To the Editor: The Australian Drug Evaluation Committee (ADEC) has recommended that thalidomide be approved for the management of erythema nodosum leprosum. This recommendation has now been accepted by the Therapeutic Goods Administration. Was ADEC unaware that the World Health Organization no longer recommends thalidomide in the management of this complication of lepromatous leprosy?1,2

In reply: When it considered thalidomide for registration for management of erythema nodosum leprosum (ENL) and another indication (myeloma), the Australian Drug Evaluation Committee (ADEC) was not aware that the World Health Organization (WHO) does not recommend the drug for this indication. ADEC bases its recommendations on review of the scientific and clinical evidence submitted concerning the efficacy and safety of products submitted for registration.

In the case of thalidomide in the management of ENL, ADEC reviewed the results of several randomised studies, together with additional published reports. Data from the US Public Health Service analysing the entire experience of thalidomide use in ENL in the United States from 1978 to 1994 were also reviewed. The committee concluded that the efficacy of thalidomide in acute ENL is beyond dispute. Moreover, thalidomide was also shown to be useful in patients with ENL already treated with corticosteroids and dapsone. ADEC discussed the side-effect profile of thalidomide in the ENL studies and concluded that skin rashes, sometimes with eosinophilia, were somewhat more common than in the myeloma studies that were also reviewed.

In regard to safety concerns relating to thalidomide’s teratogenicity, the committee was informed of the sponsor’s proposed risk management program, which is based on mandatory registration of prescribing doctors, patients and dispensing pharmacists. This program is based on an effective program in the US, where the Food and Drug Administration has registered thalidomide for treatment of ENL. ADEC felt that the risk–benefit ratio favoured registration for ENL (and myeloma). However, the committee resolved that a boxed warning should be included stating:

I have reviewed the WHO documents referred to by Crawford,1,2 and consulted Medline. I have also had access to a review article in press in the Lancet.3 I believe the evidence indicates that thalidomide is superior to steroids in controlling ENL. Britton and Lockwood state that thalidomide is the drug of choice for men with ENL;3 however, they comment that using thalidomide in women with ENL is a difficult decision for a woman and her doctor. The WHO documents emphasise that any benefit from thalidomide must be balanced against its known toxicity, and conclude that experience has shown that it is virtually impossible to develop and implement a foolproof surveillance mechanism to combat thalidomide toxicity.

ADEC concludes that thalidomide is an effective and useful drug in the management of ENL, and that the risk management program which is to be established in Australia, together with the inclusion of a boxed warning, will ensure that the risk–benefit profile of thalidomide use in ENL is favourable.