Risk of multiple drug interactions potentially linked to safety in patients receiving pangenotypic direct-acting antivirals for the treatment of Hepatitis C

ISSN: 1665-2681

Annals of Hepatology (AoH) is an international, open access journal published bi-monthly with funds from the Fundación Clínica Médica Sur. It is the official journal of the Mexican Association of Hepatology (AMH), the Latin American Association for the Study of the Liver (ALEH), the Canadian Association for the Study of the Liver (CASL) and the Czech Society of Hepatology (CSH). AoH publishes editorials, opinions, concise reviews, original articles, brief reports, letters to the editor, news from affiliated associations, clinical practice guidelines and summaries of congresses in the field of Hepatology.

Topics covered by AoH include alcoholic liver disease, autoimmune hepatitis, biliary diseases, drug-induced liver injury, genetic liver diseases, NAFLD/NASH and viral hepatitis (HAV, HBV, HCV, HDV, HEV). Our journal seeks to publish articles on basic clinical care and translational research focused on preventing rather than treating the complications of end-stage liver disease.

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Previous studies have evaluated the risk of drug-drug interactions (DDI) in HCV patients receiving pangenotypic direct-acting antivirals (pDAA), but all are based on pairwise interaction. The aim of the study was to describe the prevalence of the risk of potential multiple DDI (multi-DDI) and its clinical impact in patients treated with pDAAs.

Materials and Methods

Retrospective observational study from a Spanish database of 1.8 million inhabitants, including patients treated with Sofosbuvir/Velpatasvir [SOF/VEL] or Glecaprevir/Pibrentasvir [GLE/PIB] (2017- 2020). Demographics, comorbidities, comedications, and DDIs were evaluated for the pDAA therapy period. The severity and impact of the DDIs were evaluated using the University of Liverpool tool. Additionally, the ICD-9 coding system was used to identify the presence of suspected adverse drug reactions (SADR) during the treatment with pDAAs. An indirect indicator of effectiveness was evaluated (requirement of a new DAA in the six months after the end of the pDAA).

Results

1620 patients were included; 730 with SOF/VEL (median age: 55 y; 62% men; 37.8% F3/4) and 890 with GLE/PIB (53 y; 60% men; 28% F3/4). The most prescribed drugs were nervous drugs (35.8%), digestive (24.1%) and cardiovascular (14.2%). 77.5% of patients received ≥2 comedications. The number of patients receiving ≥ 2 comedications at risk of multi-DDI with pDAAs was 123 (9.8%, 123/1256), 52 with SOF/VEL and 71 with GLE/PIB. Patients showing increased risk in comedication as a DDI outcomes were 31% (22) with GLE/PIB and 11% (6) with SOF/VEL (p <0.001). The risk of decrease in pDAA with GLE/PIB was 32% (23) and with SOF/VEL 46% (24) (p=NS). Regarding SADR, there was a higher number in the GLE/PIB group (14) vs. SOF/VEL group (4) (p<0.05). 84% (16/18) of patients with SADR had a multi-DDI profile. 13% of total multi-DDIs patients showed SADR; GLE/PIB group showed SADR in 18% (13/71) vs. 6% (3/52) in SOF/VEL group (p <0.05). Most SADR were reported with statin group, being the percentage higher in the GLE/PIB group vs. SOF/VEL group (p <0.05).

Both pDAAs showed a similar percentage of patients restarting a new pDAA within the six months after the end of treatment (1.0% and 1.1%, respectively, p=NS).

Conclusions

In Spain, about 10% of HCV patients taking ≥ 2 comedications are at risk of multiple DDI with pDAAs. The potential risk of increased comedication as DDI outcome and the presence of suspected adverse reactions were higher in GLE/PIB in comparison with SOF/VEL.

Funding

The resources used in this study were from the hospital without any additional financing

Declaration of interest

The authors declare no potential conflicts of interest.

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