Hepatitis C — Implications for Managed Care Organizations

Hepatitis C viral infection becomes chronic in most people who acquire the infection. Some of these people progress to end-stage liver disease, which can be life-threatening. There are six known variants of HCV called genotypes; while these viruses are closely related, the clinical course of infection that they cause and their susceptibility to therapy differ from each other. Infection with a strain of the virus called genotype 1 is most common in the U.S.³ (about 70%-80% of infected individuals), and is the most difficult to treat. Genotype 1 is further subdivided into 1a and 1b, which also differ in their susceptibility to medications.

Chronic HCV infection has been dubbed the "silent epidemic" because the infection remains quiescent for years, even decades, before clinically significant symptoms appear. Symptoms usually only develop after the establishment of advanced stages of liver disease. The majority of currently infected individuals have not yet been diagnosed. Estimates indicate that three-quarters of all the infected people in the U.S. were born between 1945 and 1965¹. Given that progression to chronic liver disease takes decades, some of these people are now presenting with evidence of chronic liver disease.

New Treatments

Two new treatment options arose in 2014 that dramatically altered the approach to treatment. These new medications, Harvoni (ledipasvir/sofosbuvir) and Viekira (ombitasvir/paritaprevir/ritonavir/dasabuvir) bring vastly more effective treatment outcomes for patients with genotype 1 infections — with complete viral clearance in more than 90% of patients.^5,7 At the same time, these new agents offer significant advantages such as the elimination of the need for injections, reduction in side effects from interferon, which are considerable, and the reduction in treatment duration.

Harvoni is easier to administer with a dosing of one tablet once a day.⁵ Viekira requires a higher daily "pill burden" and may have more side effects, but is still highly effective.⁷ Viekira also requires adding ribavirin to the regimen for certain patients, particularly those infected with genotype 1a. Adding ribavirin can cause anemia in some patients, requiring additional treatment.⁷

The challenge to MCOs is to set reasonable, evidence-based criteria to determine when payment should be provided or withheld to cover these medications, and under what circumstances. MCOs face the challenge of determining how often they will authorize payment for repeated courses of therapy with these new medications in the same patient, whether payment is appropriate for persons engaged in lifestyles that incur risk of reinfection, and whether patients are ready to commit to high-fidelity adherence during therapy. MCOs also may want to find ways to understand the long-term outcomes of therapy.

When to Treat

One aspect of the HCV treatment discussion that often is overlooked is that it usually takes a long time for liver failure to develop in most of those who are infected. A large majority of those who have the infection never develop liver failure in their lifetimes even if they were not treated. HCV is not easily spread from one person to another. Casual contact does not spread the virus, and transmission is rare even under conditions of intimate contact.¹⁰ In most situations, infected blood must enter the bloodstream of another person to transfer the virus (i.e., blood transfusions, needles, or trauma)¹. Treatment with medications solely as a public health measure to eradicate this virus is not as cost-effective as prevention of blood-to-blood contact, and is not recommended by public health authorities¹¹. MedImpact's P&T Committee, whose membership includes a predominance of independent physicians and pharmacists, has approved guidelines for payment authorization for medications for the treatment of chronic HCV infection.²⁰ Independent experts in the field of HCV management also reviewed these guidelines. It is important to note that guidelines do not apply to all clinical circumstances, and therefore clinical judgment and oversight is necessary. Nonetheless, some general observations are valid.

Whom to Treat

In addition to the clinical criteria above, MedImpact clinical guidelines also have provisions to ascertain whether the patient's life expectancy justifies medication therapy. This situation applies to patients with advanced, decompensated liver disease: There is limited evidence that treatment for patients with decompensated liver disease alters the clinical outcome.^14,15 Gilead, the manufacturer of Harvoni and Sovaldi, states in the package insert that the safety and efficacy of these medications have not been established in patients with decompensated cirrhosis.^5,9 The Viekira package insert states "not recommended" for this situation, and the Olysio package insert states that the drug is "contraindicated" in decompensated cirrhosis.^7,8 Therefore, payment for medications under this clinical circumstance is generally not authorized. The guidelines also attempt to ascertain whether the patient engages in lifestyle choices that promote re-infection, such as injection of illicit drugs, or whether the patient engages in excessive use of alcohol, which is a marker of poor liver health. Under these circumstances, the guidelines recommend waiting for more favorable conditions for treatment, unless clinical characteristics are more compelling. Based upon nearly unanimous agreement by the experts, the guidelines contain a provision to check an HCV RNA level ("viral load") early in treatment, as a marker of adherence. Experts agree that adherence is vital.²¹ It is important to note that some administrators have raised the issue of drug diversion where these valuable medications may be obtained for profit. MedImpact guidelines do not address the issue whether to extend coverage of medication for more than one course of therapy. Treatment failure can occur for three basic reasons: poor adherence; failure of the medication to produce the desired effect (either short or long term), or reinfection. Whether to cover a second or subsequent course of therapy, and under what circumstances, is still a subject of discussion.

