Beta-thalassemia major alters sofosbuvir/ledipasvir exposure in Hepatitis C virus infected adolescent patients - 28/10/21
, Maggie M. Abbassi a, Fatma S. Ebeid b, c, Mohamed Hassany d, Nirmeen A. Sabry a, Manal H. El-Sayed b, cBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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Highlights |
• | Beta-thalassemia patients are prone to high rate of hepatitis C virus infection. |
• | Limited number of hepatitis C virus treatment options are available for adolescents |
• | Is the current dosing regimen of the combination sofosbuvir/ledipasvir appropriate for beta-thalassemia adolescents? |
• | Drug exposure was low in >40% of beta thalassemia adolescents, yet they were cured. |
• | Dose adjustment might be needed beta-thalassemia adolescents. |
Abstract |
Background |
Hepatitis C virus (HCV) infected adolescents with beta-thalassemia major (BTM) are considered a potential population for HCV micro-elimination model development where BTM may negatively impact the pharmacokinetic exposure parameters of sofosbuvir/ledipasvir (SOF/LED).
Objectives |
The study aimed at studying the effect of BTM on SOF/LED and SOF metabolite (GS-331007) pharmacokinetics.
Methods |
A prospective, controlled study recruiting BTM and control HCV infected adolescents (Clinicaltrials.gov identifier-NCT04353986). Pharmacokinetic exposure to GS-331007 and LED was the primary pharmacokinetic outcome. No-effect boundaries were set to 90% confidence interval (CI) of exposure geometric mean ratio (GMR) within 70–143%. Dose suitability was based on the 90% CI of exposure GMR within 50-200% compared to adults. The percentage of patients achieving sustained virologic response 12 weeks post-treatment (SVR12) was the primary efficacy endpoint.
Results |
Thirteen patients were enrolled per study group. All patients were included in the pharmacokinetic analysis (n=26). BTM patients showed lower GS-331007 and LED exposure that could, respectively, be as low as 45.4% and 36.1% compared to their control group. GS-331007 exposure in BTM patients was nearly half (56.8%, 90% CI 45.3–71.2%) that observed in adults. Despite that low drug exposure in 46.2% of BTM patients may alert dose unsuitability, they achieved SVR12. Moreover, patients with total bilirubin ≥1.93 mg/dL were predicted to have low GS-331007 exposure (0.913 receiver operating characteristic area under the curve with sensitivity and specificity >80%).
Conclusion and Relevance |
The identified systematically lower drug exposure in BTM patients might partially explain relapses or treatment failures among BTM patients reported in other studies. BTM may be a hurdle towards implementing HCV micro-elimination model that may necessitate dose-adjustment.
Il testo completo di questo articolo è disponibile in PDF.Key words : Hepatitis C virus, Ledipasvir, Pharmacokinetics, Sofosbuvir, Thalassemia
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Vol 45 - N° 5
Articolo 101747- Settembre 2021 Ritorno al numero
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