Efficacy and Tolerability of Direct–Acting Antivirals for Hepatitis C in Older Adults

Chiara Mazzarelli, MD; Aisling Considine, MPharm; Kate Childs, MBBS, MPH; Ivana Carey, MD, PhD; Matteo Angelo Manini, MD; Abid Suddle, MBBS, MD; Geoffrey Dusheiko, MB, BCh; Kosh Agarwal, BMed Sci (Hons), MD; Mary D. Cannon, MB, BCh, PhD

Disclosures

J Am Geriatr Soc. 2018;66(7):1339-1345. 

In This Article

Methods

Study Design and Selection Criteria

Retrospective review identified 165 individuals aged 65 and older who consecutively presented to the viral hepatitis outpatient clinic at King's College Hospital between June 2014 and January 2017. One hundred thirteen individuals received DAA therapy through the National Health Service (NHS) England commissioned treatment scheme and were included in all subsequent analyses. Twenty individuals elected to enter clinical trials of DAA therapy and were not included in our study. Thirty–one individuals had genotype 3 HCV without evidence of advanced liver disease and were not eligible to receive interferon–free DAA treatment during the study period. Treatment for these 31 individuals was deferred until later in 2017 when more efficacious regimens would be approved for the treatment of genotype 3 HCV. One 90–year–old individual, with significant comorbidities and an expected life expectancy of less than 6 months, was not considered for treatment of HCV during the study period.

Our cohort was divided into 2 subgroups: aged 65 to 74 and aged 75 and older. All received one of the following regimens: sofosbuvir + daclatasvir ± ribavirin; sofosbuvir + ledipasvir ± ribavirin; paritaprevir, ritonavir, ombitasvir ± dasabuvir ± ribavirin; and sofosbuvir + ribavirin. Only 8 patients received treatment within the previously reported U.K. expanded access program.[20] The DAA regimen used and duration of therapy (12 or 24 weeks) were based on guidance from the NHS England commissioned treatment scheme. The starting dose of ribavirin was at the physician's discretion in accordance with international guidelines. Ribavirin was adjusted for estimated glomerular filtration rate (eGFR) in accordance with label recommendations.

Data Collection and Variable Definitions

Data were retrospectively collected using chart review. Demographic and clinical data were recorded. Stage of liver disease was determined based on imaging (ultrasound, computed tomography, or magnetic resonance imaging), transient elastography, or liver biopsy. Laboratory values analyzed were complete blood count, liver function tests, albumin, eGFR, plasma ribavirin level, and HCV ribonucleic acid (RNA). eGFR was calculated using the Modification of Diet in Renal Disease Study equation.[21] Laboratory tests were reviewed at commencement of treatment and at treatment Weeks 4, 8, and 12. Response to treatment was determined by measuring HCV RNA 4 and 12 weeks after completion of DAA treatment. AEs were systematically explored during the every–4–week clinic visits and documented. AEs were defined according to Common Terminology Criteria for AEs version 4.0. The severity of AEs was recorded using a scale on a range from Grade 1 to 5 (1=mild, 2=moderate, 3=severe, 4=life–threatening, 5=death).[22] The occurrence of anemia was assessed at treatment Weeks 4, 8, and 12, with a decline in hemoglobin to less than 10g/dL defined as a Grade 2 AE. Ribavirin dose reductions and the use of erythropoietin were at the physicians discretion. All AEs reported, treatment discontinuations, HCC occurrence, and death were included in our analysis.

Assessment of DDIs

All individuals underwent a full review of concomitant chronic medications before commencing DAA therapy. Potential DDIs were assessed using the University of Liverpool website (www.hep–druginteractions.org). Potential DDIs were assigned the following risk categories: 1) co–administration not recommended, 2) potential interaction that may require close monitoring or alteration in dose or timing of administration of medication, and 3) no clinically significant interaction expected. For individuals with DDIs in risk categories 1 or 2, medication was discontinued, they were closely monitored, or the dosage or timing of the interacting medication was altered.

Statistical Analyses

All statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY). Qualitative variables were expressed as means and standard deviations or medians and ranges. Between–group comparisons were made using parametric t–tests or nonparametric Mann–Whitney U–tests, according to the distribution of data. P<.05 was considered statistically significant. Our study was conducted as a retrospective chart review, so ethical approval was not required at our institution. Given the retrospective nature of our work, informed consent was not obtained from individuals.

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