Developing new MDT regimens for MB patients; Time to test ROM 12 month regimens globally

In this editorial we review the data on the use of multi-dose ROM (Rifampicin, Ofloxacin and Minocycline) as an alternative treatment to WHO-MDT (World Health Organisation multidrug therapy) comprising rifampicin, clofazimine and dapsone. There is now sufficient evidence to warrant a large trial of this new regimen. The adverse effects of the current MDT regimen are probably under-estimated and this new regimen would reduce these adverse effects. Ofloxacin and minocycline have been shown to be more bactericidal than dapsone and clofazimine in both mice and clinical trials. The single monthly dosing might improve compliance which is also a major challenge. In 1997 a randomised double-blind trial comparing single dose rifampicin, ofloxacin and minocycline was published and rapidly approved by the 7 Expert Committee on Leprosy in 1998 as treatment for single lesion leprosy. There were methodological problems in the study underpinning this recommendation, and at the time one of us voiced reservations about the new regimen. However, the regimen has now been used much more widely with studies being done in India and Brazil and there is now substantial experience in using it. A recent systematic review has assessed all the studies comparing ROM and MDT and found 14 studies that could be included in the review. Four of these compared single dose ROM with WHO-MDT for treating pauci-bacillary leprosy and combining these studies it was found that single dose ROM is slightly less effective than WHO-MDT with a relative risk of 0·91 (95% confidence intervals 231%) but still has a very high cure rate. Only two studies have been reported using multiple doses of ROM in lepromatous leprosy (LL). One in the Philippines by Villahermosa et al., comparing 21 patients with borderline lepromatous and LL who were given either monthly ROM (n 1⁄4 10) or the standard MDT (n 1⁄4 11) which comprised monthly rifampicin (600mg), and clofazimine (300mg) with daily dapsone (100mg) and clofazimine (50mg) for 24 months. These patients had a mean Bacterial Index (BI) of 4 (range 2·7–5·1) at entry to the study and it fell to 1·18 (range 0–3·5).