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Advancements In Treatment Options MS Relapses & Adherence
1.
2. Present at seminars sponsored by the following pharmaceutical companies:
Biogen-Idec
EMD-Serono
QuestCor
Teva Neurosciences
Engage in research for the following companies:
Biogen-Idec
Elan
EMD-Serono
Janssen
Pfizer
Roche
Teva Neurosciences
3. A disorder or group of disorders affecting the CNS -
central nervous system (brain, spinal cord)
An autoimmune process causing inflammation in the
CNS in genetically susceptible individuals after one or
more triggers
Inflammation involves myelin, causing demyelination
in the CNS, which leads to slower nerve conduction
and reduced nerve signals controlling function
Axonal injury and destruction occur early and are
associated with permanent neurological dysfunction
8. 1. Relapsing-remitting 2. Primary-progressive
3. Secondary-progressive 4. Progressive-relapsing
Time Time
Time Time
Increasingdisability
Increasingdisability
Increasingdisability
Increasingdisability
Adapted from: Lublin FD, Reingold SC. Neurology. 1996;46:907-911.
5-10%
66%
of
RRMS
5-10%
80-85%
9. Relapses
Focal disturbances of function >24 hours
Follows stability of at least 30 days
In absence of environmental, metabolic, or infectious
processes
Occur on average once a year in untreated patients (highly
variable)
Over time, frequency of relapses typically drops, even w/o
treatment (so any treatment looks favorable if not
compared with placebo or other standard DMT’s)
10. Prevent Relapses
Treat Relapses
Learn to recognize mimics / pseudoexacerbations
Manage symptoms – acutely during relapses and
chronically if they persist
Delay progression to disability (DMT)
Stabilizing or improving the MRI
12. Medical Management:
IV Therapy:
- methylprednisolone, 500-2000 mg IV for 3-5 days, sometimes
followed by a short course of prednisone over 1-3 weeks; MOA =
cortisol effect on inflammation, stabilizing the BBB
- Acthar gel, IM/SC, 80-120 units daily for 5-21 days (when IV
steroids are poorly tolerated or ineffective or if the patient has
poor IV access) – comparable in benefit and side effects, but
different MOA = cortisol + melanocortin effects (may have
advantages over steroids, with loss cortisol effects and more
immune cell effects in the brain and throughout the body)
Oral steroids:
- prednisone, methylprednisolone, or dexamethasone
- high doses are more effective and reasonably well tolerated
- used for people with poor IV access or can’t tolerate IV steroids
Other Therapy: plasmaphoresis, IVIg, cyclophosphamide
13. Diet: NMSS website. Also: The Zone Diet, by Dr. Barry Sears, hunter-gatherer
variation by Dr. Terry Wahls:
http://www.youtube.com/watch?v=KLjgBLwH3Wc&feature=youtube_gdata_player
Vitamin D3 supplementation
Exercise: stretching, weight training, aerobic conditioning; keep in the best
shape possible to be able to fight against any future challenges / attacks
Sleep: quality and quantity
Rest: planned rest periods for energy conservation
Others: relaxation exercises, biofeedback, meditation, tai chi, yoga
Foreign Substances:
eliminate tobacco use
alcohol (ok in small amounts - 1-2 beverages per day)
marijuana (probably ok in small amounts)
medications, especially sedatives, in combination with the above
Be aware of conditions or factors that may mimic or aggravate MS symptoms
stress, depression, sleep deprivation, medical conditions (UTI,
bronchitis/lung disorders, thyroid disorders, heart disease), and effects of
medications
14. Educate yourself on all available treatments
Adjust the intensity of treatment to the severity of disease (risk
vs. benefit)
Be realistic about what treatments can offer – they don’t cure
MS and may only keep you from declining
Treat early, stay positive, and stay committed to your chosen
therapy.
Don’t be afraid to change therapies if the current one isn’t right
for you (intolerable side effects or not providing benefit); on the
other hand, think twice about going off a therapy that is
working
Be open and honest with your family, physician, and most of
all, yourself
“MS is a marathon, not a sprint. It’s not how you start, but how
you finish that’s important.”
- Dr. Randall Schapiro
15. Natural course of disease
Theoretical Model
Later intervention
Later
treatment
Treatment
at diagnosis
Intervention at diagnosis
Time
Disease onset
Disability
18. 1
8
Lymph node
Bloodstream
Naïve T cells
Anti-inflammatory Th2 cells (MS-specific)
• Multiple sclerosis is a
debilitating autoimmune
disease characterized by
both inflammation and
axonal degeneration1
• In order to regulate CNS
damage, treatment of MS is
focused on restoring
immune system balance2-5
• It is important to expand our
view to consider treatment
impact on the overall
immune response
1. Kasper LH, et al. Neurology. 2010;74(Suppl1):S2-S8. 2. Ziemssen T. J Neurol. 2005;252(Suppl 5):V/38-V/45. 3. Yong VW, et al. Neurology. 2007;
68(22 Suppl 3):S32-S37. 4. Dhib-Jalbut S. Neurology. 2007;68(22 Suppl 3):S13-S21. 5. Tzartos JS, et al. Am J Pathol. 2008;172(1):146-155.
