A Comparative Clinical Trial in Multibacillary Leprosy with Long-Term Relapse Rates of Four Different Multidrug Regimens

As a participant in a multicenter trial, we evaluated the relapse rate in 189 multibacillary (MB) leprosy patients treated with four different regimens and followed-up for as many as 12 years after the initiation of treatment. Treatment regimens included 1 year of WHO MDT (a regimen including dapsone, clofazimine, and rifampin), 2 years of WHO MDT, 1 month of daily rifampin and daily ofloxacin, and 1 year of WHO MDT plus an initial 1 month of daily rifampin and daily ofloxacin. Relapse rates after 9 and 12 years from the initiation of therapy in the three regimens that included WHO MDT were 0-3%, whereas relapses occurred in those treated with the 1-month regimen alone at a signifi- cantly greater rate ( P < 0.05): 11% at 9 years and 25% at 12 years. Relapses occurred late, beginning at 5 years after the initiation of therapy, and were confined to those patients histopathologically borderline lepromatous and polar leproma- tous having a high bacterial burden. Prospects for an alternative effective short-course therapy of leprosy are presented. 1 the sulfones provided the first effective antimicro- bial therapy for leprosy, heretofore frequently a progressive, unrelenting, and deforming disease because of the unique tro- pism of the causative bacteria, Mycobacterium leprae , for the peripheral nervous system. On the sulfone of choice, dapsone, leprous skin lesions slowly resolved, and, in general, peripheral neuropathy ceased its progression. However, in the 1950s, 2 it was recognized that dapsone resistance became a clinical con- cern in some patients, and despite prolonged, often lifelong, and continued daily dapsone administration, new lesions appeared. Later dapsone resistance 3 was confirmed in the mouse model, first described by Shepard in 1960. 4 Although the incidence of drug resistance is much higher in tuberculosis after mono- therapy, even with bactericidal agents, and although dapsone is bacteriostatic in leprosy patients, surprisingly secondary dapsone resistance only affected ~2.5% of leprosy patients treated with dapsone monotherapy. 5 Furthermore, the most severe lepromatous form of leprosy is by far more bacilliferous, higher than any other human disease, and unlike in tuberculo- sis, is associated with a permanent pathogen-specific anergy. 6