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EDITORIALS: V Peter Misra The changed image of botulinum toxin BMJ 2002; 325: 1188 [Full text]

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Countering the media hype

V. Peter Misra   (27 November 2002)

The long-term safety of botulinum toxin

Anthony B Ward   (3 December 2002)

Long term effects of Botulinum Toxin

Jai Kulkarni   (10 December 2002)

On The Efficacy, Safety and Appropriate Use of Botox

Nicholas J Lowe   (21 January 2003)

Countering the media hype 27 November 2002
V. Peter Misra, Consultant in Clinical Neurophysiology The National Hospital for Neurology & Neurosurgery, London WC1NC Send response to journal: Re: Countering the media hype	Re: My editorial “ The changing image of botulinum toxin” which appeared in last week’s BMJ (BMJ 325;23:1188, November 2002). I am concerned at the slant with which some sections of the press and media have reported aspects of my editorial [1]. I write again to clarify the focus of the editorial. The editorial provided a note of caution regarding the potentially inappropriate use of botulinum toxin where use is exclusively driven by its image as a glamour drug and by the associated hype. As is the case with any new and potent drug, very long-term side effects are by definition unknown, which is what is said in the editorial. This does not mean that the drug does have long-term side effects. The simple answer to the question whether botulinum toxin has any very long term side effects is – we don’t know. There is no special reason to believe or disbelieve that very long term side effects would appear. A review of clinical trials for cervical dystonia, which ran over 7 years from 1988-95 reported that systemic side effects from botulinum toxin were rare [2]. The drug should be administered to patients when there is a clear indication and in a medical setting. The editorial states that the botulinum toxin is licensed for several conditions and that efficacy in these conditions is notable. For some of the conditions where use is unlicensed preliminary evidence seems encouraging. We must wait for the results of suitably sized randomised control trials. The media reports mainly laid stress on one aspect of the editorial and I hope to try and redress the imbalance in this response. 1. http://news.google.com/news?hl=en&q=peter+misra&btnG=Google+Search 2. Poewe W, Entner T. Studies with Dysport in cervical dystonia. In: Brin MF, Jankoivc J, Hallett M eds. Scientific and therapeutic aspects of botulinum toxin. Lippinincott Williams and Wilkins. Philadelphia, 2002:365 -9. Competing interests:   VPM has attended scientific meetings paid for by Allergan, Ipsen and Elan pharmaceuticals and conducted educational programmes paid for by Allergan. All these companies manafacture botulinum toxin. His research registrars have also been paid by the above companies for attending meetings and conduct research.
The long-term safety of botulinum toxin 3 December 2002
Anthony B Ward, Consultant in Rehabilitation Medicine North Staffordshire Hospital NHS Trust, The Haywood, Stoke on Trent, ST6 7AG. Send response to journal: Re: The long-term safety of botulinum toxin	I am writing to clarify and perhaps challenge some of the interpretations of Dr Peter Misra’s editorial on the use and safety of botulinum toxin(1). Botulinum toxin type A has been prescribed successfully for more than 15 years and used to treat thousands of patients of many age groups for a variety of therapeutic conditions – including cerebral palsy in adults and children as young as two(2). Its safe and effective use is also well documented in both short and long-term studies of the management of spasticity and various forms of dystonia, to which Dr Misra does allude. However, speculation on possible adverse long-term effects is unhelpful in the light of numerous published data over a decade from a significant number of randomised controlled trials(3). The F.D.A. would also be unlikely to grant a licence for this drug for cosmetic purposes, unless it was entirely satisfied that the evidence for efficacy and safety was robust(4). There are also data from the management of chronic spasticity following stroke and multiple sclerosis. A long-term beneficial effect has been shown with a decreased need for botulinum toxin on repeated injections and that safety remains just as good after the fourth injection as after the first(5). An audit carried out on a random sample of 50 of my own patients over a nine year period (manuscript in preparation) also shows that multiple sclerosis patients continue to benefit from repeated treatments with only a small incidence of transient adverse events and no drug related serious adverse events.. Dr Misra’s paper has perhaps rather highlighted the dramatic side of botulinum toxin A at the expense of the clinical, which is unfortunate, as the evidence points to its safety in current dosages used in clinical practice by trained physicians. References 1.Misra P. The changed image of botulinum toxin. BMJ 2002; 325: 1188. 2.Wissel J. Heinen F. Schenkel A. Doll B. Ebersbach G. Muller J. Poewe W. Botulinum toxin A in the management of spastic gait disorders in children and young adults with cerebral palsy: a randomized, double-blind study of "high-dose" versus "low-dose" treatment. Neuropediatrics 1999; 30(3):120- 4.) 3.Defazio G. Abbruzzese G. Girlanda P. Vacca L. Curra A. De Salvia R. Marchese R. Raineri R. Roselli F. Livrea P. Berardelli A. Botulinum toxin A treatment for primary hemifacial spasm: a 10-year multicenter study. Archives of Neurology 2002; 59(3):418-20. 4.Carruthers JA. Lowe NJ. Menter MA. Gibson J. Nordquist M. Mordaunt J. Walker P. Eadie N. A multicenter, double-blind, randomized, placebo- controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. Journal of the American Academy of Dermatology 2002; 46(6):840-9. 5.Gordon MF, Brashear A, Elovic E, et al. A multi-center open-label study of the safety and efficacy of repeated botulinum toxin type A doses in post-stroke upper limb spasticity. Neurology 2002; 58 (suppl 3): A221 abstr. Competing interests:   I have attended scientific meetings and advisory board meetings paid for by Allergan, Ipsen and Elan Pharmaceuticals and conducted educational programmes paid for by Allergan. I have also received educational grants from Allergan and Ipsen to conduct research studies, but the opinions expressed above are my own independent views.
