ABSTRACT
Background and Aims Hepatitis C virus (HCV) infection is a major global health problem in adults & children. The recent efficacy of Direct Acting Anti-viral therapy (DAA) has cure rates of 99% in adults and adolescents. These drugs were licensed for children 3-12 yrs during the recent coronavirus pandemic. To ensure equitable access, safe & convenient supply during lockdown, we established a virtual national treatment pathway for children with HCV in England & evaluated its feasibility, efficacy & treatment outcomes. Method A paediatric Multidisciplinary Team Operational Delivery Network (pMDT ODN), supported by NHS England (NHSE), was established with relevant paediatric specialists to provide a single point of contact for referrals & information. Referral & treatment protocols were agreed for HCV therapy approved by MHRA & EMA. On referral the pMDT ODN agreed the most appropriate DAA therapy based on clinical presentation & patient preferences, including ability to swallow tablets. Treatment was prescribed in association with the local paediatrician & pharmacist, without the need for children & families to travel to national centres. All children were eligible for NHS funded therapy;referral centres were approved by the pMDT ODN to dispense medication;funding was reimbursed via a national NHSE agreement. Demographic & clinical data, treatment outcomes & SVR 12 were collected. Feedback on feasibility & satisfaction on the pathway was sought from referrers. Results In the first 6 months, 34 children were referred;30- England;4 - Wales;median (range) age 10 (3.9 - 14.5) yrs;15M;19F: Most were genotype type 1 (17) & 3 (12);2 (1);4(4). Co-morbidities included: obesity (2);cardiac anomaly (1);Cystic Fibrosis (1);Juvenile Arthritis (1). No child had cirrhosis. DAA therapy prescribed: Harvoni (21);Epclusa (11);Maviret (2) .27/34 could swallow tablets;3/7 received training to swallow tablets;4/7 are awaiting release of granules.11/27 have completed treatment and cleared virus;of these 7/11 to date achieved SVR 12. 30 children requiring DAA granule formulation are awaiting referral and treatment. Referrers found the virtual process easy to access, valuing opportunity to discuss their patient's therapy with the MDT & many found it educational. There were difficulties in providing the medication through the local pharmacy. However there are manufacturing delays in providing granule formulations because suppliers focused on treatments for COVID, leading to delays in referring and treating children unable to swallow tablets. Conclusion The National HCV pMDT ODN delivers high quality treatment & equity of access for children & young people, 3- 18 yrs with HCV in England, ensuring they receive care close to home with 100% cure rates.
ABSTRACT
Background and aims: As a result of disengagement in addiction care during the COVID-19 pandemic, there has been a record increase in mortality associated with opioid overdoses (primarily fentanyl), particularly in North America. In the USA there were over 100, 000 overdose deaths in 2021, while over 2000 were recorded in the province of British Columbia. As we attempt to develop novel ways to increase HCV treatment following ≥30% declines during the pandemic, we evaluated publicly available adverse events (AEs) reports for opioids and DAAs to assess whether safety concerns from potential drug interactions arewarranted, particularly amongst those using fentanyl. Method: Data were downloaded from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Public Dashboard. AEswith the DAAs glecaprevir/pibrentasvir (G/P), sofosbuvir/ velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/ velpatasvir/voxilaprevir (SOF/VEL/VOX), andelbasvir/grazoprevir (EBR/ GZR) listed as the suspect product were analyzed with an initial received date from July 28, 2017-December 31, 2021, as were opioidassociated AEs for all 2017–2021. Subsequently, AEs were counted based on listed concomitant use of opioids (fentanyl, oxycodone, hydrocodone), or overdose outcomes irrespective of concomitant opioid use. Data are descriptivewithout any statistical analyses. Results: In the reporting period, 40 total AEs were recorded with concomitant DAA and fentanyl use, 14 resulting in death (G/p = 3, SOF/VEL = 11;Table 1);626 total AEs were recorded with concomitant DAA and oxycodone or hydrocodone use, 28 resulting in death. Separately, overdose events were reported 196 times, 32 resulting in death. The number of overdoses declined each year from 2018 (N = 56) to 2021 (N = 29). Fentanyl AEs showed no trend year to year. Table 1: FAERs AEs and deaths with opioids and with concomitant HCV DAAs. (Table Presented) *N represents the sum of fentanyl, oxycodone, and hydrocodone overdose AEs and deaths, whereas n’s for DAA overdose AEs and deaths are irrespective of concomitant opioids. Conclusion: With the limitations of FAERS data (under or duplicate reporting, inability to establish causation or incidence), these data showthat among ~58, 000 fentanyl, ~189, 000 oxycodone, and ~100, 000 hydrocodone AEs reported to FAERS since 2017, a small proportion (0.19%) have been reported in association with concomitant DAA therapy, with no association between recorded events and a specific DAA regimen. This should reassure HCV treaters on a lack of safety signal for concomitant opioid and DAA use.
