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Abstract
Multiple sclerosis is an inflammatory autoimmune
disorder of the central nervous system and the most
common disabling neurologic disease of young adults with
a lifetime risk of 1 in 400.
The disease is classified to four subtypes according
to the clinical course of the disease; it is relapsing
remitting, primary progressive, secondary progressive and
progressive relapsing.
Treatment of the disease is passed on the fact that it
is an inflammatory disease and differs according to the type
of the disease.
Treatment of the disease is either treatment of the
relapse or secondary prevention;
Treatment of the relapse is important as in most
cases the acute attack is the main reason why a patient with
MS, especially early in the course of the disease seeks help
from a physician, treatment with glucocorticoids is the
mainstays in the treatment of MS because of its potent
immunosuppressive and anti-inflammatory effect.
The first steroid treatment in MS was
adrenocorticotrophic hormone (ACTH); however, it caused
unselected release of steroids from the adrenal glands in
unpredictable quantities. Intravenous methylprednisolone
(IVMP) took its place after it was shown to be as
efficacious as ACTH.
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IVMP is given in a dose of 1 g for 5 consecutive
days to be given as a single daily dose, an oral taper of
prednisolone after this regime is popular in order to
substitute for the suppression of the hypothalamic-pituitaryadrenal
axis.
Plasma Exchange (PE) is another strategy for
treatment of relapses in MS however IVMP remains the
initial treatment of choice for severe CNS demyelinating
attacks, and PE should only be considered for the relatively
uncommon situation where a patient with an acute attack
has persistent, severe neurologic deficits following
treatment with corticosteroids.
Intravenous immunoglobulin is another treatment
option for patients with acute significantly disabling relapse
with inadequate response to steroids, the regimen used is
0.4 g/kg daily for 5 days.
Regarding the secondary prevention of multiple
sclerosis FDA approved 7 drugs which includes;
First line drugs include interferon β 1b (Betaseron®,
Betaferon®) given in a dose of 250 μg subcutaneous on
alternate days aiming to reduce the clinical and MRI attack
rate in patients with RRMS, also the drug has been
approved by FDA and the European agency EMEA for
treatment of SPMS patients with superimposed relapses.
Interferon β 1a (Avonex®) given in a dose of 30 μg
intramuscular every week aiming to decrease the relapse
rate in RRMS.
Interferon β 1a (Rebif ®) given in a dose of 22 μg or
44 μg subcutaneous twice weekly for prevention of relapse
and disability in patients with RRMS, it is being more
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superior than interferon β 1a given by intramuscular route
in reducing the relapse rate, also the higher dose (44 μg)
seems to decrease the active MRI lesions compared with
the smaller dose.
Glatiramer Acetate (Copaxone ®) given in a dose of
20 μg subcutaneous daily for 2 years with delayed effect
until 6 month after initiation of treatment suggesting that
there is no immediate impact on the blood-brain barrier and
that the immunological effect of GA has to accumulate
over time before becoming detectable.
Glatiramer Acetate was licensed for treatment of
patients with RRMS aiming for stabilization of the EDSS
and marked reduction in the clinical attack rate together
with reduction in the mean number of enhancing lesions in
MRI.
Second line drugs for treatment of multiple sclerosis
are Mitoxantrone and Natalizumab.
Mitoxantrone (Novantrone®) given first in an
induction phase with three monthly administrations of 12
mg/m2, followed by a maintenance phase every 3 months
for 2 years. The rationale for an induction phase is based on
the presence of very active inflammatory reactions and the
need to control rapidly disease progression. The rationale
for maintenance therapy is obvious. MS is a chronic disease
and it has been observed that effects of a short-term
treatment with Mitoxantrone are limited in time.
Mitoxantrone was licensed for treatment of patients
with worsening RRMS or SPMS as the drug shows
effectivness in reducing progression of disability and
clinical exacerbations of the disease, however because of its
potential accumulative cardiotoxicity, Mitoxantrone should
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be reserved for RRMS patients in whom disease
progression cannot be controlled by established
immunomodulatory therapeutics.
Natalizumab (Tysabri ®) given in a dose of 300 mg
intravenous infusion every four weeks in patients with
RRMS or relapsing SPMS as the drug shows effectivness
in slowing the progression of disability in patients with
relapsing MS, reduceing relapses in individuals with MS by
68%, with significant increase in the proportion of diseasefree
individuals, significantly improved assessments of
health-related quality of life in relapsing individuals,
reduced cognitive decline of a portion of individuals with
MS, reduced hospitalizations and steroid use, and
prevention of the formation of new lesions.
Natalizumab should be given in patients with
relapsing forms of multiple sclerosis with high disease
activity, particularly those on active treatment with diseasemodifying
drugs, may be considered as preferred
candidates for Natalizumab treatment. However, currently
there are not sufficient data on the efficacy and safety of
Natalizumab in patients with progressive forms of multiple
sclerosis. Therefore, at this stage, patients with secondary
progressive or primary progressive multiple sclerosis
should not be treated with Natalizumab.
There is still some lack of information about the
safty, long term efficacy and the potential of developing
resistance to Natalizumab.
Cyclophosphamide given in a dose of 1g/m² with
subsequent increase or decrease the dose by 100 or 200 mg
according to the WBC count shows a benifecial effect in
patients with MS however the lack of information
regarding the duration of treatment limites its use.
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Azathioprine has the same effect on relapse as
interferon however its toxicity limites its use.
Other new drugs are still under trial for treatment of
patients with MS shows promising results as Methotrexate,
Cladribine, Fumaric acid, Mycophenolate mofetil,
Sirolimus and Temsirolimus as well as other monoclonal
antibody other than Natalizumab as Rituximab,
Alemtuzumab and Daclizumab
In conclusion, for each clinical subform of MS, there
is an ideal treatment strategy; pulsed high-dose
glucocorticoids would be the treatment of choice in case of
acute relapse, and in escalation plasma exchange should be
considered.
Cases of clinically isolated syndrome with high risk
of developing clinically definite MS are best managed with
Interferon-beta.
In Relapsing-Remitting MS; the first line includes
Interferon-beta and Glatiramer Acetate, while the second
line includes IVIG and Azathioprine. If the relapses are
severe with rapid progression, Mitoxantrone is preferred.
In Secondary Progressive MS, if the relapses are
prominent, Interferon-beta is the ideal therapy;
Mitoxantrone is the first line of management if the course is
prominently progressive, and Cyclophosphamide is used as
a second line of management of SPMS.
There is no established therapy available for both
Primary progressive MS and Primary-Relapsing MS.