Tuesday, November 9, 2010

Rifampicin, ofloxacin and minocycline (ROM) in leprosy

Leprosy Mailing List – November 5th, 2010

Ref.:   Rifampicin, ofloxacin and minocycline (ROM) in leprosy
From: Soutar D., London , UK

Dear Salvatore,

The regimen of single dose Rifampicin + Ofloxacin +Minocycline (ROM) for single lesion paucibacillary leprosy was a recommendation of the WHO 7th Expert Committee on Leprosy which met in 1997.  For some time ROM was available in blister packs in India ,Bangladesh , Nepal and Brazil and used quite widely, particularly in India where at the time, the 7th Expert Committee reported that more than 50% of newly detected cases were classified as single lesion PB leprosy.  I do not know if ROM is still being produced in blister packs but certainly in the WHO Global Strategy 2006-2010 and the WHO Enhanced Global Strategy 2011-2015, no recommendation is made regarding the use of ROM and it is not included in the recommended regimens in the operational guidelines of both those strategies.  

The WHO HQ-based website pages dedicated to leprosyhttp://www.who.int/lep/mdt/regimens/en/index.html still indicate that ROM is part of the recommended regimens.  This, I assume, is why the leprosy section of Wikipedia http://en.wikipedia.org/wiki/Leprosy still makes reference to it and also why in a recent new publication on Ocular Leprosy there is also a reference to this as a WHO recommended regimen http://www.cehjournal.org/files/tsno9/ts09.html#06 .  This highlights the fact that websites do need to be updated on a regular basis to avoid out of date technical advice and references being perpetuated.
The 8th WHO Technical Advisory Group meeting in Aberdeen 2006 reported the following in regard to ROM:

  6. Clinical trials for treatment of PB leprosy patients with single dose of rifampicin, ofloxacin and minocycline (ROM)
Final report
These WHO-sponsored trials address two issues: (i) Effectiveness of single dose ROM in paucibacillary leprosy patients with two to five skin lesions carried out in India as a randomized double-blind trial, and (ii) Relapse rates in single-lesion paucibacillary leprosy cases treated with single dose ROM.
(i) Effectiveness of single dose ROM in paucibacillary leprosy patients with 2-5 skin lesions
The study was carried out in India to evaluate the effectiveness of single-dose ROM compared to standard, six-monthly doses of MDT regimen for PB leprosy patients with two to five skin lesions, under programme conditions.  PB leprosy cases that were smear-negative presenting with two to five lesions were included in the study.  These patients were recruited from five centres in India  All patients were treated for six months, with appropriate pre-coded drugs and identical looking placebo.  The primary outcome was complete clearance of skin lesions.  The initial plan was for six months each for intake and treatment phase followed by periodic post-treatment assessments for 36 months.  The post-treatment follow-up period was extended for another 12 months in two centres that recruited the majority of the patients in this study.  Data were analysed for these two centres with multivariate longitudinal regression analysis using Generalized Estimating Equations (GEE).
A total of 1,082 paucibacillary (PB) cases were randomly allocated to ROM (n= 539) or WHO PB-MDT (n= 543).  Baseline characteristics were similar at intake.  The total number of patients at the final follow-up was 468 (87%) in the ROM group and 477 (88%) in the WHO PB-MDT group.  Complete clearance was observed in 71% (332 out of 468) in the ROM group and 75% of (358 out of 477) in the WHO PB-MDT group. Relapse rate was more than two times higher among patients treated with ROM as compared to WHO PB-MDT (Rate ratio: 2.31; 95% confidence Interval 1.00-5.35). GEE analysis indicated that patients’ age and time of follow-up were statistically significant after adjustment for factors included in the model. The clinical score was not statistically significant between the two treatment groups (Model coefficient: -0.045; 95% CI: -0.27-0.17)

(ii) Relapse rates in single-lesion paucibacillary leprosy cases treated with single dose ROM
The objective of the study was to evaluate the effectiveness of ROM for the treatment of skin smear negative single-lesion PB leprosy patients and to determine the occurrence of relapses over a period of 54 months.  Four leprosy control units in the Chittoor and Cuddapah districts of Andhra Pradesh were selected for this trial. PB leprosy patients with only a single lesion who were untreated were enrolled for this study.  Patients were examined at the time of intake, and then every six months from the date of inclusion.  The rate of relapse was calculated using survival analysis.
A total of 1,262 patients were enrolled for this study out of which 35% (n=440) were children and 49% (n=619) were males.  The study observed 126 special events.  These were suspected relapse patients (n=19), confirmed relapse patients (n=7), migrations (n=84), deaths unrelated to leprosy (n=22) and misclassification (n=1).  At the end of 54 months, 88% (n=988) patients had complete clearance of skin lesions. The improvement and deterioration scores of patients show that 0.1% had deterioration compared to their clinical status at intake, 2% had static clinical condition and the rest showed varying degrees of improvement.  The incidence rate of suspected relapse was 3 per 1000 person- years.

Douglas Soutar

Douglas Soutar
General Secretary
International Federation of Anti-Leprosy Associations
Tel: 44 (0) 207 602 69 25 – Fax:  44 (0) 207 371 16 21 – Website: www.ilep.org.uk
E-mail: doug.soutar(at)ilep.org.uk

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