Safety and Efficacy of Clofazimine as an Alternative for Rifampicin in Mycobacterium avium Complex Pulmonary Disease Treatment

Abstract

Background

Retrospective studies have suggested clofazimine as an alternative for rifampicin in MAC-PD treatment.

Research question

Is a treatment regimen consisting of clofazimine-ethambutol-macrolide non inferior to the standard treatment regimen (rifampicin-ethambutol-macrolide) in the treatment of M.avium complex pulmonary disease?

Study design and Methods

In this single centre non-blinded clinical trial, we randomly assigned adult patients with MAC-PD in a 1:1 ratio to receive rifampicin or clofazimine as adjuncts to an ethambutol-macrolide backbone. The primary outcome was sputum culture conversion after six months of treatment.

Results

Forty patients were assigned to receive either rifampicin (n=19) or clofazimine (n=21) ) next to ethambutol and a macrolide. After 6 months of treatment, both arms showed similar percentages of sputum culture conversion based on intention to treat analysis: 58% (11/19) for rifampicin; 62% (13/21) 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 after 6 months of treatment was 79% in both groups. In the clofazimine arm, diarrhoea was more prevalent (76% vs 37%; p=0.012), while arthralgia was more frequent in the rifampicin arm (37% vs 5%; p=0.011). No difference in the frequency of QTc prolongation was seen between both 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 patients characteristics and possible drug-drug interactions should be taken into consideration when choosing an antibiotic regimen for MAC-PD.