Trip Answers

Question answered:17/04/08

The 2003 NICE guidance recommends rapid diagnosis as:  ‘This ensures that any required treatments are started, and reduces anxiety and uncertainty.’ [1]

 

NICE states that treatment recommendations are “independent of whether the symptoms arise from a first presentation or a subsequent relapse.”  Bearing this in mind, and that the studies supporting the NICE recommendations were in people with MS of varying duration, NICE recommends:

 

“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” 

 

Evidence for long term benefit is less clear: “only one study reported data for long-term follow-up, and reported no significant effect of treatment in terms of improvement or the number of new exacerbations between the methylprednisolone and placebo groups [2] AAN concur:  ‘There does not appear, however, to be any long-term functional benefit after the brief use of glucocorticoids ..’ [3]

 

Examining evidence for long-term benefit of early treatments in people with more recent diagnoses, the evidence appears inconclusive at present. The Association of British Neurologists outlines new diagnostic criteria for MS that allow MS to be diagnosed after one clinical episode. For this group of people with clinically possible MS (not all will develop MS), the guidelines note that  ‘Disease modifying treatments may reduce the development of disability through prevention of relapses that would otherwise have resulted in residual dysfunction, although the effect appears modest over the trial study periods’ [4]

 

In 2002, the AAN guidelines stated that for Interferon-Beta ‘It is possible that certain populations of MS patients (e.g., those with more attacks or at earlier disease stages) may be better candidates for therapy than others, although, at the moment, there is insufficient evidence regarding these issues..’ [3]. However, some evidence of benefit of early treatment is now beginning to emerge – at least in the mid-term. 

 

The 3-year follow up of the BENEFIT study randomised patients with a first event suggestive of MS and a minimum of two clinically silent lesions in MRI to early interferon beta-1b treatment compared with delayed treatment initiated after diagnosis of clinically diagnosed MS (CDMS) or after 2 years on the study.

 

‘After 3 years, 99 (37%) patients in the early group developed CDMS compared with 85 (51%) patients in the delayed treatment group. Early treatment reduced the risk of CDMS by 41% (hazard ratio 0.59, 95% CI 0.44-0.80; p=0.0011; absolute risk reduction 14%) compared with delayed treatment. Over 3 years, 42 (16%) patients in the early group and 40 (24%) in the delayed group had confirmed EDSS progression; early treatment reduced the risk for progression of disability by 40% compared with delayed treatment (0.60, 0.39-0.92; p=0.022; absolute risk reduction 8%)’ [5]

 
References

1. NICE. Multiple sclerosis. Management of multiple sclerosis in primary and secondary care. London, NICE, 2003. Available from: http://www.nice.org.uk/nicemedia/pdf/cg008guidance.pdf
2. The National Collaborating Centre for Chronic Conditions at the Royal College of Physicians. .Multiple Sclerosis. National clinical guideline for diagnosis and management in primary and secondary care. London, Royal College of Physicians, 2003. Available from:  http://www.rcplondon.ac.uk/pubs/books/MS/MSfulldocument.pdf
3. Goodin DS, Frohman EM, Garmany GP Jr, Halper J, Likosky WH, Lublin FD, Silberberg DH, Stuart WH, van den Noort S. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002 Jan 22;58(2):169-78. Available from: http://www.neurology.org/cgi/reprint/58/2/169.pdf
4. ABN Guidelines for treatment of multiple sclerosis with ß-interferon and glatiramer acetate. London, Association of British Neurologists, 2007. Available from: http://www.theabn.org/downloads/ABN-MS-Guidelines-2007.pdf  
5. Kappos L, Freedman MS, Polman CH, et al; BENEFIT Study Group.  Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet. 2007 Aug 4;370(9585):389-97. Pubmed
6. Nicolas R, Chataway J.  Multiple Sclerosis. In Clinical Evidence. London, BMJ, 2008.
 

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