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doi:10.1111/j.1365-3156.2011.02873.x
Systematic Review
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada
Cutis Skin Clinic and Laser centre, Belgaum, Karnataka, India
Department of Dermatology and Venereology, M.G.M. Medical College and Hospital, Kamothe, Navi Mumbai, India
Clinical Epidemiology, Jewish General Hospital, Montreal, QC, Canada
Consultant Dermatologist and Epidemiologist, Karanam Consultancy, Mumbai, India
Summary
background A combination of rifampicin, ofloxacin and minocycline (ROM) is one of the newer
recommendations for treatment of leprosy. We performed a systematic review and a meta-analysis of
studies that had evaluated the efficacy of ROM therapy in treatment of paucibacillary and multibacillary
leprosy patients.
methods Studies were identified by searching the PubMed, Embase, LILACS and Cochrane databases.
Data were abstracted from all relevant studies, and fixed effects models were used to calculate the
summary estimate of effect in paucibacillary and multibacillary leprosy patients.
results Six studies comparing ROM therapy to multidrug therapy and eight studies that evaluated the
effect of ROM therapy alone (no comparison group) were included in the review and meta-analysis. The
combined estimate for single dose ROM vs. multidrug therapy in paucibacillary leprosy patients suggested that ROM was less effective than multidrug therapy in these patients [relative risk: 0.91, 95%
confidence intervals (CI): 0.860.97]. However, the combined estimate for multiple doses of ROM vs.
multidrug therapy in multibacillary leprosy patients suggested that ROM was as effective as multidrug
therapy in reducing bacillary indices in these patients (proportion change: )4%, 95% CI )31% to 23%).
No major side effects were reported in either the ROM or the multidrug treatment groups.
conclusions Single-dose ROM therapy was less effective than multidrug therapy in paucibacillary
patients. However, there are insufficient data to come to a valid conclusion on the efficacy of multidose
ROM therapy in multibacillary leprosy, and additional studies with ROM therapy in multibacillary
leprosy are needed. Furthermore, multiple doses may be considered as another alternative even for
paucibacillary patients, and randomised controlled trials of this therapy may be useful to understand its
contribution in the treatment and control of leprosy.
keywords rifampicin, ofloxacin and minocycline therapy, leprosy, systematic review
Introduction
Leprosy, a disease known since ancient times, continues to
be a public health concern in many countries around the
world. World Health Organization (2010a) estimated that
there were about 244 000 reported cases of leprosy
globally in 2009. The majority of these cases were in Asia,
Africa and countries of South America. India alone, with
133 717 reported cases, accounted for nearly 55% of the
global cases (World Health Organization 2010a). WHO
Methods
Data sources
We performed a comprehensive literature search of the
PubMed, EMBASE, LILACS and Cochrane Database (up to
October 2010) to identify the studies that assessed the role
of ROM therapy in the treatment of leprosy. We used the
terms Rifampicin, Ofloxacin, Minocycline and Leprosy
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Sensitivity analysis
We performed sensitivity analyses on our results. For
instance, we had included data from a WHO report (Gupte
2006a) on the effect of ROM therapy (compared with data
from articles published in peer reviewed journals) in
paucibacillary leprosy patients in the meta-analysis. After
excluding this WHO report, we found that the summary
estimate changed slightly (RR: 0.87, 95% CI: 0.790.96),
even though this difference was not statistically significant
(P = 0.44). In one of the paucibacillary leprosy studies
(Deshmukh et al. 2003), we used the number of patients
that had clinically improved (compared with complete
clearance in other studies). The summary estimate after
excluding this study was nearly similar to the overall
estimate (RR: 0.91, 95% CI: 0.860.97).
