Clofazimine use for nontuberculous mycobacterial infections: 10-year experience in Belgium.

Abstract

Background: Clofazimine is increasingly recommended for nontuberculous mycobacterial (NTM) infections, despite limited evidence. In Belgium, until July 2025 access to clofazimine - outside of procurement by the national tuberculosis program - was restricted and associated with financial and administrative hurdles, creating barriers for patients.

Methods: This retrospective, multicentre study documents clofazimine use from January 2015 to December 2024 through pharmacy and medical record review at Belgium's two largest tertiary care hospitals. Collected data included indications, treatment duration, adverse events and logistic aspects related to access. Data was summarized using descriptive statistics.

Results: Among 102 clofazimine-containing treatment courses for NTM disease (61 in UZ Leuven; 41 in UZ Gent), the median patient age was 62 years; 52% were female, 56% had bronchiectasis, 28% COPD and 12% cystic fibrosis. Clofazimine was mainly used for NTM-pulmonary disease (NTM-PD) (n = 82, 87.2%), with main indications being M. abscessus complex-PD (MAB-PD; 28%), advanced or refractory M. avium complex-PD (MAC-PD; 17% and 12.2% respectively) or intolerance to another key drug (26.8%). Clofazimine was part of at least a triple-drug regimen, with 100 mg daily used in 91% of regimens for a median duration of 270 days (IQR 109-527 days). Common adverse events included ichthyosis/skin hyperpigmentation (38.3%) and gastrointestinal complaints (52.1%). Although none were severe, 20% of patients discontinued treatment prematurely. Financial reimbursement requests were submitted for 68.2% of NTM-PD treatments.

Conclusion: Our study observed that clofazimine is prescribed largely in accordance with current guideline recommendations. Given its acceptable tolerability and the recent introduction of national health insurance coverage, clofazimine use is likely to increase in Belgium, with the potential to improve patient outcomes.

Trial registration: This study did not involve a health care intervention and did not meet criteria for clinical trial registration. It was conducted as a retrospective, multicentre study at UZ Leuven and UZ Gent. Ethical approval was obtained from the Ethics Committee of UZ/KU Leuven (MP034837, S70431) and the Ethics Committee of UZ Gent (S61188, S62926).

Clinical trial number: not applicable.