Chapter 40
Multiple Sclerosis
M. Patricia Leuschen, Kathleen M. Healey, and Mary L. Filipi
Questions
Your brother had some “double” vision problems lately and has felt very tired. Your family physician sent him to a
neurologist who scheduled several tests. On follow up, the neurologist says that your brother has optic neuritis that
may potentially be associated with multiple sclerosis. The neurologist also recommends that your brother consider
beginning an interferon β therapy.
1.
What clinical data would support initiating IFNβ therapy even before a definitive diagnosis of MS?
2.
What clinical information, in association with verification of the clinical symptoms of optic neuritis and
fatigue would be sufficient to verify that the diagnosis is definitive MS using the revised MacDonald
criteria?
3.
Your brother has received information on the two FDA approved IFNβ-1a products. What are the
differences in dose, dosing schedule, potential for side effects and efficacy for the two products?
4.
Over the next year, your brother has 2 more episodes that include problems with walking and numbness
in his right hand. Are any other criteria necessary for a definitive diagnosis of MS by the revised
McDonald criteria?
5.
What would you expect an MRI to show if your brother truly has MS?
6.
Your brother has been on IFNβ-1a IM therapy for 9 months and is still complaining of flu like symptoms
and muscular aches and pain following each injection. What other therapeutic option(s) does he have?
7.
How has the diagnosis of MS changed your brother’s life expectancy?
8.
Your brother has just had a major relapse that has left him unable to walk. What is the standard therapy
for this type of acute relapse and what is the postulated mechanism of action?
9.
If the previous scenario had been your sister rather than your brother, would the prognosis have been
different?
10. Your brother continues to progress rapidly with no apparent remission even on standard
immunotherapy for RR-MS. What therapy is FDA approved for rapidly progressing MS?
11. Which of the FDA approves therapies for MS was originally designed to mimic a portion of the molecular
sequence of myelin:
a. Avonex
b. Betaseron
c. Copaxone
d. Rebif
12. Score for an individual with normal motor function on the Kurtzke EDSS
a. 0
b. 1
c. 5
d. 10
40. Multiple Sclerosis
M. Patricia Leuschen, Kathleen M. Healey, and Mary L. Filipi
2
13. The Multiple Sclerosis Functional Composite (MSFC) does not test
a. motor function of the lower extremities
b. motor function of the upper extremities
c. cognitive changes
d. bowel and bladder function
14. The primary outcome measure for phase III FDA trials for the IFNβ therapies
a. Number and time between relapses
b. Evidence of lesions on MRI
c. A significant change in the MSFC
d. Time to complete a 25-foot walk
15. Prokarin™ is a trans dermal patch containing histamine and this compound
a. glatiramer acetate
b. IFN β
c. Caffeine
d. Corticosteroida
16. A therapy that has not shown efficacy in the treatment of MS
a. IFNγ
b. IFNβ-1b
c. Natalizunab
d. Mitoxantrone
e. methyl predisolone
17. The FDA approved therapy for relapsing remitting MS with the smallest % reduction in relapses at 12
months by the Johnson Class I data
a. Avonex
b. Betaseron
c. Copaxone
d. Rebif
18. Brain atrophy is considered significant is it exceeds the these normal changes related to aging
a. <0.5-1%
b. >0.5-1%
c. >1-1.5%
d. >5%
19. This approved therapy for relapsing remitting MS included a warning to monitor depression because of a
suicide during the phase III trial.
a. Avonex
b. Betaseron
c. Copaxone
d. Rebif
20. In the Kahn head-to-head trial which of the following therapies was not evaluated?
a. Avonex
b. Betaseron
c. Copaxone
d. Rebif
40. Multiple Sclerosis
M. Patricia Leuschen, Kathleen M. Healey, and Mary L. Filipi
3
Answers
1.
What clinical data would support initiating IFNβ therapy even before a definitive diagnosis of MS?
The CHAMPS study showed that patients who were started on Avonex with your brother’s symptoms had a 1%
risk of meeting criteria for definitive MS in 18 months compared to a 16% risk for those who did not begin
therapy.
