Adoption of New Agents and Changes in Treatment Patterns for Hepatitis C: 2010-2014

New hepatitis C medications have been quickly adopted into practice and increased treatment rate. The median out-of-pocket costs of new medications were relatively low.
Published Online: June 16, 2016
Xiaoxi Yao, PhD; Lindsey R. Sangaralingham, MPH; Joseph S. Ross, MD; Nilay D. Shah, PhD; and Jayant A. Talwalkar, MD
ABSTRACT

Objectives:
A number of new hepatitis C virus (HCV) medications have become available in the United States, but little is known about how these treatments have been adopted into practice and their financial burden on patients. The aim of this study was to examine whether the introduction of new HCV medications was associated with changes in treatment rates and out-of-pocket (OOP) costs. 

Study Design: Retrospective analysis of administrative claims data from Optum Labs Data Warehouse.

Methods: We performed a retrospective analysis using a large, US commercial insurance database to identify 56,116 adults with chronic HCV between January 1, 2010, and December 31, 2014. Logistic regression was performed to calculate patients’ predicted probability of being treated before and after the new medications became available. 

Results: A total of 5436 (9.7%) of patients with HCV received treatment during an average of 1.8 years of follow-up. In the last quarter of 2014, 0.1% of patients with HCV received interferon/ribavirin as the primary treatment; no one received boceprevir or telaprevir, 1.1% received sofosbuvir combined with simeprevir, 1.4% received sofosbuvir or simeprevir alone, and 2.0% received ledipasvir/sofosbuvir. The introduction of new medications was significantly associated with an increased treatment rate, from 5.4% to 6.8% (P <.001). The increase was high among elderly patients and patients with liver transplant, liver cancer, and liver disease or cirrhosis. The median OOP costs of patients receiving new regimens were relatively low ($112-$340), but great variations existed.

Conclusions: At the end of 2014, patients were almost exclusively using new therapies, which was associated with increased treatment rate, especially among patients who may need urgent treatment but are intolerant or ineligible for interferon-based regimens.

Am J Manag Care. 2016;22(6):e224-e232
Take-Away Points
  • At the end of 2014, patients were almost exclusively using the new hepatitis C medications that were made available since 2013. 
  • New therapies increased treatment rate, especially among patients who may need urgent treatment but are intolerant or ineligible for previous interferon-based regimens. However, the treatment rate among young and relatively healthy patients decreased.
  • The median out-of-pocket costs of patients receiving new regimens were relatively low ($112-$340), but there were great variations and the mean costs were high ($1982-$2127).
Chronic hepatitis C virus (HCV) is an infection that affects nearly 3.2 million individuals in the United States.1 HCV is associated with increased risk of developing liver cirrhosis, hepatocellular carcinoma, liver failure, and death.2 Over the past 2 decades, the mainstay of treatment of HCV has been interferon alfa and ribavirin, but the treatment causes numerous adverse events, including influenza-like symptoms, depression, cytopenia, hemolytic anemia, fatigue, pruritus, and rash.3,4 It also requires long treatment duration (typically 48 weeks), and results in an average low cure rate—defined by sustained viral response (SVR)—of less than 50%.5,6 Additionally, many patients are not eligible for, or cannot tolerate, interferon-based treatment.7,8 As a result of these challenges, until recently, only 10% to 30% of adults with chronic HCV received treatment.9 Since 2011, significant advances have been made among the options for treatment of chronic HCV.

The new generation of medications, such as ledipasvir/sofosbuvir (Harvoni), sofosbuvir (Sovaldi), and simeprevir (Olysio), increase SVR to over 90% and shorten the treatment period to 12 to 24 weeks.10-14 The incidence and severity of adverse events are also lower in these new agents.11,15 Considering the efficacy, safety, tolerability, and convenience, these new treatment regimens are recommended by the clinical practice guidelines developed by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America in collaboration with the International Antiviral Society–USA.16 There is hope that these new medications may increase the historically low treatment rate in patients with chronic HCV; however, to date, little is known about how these new treatments have been adopted into practice and what their impact has been on patients’ receipt of treatment. In this study, we sought to examine whether the introduction of new HCV medications was associated with an increased treatment rate, especially among the elderly and patients with other complex chronic conditions who are likely to be ineligible for or intolerant of previous regimens.

A secondary aim of this study was to estimate the financial burden of HCV treatment on patients. The cost of the newest agents has been very controversial, with estimates ranging from $66,000 per person for simeprevir to $84,000 for sofosbuvir per person for a 12-week course of treatment.17 The high costs of the new drug regimens have raised significant concerns about insurance plan affordability and cost sharing for patients. Little is known about the patients’ cost sharing; therefore, this study aimed at describing out-of-pocket (OOP) costs of patients undergoing different treatments.

