FEATURE

The Return of Thalidomide in Leprosy do not require any specific treatment except with some Thalidomide: A few years later, however, the analgesics/antipyretics. In those drug thalidomide was suffering ENL associated neuritis, New Uses and reintroduced as treatment for a the drug of choice is Renewed complication of leprosy called prednisolone. For chronic erythema nodosum leprosum recurrent reactions the drug of Concerns (ENL). Although the evidence choice is clofazimine. Dr V Pannikar, Medical was not fully established, very soon the drug was heralded as Thalidomide in other Officer, Communicable the drug of choice for the indications Diseases (Leprosy management of ENL reactions in Group), WHO leprosy and regulatory The above points clearly authorities granted exemption demonstrate that there is no place for thalidomide in leprosy. History from licensing requirements to enable doctors to obtain limited But very often this disease is Thalidomide or α-(N- supplies of thalidomide under used as an entry point to phthalimido) glutarimide was strictly controlled circumstances reintroduce thalidomide for a marketed in 1957 for morning for use in named patients. multitude of other indications. sickness and nausea and soon Thalidomide's effectiveness in Millions of treatments are being became the ‘drug of choice to minimizing symptoms of ENL was prescribed annually and almost help pregnant women’. It went mainly due to its antipyretic all of it is for non-leprosy into general use by the following action. Its effectiveness in conditions including cancer year and was widely prescribed controlling neuritis, the major treatment and use in HIV. There in Europe, Australia, Asia, Africa cause of permanent disabilities in are limited trials demonstrating 1 leprosy, was limited. the efficacy of thalidomide in and the Americas . Allegedly, the 14,15 drug was harmless and a lethal other conditions . Each Several controlled studies dose could not even be condition must be evaluated in done in the 70's have established2. However, in the its own right and there must be demonstrated that predni- early 1960s, in what might be put in place stringent restrictions solone is more effective in described as the worst case of on its availability. In addition controlling ENL and associated pharmaceutical oversight, the there must be a monitoring neuritis4-6. In addition, it was drug was found to be associated system in place. There is no demonstrated that clofazimine, with a congenital abnormality justification in extrapolating data an anti-leprosy drug introduced causing severe birth defects in from monitoring systems for on a small scale in the early 60's children born of women who had leprosy to other conditions. The had anti-inflammatory action7,8. been prescribed this drug during medical community that support Studies showed that clofazimine pregnancy. More than 10, 000 the use of thalidomide for other is the drug of choice for the cases of birth defects were conditions should make their management of chronic, reported in over 46 nations own case for the drug. They recurrent ENL reactions, as it following thalidomide exposure. cannot base it on the leprosy had both anti-reaction and anti- Children were born with missing studies which are anything but leprosy effect. Moreover, while (amelia) or abnormal exhaustive. almost all patients given (phocomelia) legs, arms, feet thalidomide relapsed after In conclusion and hands; spinal cord defects; discontinuation of the drug, none cleft lip or palate; absent or Today, a large number of of the patients treated with abnormal external ears; heart, thalidomide babies continue to clofazimine for ENL reactions kidney, and genital be born each year16-18 possibly relapsed9-11. The drug abnormalities; and abnormal reflecting regulatory insufficiency clofazimine is now a component formation of the digestive and widespread use under of the multidrug therapy (MDT), system. It is estimated that 40% inadequate supervision. In Brazil, introduced by WHO in 1981 as of thalidomide victims died which has more than 1000 the standard treatment for within a year of birth3. Today registered thalidomide victims, leprosy. The presence of there are approximately 5000 the last officially known case was clofazimine in the combination thalidomide survivors1. The born in 199519,20. There is has significantly reduced the ‘thalidomide syndrome’ trig- evidence that second generation frequency and severity of ENL gered a world wide response. babies with similar deformities reactions world-wide12,13. Safety monitoring systems were are being born to thalidomide set up to prevent this tragedy Today ENL reaction is a rare victims21,22. In the US, Celgene ever happening again and the complication, limited to a small Corporation has had FDA drug was taken off the market in proportion of multibacillary approval to market the drug many countries in 1961. patients. Most of the ENL since 1998 for the cutaneous reactions are mild in nature and manifestations of moderate to FEATURE

