William F. Balistreri, MD

Disclosures

March 22, 2016

In This Article

Real-World Effectiveness

Second-generation DAAs have become an integral component of treatment for HCV. However, little is known about their real-world effectiveness. During The Liver Meeting 2015, several presentations included an analysis of real-world databases, which indicated that the efficacy data shown in clinical trials can be replicated in daily clinical practice and real-world observational studies.

Backus and colleagues[21] assessed the effectiveness of LDV/SOF with or without RBV in 569 treatment-naive veterans infected with HCV genotype 1 who were treated in routine medical practice. This was an observational, intention-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry. Patients receiving LDV/SOF with RBV were more likely to have cirrhosis than patients receiving LDV/SOF without RBV (73% vs 28%; P < .001). Among patients who received LDV/SOF, those with cirrhosis had lower rates of undetectable viral loads at the end of treatment than did those without cirrhosis (89% vs 95%). At the end of treatment, HCV RNA was undetectable in 97% of patients with cirrhosis receiving LDV/SOF with RBV. Among patients without cirrhosis who had baseline HCV RNA values < 6,000,000 IU/mL, HCV RNA was undetectable in 93% of those who completed 8 weeks of therapy and 97% of those who completed 12 weeks of therapy.

TRIO and TARGET Networks

Understanding the factors that are associated with treatment failure in clinical practice remains challenging, owing to the relatively few patients who do not achieve an SVR.

Afdhal and colleagues[22] examined a large real-world population to assess the characteristics of patients with HCV genotype 1 in whom all-oral DAA therapies failed. Data were collected from providers and specialty pharmacies through Trio Health's Innervation Platform. The overall SVR12 rate in this heterogeneous population was 97%. By regimen, SVR rates were 97% for LDV/SOF with or without RBV, 95% for 3D with or without RBV, and 93% for SMV+SOF with or without RBV.

Factors that were positively associated with virologic failure in real life were male sex, cirrhosis, platelet count < 100,000 cells/mL, and prior treatment failure. Treatment site, age, race, genotype subtype, viral load, and presence of HIV coinfection or transplant were not associated with treatment failure.

Patients who initiated LDV/SOF-based therapy for HCV genotype 1 in clinical practice were enrolled in HCV-TARGET, a multicenter prospective observational cohort study. They were treated according to the local standards of care at academic and community medical centers in North America and Europe, and they also achieved high rates of SVR12 (approximately 97%).[23] Adverse events were reported in 56% of patients (headache in 20%, fatigue in 18%, nausea in 8%, and diarrhea in 6%).

Lai and colleagues[24] also reported virologic responses of patients with HCV genotype 1 who received LDV/SOF with or without RBV in community practice. They reported SVR4 rates of 98% for patients receiving LDV/SOF/RBV therapy vs 94% for patients receiving LDV/SOF therapy, which are similar to the virologic responses reported in published studies.

These preliminary safety and efficacy data suggest that 8- and 12-week treatment regimens containing LDV/SOF are generally safe, well-tolerated, and highly effective across a broad spectrum of patients and clinical practices.

Rural Outreach Clinics vs Academic Medical Centers

The safety, tolerability, and effectiveness of oral DAA regimens may allow decentralization of treatment from specialists to community-based providers, which would address limitations in access to care for those who reside in medically underserved areas.

Jayasekera and colleagues[25] described their rural outreach clinic strategy in which a visiting hepatologist evaluated treatment eligibility, but subsequent routine management was devolved to licensed vocational nurses (ie, task-shifting). The hepatologist reviewed the laboratory results remotely and was available for consultation as needed. After assessing the outcomes of patients who were treated with DAAs at these clinics vs those who were treated directly by the hepatologist at an academic medical center, they found that the overall SVR12 rates were similar. SVR12 rates in noncirrhotic, cirrhotic, treatment-naive, and treatment-experienced patients with HCV genotype 1, 2, and 3 were also similar.

Task-shifting, where midlevel providers are empowered to manage treatment in medically underserved areas with remote supervision of specialists, may be an effective strategy to expand HCV treatment access and outcomes.

International Experience

Italian patients with decompensated cirrhosis or hepatocellular carcinoma within the Milan criteria who were waitlisted for liver transplantation were enrolled to receive daily SOF/RBV until liver transplantation or for a maximum of 48 weeks.[26] Of those who were HCV RNA negative for > 4 weeks, 4% had relapse after liver transplantation compared with 36% of those who were negative for < 4 weeks. These real-life data indicate that in waitlisted patients with decompensated cirrhosis, SOF/RBV appears to be safe and effective in preventing viral recurrence after liver transplantation. Viral clearance was associated with a significant improvement in liver function in a proportion of patients with advanced cirrhosis.

Adherence and Discontinuation Rates

Discontinuation rates of SOF-based medications are generally low in clinical trials. In a real-world setting, Kamble and colleagues[27] assessed SOF-based regimen discontinuation and adherence rates and identified factors associated with poor compliance. The discontinuation rate was 18%, and the percentage of patients who were considered nonadherent was 14%. On the basis of regression analysis, only older age, higher comorbidity risk score, and the use of interferon were positively associated with nonadherence to treatment plans. Non-HMO members also had a lower risk for discontinuation.

Comorbidities and Complex Polypharmacy

Comorbidities and comedications with drug/drug interactions in patients with HCV, which may pose a challenge to upscaling treatment with new DAAs, should be considered when selecting treatment options. The potential for drug/drug interactions varies substantially among DAA regimens.

Marra and colleagues[28] observed significant comorbidity and coprescribing with the potential for drug/drug interaction in patients with HCV in primary care in three countries. The most common comorbidities were depression, cardiovascular disease, and chronic obstructive pulmonary disease or asthma in the United Kingdom, compared with chronic pain syndromes and hypertension in other countries. There were large differences in the proportion of comedications contraindicated to all DAAs vs only to some, suggesting that careful selection of a DAA regimen is required for each patient.

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