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

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.