Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug-Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA)

Stefano Fagiuoli; Pierluigi Toniutto; Nicola Coppola; Domenica Daniela Ancona; Margherita Andretta; Fausto Bartolini; Fulvio Ferrante; Alessandro Lupi; Stefano Palcic; Francesca Vittoria Rizzi; Davide Re; Gema Alvarez Nieto; Candido Hernandez; Francesca Frigerio; Valentina Perrone; Luca Degli Esposti; Alessandra Mangia

doi:10.2147/TCRM.S394467

Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug-Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA)

Ther Clin Risk Manag. 2023 Jan 18:19:57-65. doi: 10.2147/TCRM.S394467. eCollection 2023.

Authors

Stefano Fagiuoli¹, Pierluigi Toniutto², Nicola Coppola³, Domenica Daniela Ancona⁴, Margherita Andretta⁵, Fausto Bartolini⁶, Fulvio Ferrante⁷, Alessandro Lupi⁸, Stefano Palcic⁹, Francesca Vittoria Rizzi¹⁰, Davide Re¹¹, Gema Alvarez Nieto¹², Candido Hernandez¹³, Francesca Frigerio¹⁴, Valentina Perrone¹⁴, Luca Degli Esposti¹⁴, Alessandra Mangia¹⁵

Affiliations

¹ Department of Medicine and Surgery, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
² Hepatology and Liver Transplantation Unit, Azienda Ospedaliero Universitaria, Udine, Italy.
³ Infectious Diseases Unit, University of Campania L. Vanvitelli, Naples, Italy.
⁴ Dipartimento Farmaceutico ASL BAT, Trani, Italy.
⁵ UOC Assistenza Farmaceutica Territoriale, Azienda Ulss 8 Berica, Vicenza, Italy.
⁶ Dipartimento Farmaceutico-Usl Umbria 2, Terni, Italy.
⁷ Dipartimento Diagnostica Ed Assistenza Farmaceutica - ASL Frosinone, Frosinone, Italy.
⁸ Struttura Complessa Di Cardiologia - ASL VCO, Omegna, Italy.
⁹ Farmaceutica Territoriale- Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), Trieste, Italy.
¹⁰ UOS Farmacovigilanza e Monitoraggio Spesa Farmaceutica- ASL BAT, Trani, Italy.
¹¹ Servizio Farmaceutico Territoriale ASL Teramo, Teramo, Italy.
¹² Gilead Sciences, Medical Affairs Italy, Milan, Italy.
¹³ Gilead Sciences, Global Medical Affairs, London, UK.
¹⁴ Clicon S.r.l., Health Economics and Outcomes Research, Bologna, Italy.
¹⁵ Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, 24127, Italy.

Abstract

Purpose: The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB).

Patients and methods: This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017-March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool.

Results: A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients >50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients).

Conclusion: This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/VEL regimen was more frequently detected on elderly patients and on those with ≥2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy.

Keywords: administrative database; glecaprevir/pibrentasvir; hepatitis C; polymedication; sofosbuvir/velpatasvir.

Grants and funding

Gilead purchased the study report that is the basis for this manuscript. This manuscript was developed with Gilead and CliCon S.r.l. Società Benefit. The views expressed here are those of the authors and not necessarily those of the supporters. The agreement signed by CliCon S.r.l. Società Benefit and Gilead does not create any entityship, joint venture, or any similar relationship between parties. CliCon S.r.l. Società Benefit is an independent company. Neither CliCon S.r.l. Società Benefit nor any of their representatives are employees of Gilead for any purpose.