Vaccination Against Herpes Zoster and Postherpetic Neuralgia in France

A Cost-Effectiveness Analysis

Xavier Bresse; Lieven Annemans; Emmanuelle Préaud; Karine Bloch; Gérard Duru; Aline Gauthier

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2013;13(3):393-406. 

In This Article

Abstract and Introduction

Abstract

This study assesses the cost–effectiveness of vaccination against herpes zoster (HZ) and postherpetic neuralgia in France, using a published Markov model. The cost–effectiveness of vaccinating individuals aged from 65 years or between 70 and 79 years was evaluated over their lifetime, from a third-party payer perspective. French-specific data were combined with results from clinical studies and international quality-of-life-based (EuroQol five-dimension questionnaire) utilities from the literature. HZ vaccination was highly cost effective in both populations. Incremental cost-effective ratios were estimated between €9513 and 12,304 per quality-adjusted life year gained, corresponding to €2240–2651 per HZ case avoided and €3539–4395 per postherpetic neuralgia case avoided. In addition to epidemiological and clinical evidence, economic evidence also supports the implementation of HZ vaccination in France.

Introduction

Herpes zoster (HZ; shingles) is a painful disease characterized by a blistering unilateral skin rash in a pattern defined by the affected dermatome.[1,2] It results from the reactivation of varicella-zoster virus (VZV) that has remained dormant within the ganglia of the spinal dorsal root or sensory cranial nerves following a primary infection with VZV (i.e., chickenpox) during childhood. HZ-related pain has a significant negative impact on patient wellbeing and quality of life (QoL) from the onset of the acute phase of the disease and throughout its evolution. Two-thirds of patients with shingles and persistent pain indicate that the pain is moderately severe to very severe, and it affects all aspects of life: social, mental, physical and functional.[3]

HZ occurs more frequently as VZV-specific cell-mediated immunity decreases, often as a result of advancing age (immunosenescence), especially from the age of 50 years, and/or in conditions associated with reduced immune function.[4] Humans have a one in four risk of suffering HZ during their lifetime,[5,6] and two-thirds of cases occur in people aged 50 years or older, one half occurs after 60 years and one third after 70 years.[7,101] Both the risk and severity of HZ increase with age.[8] Almost all European adults (>95%) are at risk of developing HZ, as they have latent VZV following infection with varicella during childhood. In Europe, seroprevalence of VZV antibodies is approximately 50% in children aged up to 4 years and is at least 95% in adults by the time they reach the age of 40 years.[9–11] With a lifetime risk of developing HZ of approximately 25%, it has been estimated that at least 1.8 million new cases of HZ will occur in Europe each year.[8,12,102]

Postherpetic neuralgia (PHN) is a long-lasting pain associated with HZ and it can persist for months to several years following a distinctive prodromal period during which the initial HZ rash and pain have subsided.[13,14] It is generally defined as persisting for 3 months after rash onset,[15–17] and can last several years, particularly in elderly subjects.[6] PHN is the most common complication of HZ, and develops in 20–50% of patients with HZ who are older than 50 years and in 70% of those above 70 years of age.[18,19] Both the severity and risk of PHN increase with age, doubling with each decade of life.[20–24]

PHN is a debilitating pain that lowers QoL to a degree similar to that reported by patients with congestive heart failure, myocardial infarction, Type 2 diabetes and major depression.[24] It is most commonly observed in persons aged 70 years and older, and the consequences of the disease on daily life are considerable since they can interfere with social functioning and, ultimately, potential loss of autonomy.[25]

If taken early, antiviral medications can help control HZ pain in its acute stage; however, these medications have a limited effect on PHN (which can persist afterwards) even if they were taken within the first 72 h after rash onset.[26,27] A wide range of drugs have been used to treat PHN, including analgesics, anticonvulsants and antidepressants. They often require challenging step-by-step personalized treatment implementation as there is a potential risk of drug–drug interactions, which may result in serious adverse effects in elderly people, and in this regard confusion and falls are a particular concern.

Prevention of HZ and PHN is now possible following the introduction of an HZ vaccine.[103] The first HZ vaccine available in Europe is a live-attenuated zoster vaccine licensed for prevention of HZ and PHN for persons aged 50 years and over,[103] and it is manufactured by Merck (NJ, USA) as Zostavax®. In the pivotal randomized Shingles Prevention Study (SPS), a double-blind, placebo-controlled, randomized trial that enrolled 38,546 adults aged 60 years and older, Zostavax was shown to reduce the incidence of HZ by 51.3% (95% CI: 44.2–57.6), the incidence of PHN by 66.5% (95% CI: 47.5–79.2), and the HZ burden of illness, a composite end point sensitive to the incidence, severity and duration of HZ pain, by 61.1% (95% CI: 51.1–69.1),[6] with a good safety profile. In another randomized controlled trial involving 22,439 subjects aged 50–59 years, vaccine efficacy in reducing HZ incidence was found to be 69.8% (95% CI: 54.1–80.6%).[28] Persistence of the efficacy of the HZ vaccine has also been reported in long-term follow-up studies.[29,103]

In France, 250,000–280,000 persons experience shingles each year, and more than half of these cases occur in people aged 60 years and older.[7,101] The older population, notably individuals aged 70 years and above, has a higher epidemiological burden, including more severe PHN, deterioration of QoL, potential loss of autonomy and problems with receiving effective care. As treatment of older individuals with HZ and PHN with antiviral drugs and complex pain management is both difficult and often ineffective, the availability of an efficacious and safe vaccine has been a major advance.

In the context of the aging population across Europe, HZ vaccination can contribute to maintenance of individual autonomy and social engagement for the elderly generation. Routine use of HZ vaccine in French citizens aged 50 years and older could therefore be considered as a relevant step to help promote active and healthy aging.

In addition to epidemiological and clinical evidence, health economic evidence is also required before adopting any vaccination policy. The aim of this study was therefore to assess the cost–effectiveness of HZ vaccination of older persons in France and to provide economic evidence supporting the implementation of a new HZ vaccination program under different age-based scenarios.

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