severe erythema nodosum cases. Bull World Health Org leprosum. In Europe, the US 1971, 45: 719. company Pharmion Corp and 10. Iyer CG, Ramu G. An open trial French rival Laphal have both with clofazimine in the management of recurrent lepra secured orphan drug status for reaction using thalidomide as a thalidomide and have applied to control drug. Leprosy in India, market the drug as a therapy for 1976, 48: 690. multiple myeloma and for ENL in 11. Ramanujam K, Iyer CG, Ramu the EU. The EU is currently G. Open trial with clofazimine in holding discussions on the re- the management of recurrent launch of thalidomide. Whatever lepra reaction and of sulphone the outcome of the EU sensitive cases: A preliminary discussions, it cannot be over report. Leprosy Review, 1975, emphasized that any potential 46 (supplement): 117. 12. Becx-Bluemink M, Berhe D. benefit with thalidomide must be Occurrence of reactions, their balanced with the known toxicity diagnosis and management in and the accompanying ethical leprosy patients treated with and legal constraints on its use. multidrug therapy; experience Experience has shown that it is in the Leprosy Control virtually impossible to develop Programme of All Africa Leprosy and implement a fool-proof and Rehabilitation Training surveillance mechanism to Centre (ALERT) in Ethiopia. combat misuse of thalidomide. International Journal of Leprosy and Other Mycobacterial References: Diseases, 1992, 60(2): 173. 1. What is Thalidomide? TVAC: 13. Willcox, M.L. The impact of Thalidomide Victims Association multidrug therapy on leprosy of Canada, September 01, disabilities. Leprosy Review, 1999. Available: 1997, 68: 350. http://www.thalidomide.ca 14. Wines, N.Y., Cooper, A.J. and 2. James JS. (ATN) Thalidomide Wines, M.P. Thalidomide in and HIV: Background. AIDS dermatology. Australian Journal Treatment News Issue #179, of Dermatology, 2002, 43(4): July 23, 1993. Available : 229. http://www.aegis.com/pubs/atn 15. Gaspari A. Thalidomide /1993/ATN17902.html neurotoxicity in dermatological 3. Lenz W. The History of patients: The next “STEP”. The Thalidomide. TVAC: Thalidomide Journal of Investigative Victims Association of Canada, Dermatology, 2002, 119: 987. September 01, 1999. Available: 16. FDA tries to plug risky drug http://www.thalidomide.ca loopholes. The Associated Press, 4. Dharmendra. Leprosy Volume 1, ABCNEWS.com, December 9, 1978, Kothari Medical Publishing 2002. Available: House, Bombay, India. http://www.boston.com/globe 5. WHO. The final push strategy to 17. Kranish, M. New use is found for eliminate leprosy a public health thalidomide: Fighting cancer. problem, questions & answers, Boston Globe Online, October second edition, 2003, WHO, 20, 2002 Geneva. 18. 40 years after the thalidomide 6. Ramu G and Iyer CG. Treatment holocaust. Available: of reactions in leprosy. In : A www.thalidomide.org/FfdN/Grun window on leprosy, 1978. Edited en/Grunthl.html by Chatterjee BR., published by 19. Castilla EE et al. Thalidomide, a Gandhi Memorial Leprosy current teratogen in South Foundation America. Teratology1996, 54: 7. Browne SG. B 663 - possible 273. anti-inflammatory action in 20. Communication from CEATOX - lepromatous leprosy. Leprosy Centro de Assistência Review, 1965, 36: 9. Toxicológica, Instituto da 8. Waters MFR. Transactions of the Criança Prof. Pedro de Ninth International Leprosy Alcantara, Hospital das Clinicas Congress, International Journal da Faculdade de Medicina da of Leprosy, 1968, 36: 560. U.S.P, Brazil. 9. Iyer CG et al. WHO coordinated 21. "Second generation" short term double blind trial Thalidomide claims. BBC News, with thalidomide on the Health, October 2, 2000. treatment of acute lepra 22. A curse on my baby. Sunday reactions in male lepromatous Times Focus, July 20, 1997.