Tuesday, August 4, 2015

Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States

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Medicine and Public Issues | 4 August 2015

Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States 
Soumitri Barua; Robert Greenwald, JD; Jason Grebely, PhD; Gregory J. Dore, MBBS, PhD; Tracy Swan; and Lynn E. Taylor, MD

This article was published online first at www.annals.org on 30 June 2015.

Discussion Only

Considerable heterogeneity is present in Medicaid reimbursement criteria for sofosbuvir across the United States. Restrictions based on liver disease severity are common, with three quarters of states restricting sofosbuvir to persons with advanced fibrosis (F3) or cirrhosis (F4). One quarter of states require that persons living with HIV receive ART or have suppressed HIV RNA levels, whereas two thirds restrict sofosbuvir on the basis of prescriber type. Drug or alcohol use is included in the eligibility criteria of 88% of state Medicaid committees, with half requiring a period of abstinence and two thirds requiring urine drug screening. The restrictions are not consistent with the FDA-approved labeling for sofosbuvir or evidence-based recommendations and should be reconsidered (23).

Most states restrict sofosbuvir reimbursement to persons with advanced fibrosis (F3) or cirrhosis (F4), which is inconsistent with recent AASLD/IDSA recommendations (20). These recommendations state that HCV treatment is indicated for all patients with chronic HCV (regardless of disease stage) because HCV therapy is curative; improves quality of life; slows liver disease progression; and reduces the risk for cirrhosis, end-stage liver disease, HCC, and all-cause mortality (21). The recommendations state that patients at highest priority for immediate treatment include those with advanced fibrosis (F3) or compensated cirrhosis (F4) because of the higher risk for severe complications (for example, hepatic decompensation or HCC). Patients with fibrosis (F2) are listed in the next priority group for treatment because of their high risk for complications (21). However, most states do not include persons with fibrosis (F2) in their Medicaid reimbursement criteria. Note that persons with advanced fibrosis remain at risk for HCC even after achieving sustained virologic response (SVR) and must have long-term surveillance (24). In contrast, once HCV is cured in persons with mild to moderate liver disease, liver disease progression is rare. Requiring liver biopsy may pose the highest risk for death in HCV care with all-oral regimens.

The requirement that HIV-infected persons receive ART or have suppressed HIV RNA levels is also inconsistent with AASLD/IDSA recommendations indicating that persons co-infected with HIV and HCV are also at high priority for treatment because of their high risk for complications (21). HIV accelerates the HCV disease course, with faster progression to cirrhosis, liver failure, and increased HCV-related mortality (2527). The safety and efficacy of sofosbuvir-based, interferon-free combination therapy for co-infected persons are similar to those among patients with HCV monoinfection (21, 2829). Reasons are varied about why co-infected persons may not receive ART (for example, normal CD4+ T-cell counts and low HIV RNA levels) or have suppressed HIV RNA levels (for example, drug-resistant HIV). Physicians who treat such co-infected persons may prefer to commence and complete HCV treatment first, before ART initiation, because HCV therapy is brief; further, DAA therapy often limits which antiretrovirals can be used concomitantly because of drug–drug interactions.

Two thirds of states have restrictions based on physician type, which is inconsistent with current practice whereby internists, other primary care physicians, HIV physicians not trained as infectious diseases specialists, nurse practitioners, and physician assistants treat HCV with pegylated interferon and ribavirin. The availability of sofosbuvir-based, interferon-free regimens simplifies therapy and reduces treatment-associated toxicities, which offers an opportunity for an expanded provider base for HCV treatment in patients without advanced cirrhosis (30).

