Safety and Efficacy of Clofazimine as an Alternative for Rifampicin in Mycobacterium avium Complex Pulmonary Disease Treatment: Outcomes of a Randomized Trial.

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, nonanonymized 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 corrected QT interval 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.
Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. has a relationship with AbbVie and Bionano Genomics. J. v. I. is an advisory board member for Paratek, AN2, Insmed, MannKind, and Janssen. W. H. has received a Stichting Management Apothekers en de Gezondheidszorg (Stimag) Grant for an investigator-initiated trial (“Pharmacokinetic study of minocycline in patients with pulmonary nontuberculous mycobacterial disease”). S. M. H. Z. reports funding as stated for this article. None declared: (M. J. B., R. A., R. S., C. M.-E.).
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