International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes
Ponnaiah Manickam1, Sanjay M Mehendale1, Bathyala Nagaraju1, Kiran Katoch2, Abdul Jamesh3, Ramalingam Kutaiyan4, Shen Jianping5, Shivakumar Mugudalabetta6, Vitthal Jadhav7, Prabu Rajkumar1, Jayasree Padma1, Kanagasabai Kaliaperumal1, Vijayakumar Pannikar8, Padabettu Krishnamurthy6, Mohan D Gupte1
1 International Trial Co-ordinating Centre, National Institute of Epidemiology (ICMR), Chennai, India
2 National JALMA Institute of Leprosy and Other Mycobacterial Diseases, Agra, India
3 Former Additional Director of Medical Services (Leprosy), Office of the Director of Medical & Rural Health Services, Chennai, India
4 Former Joint Director of Medical Services (Leprosy), Tiruvannamalai, India
5 Department for Leprosy Control, National Center for STD and Leprosy Control, Nanjing, P.R. China
6 Damien Foundation Trust, Chennai, India
7 U-MDT Trial Pune Site, Pune, India
8 WHO Global Leprosy Programme, New Delhi, India
National Institute of Epidemiology, Indian Council of Medical Research, R127, TNHB, Ayappakkam, Chennai 600 077, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background & objectives: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance.
Methods: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated.
Results: A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable.
Interpretation & conclusions: We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696]