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. 2001 Jan 27;322(7280):236.

Revised guideline for prescribing vigabatrin in children

Guideline's claim about infantile spasms is not based on appropriate evidence

Andrew L Lux 1,2,3,4,5,6,7,8, Stuart W Edwards 1,2,3,4,5,6,7,8, John P Osborne 1,2,3,4,5,6,7,8, Eleanor Hancock 1,2,3,4,5,6,7,8, Anthony L Johnson 1,2,3,4,5,6,7,8, Colin R Kennedy 1,2,3,4,5,6,7,8, Finbar J K O'Callaghan 1,2,3,4,5,6,7,8, Richard W Newton 1,2,3,4,5,6,7,8, Christopher M Verity 1,2,3,4,5,6,7,8
PMCID: PMC1119485  PMID: 11159628

Editor—The Vigabatrin Paediatric Advisory Group, which in 1998 produced a guideline to “help clinicians when prescribing vigabatrin in children,” has now revised it.1,2 We, the steering committee of the United Kingdom infantile spasm study (UKISS), responded to the original guideline.3 Our opinion was that there is no evidence that vigabatrin is a better treatment of infantile spasms than hormonal treatments, such as prednisolone and synthetic adrenocorticotrophic hormone preparations.

When we challenged the claim that vigabatrin is the drug of choice, the advisory group offered no rebuttal. Now the claim is stated again, without any appropriate new evidence being produced. Indeed, the finding that visual field losses attributable to vigabatrin occur in children as well as adults strengthens any challenge to the guideline's claim.

We stand by our argument that no one has yet determined the best first line treatment for infantile spasms. To back our challenge we cited the one randomised trial that has compared vigabatrin and adrenocorticotrophic hormone; confidence intervals for this suggest that vigabatrin is unlikely to have a superior treatment effect.4 Also, we pointed to a lack of studies using neurodevelopmental outcome measures and to new and emerging information about the safety of vigabatrin.

Our desire to gather reliable data is shared by many paediatricians and paediatric neurologists: consultants in over 140 health districts are helping our study to collect evidence about these treatments. Before clinicians can decide if any of the first line treatments for infantile spasms might reasonably be described as the drug of choice they will need to examine (when they become available) the results of studies such as the United Kingdom infantile spasm study.

References

  • 1.Appleton RE. Guideline may help in prescribing vigabatrin. BMJ. 1998;317:1322. doi: 10.1136/bmj.317.7168.1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Vigabatrin Paediatric Advisory Group. Guideline for prescribing vigabatrin in children has been revised. BMJ. 2000;320:1404–1405. . (20 May.) [PMC free article] [PubMed] [Google Scholar]
  • 3.Osborne JP, Edwards SW, Hancock E, Lux AL, O'Callaghan F, Johnson T, et al. Infantile spasms and vigabatrin. BMJ. 1999;318:56–57. doi: 10.1136/bmj.318.7175.56a. [DOI] [PMC free article] [PubMed] [Google Scholar]
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BMJ. 2001 Jan 27;322(7280):236.

Advisory group's reply

Vigabatrin Paediatric Advisory Group1

Editor—Both of Lux et al's letters (this one and that in 1999) have largely, and understandably, promoted the United Kingdom infantile spasm study; their comments have been of little relevance to both the initial1-1 and revised1-2 pragmatic clinical guideline. At the time that we wrote both guidelines, vigabatrin was the drug of first choice, on the basis of efficacy and safety evidence, in treating infantile spasms; it still remains the drug of choice.

We agree with Lux et al that there is no convincing evidence that vigabatrin shows superior efficacy to adrenocorticotrophic hormone or prednisolone either in controlling spasms or in long term neurodevelopmental outcome. It is disingenuous, though, to ignore the recognised benefits of using vigabatrin in treating infantile spasms–namely, that the drug seems to be effective in at least half of patients1-3; that its effect is rapid (usually less than seven days in patients responsive to vigabatrin1-3,1-4); and that, unlike adrenocorticotrophic hormone and prednisolone, it does not cause severe side effects.1-5 The information currently available on visual field constriction does not alter this opinion, the reasons for which have been discussed recently in more detail.1-6 With these issues in mind, the justification for the content of the pragmatic guideline should be obvious.

Although we support Lux et al's call for large and well designed comparative studies, methodological and ethical concerns about their study have precluded universal participation in it. Roughly 300 British children develop infantile spasms each year. For these children, their parents and carers, and their clinicians, treatment cannot be deferred pending the findings of the United Kingdom study, whose results will not be available for many years. In addition, because infants who have infantile spasms (and West's syndrome) do not constitute a homogeneous population, the study findings may prove inconclusive. In the interim the guideline simply provides clinicians with pragmatic advice about how and when to use vigabatrin in the paediatric epilepsies, including infantile spasms.1-2

We should emphasise that our opinion is shared by many paediatric neurologists outside the United Kingdom,1-3,1-4,1-7 including paediatric neurologists in the United States (personal communication).

References

  • 1-1.Appleton RE. Guideline for prescribing vigabatrin. BMJ. 1998;317:1322. doi: 10.1136/bmj.317.7168.1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-2.Vigabatrin Paediatric Advisory Group. Guideline for prescribing vigabatrin in children has been revised. BMJ. 2000;320:1404–1405. . (20 May.) [PMC free article] [PubMed] [Google Scholar]
  • 1-3.Aicardi J, Mumford JP, Dumas C, Wood S. (With Sabril IS, investigator, and peer review groups.) Vigabatrin as initial therapy for infantile spasms: a European retrospective survey. Epilepsia. 1996;37:638–642. doi: 10.1111/j.1528-1157.1996.tb00627.x. [DOI] [PubMed] [Google Scholar]
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  • 1-5.Riikonen, Donner M. ACTH therapy in infantile spasms: side effects. Arch Dis Child. 1980;55:664–672. doi: 10.1136/adc.55.9.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-6.Appleton RE, Peters ACB, Mumford JP, Shaw DE. Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia. 1999;40:1627–1633. doi: 10.1111/j.1528-1157.1999.tb02049.x. [DOI] [PubMed] [Google Scholar]
  • 1-7.Fejerman N, Cersosimo R, Caraballo R, et al. Vigabatrin as a first-choice drug in the treatment of West syndrome. J Child Neurol. 2000;15:161–165. doi: 10.1177/088307380001500304. [DOI] [PubMed] [Google Scholar]

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