Dose-related treatment outcomes in South African patients prescribed clofazimine for drug-resistant tuberculosis

BACKGROUND: Optimal drug levels and minimal toxicity are critical factors in improving treatment outcomes for patients' prescribed new and repurposed medicine for drug-resistant (DR) tuberculosis (TB). The optimal dose of clofazimine (CFZ), a repurposed medicine for DR-TB, that is safe and effective in the South African (SA) population is unknown. OBJECTIVES: To report on dose-related final treatment outcomes in patients receiving CFZ plus a background regimen for DR-TB. METHODS: In a retrospective review of patient folders from 2012 to 2014, treatment outcomes documented for patients receiving high-(&gt;200 mg) and low-dose (100 mg) CFZ in a centralised DR-TB hospital in KwaZulu-Natal Province, SA, were investigated for an association between dose-weight interactions and outcomes. RESULTS: A total of 600 patients were included, of whom 169 (28.2%) received 100 mg. Of these, 87 (51.5%) weighed <50 kg and 82 (48.5%) &gt;50 kg. Four hundred and thirty-one (71.8%) received &gt;200 mg, of whom 41 (9.5%) were <50 kg and 390 (90.5%) &gt;50 kg. Overall 77.2% were HIV-positive, with 93.95% on antiretroviral medicine. The majority of patients presented with extremely drug-resistant TB (55.3%). Forty-seven and a half percent of patients received a standardised background regimen, and 52.5% received an individualised regimen containing a new or repurposed medicine including CFZ. On multivariate analysis, adjusting for age, gender, HIV status and concomitant antiretrovirals, previous TB history, type of TB and background regimen, patients &gt;50 kg prescribed 100 mg CFZ were 60% less likely to have a successful outcome (adjusted odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2 - 0.8; p=0.009) compared with patients <50 kg receiving 100 mg CFZ. Patients <50 kg who received &gt;200 mg were 40% less likely to have a successful treatment outcome (adjusted OR 0.6, p=0.3), and were found to have a higher risk of adverse events than patients <50 kg receiving 100 mg CFZ (82.9% v. 65.5%). CONCLUSIONS: Dose-weight interaction plays a role in the odds of a successful outcome. There is an association between dose-weight interactions, outcomes and adverse events. Weight-based dosing in patients <50 kg and &gt;50 kg must be considered to achieve optimal treatment outcomes and reduce adverse events. Active drug safety monitoring must be implemented as a package of care for patients receiving CFZ as part of a DR-TB treatment regimen.

Bibliographic Details

Main Authors:	Misra,N, Padayatchi,N, Naidoo,P
Format:	Digital revista
Language:	English
Published:	South African Medical Association 2021
Online Access:	http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742021000100017
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