Response to treatment by multidrug regimens in the THELEP controlled clinical drug trials

Abstract

During the period 1977-1983, clinical trials of five multidrug regimens were conducted among 215 patients with previously untreated multibacillary leprosy at the Institut Marchoux, Bamako, Mali, and the Central Leprosy Teaching and Research Institute, Chingleput, South India. The trials were designed primarily to permit measurement of the proportions of persisting Mycobacterium leprae in the patients' skin lesions. In addition, the combination of the large number of patients studied, the large volume of carefully standardized data, and the employment of multidrug regimens provided a unique opportunity to measure the clinical response of patients to treatment by these regimens. Persisting M. leprae were detected in 7.8% of all specimens; the frequency did not vary with centre, regimen, or duration of treatment. The bacterial index (BI) decreased by a mean annual rate of 75%, the logarithmic biopsy index by a mean annual rate of 87%, and the logarithm10 number of acid-fast bacilli per g tissue by a mean annual rate of 69%. The rate of decrease of these measures of the numbers of M. leprae was related to the 'strength' of the regimen. Although no difference of clinical status as a function of regimen was demonstrated, a difference was observed between the two centres, probably the result of different clinical criteria employed by the responsible physicians. A change of histopathological classification in the course of the trials was recorded for 12% of the patients, most representing upgrading from LL(s) to BL, without relation to regimen or treatment centre. ENL was less severe for the patients treated by the maximal regimen in Chingleput, which included daily clofazimine; as expected, the majority of patients treated by this regimen were found to have maximal pigmentation. Prednisolone was evidently preferred for treatment of ENL in Chingleput, whereas thalidomide was preferred in Bamako. Fourteen cases of jaundice were observed, primarily among the patients treated by the maximal regimens, that included daily administration of rifampicin for the entire two years of the trials. Measurements of weight and blood pressure, and studies of the blood and of hepatic and urinary tract function revealed only negligible differences among regimens and between centres. In many cases, those differences that were observed were associated with ENL.