Clofazimine Serum Concentration and Safety/Efficacy in Nontuberculous Mycobacterial Pulmonary Disease Treatment.

BACKGROUND

Clofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD.

METHODS

This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included.

RESULTS

The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P<0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95% confidence interval [CI], 3.9-25.4) from baseline. Culture conversion was achieved in 33 (51.6%) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95% CI, 1.3-38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study.

CONCLUSION

CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fumiya Watanabe reports financial support was provided by Pharmaceutical Society of Japan. Kozo Morimoto reports financial support was provided by Japan Agency for Medical Research and Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.