Is it a "Cure"?

Gilead Pharmaceuticals has launched an advertising campaign aimed at primary care providers and people at risk for HCV infection that equates viral clearance with "cure."^4,16 While this assertion is intuitively appealing, it may not be completely accurate. There is evidence that the virus may become latent in some patients only to re-emerge later despite apparent successful eradication of HCV from the blood.^11,12,13,17 There is also evidence to show that some patients' liver disease may progress to cirrhosis despite successful eradication of HCV.^11,12,13 However, none of these studies takes the new medications into account, so the long-term outcomes are unknown.²

Cost-Effectiveness of Treatments

The cost-effectiveness of the new medications to treat HCV is a hotly debated issue. On the one hand, the manufacturers tout savings in terms of avoidance of liver transplantations and deaths from HCV.⁶ These projections may overestimate the actual risk of progression to end-stage liver disease in the affected population. On the other hand, a recent study asserts that the additional cost of the new medications cannot be justified in terms of the additional economic benefit. The study found that spending $136 billion on new medications over the next 5 years would return only $16 billion in terms of cost avoidance.^18,19 The study concluded, "Price reductions and value-based patient prioritization are needed to manage HCV patients effectively."¹⁸ If one assumes that the benefits of the older, interferon-based therapies were worth the cost, then by comparison, the recent MedImpact-generated discounts render the new drugs better in terms of cost-effectiveness compared to the older ones.

Summary

MedImpact has approached these medications employing the same proven methodology that has formed the backbone of MedImpact's reputation for clinical excellence over many years: to create well-designed coverage guidelines (prior authorization guidelines) that favor utilizing these new medication technologies for those patients who are likely to benefit most, based largely on the clinical characteristics of their disease. The guideline logic also is designed to identify those patients who are the most likely to complete the regimen successfully, so that resources are used wisely. The guidelines also contain logic to identify those patients who are less likely to re-infect themselves. Successful eradication of HCV with these medications does not produce lifelong immunity, and therefore people who continue to expose themselves voluntarily to re-infection should be deferred until such time as they have made a commitment to lifestyle modification, as long as any given patient is not in danger of progressing rapidly to liver failure. The patients with mild disease, which constitutes the great majority, are in a good position to wait until the time is right.

The clinical aspects of MedImpact guidelines, such as what medication to choose under certain clinical circumstances, are consistent with the AASLD/IDSA clinical guideline recommendations, as well as FDA approvals and published studies. It is important to note that MedImpact does not specify how to treat individual patients with HCV through the application of these guidelines; these guidelines constitute recommendations to health plans and other payors as to whether a certain medication should be covered for payment purposes under certain specified clinical circumstances.

In summary, the new medications, Harvoni and Viekira, have similar clinical outcomes when compared to each other, and these outcomes are far superior to older regimens to treat chronic genotype 1 HCV infection. Harvoni has a clinical advantage over Viekira in terms of side effects, complexity of drug regimen, and perhaps non-pharmaceutical costs, which are magnified when ribavirin is added to the regimen. However, these factors may not constitute issues of significant magnitude in most clinical situations. Each medication has a place in current clinical therapy of HCV. It is likely that clinicians will favor Harvoni for many of the reasons stated above.

Article contributors:

Doug McCann, Manager, Clinical Account Services
Louis Tripoli, M.D.,Medical Director
Crystal Maas Patel, PharmD, Drug Information Pharmacist
Steve Boekenoogen, Director, Clinical Account Services
Steven Avey,RPh, MS, FAMCP, VP, Specialty Programs
Debra Minich, RPh, VP, Clinical Account Services

References:

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20. MedImpact P&T approved prior authorization guidelines for Viekira Pak and Harvoni.
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