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

Results

One hundred thirteen individuals aged 65 and older treated with DAA regimens were identified and included in our analysis. Of these, 88 (78%) were aged 65 to 74 and 25 (22%) aged 75 and older at the start of treatment. The mean age of the younger group was 68, 56% were male, and 82% were white; the majority had a history of prior HCV treatment failure with pegylated interferon and ribavirin (67%). The mean age of the older group was 78, 44% were male, 40% were black, 44% were white; 20% had a history of a prior hematological or solid organ cancer. The eGFR in the older cohort was significantly lower than that of the younger cohort (mean 64.4 vs 75.8 mL/min/1.73 m2, p=.02), consistent with the reported decline in eGFR that occurs with advancing age.[23] There was no difference between the 2 groups in terms of pretreatment HCV RNA, presence of cirrhosis, or baseline comorbidities. The characteristics of the study population are illustrated according to age in Table 1.

Concomitant Medications, Treatment Regimens, and DDIs

Individuals aged 75 and older were more likely to be taking more than 2 medications per day for chronic diseases (84% vs 62%, p=.02) and to be taking 5 or more pills per day (56% vs 39%, p=.008). DAA regimens are depicted according to age in Table 1. Eighty–six individuals (76%) underwent a treatment regimen that included ribavirin, with those aged 75 and older less likely to be treated with ribavirin than those aged 65 to 74 (60% vs 81%, p=.20).

Individuals in the older group had a greater frequency of Category 1 or 2 DDIs identified during the pretreatment assessment (80% vs 36%, p=.001) (Figure 1). Adjustment or cessation of medication before DAA therapy was necessary in 64% of individuals aged 75 and older and 31% of those aged 65 to 74. This remained true when restricted to those with cirrhosis, with the older cohort more likely to require adjustment in medications (81% vs 35%, p=.001). The commonest medications requiring dose modification or discontinuation in individuals treated with the most commonly prescribed regimens are shown in Table 2.

Figure 1.

Percentage of participants with clinically significant Category 1 or 2 drug–drug interactions with their prescribed direct–acting antiviral regimen according to age.

Treatment Efficacy

It was possible to analyze sustained virologic response 12 weeks after completion of DAA therapy (SVR12) in 111 of 113 patients. Only 2 individuals discontinued the treatment prematurely: One younger than 75, treated for HCV recurrence after liver transplantation, died of a non liver related cause at treatment Week 5. The other was aged 75 and older and discontinued treatment at Day 3 because of an episode of severe anxiety and did not wish to restart treatment. All individuals who completed treatment had documented optimal adherence to their DAA regimen. All attended for review every 4 weeks to collect a 4–week medication supply and undergo assessment for AEs.

Just three individuals experienced virologic failure, with SVR12 of 97.7% (85/87) for those aged 65 to 74 and 95.8% (23/24) for those aged 75 and older. Of the 12 individuals with Child–Pugh B or C cirrhosis, 8 experienced an improvement in Child–Pugh score at posttreatment Week 12. Similar results were seen when reviewing Model for End–stage Liver Disease score, with 3 individuals having a stable score and 5 demonstrating improvement.

AEs and Tolerability Analysis

Overall, no Grade 3 to 5 AEs related to DAA therapy were observed in during the treatment period. The only death observed on treatment was due to cancer in an individual younger than 75. Individuals aged 75 and older were more likely to experience a Grade 1 AE during DAA treatment than those in the younger cohort (50% vs 26%, p=.03). The profile of AEs is illustrated in Figure 2. Of the 86 individuals treated with a ribavirin–containing regimen, 23% (n=20) experienced significant anemia (hemoglobin <10 g/dL), classified as a Grade 2 AE, which was treated with a ribavirin dose reduction (Figure 2). Erythropoietin supplementation was commenced for just 8 individuals, with 6 of these having a baseline eGFR of less than 50 mL/min per 1.73 m2. Individuals aged 75 and older were more susceptible to ribavirin–related anemia than those aged 65 to 74 (60% vs 20%, p=.02), despite receiving a lower ribavirin dose (median 400 vs 800 mg/d). No significant difference in plasma ribavirin levels was observed between the 2 groups (median 3.15 vs 3.39 mg/mL), but individuals aged 75 and older had a smaller change in their red blood cell distribution width from baseline to Week 4 of treatment than the younger cohort (change in red blood cell distribution width: 1.4 vs 2.8, p=.03). No difference between pre– and posttreatment eGFR was observed in either cohort.

Figure 2.

Percentage of participants with Grade 1 or 2 adverse events according to age. Frequency of anemia is reported only for participants who received ribavirin containing direct–acting antiviral regimens. Others include myalgia and headache.

Follow–up

During a median posttreatment follow–up period of 38 weeks (range 12–132 weeks), 4 individuals died. All were aged 65 to 74, and all had achieved SVR12. One with a history of liver transplantation died from causes unrelated to hepatitis C. The other 3 had Child–Pugh B cirrhosis, with 1 death from sepsis and 2 deaths after surgery.

Eight percent (9/113) of individuals had a history of a HCC before antiviral treatment, with a complete response to treatment and no recurrence during at least 1 year of posttreatment follow–up before commencement of DAA therapy. Seven percent (8/113) had an active HCC at the start of therapy. All individuals with an active HCC at treatment start achieved SVR12. The rate of recurrence of HCC in individuals with prior or current HCC was 17% (3/17), and the rate of de novo HCC was 3% (3/96).

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