Updated Recommendations for Use of VariZIG — United States, 2013

Updated Recommendations for Use of VariZIG — United States, 2013

BACKGROUND Statins are commonly prescribed worldwide and recent evidence suggests they may increase the risk of herpes zoster. Results The median age of the cases and controls was 62 years. Yawn (2009). Participants 144 959 adults diagnosed with zoster between 2000 and 2011; 549 336 age, sex, and practice matched controls. Previously available under an investigational new drug (IND) expanded access protocol, VariZIG, a purified immune globulin preparation made from human plasma containing high levels of anti–varicella-zoster virus antibodies (immunoglobulin G), is the only varicella zoster immune globulin preparation currently available in the United States. Incidence of HZ is also high in individuals who are immunocompromised as a result of disease or its treatment. Widespread use of this vaccine may be beneficial in reducing the opportunities for varicella-zoster virus introductions in health care settings.

CDC also has revised the patient groups recommended by the Advisory Committee on Immunization Practices (ACIP) to receive VariZIG by extending the period of eligibility for previously recommended premature infants from exposures to varicella-zoster virus during the neonatal period to exposures that occur during the entire period for which they require hospital care for their prematurity. The CDC recommendations for VariZIG use are now harmonized with the American Academy of Pediatrics (AAP) recommendations (3). This report summarizes data on the timing of administration of varicella zoster immune globulin in relation to exposure to varicella-zoster virus and provides the CDC updated recommendations for use of VariZIG that replace the 2007 ACIP recommendations. It is a common disease in older people,1 with a lifetime risk of up to 30% rising to 50% among those living to 85 years.2 Zoster typically presents as a painful unilateral vesicular dermatomal rash that causes acute morbidity lasting two to four weeks.3 A severe complication—postherpetic neuralgia—although uncommon in patients aged under 50, develops in 12% of zoster patients aged 50 years or over14; it causes intense pain that can last from months to years and is associated with considerable impairment of quality of life. ZIG also lowered attack rates and modified disease severity among susceptible immunocompromised children when administered within 72 hours after household exposure (5,6). Current vaccines are contraindicated in people at the greatest risk of zoster, highlighting the need for alternative risk reduction strategies in these groups. The first commercial varicella zoster immune globulin preparation available in the United States, VZIG, was prepared from plasma obtained from healthy, volunteer blood donors identified by routine screening to have high antibody titers to varicella-zoster virus, and became available in 1978.

Updated Recommendations for Use of VariZIG — United States, 2013
Short-term illness in the elderly can lead to long-term loss of independence. In a study of immunocompromised children who were administered VZIG within 96 hours of exposure, approximately one in five exposed children developed clinical varicella, and one in 20 developed subclinical disease compared with 65%–85% attack rates among historical controls (8). Among those in the study who became ill, the severity of clinical varicella (evaluated by percentage of patients with >100 lesions or with complications) was lower than expected on the basis of historic controls. The effectiveness of VZIG when administered >96 hours after initial exposure was not evaluated. Based on these findings and the licensure indications of the VZIG available in the United States, ACIP recommended VZIG for use within 96 hours of exposure (9). This study therefore aimed to quantify the effects of various proposed risk factors for zoster and explore whether their effects differ by age group, to help to identify any groups of patients at high risk who are not currently targeted for vaccination. These recommendations reflect the ACIP work group discussions and review of scientific evidence related to use of varicella zoster immune globulin conducted during the development of the ACIP statements on prevention of varicella as well as a review of published literature to include reports with immune globulins with high anti–varicella-zoster virus antibodies used outside the United States >4 days after exposure to varicella-zoster virus.

When data were not available, expert opinion was considered. Timing of VariZIG administration. In May 2011, the FDA approved amendment of the IND protocol to extend the period for administration of VariZIG after exposure to varicella-zoster virus from 4 days (96 hours) to 10 days. Subsequently, in 2012, CDC published notification of FDA agreement with administration of investigational VariZIG as soon as possible after exposure and within 10 days (11). Limited experience from outside the United States with use of other immune globulin products with high levels of anti–varicella-zoster virus antibodies suggested that, compared with administration of the immune globulins within 4 days of exposure, administration >4 days (up to 10 days) after exposure resulted in comparable incidence of varicella and attenuation of disease (12–15). One study indicated an increase in varicella incidence with increasing time between exposure and administration of ZIG, but disease was attenuated in all cases (16). Considering these data, CDC recommends that VariZIG be administered as soon as possible after exposure and within 10 days.

We identified all potential controls for each case and used incidence density sampling to select up to four controls per case at random.21 Controls were registered with the practice at the index date of the case and for at least 12 months before and were matched to cases by practice, sex, and age (within 1 year). Patient groups for whom VariZIG is recommended. In anticipation of availability of a licensed product for which the supply is projected to be adequate and to harmonize with recommendations from AAP, CDC revised the patient groups previously recommended by ACIP for use of VariZIG. The change refers to extending the period of eligibility for VariZIG administration for previously recommended premature infants from exposures to varicella-zoster virus during the neonatal period to exposures that occurred during the entire period for which they require hospital care for their prematurity. The risk for complications of postnatally acquired varicella in premature infants is unknown. Because the immune systems of premature infants (some of whom might be extremely low birthweight and spend months in neonatal intensive care units) might be compromised, they are considered, on the basis of expert opinion, at high risk for severe varicella; this increased risk is likely continued for as long as these infants remain hospitalized. Patients receiving monthly high-dose (≥400 mg/kg) immune globulin intravenous (IGIV) are likely to be protected and probably do not require VariZIG if the most recent dose of IGIV was administered ≤3 weeks before exposure (9).

The decision to administer VariZIG depends on three factors: 1) whether the patient lacks evidence of immunity to varicella, 2) whether the exposure is likely to result in infection, and 3) whether the patient is at greater risk for varicella complications than the general population. For high-risk patients who have additional exposures to varicella-zoster virus ≥3 weeks after initial VariZIG administration, another dose of VariZIG should be considered.

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