Trip Answers

Question answered:22/02/06 Warning! this question is over two years old.

The 2003 NICE Guideline on Multiple Sclerosis [1], section 4.4, discusses the available evidence relating to efficacy and risks of using steroids for the treatment of MS.  In view of the level of detail in the guideline, we have highlighted a number of paragraphs below, and provided a link to the full guideline in the references section:

"4.4 Treatment of acute episodes
Acute episodes of neurological symptoms that lead to first presentation or to the recognition of a relapse are thought to be secondary to an episode of demyelination. Hence treatments that affect the inflammatory process and immune system are used, especially corticosteroids.

Currently, the use of corticosteroids is recommended as the standard treatment of acute MS relapses but clinical practice varies widely. Several preparations of steroids exist, and the recent trend has been away from adrenocorticotropic hormone (ACTH) (no longer available) and oral prednisolone to more potent preparations such as methylprednisolone and dexamethasone. Although there are many studies, they often address different questions making a synthesis of the evidence difficult. Furthermore many doctors use (and many patients prefer) oral corticosteroids and again the evidence about the efficacy or otherwise of this is simply absent. Lastly it should be recognised that both acute short-term and longer-term use of steroids may have side effects but, again, evidence on the clinical importance of this risk, and relative risk-benefit ratios is absent."

"Side effects were reported in two of the systematic reviews and two RCTs. These included herpes simplex, herpes zoster, severe ankle oedema, fractured neck of femur, acute anxiety and severe depression; weight gain, oedema, gastrointestinal symptoms and psychological symptoms; raised blood glucose; infection and raised blood pressure. One review reported that the major side effects were significantly more frequent in the intervention group compared to the control group. The frequency of minor side effects was high in all the studies."

"One may conclude that many factors should be considered when comparing alternative methods of methylprednisolone delivery and that there is little formal evidence on any of these. As a result there is no clearly dominant treatment in terms of clinical effectiveness or resource use, and the group was unable to make a recommendation for the preferred method of administration of high dose steroids."

"From evidence to recommendations
The evidence, although extensive, is difficult to use because the research has not considered many of the questions such as the relative effectiveness of different doses, different durations of treatment, different preparations, or different routes of administration. The guideline developers discussed the matter extensively and the recommendations below draw upon the evidence, experience and evidence in other areas of medicine, and current practice. We agreed that a single set of recommendations covering acute episodes including optic neuritis (and transverse myelitis, where there was no evidence) would be appropriate.

RECOMMENDATIONS
R47 Any individual who experiences an acute episode (including optic neuritis) sufficient to cause distressing symptoms or an increased limitation on activities should be offered a course of high-dose corticosteroids. The course should be started as soon as possible after onset of the relapse and should be either:
¡ñ intravenous methylprednisolone, 500mg ¨C 1g daily, for between three and five days
or
¡ñ high-dose oral methylprednisolone, 500mg ¨C 2g daily, for between three and five days.
R48 An individual should be given a clear explanation of the risks and benefits involved in taking corticosteroids.
R49 Frequent (more than three times a year) or prolonged (longer than three weeks) use of  corticosteroids should be avoided.
R50 Other medicines for the treatment of an acute relapse should not be used unless as part of a formal research protocol."

As regards treatment in the community, Appendix E of the NICE guideline states:

"The methods are compared in relation to their effect on relapse. The only formal comparative clinical evidence comes from two RCTs comparing oral methylprednisolone with intravenous administration as a hospital day case; these show equal efficacy. There is no formal clinical evidence comparing home intravenous administration with either hospital intravenous or oral administration. Assuming comparable regimens there is probably no reason to expect a
difference in efficacy between home and hospital intravenous administration. However, this does not take into account potential problems or side effects of treatments."

The BMJ's Clinical Evidence¡± publication summarises the benefits and harms of Corticosteroids for MS, based on one of the systematic reviews referred to in the NICE guideline, as follows [2]:

"Benefits
We found one systematic review (search date 1999, 377 people with multiple sclerosis requiring treatment for acute exacerbations, 4 RCTs of methylprednisolone, 2 RCTs of corticotrophin v placebo.  The systematic review found that, compared with placebo, methylprednisolone or corticotrophin significantly reduced the proportion of people whose symptoms were worse or unimproved within 5 weeks of treatment (5 RCTs; worse or unimproved within 5 weeks from randomisation: 63/175 [36%] with methylprednisolone or corticotrophin v 94/155 [60%] with placebo; OR 0.37, 95% CI 0.24 to 0.57). A small subgroup analysis using an indirect comparison suggested no difference between 5 days and 15 days of treatment with methylprednisolone. One of the included RCTs (51 people) found no significant difference between oral methylprednisolone and placebo in the prevention of new relapses or in disability after 1 year (proportion who relapsed: 17/26 [65%] with methylprednisolone v 13/25 [52%] with placebo; RR 1.26, 95% CI 0.79 to 2.01).

Harms
The review found that gastrointestinal symptoms occurred more often in people taking oral high dose methylprednisolone than in people taking placebo (38% v 8%; CI not reported).  It also found that psychiatric disorders (insomnia, elevated mood, ¡°psychosis¡±, or dysphonia) were more common in people receiving oral high dose methylprednisolone than in people receiving placebo, although the difference was not significant (11/50 [22%] v 5/44 [11%]; RR 1.87, 95% CI 0.77 to 4.55). Weight gain and oedema were more frequent in people receiving corticotrophin than in people receiving placebo (absolute numbers and CI not reported)."

A search of PubMed was carried out but we found no studies published subsequent to the NICE Guideline which significantly add to or refute the evidence set out above.

References
1. NICE Guideline ¨C Multiple Sclerosis. National Clinical Guideline for diagnosis and management in primary and secondary care. 2003.
http://www.nice.org.uk/page.aspx?o=89907

2. BMJ Clinical Evidence.  Multiple Sclerosis ¨C Corticosteroids.  November 2004.
http://www.clinicalevidence.com/ceweb/besttreatments/nud/1202/1202_i2.jsp?btuk=1
 

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