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Letters

Revised guideline for prescribing vigabatrin in children

BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7280.236 (Published 27 January 2001) Cite this as: BMJ 2001;322:236

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

  1. Andrew L Lux (andrew.lux{at}ruh-bath.swest.nhs.uk), clinical research fellow,
  2. Stuart W Edwards, UKISS research coordinator,
  3. John P Osborne, professor of paediatrics and child health,
  4. Eleanor Hancock, specialist registrar in paediatric neurology,
  5. Anthony L Johnson, statistician,
  6. Colin R Kennedy, consultant paediatric neurologist,
  7. Finbar J K O'Callaghan, specialist registrar in paediatric neurology,
  8. Richard W Newton, consultant paediatric neurologist,
  9. Christopher M Verity, consultant paediatric neurologist
  1. Bath Unit for Research in Paediatrics, Children's Centre, Royal United Hospital, Bath BA1 3NG
  2. Royal United Hospital, Bath BA1 3NG
  3. Chelsea and Westminster Hospital, London SW10 9NH
  4. MRC Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR
  5. Southampton General Hospital, Southampton SO9 4XY
  6. Royal Manchester Children's Hospital, Manchester M27 1HA
  7. Addenbrooke's Hospital, Cambridge CB2 2QQ
  8. Members of the group are: Richard Appleton, consultant paediatric neurologist, Liverpool (to whom correspondence should be addressed at the Roald Dahl EEG Unit, Alder Hey Children's Hospital, Liverpool L12 2AP); Peter Baxter, consultant paediatric neurologist, Sheffield; David Calver, consultant ophthalmologist, London; Celia Cramp, consultant paediatrician, Shrewsbury; John Gibbs, consultant paediatrician, Chester; Graham Harding, consultant clinical neurophysiologist, Birmingham; John Livingston, consultant paediatric neurologist, Leeds; Richard Robinson, consultant paediatric neurologist, London; Isabelle Russell-Eggitt, consultant paediatric ophthalmologist, London; Sheila Wallace, consultant paediatric neurologist, Cardiff; and John Wild, senior lecturer in vision sciences, Birmingham.

    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

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    Advisory group's reply

    1. Vigabatrin Paediatric Advisory Group.
    1. Bath Unit for Research in Paediatrics, Children's Centre, Royal United Hospital, Bath BA1 3NG
    2. Royal United Hospital, Bath BA1 3NG
    3. Chelsea and Westminster Hospital, London SW10 9NH
    4. MRC Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR
    5. Southampton General Hospital, Southampton SO9 4XY
    6. Royal Manchester Children's Hospital, Manchester M27 1HA
    7. Addenbrooke's Hospital, Cambridge CB2 2QQ
    8. Members of the group are: Richard Appleton, consultant paediatric neurologist, Liverpool (to whom correspondence should be addressed at the Roald Dahl EEG Unit, Alder Hey Children's Hospital, Liverpool L12 2AP); Peter Baxter, consultant paediatric neurologist, Sheffield; David Calver, consultant ophthalmologist, London; Celia Cramp, consultant paediatrician, Shrewsbury; John Gibbs, consultant paediatrician, Chester; Graham Harding, consultant clinical neurophysiologist, Birmingham; John Livingston, consultant paediatric neurologist, Leeds; Richard Robinson, consultant paediatric neurologist, London; Isabelle Russell-Eggitt, consultant paediatric ophthalmologist, London; Sheila Wallace, consultant paediatric neurologist, Cardiff; and John Wild, senior lecturer in vision sciences, Birmingham.

      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 and revised2 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 patients3; that its effect is rapid (usually less than seven days in patients responsive to vigabatrin 3 4); and that, unlike adrenocorticotrophic hormone and prednisolone, it does not cause severe side effects.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.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.2

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

      References

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      View Abstract