Use of thalidomide in leprosy
Thalidomide or α-(N-phthalimido) glutarimide was first marketed in 1957 for morning sickness and nausea and soon became the ‘drug of choice to help pregnant women’.
By the early 1960s the drug was found to be associated with a congenital abnormality causing severe birth defects in children born of women who had been prescribed this drug during pregnancy. More than 10,000 cases of birth defects were reported in over 46 nations following exposure to the drug. Children were born with missing or abnormal legs, arms, feet and hands; spinal cord defects; cleft lip or palate; absent or abnormal external ears; heart, kidney, and genital abnormalities; and abnormal formation of the digestive system.
A few years later, however, thalidomide was reintroduced as the treatment for a complication of leprosy called erythema nodosum leprosum (ENL). Although the evidence was not fully established, very soon the drug was heralded as the drug of choice for the management of ENL reactions in leprosy and regulatory authorities granted exemption from licensing requirements to enable doctors to obtain limited supplies of thalidomide under strictly controlled circumstances for use in named patients. Thalidomide's effectiveness in minimizing symptoms of ENL was mainly due to its antipyretic action. Its effectiveness in controlling neuritis, the major cause of permanent disabilities in leprosy, was limited.
Several controlled studies done in the 1970s have demonstrated that prednisolone is more effective in controlling ENL and associated neuritis. In addition, it was demonstrated that clofazimine, an anti-leprosy drug introduced on a small scale in the early 1960s had anti-inflammatory action. Studies showed that clofazimine is the drug of choice for the management of chronic, recurrent ENL reactions, as it had both anti-reaction and anti-leprosy effects.
The drug clofazimine is now a component of the multidrug therapy (MDT), introduced by WHO in 1981 as the standard treatment for leprosy and now supplied free of charge to all patients worldwide. The presence of clofazimine in the combination has significantly reduced the frequency and severity of ENL reactions.
Because of its known teratogenic effects, WHO does not recommend the use of thalidomide in leprosy. Experience has shown that it is virtually impossible to develop and implement a fool-proof surveillance mechanism to combat misuse of the drug. Today, a number of thalidomide babies continue to be born each year reflecting regulatory insufficiency and widespread use under inadequate supervision.