Long term effects of Botulinum Toxin 10 December 2002
Jai Kulkarni, Consultant in Rehabilitation Medicine Manchester Royal Infirmary. M13 9WL Send response to journal: Re: Long term effects of Botulinum Toxin	Editor; Misra mentions that the long term effects of botulinum toxin are unknown (1). Though this may well be true, a considerable number of clinicans in UK, Continent and USA, have been involved in the usage of this toxin for well over a decade. Our experience of the last seven years of injection therapy under electromyography control for focal spasticity, with ongoing follow up of more than 150 patients, has not depicted any long term effects over seven years. The only early side effects, all of which occurred within one week of injections, have been local discomfort and mild flu like symptoms.(2) The effectiveness and efficacy of this treatment has been notably significant, with measurable improvements in over three quarters of the patients. Currently the benefit: risks ratio, is in favour of this treatment modality, but clinicians do need to maintain a long term follow up of these patients, so that any untoward long term effects can be monitored. 1. Misra PV. The changed image of botulinum toxin. BMJ 2002; 325: 1188 (23 November) 2. Kulkarni J, Deshpande M. Botulinum toxin: therapy for spasticity in neurorehabilitation unit. Progress in Neurology and Psychiatry. 2000; 4, 3: 30-35. Competing interests:   None declared
On The Efficacy, Safety and Appropriate Use of Botox 21 January 2003
Nicholas J Lowe, Consultant Dermatologist 19a Cavendish Square, 3 Harcourt House, London W1M 9AD Send response to journal: Re: On The Efficacy, Safety and Appropriate Use of Botox	This editorial discusses important aspects about current treatment practices with Botulinum toxin type A (BTX-A). I agree about the need for its medically appropriate use. By appropriate, I mean treatment in a medical setting by a specialist physician trained in the administration of BTX-A. The advertising of Botox by non-medical Cosmetic Clinics is inappropriate and the concept of the high street pharmacist or non-medical cosmetician offering BTX-A treatment ill advised. The Care Commission and GMC would not hopefully allow Cosmetic Clinics to prescribe medications for the treatment of diseases. While Botox for facial lines is not yet approved in Europe, it is in several countries. It has been confirmed to be highly effective and safe in multicentre randomised studies involving over 500 patients in the United States and Canada of glabellar forehead lines (1). These studies showed the safety of Botox after repeat injections. It has been used aesthetically in the USA by specialist physicians for at least 14 years and for about 10 years in the UK. BTX-A is a valuable treatment for severe axillary hyperhidrosis (2,3). A large placebo-controlled study published in this journal confirmed its effectiveness and safety (4). This study enabled Botox to be licensed in the United Kingdom and some other countries as a treatment for severe focal axillary hyperhidrosis. The quality of life of these patients can be transformed by its use as recently reported. (5). The long term safety of Botox over at least twenty years of use in a variety of disorders has been well established providing correct injection techniques are followed - which brings me back to appropriate use by appropriately trained specialist physicians. Summary: Botox A is valuable and has an excellent safety record in many approved and non-approved indications. In some countries, it is approved for aesthetic use, however, its availability in situations such as Botox Parties and non-medical Aesthetic Clinics raises important ethical, professional and public safety issues. Dr Nicholas J Lowe, MD FRCP Consultant Dermatologist Cranley Clinic for Dermatology London, The Middlesex Hospital, London & UCLA School of Medicine, Los Angeles, California Correspondence: Cranley Clinic, 3 Harcourt House, 19A Cavendish Square, London. W1G OPN Dr Lowe has received research grants and consultant payments from Allergan Pharmaceutical and Elan in the USA. All views stated are personal. REFERENCES 1. Carruthers JA, Lowe NJ, Menter A et al. A multicentre double- blind, randomised placebo controlled study on the safety and efficacy of Botulinum Toxin Type A in the treatment of glabellar lines. JAA Derm 2002.46.840-849. 2. Bushara KO, Park DM, Jones JC, Schutta HS. Botulinum toxin - a possible new treatment for axillary hyperhidrosis. Clin Exp Dermatol 1996.21:276-8. 3. Heckmann M, Ceballos-Baumann AO, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med 2001.344;488- 93. 4. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis, randomised, parallel group, double blind, placebo controlled trial. BMJ 2001.323:596-9. 5. Naumann MK, Hamm H, Lowe NJ. Effect of Botulinum toxin type A on quality of life measures in patients with excessive axillary sweating, a randomised controlled trial. Br J Derm 2002.147,1218-1226. Competing interests:   Dr Lowe has received research grants and consultant payments from Allergan Pharmaceutical and Elan in the USA.