The overwhelming majority of states restrict access to sofosbuvir for persons who inject drugs (PWID), those receiving treatment for drug dependency (for example, opioid substitution therapy), and those drinking alcohol. Most new and existing cases of HCV in the United States exist among current or former PWID (31). Since 2002, the National Institutes of Health HCV guidelines support HCV treatment regardless of injection drug use (32), and the AASLD/IDSA, European Association for the Study of the Liver, International Network on Hepatitis in Substance Users, and World Health Organization all advocate for inclusion of persons who use drugs in HCV treatment (21, 3335). A growing body of evidence shows that there is no justification for systematically withholding HCV treatment from PWID (21, 33, 36). The SVR rates are similar in PWID with or without opiate replacement therapy (21, 33, 3639). Drug use in the 6 months preceding HCV therapy initiation is not necessarily associated with poorer response to HCV therapy (4042). Reported rates of reinfection after SVR among PWID are low—generally 1% to 5% per year, although concerns about reinfection rates in other subpopulations, such as surgeons, do not garner similar attention (33, 43). Rather than recommending the exclusion of PWID, AASLD/IDSA guidelines include PWID with earlier liver disease stages among a second-order priority group because of the prevention benefit of potential treatment; HCV treatment among PWID may decrease HCV transmission (21). In addition, evidence shows that HCV treatment of current and former PWID is cost-effective, particularly when the prevention benefits are considered (44). Further, Medicaid does not similarly deny medications for other diseases to persons who use or have used drugs or alcohol.

Alcohol misuse and HCV infection frequently coexist (4548). Hepatitis C virus and alcohol act synergistically in causing more severe liver injury than seen with either disease alone (4, 4849). Persons with coexisting alcohol disorders are at a higher risk for HCV-related complications (4, 4849). Curing HCV is easier than curing alcohol disorders because pharmacotherapy for alcohol misuse is limited, and behavioral interventions are not always successful. The SVR rates are similar in drinkers and nondrinkers (4950). Further, the AASLD/IDSA recommendations have no HCV treatment restrictions regarding alcohol use.

This study examined criteria in Medicaid fee-for-service programs only—not in Medicaid managed care organizations. Results therefore reflect a subset of overall state Medicaid reimbursement criteria for sofosbuvir rather than a comprehensive catalog of all restrictions in state Medicaid programs. Future research on reimbursement criteria in Medicaid managed care organizations will be important to develop a more thorough understanding of Medicaid enrollees' access to sofosbuvir.

Current restrictions may violate federal Medicaid law, which requires states to cover drugs consistent with their FDA labels. Under the federal Medicaid statute, virtually all drugs from pharmaceutical manufacturers that have rebate agreements with the Secretary of Health and Human Services (which includes the manufacturer of sofosbuvir) must be available under state Medicaid programs, with only limited methods of restricting coverage (19). None of the restrictions on sofosbuvir coverage detailed here seem to meet the criteria for permissible restrictions. Although the price of new therapies creates financial challenges for federal and state Medicaid budgets, decisions for prioritizing patients for more immediate therapy should be based on clinical criteria and medical evidence. It is recommended that the restrictions be removed; apart from potentially being a human rights violation, they do not make (economic) sense in terms of clinical, public, and long-term health. In setting restrictions as a concession to economic constraints, the significant longer-term public health and economic benefits of curing HCV should be considered and weighed against the upfront treatment costs.

Concerns include that full coverage for HCV treatment could, in the short term, mean less coverage for other conditions. It is unrealistic, however, to expect that all potential candidates will immediately seek HCV treatment. One example of this is Massachusetts. Despite relatively unrestricted sofosbuvir access in its Medicaid fee-for-service program, recent data indicate that only 14% of Massachusetts Medicaid enrollees known to be diagnosed with HCV are engaged in treatment (51).

Transparent, easily accessible, consistent, and evidence-based Medicaid criteria will permit greater and more equitable access to DAAs. As the HCV standard of care changes over time, it will be inefficient and costly to have differing treatment access protocols in the 51 fee-for-service programs and many more Medicaid managed care plans, with all of them being revised over time. More consistency is needed across the system so that where a Medicaid patient lives does not dictate what treatment she or he receives. Although this study examined sofosbuvir in particular, the first FDA-approved DAA as part of an interferon-free regimen, Medicaid may be setting a precedent as new DAAs are approved. Medicaid policies should be responsive to changes in standards of care and new treatment developments. State Medicaid pharmacy and therapeutics committees (or their equivalent) are generally responsible for implementing these policy changes and should be expected to act as expeditiously as possible to ensure that significant clinical changes are addressed in state Medicaid programs. These data suggest that state Medicaid policies for access to new DAAs should be reviewed and revised in line with national clinical recommendations.

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