Treatment Strategies for MS Flashcards
General ways of managing MS?
- education and counselling
- management of acute attacks-> high dose IV methylprednisolone
- prevention of disease activity (disease modifying treatments)
- symptomatic therapy (spasticity, paroxysmal pain, chronic dysaesthetic pain, fatigue, depression, immobility)
- physical therapy
- treating complications
Types of pharmacological treatments for MS?
Acute attacks: high dose steroids
Preventing relapses/disability: immunomodulatory/immunosuppressive
Symptomatic
Standard MS treatment to accelerate recovery?
High dose IV methylprednisolone (500-1000 mg/day x 3-5 days); (can also be orally given)
[standard dose oral steroids e.g. prednisolone 60mg is NOT recommended]
Treating spasticity in MS
- stretching/physical therapy
- baclofen: oral/intrathecal
- Tizanidine
- benzodiazepines
- botulinum toxin (more selective effect)
Baclofen side effects?
[if given orally]
- drowsiness
- hypotonia
Treating pain in MS
Paroxysmal pain:
- Gabapentin 900mg/day to max 1.8g/day
- Carbamazepine 100-800mg/day
Chronic dysaesthetic pain:
- Amytripyline 20-100 mg/day
- (other antiepileptic/antidepressants)
[narcotics and NSAIDS are ineffective for neuropathic pain]
Treating fatigue in MS
[limited options]
- “energy savings” (day planning, devices)
Pharmacological
- amantadine (unconfirmed)
- antidepressants
- modaffinil
Examples of mobility treatment in MS?
- encourage activity
- physiotherapy
- orthotics/aids (e.g. a brace)
- functional stimulation
- managing spasticity
“First-line” MS treatment?
- Interferon-β (subcut/IM every other day)
- Glatiramer acetate (GA) (subcut, daily)
- Dimethyl Fumarate (Tecfidera®)
Interferon-β mechanism of action?
- Immunomodulatory effects
Reducing T cell activation - Reducing IFN-g, IL-12, TNF secretion (controversial)
- Modulating BBB via inhibition of MMP-9 and VLA-4/VCAM-1 interactions
Common side effects for Interferon-β
- Injection site reaction
- Flu-like symptoms
- Depression
- Raised LFTs
(overall good long term safety)
Glatiramer Acetate (GA) mechanism of action
- Binds to HLA-DR2
- Inhibtion/anergy of MBP reactive cells
- Cytokine shift Th1 -> Th2
- neuroprotective
Oral drugs for MS?
- Fingolimod
- Dimethyl Fumarate (Tecfidera®)
- Teriflunomide (Aubagio®)
Fingolimod mechanism of action?
Agonist at the S1P1 receptors on T cells
Interferes w/ T-cells trafficking- reduced response to chemotactic cues and reduced exit from lymphoid organs
Fingolimod licensing and efficacy?
Licensed for use in highly active MS
Good efficacy on active inflammation and relapses
reduces relapse-related disability
Fingolimod side effects?
- MAINLY: Cardiac: (S1P1 and S1P3 in atrial myocytes) -> bradycardia
- herpes infections, skin cancers, raised LFTs, lymphopenia
Dimethyl Fumarate (Tecfidera®) mechanism of action
Methyl ester of fumaric acid, blocking pro-inflammatory cytokines production
Dimethyl Fumarate (Tecfidera®) licensing and efficacy?
Licensed for use in active MS
Good efficacy on active inflammation and relapses
(reduces relapse-related disability
Dimethyl Fumarate (Tecfidera®) side effects?
Flushing and GI symptoms
Teriflunomide (Aubagio®) mechanism of action
Decreases proliferation of T and B autoreactive lymphocytes
Teriflunomide (Aubagio®) licensing and efficacy
Licensed for use in active MS (if pt can’t tolerate injectibles)
Moderately effective in reducing relapse rate
Monoclonal antibodies in MS?
- Natalizumab (Tysabri®)
- Alemtuzumab (Lemtrada®)
- Ocrelizumab (Ocrevus®)
- Cladribine (Mavenclad®)
MoA of monoclonal Abs in MS
Natalizumab: reduced transmigration (against α4 integrin subunit)
Alemtuzuab: depletes T and B cells
Cladribine: T and B cell depletion
Ocrelizumab: targets CD20+ B-cells
Monoclonal Abs licensing and efficacy?
Natalizumab used for highly active MS
All licensed for highly active MS
Natalizumab (Tysabri®) side effects?
Progressive Multifocal Leukoencephalopathy PML- (seen in immunosuppressed pts)
Caused by JC virus -> active replication in glial cells -> oligodendrocyte death -> fatal
PML risk factors?
- no. of infusions
- JCV titre (>1.5 high risk)
- prior immunosuppressant use
PML management?
- stop natalizumab
- plasma exchange to remove natalizumab
- Possible strategy??: combination of filgrastim (restore lymphocyte adhesion), oral maraviroc (modulates T cell recruitment) and mefloquin/mirtazapine (possible anti-JCV effects)
Alemtuzumab (Lemtrada®) side effects?
- autoimmunity: (hyperthyroidism/Graves’, ITP, Goodpastures)
- infusion reactions
- infections (herpetic)
Role of Haematopoietic Stem Cell Transplantation (HSCT) in MS?
Resets immune system completely from pt’s own naive cells -> new immune profile
Haematopoietic Stem Cell Transplantation (HSCT) efficacy?
Great results, very cheap
BUT transplant related mortality of HSCT ~2% (compared to MS not being life-threatening)
