Clofazimine Is a Safe and Effective Alternative for Rifampicin in Mycobacterium avium Complex Pulmonary Disease Treatment: Outcomes of a Randomized Trial

Sanne M H Zweijpfenning; Rob Aarnoutse; Martin J Boeree; Cecile Magis-Escurra; Ralf Stemkens; Bram Geurts; Jakko van Ingen; Wouter Hoefsloot

doi:10.1016/j.chest.2023.11.038

Clofazimine Is a Safe and Effective Alternative for Rifampicin in Mycobacterium avium Complex Pulmonary Disease Treatment: Outcomes of a Randomized Trial

Chest. 2023 Nov 29:S0012-3692(23)05830-0. doi: 10.1016/j.chest.2023.11.038. Online ahead of print.

Authors

Sanne M H Zweijpfenning¹, Rob Aarnoutse², Martin J Boeree³, Cecile Magis-Escurra³, Ralf Stemkens², Bram Geurts⁴, Jakko van Ingen⁵, Wouter Hoefsloot³

Affiliations

¹ Department of Pulmonary Diseases, TB Expert Center, Research Institute for Medical Innovation, Radboud University Medical Center, Radboudumc Center for Infectious Diseases, Nijmegen, The Netherlands. Electronic address: sanne.zweijpfenning@radboudumc.nl.
² Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center, Radboudumc Center for Infectious Diseases, Nijmegen, The Netherlands.
³ Department of Pulmonary Diseases, TB Expert Center, Research Institute for Medical Innovation, Radboud University Medical Center, Radboudumc Center for Infectious Diseases, Nijmegen, The Netherlands.
⁴ Department of Radiology, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
⁵ Department of Medical Microbiology, Research Institute for Medical Innovation, Radboud University Medical Center, Radboudumc Center for Infectious Diseases, Nijmegen, The Netherlands.

PMID: 38040054
DOI: 10.1016/j.chest.2023.11.038

Abstract

Background: Results of retrospective studies have suggested clofazimine as an alternative for rifampicin in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD).

Research question: Is a treatment regimen consisting of clofazimine-ethambutol-macrolide noninferior to the standard treatment regimen (rifampicin-ethambutol-macrolide) in the treatment of MAC-PD?

Study design and methods: In this single-center, nonblinded clinical trial, adult patients with MAC-PD were randomly assigned in a 1:1 ratio to receive rifampicin or clofazimine as adjuncts to an ethambutol-macrolide regimen. The primary outcome was sputum culture conversion following 6 months of treatment.

Results: Forty patients were assigned to receive either rifampicin (n = 19) or clofazimine (n = 21) in addition to ethambutol and a macrolide. Following 6 months of treatment, both arms showed similar percentages of sputum culture conversion based on an intention-to-treat analysis: 58% (11 of 19) for rifampicin and 62% (13 of 21) for clofazimine. Study discontinuation, mainly due to adverse events, was equal in both arms (26% vs 33%). Based on an on-treatment analysis, sputum culture conversion following 6 months of treatment was 79% in both groups. In the clofazimine arm, diarrhea was more prevalent (76% vs 37%; P = .012), while arthralgia was more frequent in the rifampicin arm (37% vs 5%; P = .011). No difference in the frequency of QTc prolongation was seen between groups.

Interpretation: A clofazimine-ethambutol-macrolide regimen showed similar results to the standard rifampicin-ethambutol-macrolide regimen and should be considered in the treatment of MAC-PD. The frequency of adverse events was similar in both arms, but their nature was different. Individual patient characteristics and possible drug-drug interactions should be taken into consideration when choosing an antibiotic regimen for MAC-PD.

Clinical trial registration: EudraCT; No.: 2015-003786-28; URL: https://eudract.ema.europa.eu.

Keywords: Mycobacterium avium complex; clofazimine; nontuberculous mycobacteria; nontuberculous mycobacterial pulmonary disease; treatment.