Thalidomide and its analogues: comparative clinical efficacy and safety, and cost-effectiveness.

Thalidomide was banned worldwide in the 1960s due to its teratogenicity, and remained so until the late 1990s when it returned to physicians’ armamentarium as a medicine for a variety of inflammatory diseases and hematological malignancies that were difficult to treat. A landmark event in this resurgence was the discovery that thalidomide inhibited angiogenesis in the rabbit cornea micropocket assay (1994) and the subsequent successful clinical testing in patients with advanced multiple myeloma 1. Brazilian experience with this unique drug extends over five decades and has no rival in the world. Unlike in other countries, thalidomide use was never completely discontinued in Brazil because of an unexpected indication for a neglected disease. In 1964, Jacob Sheskin prescribed thalidomide as a sedative to patients with erythema nodosum leprosum (ENL, or Hansen disease type-II reaction) and noticed a dramatic resolution of their skin lesions. Sheskin’s discovery was published in 1965 and further confirmed by controlled clinical trials. As the prevalence of Hansen’s disease is high in some regions of the country, thalidomide is an essential drug in Brazil 1. In 1994, an active search undertaken by nongovernmental organizations (NGOs) brought to light a number of cases of thalidomide embryopathy born after 1965 that had remained almost unnoticed for nearly three decades 1. Appearance of “avoidable cases” of thalidomide embryopathy in Brazil prompted health authorities to issue a regulation (Directive n. 354/MS/SVS, 1997) that prohibited thalidomide prescription to women of childbearing age except in very special circumstances and under strictly controlled conditions. In 2003, the Brazilian Congress passed a law (Law n. 10,651, April 2003) that forbade the sale and/or dispensing of thalidomide in commercial pharmacies and also stated that it should be distributed to public health units/hospitals and dispensed to patients through programs approved by the Brazilian Ministry of Health. Notwithstanding the foregoing stringent regulations, at least five more cases of thalidomide embryopathy were diagnosed in babies born between 2005 and 2010 1. The recurrence of birth defects associated with misuse during pregnancy, and concerns about the uncontrolled use of off label indications led the Brazilian National Agency for Sanitary Surveillance (ANVISA) to issue a set of new rules (RDC n. 11, 2011) controlling the dispensing and prescription of thalidomide. Currently, thalidomide holds a unique position in the Brazilian pharmaceutical care and regulation systems. It is the only medicine regulated by a specific Federal law that prohibits its sale and dispensing in commercial pharmacies. Moreover thalidomide is manufactured exclusively