Treatment Strategies for MS Flashcards Preview

NMH: Module 2 > Treatment Strategies for MS > Flashcards

Flashcards in Treatment Strategies for MS Deck (30)
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1

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

2

Types of pharmacological treatments for MS?

Acute attacks: high dose steroids

Preventing relapses/disability: immunomodulatory/immunosuppressive

Symptomatic

3

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]

4

Treating spasticity in MS

- stretching/physical therapy
- baclofen: oral/intrathecal
- Tizanidine
- benzodiazepines
- botulinum toxin (more selective effect)

5

Baclofen side effects?

[if given orally]

- drowsiness
- hypotonia

6

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]

7

Treating fatigue in MS

[limited options]

- "energy savings" (day planning, devices)

Pharmacological
- amantadine (unconfirmed)
- antidepressants
- modaffinil

8

Examples of mobility treatment in MS?

- encourage activity
- physiotherapy
- orthotics/aids (e.g. a brace)
- functional stimulation
- managing spasticity

9

"First-line" MS treatment?

- Interferon-β (subcut/IM every other day)

- Glatiramer acetate (GA) (subcut, daily)

- Dimethyl Fumarate (Tecfidera®)

10

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

11

Common side effects for Interferon-β

- Injection site reaction
- Flu-like symptoms
- Depression
- Raised LFTs

(overall good long term safety)

12

Glatiramer Acetate (GA) mechanism of action

- Binds to HLA-DR2
- Inhibtion/anergy of MBP reactive cells
- Cytokine shift Th1 -> Th2
- neuroprotective

13

Oral drugs for MS?

- Fingolimod
- Dimethyl Fumarate (Tecfidera®)
- Teriflunomide (Aubagio®)

14

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

15

Fingolimod licensing and efficacy?

Licensed for use in highly active MS

Good efficacy on active inflammation and relapses
(reduces relapse-related disability)

16

Fingolimod side effects?

- MAINLY: Cardiac: (S1P1 and S1P3 in atrial myocytes) -> bradycardia

- herpes infections, skin cancers, raised LFTs, lymphopenia

17

Dimethyl Fumarate (Tecfidera®) mechanism of action

Methyl ester of fumaric acid, blocking pro-inflammatory cytokines production

18

Dimethyl Fumarate (Tecfidera®) licensing and efficacy?

Licensed for use in active MS

Good efficacy on active inflammation and relapses
(reduces relapse-related disability

19

Dimethyl Fumarate (Tecfidera®) side effects?

Flushing and GI symptoms

20

Teriflunomide (Aubagio®) mechanism of action

Decreases proliferation of T and B autoreactive lymphocytes

21

Teriflunomide (Aubagio®) licensing and efficacy

Licensed for use in active MS (if pt can't tolerate injectibles)

Moderately effective in reducing relapse rate

22

Monoclonal antibodies in MS?

- Natalizumab (Tysabri®)

- Alemtuzumab (Lemtrada®)

- Ocrelizumab (Ocrevus®)

- Cladribine (Mavenclad®)

23

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

24

Monoclonal Abs licensing and efficacy?

Natalizumab used for highly active MS

All licensed for highly active MS

25

Natalizumab (Tysabri®) side effects?

Progressive Multifocal Leukoencephalopathy PML- (seen in immunosuppressed pts)

Caused by JC virus -> active replication in glial cells -> oligodendrocyte death -> fatal

26

PML risk factors?

- no. of infusions
- JCV titre (>1.5 high risk)
- prior immunosuppressant use

27

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)

28

Alemtuzumab (Lemtrada®) side effects?

- autoimmunity: (hyperthyroidism/Graves', ITP, Goodpastures)
- infusion reactions
- infections (herpetic)

29

Role of Haematopoietic Stem Cell Transplantation (HSCT) in MS?

Resets immune system completely from pt's own naive cells -> new immune profile

30

Haematopoietic Stem Cell Transplantation (HSCT) efficacy?

Great results, very cheap

BUT transplant related mortality of HSCT ~2% (compared to MS not being life-threatening)