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Recommendations Regarding Corticosteroids in the Management of Multiple Sclerosis
bioavailability are comparable,
12
and the therapy is well tolerated.
13
Oral high-dose IVMP. For example, in optic neuritis trials high-dose IVMP seemed
therapy is more convenient for the patient and clinician, and is less expensive to produce a more rapid recovery of vision, although this was not significant
than traditional IV therapy.
14
Furthermore, comparable oral doses may be given at all time-points.
3
This trial also reported an increased rate of recurrent optic
twice daily with food to reduce the number of tablets to be consumed with neuritis with oral prednisone, although this observation may be spurious.
8
each dose. Several methods have been suggested for administering high-dose Higher-dose therapy is used more often because there are better data
oral steroids, although none has been adequately tested. Potential regimens demonstrating its efficacy. Nevertheless, some patients recover quickly
include a three- to seven-day course of oral methylprednisolone 1,000mg, oral following 10–14 days of low-dose oral therapy, and some neurologists prefer
dexamethasone at a dosage of 176mg/day, as 44mg tablets, or oral prednisone this approach in selected cases. It is, of course, impossible to determine
1,250mg.
12
In the first large-scale clinical trial to address this issue, a dose of whether an individual patient would recover from a relapse spontaneously
1,400mg of oral MP will be compared with 1,000mg of IVMP, to allow for an without steroid therapy, whether high- or low-dose.
estimated 70% absorption rate of the oral preparation.
Although on the basis of several relatively small studies
4,15–17
similar
high doses of PO and IV steroids seem to have similar therapeutic benefit It is important for the physician to be
in treating MS relapses, it would be more reassuring if this apparent
aware of the multiple factors that
equivalence were confirmed in a larger study population. Additionally,
adequate studies have not yet been performed to confirm the oral dose of influence decisions of when and how to
each agent that is bioequivalent to 1,000mg IVMP. Patient reports are varied
treat, and to proceed accordingly.
among those who were treated with both regimens, with some preferring
IVMP, which is often administered at home by a nurse, and others oral therapy.
Side Effects of High-dose Corticosteroids Long-term Pulse Therapy
Short courses of high-dose corticosteroids are usually safe and reasonably Pulse therapy is often used as a single- or multiday treatment (three to five
well-tolerated, but they do have numerous potential adverse effects. The most days) every few months (three to four months), or as an add-on to
common but usually not serious adverse effects associated with short disease-modifying therapies at doses comparable to those used to treat
courses of IV or oral corticosteroids include insomnia, dysphoria, anxiety, relapses. In practice, it is used most often for people who are developing
hyperglycemia, headache, myalgia, easy bruising, edema, palpitations, metallic secondary progressive disease who have failed other therapies and before
taste, increased appetite, acne, flushing, and gastrointestinal distress. Although using mitoxantrone.
19
Research to date has focused on whether long-term
uncommon, several important adverse effects have occurred with short pulse IVMP therapy may delay the progression of brain atrophy or disability in
courses of corticosteroids, including anaphylaxis (extremely rare), various patients with progressive disease. In summary:
mental disturbances (e.g. manic psychosis, euphoria, or suicidal depression),
avascular necrosis of bone (especially of the femoral head), hypokalemia, and • a five-year, phase II clinical trial of IVMP in patients with RRMS
19
showed
gastrointestinal perforation. Exacerbations of pre-existing peptic ulcer disease, that prolonged treatment with pulsed IVMP slowed the rate of whole-
diabetes, and hypertension have also been reported. Patients in high-risk brain atrophy, the development of destructive lesions (T1 black holes), and
groups should be tested for potential problems related to steroid treatment. the development of sustained physical disability compared with controls;
For example, diabetic patients should undergo glucose testing, patients on • pulse IVMP prevented the development of brain atrophy in 11 patients
warfarin sodium should have their International Normalized Ratio (INR) with primary progressive MS (PPMS);
20
checked, those with liver disease should be monitored, and patients with • a small retrospective study of patients who had received monthly pulses
hypertension should be treated cautiously. Daily blood glucose testing is of IVMP showed that the treatment was associated with improvement in
recommended as there have been rare instances in which patients without a fatigue, spasticity, and motor strength.
21
No acute exacerbations occurred
history of diabetes have developed diabetic ketoacidosis while taking high- in nine of 10 patients with PPMS or secondary progressive MS (SPMS);
dose steroids. There is a low risk of electrolyte imbalance depending on which • pulse IVMP has also been shown to prevent sustained disability. In a phase
steroid is used and the dose and duration of therapy. Other known metabolic II study of 108 patients with SPMS, IVMP therapy was associated with a
abnormalities should be monitored as deemed appropriate. The incidence of marginally significant delay in the onset of sustained disability;
22
and
problems is small in patients with relapsing–remitting MS (RRMS), most of • in contrast, a single course of IVMP during an attack of acute optic
whom are young and have few medical comorbidities. The clinician’s best neuritis failed to prevent the development of optic nerve atrophy.
23
medical judgment should be applied on an individual basis. Repeated courses
of high-dose steroids increase the risk for osteoporosis, cataracts, glaucoma, Several studies have investigated the effect of glucocorticosteroids as
Cushingoid features, and the suppression of inflammatory and immune an add-on to standard disease management therapy, and several multicenter
responses, increasing the risk for opportunistic infections.
18
Even at low doses, combination trials have either been presented in a preliminary fashion or are
prolonged daily steroid therapy carries similar risks and should be avoided. ongoing. A recent study
24
added steroids (IVMP 1,000mg) for three
successive days every other month to Avonex
®
, and also evaluated the
Low-dose Oral Prednisone—Does It Have a Place in the combination of Avonex, IVMP, and methotrexate. Data showed favorable,
Therapeutic Armamentarium? although not statistically significant, trends. Another double-blind controlled
In general, low-dose oral prednisone (approximately 1mg/kg) is not trial will evaluate the efficacy of interferon (IFN)β-1b (Betaseron
®
) alone or in
considered to be as effective as either high-dose oral prednisone or combination with bi-monthly IVMP in SPMS patients. The ASSERT study is
US NEUROLOGY 23
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