# Outcomes of alternative therapy in HLA-B* 13:01 positive leprosy patients without dapsone versus standard MDT in negative patients: A comparative effectiveness study

## TL;DR

This study shows that dapsone-free treatment for leprosy in HLA-B*13:01-positive patients is as effective and safe as standard treatment, offering a safer option for those at risk of dapsone hypersensitivity.

## Contribution

The study provides real-world evidence that dapsone-free regimens are comparable to standard MDT in HLA-B*13:01-positive leprosy patients.

## Key findings

- Dapsone-free regimens showed comparable cure rates (67.6% vs. 65.8%) to standard MDT at Year 5.
- Alternative therapy had similar bacterial index decline (89.92% vs. 95.11%) and relapse rates (0.46 vs. 0.20 per 100 person-years).
- Safety profiles were comparable (1.67% vs. 2.65% adverse events).

## Abstract

In HLA-B*13:01-positive multibacillary (MB) leprosy patients, dapsone-containing multidrug therapy (MDT) carries a high risk of dapsone hypersensitivity syndrome (DHS). Alternative regimens (dapsone-free) are adopted, but their long-term efficacy compared with standard MDT in HLA-B*13:01-negative patients remains inadequately characterized.

This retrospective cohort study analyzed MB patients (2015–2023) from the National Leprosy Prevention and Control Management Information System (LEPMIS) with ≥1-year follow-up. Primary outcomes (cure/relapse rates, bacterial index (BI), leprosy reactions, and disability progression) and secondary outcomes (adverse events and treatment duration) were compared between HLA-B*13:01-positive patients receiving alternative therapy (rifampicin + clofazimine ± clarithromycin/ofloxacin/minocycline) and negative patients receiving standard MDT (rifampicin + clofazimine + dapsone).

Among the 271 enrolled MB patients (120 HLA-B*13:01-positive, 151 negative), alternative therapy showed comparable efficacy to standard MDT in cure rates (67.6% vs. 65.8% at Year 5), the rate of BI decline (89.92% vs. 95.11% at Year 5), smear negativity rates (71.43% vs. 75.00% at Year 5) and relapse rates (0.46 vs. 0.20 per 100 person-years). Kaplan-Meier survival functions revealed no significant differences in leprosy reactions or disability progression. Additionally, alternative therapy demonstrated comparable safety to MDT (1.67% vs. 2.65%, P = 0.70).

In our study, dapsone-free alternative regimens demonstrated comparable clinical efficacy and safety to standard MDT in MB patients, providing a viable option for HLA-B*13:01 carriers. These findings, limited by the observational design and regimen heterogeneity, warrant further investigation in prospective trials.

Leprosy remains a major global health challenge. Although WHO-recommended multidrug therapy (MDT) is the standard regimen, the component dapsone (DDS) may cause fatal dapsone hypersensitivity syndrome (DHS). Pretreatment HLA-B*13:01 screening identifies carriers, enabling DDS-free regimens to reduce DHS risk; however, whether their efficacy matches standard MDT remains unclear. This study compared the long-term effectiveness and safety of DDS-free regimens versus standard MDT in multibacillary (MB) leprosy patients, providing critical evidence for clinical decision-making. In a retrospective cohort of 271 MB patients (120 HLA-B*13:01-positive, 151 negative) from National Leprosy Prevention and Control System (2015–2023), we assessed cure/relapse rates, bacterial index (BI) change, leprosy reactions, disability progression, and adverse events. Alternative regimens (rifampicin + clofazimine ± clarithromycin/ofloxacin/minocycline) demonstrated comparable efficacy and safety to standard MDT, despite numerically lower BI decline rates and a non-significantly longer mean treatment duration (1.68 vs. 1.60 years, P > 0.05), providing a viable option for HLA-B*13:01 carriers. This study offers critical real-world evidence to optimize leprosy management in genetically susceptible populations, aligning with global efforts to eliminate DHS risks while maintaining therapeutic outcomes.