2.
What clinical information, in association with verification of the clinical symptoms of optic neuritis and
fatigue would be sufficient to verify that the diagnosis is definitive MS using the revised MacDonald
criteria?
The presence of lesions on a brain MRI with and without gadolinium (Gd) to evaluate for the presence of recent
and evolving plaques CSF and EMG data are often also used to verify MS.
3.
Your brother has received information on the two FDA approved IFNβ-1a products. What are the
differences in dose, dosing schedule, potential for side effects and efficacy for the two products?
The two FDA approved IFNβ-1a products are Avonex® (Biogen-Idec) which is the lowest total weekly dose
available at 33mcg IFNβ-1a to be injected intramuscularly (IM) once a week and Rbif® (Serono) which is
available in doses of 22 mcg and 44 mcg for subcuntaneous (SQ) injection three times weekly. Both reduce MS
relapses significantly. Both have similar side effect profiles. The lower dose may cause fewer side effects but
there is also some evidence that the lower the dose the less effective in reducing relapses.
4.
Over the next year, your brother has 2 more episodes that include problems with walking and numbness
in his right hand. Are any other criteria necessary for a definitive diagnosis of MS by the revised
McDonald criteria?
If an MRI confirms the presence of active lesions, and your brother has clinical verification of at least 2
episodes separated by time in at least two different sites. MacDonald criteria are met.
5.
What would you expect an MRI to show if your brother truly has MS?
There should be evidence of lesions within the brain or spinal cord as a result of the recent exacerbations. Since
they are relatively recent, one would expect Gd to infiltrate the brain parenchyma through breaches in the
cerebrovascular endothelium.
6.
Your brother has been on IFNβ-1a IM therapy for 9 months and is still complaining of flu like symptoms
and muscular aches and pain following each injection. What other therapeutic option(s) does he have?
There are several options that should be discussed with his neurologist. He could first try pre-medicating with
an over the counter NSAID before his weekly injection. Ibuprofen and naproxen are effective in alleviating
some flu like symptoms in some patient. If that is not effective, there is also evidence that oral corticosteroids
taken in conjunction with the IFNβ injection will decrease the inflammatory side effects. The other possibility
is to change to a non IFNβ therapy. Glatiramer acetate (Copaxone®) has a similar efficacy profile without the
flu like side effects.
7.
How has the diagnosis of MS changed your brother’s life expectancy?
Prior to approval of the current therapies, life expectancy form MS was only decreased by 2-3 years. Since the
longest any approved therapy has been available is approximately 10 years, there is no additional information
available. In general with all things considered, his expectancy should not be significantly different that yours.
8.
Your brother has just had a major relapse that has left him unable to walk. What is the standard therapy
for this type of acute relapse and what is the postulated mechanism of action?
The standard of therapy is a Methyl prednisolone (Solu-Medrol™)with IV treatment for 3-5 days at 500 to 1000
mg/day. There is no evidence that steroids reduce the relapse rate but they are effective in treating the acute
inflammation.
40. Multiple Sclerosis
M. Patricia Leuschen, Kathleen M. Healey, and Mary L. Filipi
9.
4
If the previous scenario had been your sister rather than your brother, would the prognosis have been
different?
Men often have a more aggressive and progressive MS than women. With frequent clinical and MRI
monitoring to determine if the current therapy is adequate, his prognosis should be better than if he were
diagnosed 10 years ago.
10. Your brother continues to progress rapidly with no apparent remission even on standard
immunotherapy for RR-MS. What therapy is FDA approved for rapidly progressing MS?
The only FDA approved therapy is mitoxantrone (Novantron®) with a recommended dosage for treatment of
multiple sclerosis at 5 to 12 mg/mL IV every 3 months. Acute side effects of mitoxantrone include nausea and
alopecia. Because of cumulative cardiotoxicity, the drug can be used for only two to three years (or for a
cumulative dose of 120 to 140 mg per m2).
11.
c
12.
a
13.
d
14.
a
15.
c
16.
a
17.
a
18.
b
19.
d
20.
d