A total of 307 patients with
lepromatous leprosy and
borderline lepromatous leprosy were randomized to
dapsone monotherapy or to one of two types of
drug combinations. A 3-year treatment phase was followed by a 5-year observation phase. The evaluation included 233 patients for whom together there were 1,404 years of observation. A total of 1,956 blinded histopathological specimens were processed centrally. When entering the trial isolates from 13 patients (5.6%) showed
dapsone resistance in the mouse footpad test, and these patients were evaluated separately.
Dapsone monotherapy (68 patients) had the same frequency of cure as the combination of
dapsone and
rifampin (77 patients) or the four-
drug regimen consisting of
dapsone,
rifampin,
isoniazid, and
prothionamide (75 patients). We did not find a significant difference in the clearance of bacteria either between the monotherapy and the two-
drug combination or the monotherapy and the four-
drug combination. Six months after the initiation of treatment, disease in 15% of the patients who received
dapsone monotherapy but none of the patients who received combined treatment were clinically progressive. After another 1 to 9 months of treatment the disease in all patients was stable or regressive. There was no difference in the type or frequency of reactions. Only after the end of the scheduled observation phase three relapses were reported. All three treatment regimens well tolerated.
Dapsone monotherapy is highly effective in the treatment of
multibacillary leprosy under the conditions of well-controlled treatment. Combination regimens seem only to accelerate the regression of the active disease when they are compared with monotherapy with
dapsone. The mouse footpad test does not reflect the clinical resistance and cannot be recommended for use in making therapeutic decisions.