METHODS
Data Source

We conducted a retrospective analysis of administrative claims data from Optum Labs Data Warehouse (OLDW), which includes privately insured and Medicare Advantage enrollees throughout the United States. The database contains health information on over 100 million enrollees over the last 20 years from geographically diverse regions across the United States, with greatest representation from the South and Midwest.18 The included health plans provide claims for professional (eg, physician), facility (eg, hospital), and outpatient prescription medication services.19 The Mayo Clinic Institutional Review Board exempted this study from approval as it represents research on preexisting, deidentified data.

Study Population

We identified all adults (18 years or older) who were diagnosed with chronic HCV between January 1, 2010, and December 31, 2014. Patients were considered to have chronic HCV if they had at least 1 chronic HCV diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes: 070.44 and 070.54), or at least 2 unspecified HCV diagnoses (ICD-9-CM: 070.70, 070.71 and V02.62) on different dates. Patients entered the cohort once they had at least 12-month continuous enrollment in medical and drug health plans and at least 1 HCV diagnosis during these 12 months. Due to the changes in enrollment and disenrollment in health plans, patients entered and left the cohort at different times. The date of entry was defined as the index date, and the 12 months prior to the index date was defined as baseline. We excluded patients who received any HCV treatment at baseline. A detailed flowchart illustrating the cohort creation process can be found in eAppendix Figure 1 (eAppendices available at www.ajmc.com).

Outcomes

The primary outcome of interest was whether patients received any HCV treatment and which treatment they received. We followed the patients from the index date until they were no longer enrolled in the health plans or until end of the study period (December 31, 2014). We assessed 6 treatment regimens available during the study period: 1) interferon/ribavirin, 2) boceprevir (Victrelis), 3) telaprevir (Incivek), 4) simeprevir or sofosbuvir (not combined), 5) simeprevir and sofosbuvir (combined), and 6) ledipasvir/sofosbuvir (see eAppendix Table 1 for the generic names, brand names, Current Procedural Terminology, Version 4 (CPT-4)/Healthcare Common Procedure Coding System codes, and the FDA approval dates). We separated patients who received the combined sofosbuvir and simeprevir from those who received only 1 of the 2 agents due to highly differing costs. We did not separate patients who received only eprevir from those who received only sofosbuvir, because a single patient in the cohort received simeprevir alone.

Treatment regimens 2 through 4 (from above) include the use of ribavirin and/or interferon. If patients received interferon/ribavirin with another medication at the same time, they were considered receiving the other treatment regimen. For example, if patients received boceprevir with interferon and ribavirin, they were considered to be on the boceprevir regimen. We calculated the percentage of patients receiving treatment, and the percentages of patients receiving each of the 6 regimens per study quarter. Patients were considered being treated or being on a specific treatment regimen during the time from the fill date of a medication through the end of this medication fill (fill date + days of supply – 1). Many patients may be cured after treatment, and patients need to be monitored for at least 12 to 24 weeks to determine whether the treatment was successful. If the treatment failed, some patients may not be eligible or willing to receive another treatment11,20; therefore, most treated patients no longer needed treatment—at least in the short term—so we excluded them from both the numerator and denominator of the percentages after the conclusion of their last treatment. Patients were not counted prior to the index date or after they disenrolled from the health plan.

The secondary outcome was patients’ OOP cost, defined as the sum of the deductible and copayment of the medications. All the costs were adjusted to 2014 dollars using the personal consumption expenditures inflation factor.21 We calculated the descriptive statistics of costs stratified by patients’ most recent treatment regimens.

Statistical Analysis

We used multivariable logistic regression analysis to estimate the predicted probability of receiving treatment prior to and after the new medications became available. We divided patients into 2 groups: 1) “pre-group,” which includes patients whose enrollment ended before December 1, 2013, approximately when simeprevir and sofosbuvir became available; and 2) “post group,” which includes patients who had enrollment on or after December 1, 2013. In this analysis, we excluded 1565 patients who were in the post group but finished treatment prior to December 2013.

Other covariates included demographics and socioeconomic characteristics at index date (ie, age, gender, race, household income, and residence region), baseline comorbidities, Charlson-Deyo Comorbidity Index (CDCI),22 and the length of follow-up. We adjusted for comorbidities that can influence patients’ treatment decisions, including depression (ICD-9-CM codes: 296.2x, 296.3x, 311), liver cancer (ICD-9-CM: 155.0, 155.2), liver disease or cirrhosis (ICD-9-CM: 571.2, 571.5, 571.6, 571.8, 571.9), and liver transplant (ICD-9-CM: V42.7, 996.82; ICD-9-CM procedure: 50.5, 50.51, 50.59; CPT-4 codes: 47135, 47136). The CDCI was used to assess a patient’s overall comorbidity burden. Statistically significant interactions between the main independent variable and other covariates (ie, age, gender, region, and comorbidities) were also included in the model. All analyses were conducted using SAS 9.3 (SAS Institute Inc, Cary, North Carolina) and Stata 13.1 (Stata Corp, College Station, Texas).

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