactions also occur, but can be minimised with good technique and rotation of sites.
• 10 years of clinical experience show a 30-40% relapse reduction.^10,11
• There is some evidence for greater efficacy with Betaseron® and Rebif®, compared to Avonex®.¹²
• Any woman receiving disease modifying therapy, e.g. interferon, must stop treatment for at least 12 months before trying to conceive.

Glatiramer acetate

Glatiramer (Copaxone®) is licensed for reducing the frequency of relapses in ambulatory patients with relapsing-remitting multiple sclerosis who have had at least 2 clinical relapses in the past 2 years.
It is designed to mimic the effects of the main proteins in myelin.

• 8 years of clinical experience show a 30% relapse reduction rate.¹³
• It is given daily by subcutaneous injection.
• Injection site reactions are common, as are flu-like symptoms. These decrease over time.
• Sporadic, short-lived chest tightness and shortness of breath has been reported.

Cannabinoids

There is a great deal of anecdotal evidence for the therapeutic benefits of cannabis for a variety of MS symptoms, including spasticity, tremor, bladder problems and pain.¹⁴ However convincing evidence that cannabinoids are effective in MS is still lacking.¹⁵ Sativex oromucosal spray is now licensed in the UK on a named patient basis.

Natalizumab (Tysabri®)

• This is a recombinant humanised monoclonal antibody, produced in murine myeloma cells. First licensed by the US FDA in June 2006. NICE appraisal due March 2007.
• Given monthly by IV infusion
• 68% relapse reduction¹⁶
• Well tolerated, but 3 cases of progressive multifocal leukoencephalopathy (PML) in 3000 treated patients¹⁷

CAMPATH-1H

This works by destroying T cells. Is also used in leukaemia and treatment of organ rejection. Given as IV infusion, daily for 5 days. Once a year.

• 90% reduction in agressive MS¹⁸
• No reduction in longterm disability in secondary progressive MS
• Risk of rebound auto-immune problems e.g. thyroid or idiopathic thrombocytopaenic purpura
• Possible long-term risk of lymphopenia

Mitoxantrone

• Is a cytotoxic immunosuppressant
• Given by monthly infusion
• 70-90% reduction in very active MS relapses¹⁹
• Possible risk of cumulative cardiotoxicity after 2-3 years
• 1 in 400 risk of late leukaemia