Treatment Strategies for Multiple Sclerosis Flashcards
Discuss the main categories of treatments for MS Describe the phases of clinical trial development Discuss clinical trial evidence that supports disease modifying treatments for MS Critically evaluate the approved disease modifying treatments and the key aspects of their mechanisms, efficacy, and risks Discuss new treatments in the late stage of clinical development Critically evaluate potential approaches to preventing MS Discuss what a cure for MS should achieve
What does the management of MS involve?
Education, counselling, managing acute attacks, preventing disease activity, symptomatic therapy, physical therapy, treating complications
Give 2 causes of pseudo-relapses
Heat and fever
What is the standard treatment for accelerating recovery from a relapse?
High-dose IV methylprednisolone (500-1000mg/day) for 3-5 days
How does steroid treatment affect recovery from a relapse?
It makes it faster - but it does not affect the degree of recovery
How is spasticity treated?
Stretching, physical therapy, and drugs including baclofen, tizanidine, and benzodiazepines. In severe cases, botulinum toxin
What causes spasticity in MS?
Damage to the corticospinal tract
How is paroxysmal pain in MS treated?
Gabapentin (900mg-1.8g/day) or carbamazepine (100-800mg/day)
How is chronic dysaesthetic pain (pain when touched due to nerve damage) treated in MS?
Amitriptyline 20-100mg/day
How is fatigue treated in MS?
Lifestyle advice to save energy (regular sleep pattern, day planning), occasionally drugs (amantadine, modafinil, some antidepressants)
How is mobility impairment treated in MS?
Physiotherapy, encouraging light activity, functional stimulation, orthotics and mobility aids
What are the aims of treatment of primary progressive MS?
Suppressing relapses, preventing disease progression, preventing new white matter lesions, reducing the rate of brain atrophy, and preventing conversion to secondary progressive MS
Name at least 3 disease-modifying treatments approved for relapsing-remitting MS
Teriflunomide, interferon beta-1a, interferon beta-1b, daclizumab, peginterferon beta-1a, ocrelizumab
Name a disease-modifying treatment approved for secondary progressive MS
Interferon beta, mitoxantrone
Name a disease-modifying treatment approved for primary progressive MS
Ocrelizumab
Give a randomised controlled trial endpoint in a study of relapsing-remitting MS
Annualised relapse rate, proportion of relapse-free patients
Give a randomised controlled trial endpoint in a study of secondary progressive MS
Time to progression of disability
Give a randomised controlled trial endpoint in a study of clinically isolated syndrome
Time to second attack
What is the first line injectable drug for relapsing-remitting MS?
Interferon beta - either interferon-beta1a or interferon-beta1b
Describe the effect of interferon beta on MS
Reduces T cell activation, reduces secretion of IFN-gamma, IL-12, and TNF, modulates the blood-brain barrier by inhibiting interaction between VLA-4 on T cells and VCAM-1 on endothelial cells
How is interferon beta administered?
IM or SC injection
What are the side effects of interferon beta?
Reactions at the injection site, flu-like symptoms, depression, elevated liver function tests
What is glatiramer acetate?
A 4 amino acis synthetic co-polymer based on myelin basic protein
How does glatiramer acetate mofidy disease in MS?
It binds to HLA-DR2, inhibitits myelin basic protein reactice cells, and shifts cytokines to an anti-inflammatory phenotype
How is glatiramer acetate administered?
Daily or 3x week SC injections
What is fingolimod?
An agonist at the S1P1 receptors on T cells
How does fingolimod reduce disease activity in MS?
It keeps lymphocytes in the lymph nodes by interfering with T cell trafficking
How does fingolimod compare to IFN-beta 1a?
Significantly more affective at reducing the annualised relapse rate, even in highly active MS
What are the side effects of fingolimod?
Opportunistic infections, skin cancers, elevated liver enzymes, lymphopaenia, macular oedema, hypertension, dyspnoea, bronchitis, diarrhoea, cardiac effects
Why is fingolimod only licensed in highly-active relapsing-remitting MS?
Extensive side effects profile, necessity for 12 month monitoring with CT
What are the side effects of dimethyl fumarate?
Flushing, nasopharyngitis, headache, diarrhoea, UTI, URTI, nausea, fatigue, back pain, upper abdominal pain, proteinuria
How does teriflunomide reduce disease activity in MS?
It decreases the proliferation of T and B autoreactive lymphocytes
Why is frequent blood monitoring required for patients on teriflunomide?
Raised ALT
Which patient group is teriflunomide prescribed in?
Those who cannot tolerate dimethyl fumarate due to severe GI side effects
What are the highest efficacy drugs for MS?
Monoclobal antibodies
How does natalizumab reduce disease activity in MS?
Binds to lymphocytes and prevents their adhesion to VCAM receptors on endothelial cells of the blood brain barrier, so they cannot enter and form lesions
Why do patients require counselling before receiving natalizumab?
Rarely, it lead to JC virus infection and progressive multifocal leukoencephalopathy, which causes oligodendrocyte death and patient death. There is no treatment
Which patient group can be treated with natalizumab?
Those with highly-active MS which has not responded to treatment, or young-onset patients with highly active disease at high risk of early secondary progression
Describe the presentation of progressive multifocal leukoencephalopathy
Progressive and rapid (weeks) deterioration of cognitive function, behaviour, and language with hemiparesis and seizures
What is alemtuzumab?
A humanised monoclonal antibody that selectively targets CD52 positive T and B lymphocytes and works as an induction therapy
What are the side effects of alemtuzumab?
Infusion reactions, opportunistic infections, reactive autoimmunity (Graves’ disease in up to 50%, immune thrombocytopaenic purpura, Goodpasture’s syndrome)
What is ocrelizumab?
A humanised monoclonal antibody against CD20 positive B lymphocytes
Why is haematopoeitic stem cell transplantation not yet approved for MS?
It has a mortality of around 2%, whereas MS is not usually life-threatening
