| Summary: | Introduction and Objectives: 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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