Discussion
The present systematic review and meta-analysis present
information on the role of ROM therapy in the treatment
of leprosy. Of the studies included for the systematic
review, six compared ROM therapy to the multidrug
therapy and eight studied the effectiveness of ROM
therapy alone. The combined estimate for single-dose
ROM vs. multidrug therapy in paucibacillary leprosy
patients suggested that ROM was less effective that
multidrug therapy in these patients (RR: 0.91, 95% CI:
0.860.97). However, the combined estimate for multiple
doses of ROM vs. multidrug therapy in multibacillary
leprosy patients (proportion change: )4%, 95% CI: )31%
to 23%) did not provide enough information to substantially conclude on the efficacy of multidose ROM therapy
in multibacillary leprosy and additional studies with ROM
therapy in multibacillary therapy are needed. No major
side effects were reported in either the ROM or the MDT
treatment groups.
Even though the ROM regimen was recommended only
in 1997, many previous clinical and animal studies had
suggested the utility of these medications in leprosy.
Indeed, some studies in the 1970s demonstrated the
bactericidal effect of rifampicin on Mycobacterium leprae.
Rees et al. (1970) demonstrated that rifampicin inhibited
the growth of Mycobacterium leprae in mice; this
inhibition was seen in both dapsone sensitive and resistant
bacilli. In the same study, rifampicin in a dose
600 mg day was effective in treating lepromatous
patients. Subsequent studies in humans and animal
models confirmed the role of rifampicin in treating
leprosy. (Shepard et al. 1971, 1972, 1974; Levy et al.
1976). Ji et al. (1992, 1996) initially reported that
rifampicin was highly bactericidal even in a single dose
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multibacillary leprosy are required. It appears that multiple doses of ROM therapy are as effective as multidrug
therapy compared with single dose; we have to highlight,
however, that these two different types of doses were used
in different types of leprosy.
The other group of studies, i.e., those that included
only the ROM therapy group, also showed a clinical
improvement in the patients, although the proportion
varied across different studies. All but one study had used
ROM as a single-dose therapy for treatment of paucibacillary leprosy patients. The study by Mane et al. (1997)
from Senegal had used multiple doses of ROM once a
month for 6 months in paucibacillary leprosy patients and
for 24 months in multibacillary patients and found
good clinical response among these paucibacillary leprosy
patients. Revankar et al. (1999) used single-dose therapy
in both single-lesion and multilesional (two to five lesions)
paucibacillary leprosy patients; they reported nearly
similar clinical outcomes in both these groups. Interestingly, one study (Alam et al. 2007) in this group had a
long average follow-up of 6.3 years (as reported to us by
one of the co-authors of the study), and the authors
reported a high relapse rate (5.09 per 1000 person years).
Even though this study did not include comparison
groups, the findings are useful to understand the clinical
outcomes in leprosy patients and for the design of future
studies.
ROM therapy has its own advantages; it is administered
as single dose (or multiple doses every month) and may
lead to better patient compliance, an issue that has been
highlighted as one problem of the WHO multidrug therapy
regimen (Gautam 2009). Another socially relevant
advantage discussed by Villahermosa et al. (2004) is the
pigmentation because of clofazimine in the multidrug
therapy. They suggest that as none of the medications in
the ROM therapy will cause the type of pigmentation
associated with clofazimine, ROM will help maintain the
anonymity of these patients. Indeed, this was also highlighted by a WHO report on treatment of leprosy (WHO
1998). Even though individually each of these medications
rifampicin, ofloxacin, and minocycline may have side
effects including some very severe ones (Halkin 1988; Ji
et al. 1993, 1994; Vijayakumaran et al. 1997; WHO 1998;
Namisato & Ogawa 2000), severe reactions were not
observed in the included studies.
Another important aspect of leprosy therapy is the rate
of relapses in treated patients. Although relapses were not
mentioned in some of the included studies, many had
evaluated these in their study populations. The study with
a relatively longer average follow-up period reported a
relapse rate of 5.09 per 1000 person years (Alam et al.
2007). Others have reported that paucibacillary patients
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Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Table S1. Publication details, Inclusion exclusion criteria, description of study population, findings, side
effects reactions relapses and other characteristics of the
Corresponding Author Maninder Singh Setia, Consultant Dermatologist and Epidemiologist, Karanam Consultancy,
Ground Floor-66, Hi Life P M Road, Santacruz West Mumbai - 400 054, India. E-mail: maninder.setia@karanamconsultancy.in
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