Meeting Coverage > > CROI– Questionable effectiveness, prospective toxicity “pointers the scales” versus clofazimine-based program
by Katherine Kahn, Staff Writer, MedPage Today March 11, 2024
DENVER– Most clients with tuberculosis (TB) who got a treatment program that consisted of the repurposed leprosy drug clofazimine transformed to unfavorable sputum cultures after 12 weeks, however a significant percentage went on to have undesirable results, according to an interim analysis of the stage IIc CloFast trial.
After 12 weeks of treatment with a clofazimine/rifapentine-containing program, 89% of individuals with extreme TB evaluated unfavorable on a sputum culture, which resembled the 90% of those getting a standard-of-care program (changed HR 1.17, 90% CI 0.79-1.73), reported John Metcalfe, MD, PhD, MPH, of the University of California San Francisco, at the Conference on Retroviruses and Opportunistic Infections.
At 65 weeks, 41% of clients on the clofazimine program established undesirable scientific or bacteriologic results versus 29% in the standard-care group.
These findings caused the trial being ended early, Metcalfe informed guests.
Metcalfe mentioned that 69% of individuals had actually advanced, extreme TB validated on chest x-ray, and 26% had a 3+ sputum acid-fast bacillus level. “This was not a low- or limited-risk population in any method,” he stated.
Standard TB treatment includes a multidrug routine that needs to typically be considered a minimum of 6 months and has high rates of nonadherence and drug resistance. To deal with these concerns, there has actually been interest in repurposing clofazimine, which revealed pledge of being quickly and extremely efficient versus TB in a mouse design, Metcalfe described.
Metcalfe presumed that the mouse design that the CloFast trial brought into play was most likely not appropriate to more extreme TB pathology in human lungs which the human-equivalent dosage of clofazimine might likewise have actually been incorrect.
Throughout a Q&A session, Nicholas Paton, MD, of the National University of Singapore and detective in the Truncate-TB trial, kept in mind that “we had an extremely comparable high-dose clofazimine routine for 2 months and had fairly low rates of undesirable results in the order of 11-13%. The distinctions are that we utilized two times the dosage that you utilized and the research study population clearly had milder illness. Before we completely dismiss clofazimine, it would work to attempt and put that information together.”
Metcalfe stated that another significant disadvantage to the clofazimine routine was the variety of severe unfavorable occasions that emerged throughout the trial. Amongst individuals getting the clofazimine-based routine, 45% established grade 3 or greater unfavorable occasions through week 65 versus 16% in the standard-of-care arm. This distinction was driven by a modification in creatinine clearance, he stated, and other than for another trial, that finding had actually not been formerly explained.
“We do not understand whether this is a disturbance with the creatinine assay or if it shows real short-term kidney injury,” he stated. Fairly couple of individuals treated with clofazimine experienced distress from skin hyperpigmentation,