Pangenotypic DAA Therapy Safe, Effective in Children with HCV, Study Finds

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An 8-week treatment regimen with glecaprevir/pibrentasvir is safe and effective for the treatment of hepatitis C virus (HCV) in children, according to findings from a retrospective multicenter study.

Sustained virologic response (SVR) assessed at 12 weeks after the end of treatment was 100% among the cohort, with all analyzed participants completing the course of treatment and no adverse events leading to treatment modification or discontinuation.¹

“Data on the efficacy and safety of DAA therapies in children in clinical practice are limited. Previous studies in young children have focused on other, non-pangenotypic therapeutic options, such as SOF/LDV,” wrote Malgorzata Pawlowska, MD, PhD, professor in the department of infectious diseases and hepatology at Nicolaus Copernicus University, and colleagues.¹

An estimated 3.5-5 million children worldwide have chronic HCV infection. According to the World Health Organization, direct-acting antiviral medicines (DAAs) can cure more than 95% of HCV cases. This success has been replicated among pediatric patients, although data are limited and warrant further examination.^1,3

To assess the effectiveness and safety of anti-HCV treatment based on a pangenotypic DAA regimen with glecaprevir/pibrentasvir in children, investigators retrospectively collected patient data using a nationwide database of treated patients with HCV in the multicenter EpiTer-2 project, a research program supported by the Polish Society of Epidemiologists and Infectious Disease Physicians. Pediatric patients diagnosed with hepatitis C who were treated at specialized centers in Gdańsk, Bydgoszcz, and Warsaw from November 2022 to January 2023 were included in the study.¹

Of the 25 patients treated from 2022–2023 with glecaprevir/pibrentasvir regimen, 2 were excluded due to being 18 years of age at the time of treatment and therefore considered to be adults. The remaining 23 patients were included in the study, including 13 girls and 10 boys with a mean age of 9.61 (Standard deviation, 3.68) years. Among the cohort, the most common HCV genotypes were GT1b (39.1%), GT1a (26.1%), and GT3 (21.7%).¹

Patients were divided based on the form of drug administration, with 10 patients on tablets and 13 on granules. Additional analysis based on formulation showed a slightly greater proportion of female participants in the granule group (61.5%) compared to the tablet group (38.5%). The genotype distribution was different between the groups, with 1 patient presenting GT1a in the tablet group compared to 5 patients in the granule group.¹

The effectiveness endpoint was SVR, defined as undetectable HCV ribonucleic acid (RNA) at least 12 weeks after the end of treatment. Safety data were collected during treatment and for 12 weeks after the end of treatment, including modification or discontinuation of therapy, occurrence of adverse events, severe adverse events, and deaths.¹

The median HCV RNA measured at baseline was 645,000 IU/mL (Interquartile range [IQR], 229,324–1,865,000) and alanine transaminase (ALT) activity was 46 IU/L (37.5–58.5) for the entire cohort. In the granules group, the median HCV RNA was 735,000 IU/mL (IQR, 107,000–2,030,000) and was greater than in the tablet group (521,500; IQR, 353,000–1,437,500).¹

Investigators pointed out ALT and bilirubin levels were slightly increased in the tablet group (47.5 vs 43 IU/L and 0.51 vs 0.43 mg/dL, respectively), while platelet counts were lower (242 vs 367 ×1000/µL). Patients treated with tablets (0.62 mg/dL; IQR, 0.54–0.77) had greater creatine levels than those treated with granules (0.42 mg/dL; IQR, 0.39–0.45).¹

All participants completed the course of treatment, and none required treament modification. The SVR assessed at 12 weeks after the end of treatment was 92.3% in the intent-to-treat analysis for girls and 100% for boys. However, investigators pointed out per-protocol analysis showed a loss of 1 patient to follow-up, resulting in a 100% SVR rate among female patients. Adverse events occurred only in the tablet-treated group and presented as nausea (n = 1) and fatigue (n = 1), neither of which led to treatment modification or discontinuation.¹

“Our research is the first study in Europe describing the treatment of HCV-infected children with an 8-week GLE/PIB pangenotypic therapy in routine clinical practice. It unequivocally confirms the very high (100%) effectiveness, safety and good tolerance of the currently shortest antiviral therapy in the treatment of HCV in adolescents and children, including in the group of the youngest children,” concluded investigators.¹

References:

1. Pawlowska M, Dobrowolska K, Moppert J, et al. Real-World Efficacy and Safety of an 8-Week Glecaprevir/Pibrentasvir Regimen in Children and Adolescents with Chronic Hepatitis C—Results of a Multicenter EpiTer-2 Study. Journal of Clinical Medicine. 2023; 12(21):6949. https://doi.org/10.3390/jcm12216949
2. HCVGuidelines.org. HCV in Children. Unique Populations. October 24, 2022. Accessed November 30, 2023. https://www.hcvguidelines.org/unique-populations/children
3. World Health Organization. Hepatitis C. July 18, 2023. Accessed November 30, 2023. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c