Varicella zoster immune globulin (human) (VARIZIG) in immunocompromised patients: a subgroup analysis for safety and outcomes from a large, expanded-access program

Hayley Gans,Roy F Chemaly

doi:10.1186/s12879-020-05656-6

Abstract

BackgroundImmunocompromised children and adults are at increased risk for severe disease and death following varicella zoster virus infection. Varicella zoster immune globulin (human) (VARIZIG) is recommended for post-exposure prophylaxis to prevent or attenuate varicella infection in high-risk individuals.MethodsAn open-label, expanded-access program provided VARIZIG to high-risk individuals exposed to varicella or herpes zoster. Immunocompromised participants were stratified by type of immunocompromising condition (“oncologic immunodeficiency”, “primary immunodeficiency”, “solid organ transplant” [SOT], “hematopoietic cell transplant” [HCT], and “other”). Patient characteristics, type of exposure and varicella outcome, and safety data were assessed.ResultsThis analysis included 40 adults (primary [n = 6] or oncologic [n = 10] immunodeficiencies, history of SOT [n = 5] or HCT [n = 6], and other [n = 13]), and 263 children (primary [n = 13] or oncologic [n = 152] immunodeficiencies, history of SOT [n = 36] or HCT [n = 17], and other [n = 45]). Among adults and children, 48% vs 72% were exposed to varicella, 38% vs 16% were exposed to herpes zoster, and 15% vs 12% had an unspecified exposure. Overall incidence of varicella infection in adults after VARIZIG use was 6%; incidence of varicella infection in children after VARIZIG use was 7%. Similar rates were noted in each subgroup. Most cases of varicella were mild, with two children developing > 100 lesions and no cases of varicella-related pneumonia or encephalitis. Varicella-related hospitalizations occurred primarily in children with oncologic immunodeficiencies. One serious adverse event (serum sickness) was considered related to VARIZIG and occurred in a child with oncologic immunodeficiency. There were no varicella- or VARIZIG-related deaths.ConclusionsThese data indicate that VARIZIG may reduce severity of varicella in immunocompromised children and adults.Trial registrationThis study was retrospectively registered with the public clinical trial identification NCT00338442 at https://www.clinicaltrials.gov on 20 June 2006.

Highlights

Immunocompromised children and adults are at increased risk for severe disease and death following varicella zoster virus infection
Immunocompromised children and adults are at increased risk for severe disease following infection with varicella zoster virus (VZV) [1, 2], including an increased risk of visceral dissemination, secondary bacterial infections, and mortality [2,3,4,5]
Passive immunization after exposure with immune globulin targeting VZV has been shown to reduce the severity of varicella infection, and is the generally accepted strategy for prevention in exposed immunocompromised individuals [10,11,12]

Summary

Introduction

Immunocompromised children and adults are at increased risk for severe disease and death following varicella zoster virus infection. Varicella zoster immune globulin (human) (VARIZIG) is recommended for postexposure prophylaxis to prevent or attenuate varicella infection in high-risk individuals. Immunocompromised children and adults are at increased risk for severe disease following infection with varicella zoster virus (VZV) [1, 2], including an increased risk of visceral dissemination (i.e. varicellarelated pneumonia, encephalitis, hepatitis), secondary bacterial infections, and mortality [2,3,4,5]. Even in individuals who previously received two doses of varicella vaccine, an important risk factor is waning immunity as a result of immunosuppressive therapy [6]. There is no official guidance on use of antiviral prophylaxis after varicella exposure, use of antiviral therapy started between 6 and 10 days after exposure and continued for 7 days has been reported to prevent varicella infection after exposure [13]

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