The Impact of Direct-Acting Antiviral Agents on Liver and Kidney Transplant Costs and Outcomes

D. A. Axelrod; M. A. Schnitzler; T. Alhamad; F. Gordon; R. D. Bloom; G. P. Hess; H. Xiao; M. Nazzal; D. L. Segev; V. R. Dharnidharka; A. S. Naik; N. N. Lam; R. Ouseph; B. L. Kasiske; C. M. Durand; K. L. Lentine

Disclosures

American Journal of Transplantation. 2018;18(10):2473-2482. 

In This Article

Abstract and Introduction

Abstract

Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007–2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.341.852.10, P < .0001) and death (aHR 1.471.681.91, P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.340.671.32, P = .25) or graft failure (aHR 0.320.641.26, P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% (0.190.430.95, P = .04) and graft loss by 46% (0.270.541.07, P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.

Introduction

Direct-acting antivirals (DAAs) have dramatically altered the care of patients with chronic hepatitis C virus (HCV) infection.[1–6] For the last 2 decades, chronic HCV infection was the leading indication for liver transplant (LT) in the United States. Treatment of HCV infection prior to 2014 consisted primarily of interferon- and ribavirin-based treatment regimens, which had limited efficacy, were associated with debilitating side effects, and, generally, were contraindicated in patients with decompensated cirrhosis or, in the case of ribavirin, advanced chronic kidney disease (CKD).[7,8] DAAs reduce morbidity and result in sustained virological response 12 weeks after completing treatment (SVR12) rates >94% for most genotypes in both compensated and decompensated patients.[4,9,10] DAAs have also been safely used in the post LT setting to prevent recurrent inflammation and fibrosis, which was universal in the absence of effective pretransplant treatment. Historically, recurrence of HCV in the liver graft resulted in cirrhosis in 20%–30% of LT recipients and fibrosing cholestatic hepatitis C in 2%–9% within the first 12 months.[11,12] DAAs have been shown to achieve SVR12 after LT in multiple clinical trials, although the impact of DAAs on longer-term LT and KT outcomes has not been reported.[12]

Among patients with end-stage renal disease (ESRD), HCV prevalence is 5 times greater than in the general population.[13,14] Historically, HCV-infected ESRD patients on dialysis were 60% more likely to die than their noninfected counterparts. Prior to DAAs, interferon-based regimens had low levels of efficacy and high rates of intolerability in this population and were generally contraindicated in HCV-infected KT recipients because of unacceptable rates of rejection and allograft dysfunction. Because most HCV-infected KT recipients in the pre-DAA era were therefore either untreated or intolerant to pretransplant interferon/ribavirin, these patients experienced higher rates of graft loss and death than noninfected patients.[15] In contrast, DAAs are both safe and well tolerated in patients with advanced CKD, with SVR12 rates from 95% to 98%.[16,17] DAA treatment in KT recipients successfully eradicates the virus without negatively affecting graft function in clinical series.[18,19]

While DAA treatment is revolutionary, access to it has been hampered nationally by its high cost.[20–22] Initial regimens resulted in total healthcare expenditures exceeding $100 000 USD (United States dollars) per treatment course. As more DAAs have entered the market and competition has increased, costs have diminished, but remain in excess of $25 000 per course, depending on specific agent. Consequently, major private payers developed preauthorization processes that initially restricted use to patients with defined clinical conditions such as demonstrated hepatic fibrosis, cirrhosis, or advanced kidney disease, despite evidence suggesting clinical benefits even in patients without advanced liver disease.[23] While long-term economic analyses suggest that DAAs are cost effective, few are cost saving despite reducing the need for transplant.[24–26] Furthermore, the cost savings are accrued far in the future when many patients have changed health insurance, diminishing enthusiasm for broader treatment of patients without qualifying conditions.

While clinical trial experience with DAAs in the posttransplant LT and KT populations have demonstrated high SVR rates, no large-scale, population-based assessment of access to DAA treatment, effects on longer-term transplant outcomes, or increases in the cost of treatment has been conducted. Using a unique data set linking pharmacy claims data and transplant registry outcomes, we developed a national cohort of HCV-positive transplant recipients with sufficient power to assess DAA use in LT and KT recipients before and after introduction of DAAs, characteristics associated with posttransplant HCV treatment, and the independent impact of these medications on patient and graft outcomes.

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