Article Sidebar
Published:
Sep 5, 2022Article Details
Copyright remains in the Author’s name. The work is licensed under a Creative Commons Attribution - Noncommercial Works License. Authors are required to complete and sign an Author Agreement form that outlines Author and Publisher rights and terms of publication. The Agreement form should be uploaded along with other submissions files and any submission will be considered incomplete without it [forthcoming].
Material submitted for publication in the SAMJ is accepted provided it has not been published or submitted for publication elsewhere. Please inform the editorial team if the main findings of your paper have been presented at a conference and published in abstract form, to avoid copyright infringement. The SAMJ does not hold itself responsible for statements made by the authors.
Previously published images
If an image/figure has been previously published, permission to reproduce or alter it must be obtained by the authors from the original publisher and the figure legend must give full credit to the original source. This credit should be accompanied by a letter indicating that permission to reproduce the image has been granted to the author/s. This letter should be uploaded as a supplementary file during submission.
Main Article Content
Dose-related treatment outcomes in South African patients prescribed clofazimine for drug-resistant tuberculosis
Abstract
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- (≥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%) ≥50 kg. Four hundred and thirty-one (71.8%) received ≥200 mg, of whom 41 (9.5%) were <50 kg and 390 (90.5%) ≥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 ≥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 ≥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 ≥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.