Proinflammatory Th1 cells (MS-specific)
19. 1
9
MS-specific proinflammatory
immune cells cross from the
bloodstream into the central
nervous system (CNS),
secrete proinflammatory
cytokines, and eventually
destroy myelin and facilitate
neuronal death.
1. Ziemssen T. J Neurol. 2005;252(Suppl 5):V/38-V/45. 2. Yong VW, et al. Neurology. 2007;68(22 Suppl 3):S32-S37. 3. Dhib-Jalbut S. Neurology.
2007;68(22 Suppl 3):S13-S21. 4. Tzartos JS, et al. Am J Pathol. 2008;172(1):146-155.
Proinflammatory cytokinesProinflammatory Th1 cells (MS-specific)
Proinflammatory cells
release destructive cytokines
and neurotoxic agents
Blood-brain barrier
Th1 cell crossing
blood-brain barrier
21. Step 1: Main (Platform) medications
Interferon beta (Avonex, Rebif, Betaseron, Extavia)
Glatiramer acetate (Copaxone)
Natalizumab (Tysabri)
Fingolimod (Gilenya)
Teriflunomide (Aubagio)
Dimethyl Fumarate (Tecfidera)
Step 2: Switch between the platform agents if an agent is
ineffective (based on several factors) or poorly tolerated
Step 3: Add IV methylprednisolone or IM/SC ACTHAR (short
course vs. pulses); pulse therapy is not permitted in
combination with Tysabri
Step 4: Switch to or add (except Tysabri) immunosuppressants
Imuran, CellCept -> methotrexate -> cyclophosphamide or mitoxanthrone
22. Other alternatives: Experimental agents prior to release onto
the market; some protocols contain a placebo arm; relapsing
and progressive MS (Melbourne, Vero Beach, Orlando,
Maitland)
Future oral agents (daily) - laquinimod (2013/2014)
Infusions – alemtuzumab (IV yearly), rituxumab / ocrelizumab
(IV every 6 months)
Injections: daclizumab (IM every 2 weeks)
Stem cells – currently limited to RRMS
Bone marrow transplantation
Implanting stem cell and other immature cells, such as
oligodendrocyte progenitor cells in brain / spinal fluid
23. Closely monitor disease activity and response to therapy
Careful history of relapses, progression, and side effects of medications
Neurological examination
MSFC (Multiple Sclerosis Functional Composite: Timed 25ft Walk, 9-
hole peg test, PASAT)
EDSS (Expanded Disability Status Score): cognitive, visual, brainstem,
motor, cerebellar, sensory, bowel/bladder
Neuropsychological testing (Cognitive/Emotional)
MRI’s of the brain and upper (C-/T-) spine
Evoked potentials
OCT / V.A. (especially with varying contrasts) / Visual Field testing
Blood work (25-hydroxy-vitamin D levels, CBC/LFT’s)
Quality of Life
25. The ability to follow the treatment plan
that you and your health care
provider agreed upon (a contract)
Average adherence = 50%
26. Factors interfering with adherence:
treatment (especially needle) fatigue
loss of motivation / complacency
financial challenges
lack of curative benefit
unrealistic expectations (of cure, reversal of
disability, resolution of current symptoms)
adverse effects of medications
pregnancy
doctor recommended against it
treatment was “a hassle”
27. Patients who stopped DMTs had:
more severe disability, including SPMS
more relapses
poor to fair health
depressed mood
28. Reasons for never using DMT:
my MS was not severe enough
doctor didn’t recommend it or advised against it
fear of DMT making things worse of causing
adverse effects
cost
used other therapies
fear of needles
didn’t know about the DMTs
29. Improving adherence:
encouragement
education, especially importance of treatment
manage medication side effects
injection technique and follow-up
work with emotional issues (anxiety and
depression)
recognize and work around cognitive deficits
integrate a treatment schedule into the patient’s
lifestyle
encourage a team approach – patient, family,
friends, nurses, clinicians, self-help groups, and
pharmaceutical support programs
30. Determine what’s most important in your life - prioritize
based on your limitations at any given time
Keep active with family and friends
Be active in your church, synagogue, and community
Improve your lifestyle - exercise regularly, do yoga and tai
chi, eat a balanced diet, with small amounts through the
day, avoid tobacco, avoid excessive alcohol
Look at the “big picture” – don’t sweat the small stuff
Don’t dwell on the things you can’t change; focus on what’s
truly important…