Data presented at ECCMID 2016 showed that a 24-week or longer regimen of Sirturo was well-tolerated and effective against multidrug-resistant tuberculosis.
Researchers evaluated 44 patients with MDR-TB who initiated Sirturo (bedaquiline, Janssen Therapeutics) treatment from January 2011 through December 2013. Seventy-seven percent of the patients were previously treated for TB. Among them, 39% showed resistance to fluoroquinolones or second-line injectables, and 52% showed resistance to both drug classes. The researchers reported that TB strains were resistant to a median of nine drugs.
Ninety-three percent of patients received more than 24 weeks of bedaquiline. In addition to bedaquiline, the most commonly prescribed drugs included Zyvox (linezolid, Pfizer; 96%), PAS (89%), cycloserine (73%), amikacin (70%), imipenem-amoxiciline/clavulanate (61%), and moxifloxacin (52%).
According to study data, of the 40 patients with positive sputum culture at baseline, 25 achieved culture conversion after 3 months of treatment, and 39 met conversion after 6 months. The average time to culture conversion was 88 days.
Four patients experienced QTcF interval values greater than 500 ms after receiving bedaquiline for a median duration of 3 months, which led to two patients discontinuing treatment. None of the patients experienced adverse cardiac effects, and no other adverse events attributed to bedaquiline were reported; however, one patient relapsed after 449 days of treatment.
“Long-term bedaquiline treatment was safe and effective in this cohort of patients with advanced resistance patterns and extensive disease,” the researchers concluded. “Prolongation of bedaquiline beyond 24 weeks should be considered in selected MDR-TB cases.”
Similar findings published in Clinical Infectious Diseases also demonstrated that bedaquiline, combined with other drugs, resulted in culture conversion in almost all patients with MDR-TB (97%) after 6 months of treatment.
The researchers performed a retrospective cohort study that included 35 patients with MDR-TB who received at least 1 month of bedaquiline between from January 2010 to July 2013. Nineteen of the patients had extensively drug-resistant TB. Twenty-six of the patients received bedaquiline as part of their initial MDR-TB treatment; the other nine patients had received a median of 85 days of treatment before bedaquiline initiation. All patients received a median of four additional antibiotics.
Among 29 patients who had culture-positive pulmonary TB at bedaquiline initiation, 28 achieved culture conversion after 6 months of treatment. Sputum-smear conversion occurred in 20 of the 29 patients initially smear-positive. The median time to culture conversion was 85 days, and the median time to sputum-smear conversion was 103 days.
In a multivariable analysis, the researchers found that the presence of lung cavities (HR=0.04; 95% CI, 0.01-0.2) and a hepatitis C virus infection (HR=0.21; 95% CI, 0.08-0.54) were associated with slower time to culture conversion. Treatment with any fluoroquinolone for 30 days or more, however, was associated with a faster time to culture conversion (HR=3.28; 95% CI, 1.3-8.27).
“Of interest, bedaquiline was combined with linezolid in 94% of our patients,” the researchers wrote. “The relevant role of linezolid in the treatment of MDR-TB and particularly of fluoroquinolone-resistant strains has been recently highlighted and could partially explain our satisfactory results.”
Guglielmetti L, et al. Abstract 7614. Presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 9-12, 2016; Amsterdam.
Disclosure: Three researchers report receiving fees, payment or research grants from AstraZeneca or Janssen Pharmaceuticals. Infectious Disease News was unable to confirm other relevant financial disclosures at the time of publication.