ABSTRACT
Background and aims: Hepatitis C virus (HCV) infection is a major global health problem in adults & children. The recent efficacy of Direct Acting Anti-viral therapy (DAA) has cure rates of 99% in adults and adolescents. These drugs were licensed for children 3–12 yrs during the recent coronavirus pandemic. To ensure equitable access, safe & convenient supply during lockdown, we established a virtual national treatment pathway for children with HCV in England & evaluated its feasibility, efficacy & treatment outcomes. Method: A paediatric Multidisciplinary Team Operational Delivery Network (pMDT ODN), supported by NHS England (NHSE), was established with relevant paediatric specialists to provide a single point of contact for referrals & information. Referral & treatment protocolswere agreed for HCV therapy approved byMHRA& EMA. On referral the pMDT ODN agreed the most appropriate DAA therapy based on clinical presentation & patient preferences, including ability to swallow tablets. Treatment was prescribed in association with the local paediatrician & pharmacist, without the need for children & families to travel to national centres. All children were eligible for NHS funded therapy;referral centres were approved by the pMDT ODN to dispense medication;funding was reimbursed via a national NHSE agreement. Demographic & clinical data, treatment outcomes & SVR 12 were collected. Feedback on feasibility & satisfaction on the pathway was sought from referrers. Results: In the first 6 months, 34 childrenwere referred;30- England;4-Wales;median (range) age 10 (3.9–14.5) yrs;15M;19F: Most were genotype type 1 (17) & 3 (12);2 (1);4 (4). Co-morbidities included: obesity (2);cardiac anomaly (1);Cystic Fibrosis (1);Juvenile Arthritis (1). No child had cirrhosis. DAA therapy prescribed: Harvoni (21);Epclusa (11);Maviret (2). 27/34 could swallow tablets;3/7 received training to swallowtablets;4/7 are awaiting release of granules.11/27 have completed treatment and cleared virus;of these 7/11 to date achieved SVR 12. 30 children requiring DAA granule formulation are awaiting referral and treatment. Referrers found the virtual process easy to access, valuing opportunity to discuss their patient’s therapy with the MDT & many found it educational. There were difficulties in providing the medication through the local pharmacy. However there are manufacturing delays in providing granule formulations because suppliers focused on treatments for COVID, leading to delays in referring and treating children unable to swallow tablets. Conclusion: The National HCV pMDT ODN delivers high quality treatment & equity of access for children & young people, 3–18 yrs with HCV in England, ensuring they receive care close to home with 100% cure rates.
ABSTRACT
Background: Early studies show that the COVID-19 pandemic has led to reduced prescription of direct-acting anti-viral (DAA) treatment for hepatitis C (HCV) infection. We sought to characterize HCV patients started on DAAs during the pandemic in British Columbia, Canada. Methods: A retrospective chart review of multiple sites was conducted using the British Columbia HCV Network. Patients initiated on DAA for HCV treatment from 09/17/2018- 09/17/2021 were included. Those treated for 18 months prior to 03/17/2020 were included as the pre-pandemic group (pre-PG) and those treated after 03/17/2020 comprised the pandemic group (PG). Results: A total of 393 patients were included, with 221 pre-PG patients and 172 PG patients, representing a 23% decline in HCV treatment during the pandemic. PG patients were significantly younger with mean age 55 years (vs 56 years pre- PG, p<0.01) and a higher proportion were on opioid agonist therapy (OAT) at 28% (vs 12% pre-PG, p<0.01). Rates of alcohol and active substance use were similar between both groups. Both groups had similar HCV genotypes, viral load, and FIB-4 scores. Pre-treatment transient elastography (TE) within 3 months of initiating treatment was completed in significantly fewer PG patients at 37% compared with 70% pre-PG (p<0.01). Of PG and pre-PG patients who completed TE, cirrhosis was found in 15 (9%) and 32 (14%) respectively, with mean liver stiffness measure of 8.69 kPa and 10.21 kPa, respectively. Beyond less utilization of TE, the pandemic also led to reduced total appointments at mean 3.1 visits per PG patient compared to 4.2 visits per pre-PG patient (<0.01). Considering the different types of appointments, PG patients had fewer office appointments at mean 1.6 per PG patient (vs 3.1 per pre-PG patient, p <0.01) but more telehealth appointments at mean 2.5 per PG patient (vs 2.1 per pre-PG patient, p <0.01). Treatment regimen was similar in both groups with predominant use of glecaprevir/pibrentasvir and sofosbuvir/velpatasvir. Treatment completion rate was 95% in PG patients compared to 89% pre-PG (p=0.03). Fewer PG patients completed lab work for sustained virologic response (SVR) at 61% (vs 88% pre-PG) however, SVR rate was similar between both groups (96% pre-PG and 99% PG, p=NS). Active drug use or OAT was not associated with treatment completion or SVR in either group. Conclusion: The COVID-19 pandemic has led to a decrease in HCV treatment rates. However, treatment completion and SVR rates remained high among those treated, suggesting minimal-pre-treatment investigations and use of telemedicine can optimize scarce resources with similar efficacy. (Figure Presented)