http://neurology.medscape.com/Medscape/PhysicianAsst/AskExperts/2001/09/PA-ae61.html

09/20/2001

Question

Is there benefit in using low-dose steroids in multiple sclerosis (MS) patients who take immunomodulator drugs such as Avonex, Betaseron, or Copaxone?

Carol A. Calderazzo, PA-C

Response

from Blaine P. Carmichael, MPAS, PA-C, 09/20/01

Specialists in the treatment of MS have become considerably more aggressive in starting and maintaining patients on the "ABC" medicines: Avonex (interferon beta-1a), Betaseron (interferon beta-1b), and Copaxone (glatiramer acetate). Drug treatment is begun as soon as a lumbar puncture and analysis of cerebral spinal fluid confirms the diagnosis. Early treatment retards or even arrests the "ABCDs" that can take place in MS: axonal loss, brain atrophy, cognitive dysfunction, and disability.[1] Deciding among the 3 available medicines takes considerable experience and discussion between patients and their healthcare professionals.

Many clinicians will give a small dose of prednisone for a few weeks at the start of interferon treatment, and that seems to be helpful. The use of low-dose steroids in MS has been studied but reveals mixed results in the literature. Early trials showed that neither low doses of oral prednisolone[2] nor intramuscular adrenocorticotropic hormone[3] had any benefits after 18 months of treatment when compared with placebo.

The utility of low-dose steroids in ameliorating the side effects of the "ABC" drugs is open to some question. Anecdotally, however, many expert clinicians use low-dose steroids for side effects treatment. It is important to premedicate with acetaminophen, ibuprofen, or naproxen and take these medications around the clock to minimize adverse effects. Administer the immunomodulating agent at bedtime to allow the patient to sleep though the side effects. Other recommendations include the use of pentoxifylline (Trental) 400 mg twice a day on the day of injection and day following the injection. Pentoxifylline is very safe and has minimal stomach upset as a side effect. Finally, low-dose prednisone, 10 mg, on the day of injection is useful when given in the morning. This last treatment is almost always effective, according to Herman Weinreb, MD, now deceased, who was associate professor of Clinical Neurology and Psychiatry, New York University Medical Center, in his comments for the International MS Support Foundation at: http://www.msnews.org/faqavonex.shtml.

In a study[4] to determine whether low-dose prednisone reduces flu-like symptoms at the initiation of interferon beta-1b or interferon beta-1a, researchers studied 71 patients with clinically definite, relapsing, or remitting MS who were started on interferon beta-1b. Patients were randomized to receive prednisone plus acetaminophen or only acetaminophen and were monitored for side effects. Systemic side effects were minimal in the steroid group compared with the nonsteroid group during the first 15 days of treatment (P = .005). At 3 months, both groups showed a similar frequency of flu-like symptoms. No differences in local reaction between the 2 groups were observed throughout the study.

Among the available medicines, only interferon beta-1a has proven to significantly retard the disability in relapsing forms of MS over time.[5] Some studies now emerging indicate that interferon beta-1a might also have a positive effect on delaying brain atrophy and even improving cognitive problems in MS.[6]

Interferon beta-1b also has its share of adverse effects (flu-like symptoms, muscle aches, and fatigue), and patients with secondarily progressive MS were sensitive to them, but most of these are manageable.

Glatiramer acetate is a mixture of polypeptides that have been synthesized randomly from a pool of 4 amino acids -- L-glutamic acid, L-alanine, L-lysine, and L-tyrosine. Glatiramer acetate was originally designed to mimic myelin basic protein. Its mode of action has not been defined, although it is thought to involve inhibition of lymphocyte migration[7] and suppression of T-cell activation.[8] It may exert its effects by competing with myelin basic protein and perhaps other myelin autoantigens for binding to major histocompatibility class II molecules expressed on antigen-presenting cells.[9] A 2-year study demonstrated a 29% reduction in the relapse rate in patients with relapsing-remitting MS.[10,11] Glatiramer acetate is given daily at a dose of 20 mg subcutaneously. It is generally well tolerated, with the most common adverse experience being injection-site reaction. In addition, about 15% of patients may experience brief episodes (30 seconds to 30 minutes) of facial flushing and chest tightness, sometimes with palpitations, anxiety, and dyspnea. Low-dose steroids may be of value in controlling these generally mild side effects.

References

1. Fox RJ, Cohen JA. Multiple sclerosis: the importance of early recognition and treatment. Cleve Clin J Med. 2001;68:157-171.
2. Miller H, Newell DJ, Ridley A. Multiple sclerosis: trials of maintenance treatment with prednisolone and soluble aspirin. Lancet. 1961;1:127-129.
3. Millar JHD, Vas CJ, Noronha MJ, et al. Long-term treatment of multiple sclerosis with corticotrophin. Lancet. 1967;2:429-431.
4. Rio J, Nos C, Marzo ME, Tintore M, Montalban X. Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-1b in relapsing-remitting MS. Neurology. 1998;50:1910-1912.
5. Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and multiple sclerosis. Evidence based management strategies for fatigue in multiple sclerosis. Washington, DC: Multiple Sclerosis Council for Clinical Practice Guidelines; 1998.
6. Clanet MG, Brassat D. The management of multiple sclerosis patients. Curr Opin Neurol. 2000;13:263-270.
7. The IFNB Multiple Sclerosis Study Group, the University of British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology. 1995;45:1277-1285.
8. Goodkin DE. Role of steroids and immunosuppression and effects of interferon beta-1b in multiple sclerosis. West J Med. 1994;161:292-298.
9. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996;39:285-294.
10. Investigators report on new MS drug (special report). MS Quarterly Rep. 1994;13:1-2.
11. Simon JH, Jacobs L, Cookfair D, et al. The natural history of MS based on an annual MR snapshot: results from the MSCRG study of intramuscular recombinant interferon beta-1a (abstract). Neurology. 1995;45(suppl 4):A418.