Sign Out
Pharmacology: Pharmacodynamics: Mechanism of action: VARILRIX produces an attenuated clinically inapparent varicella infection in susceptible subjects.
The presence of antibodies is accepted to be an indication of protection.
Pharmacodynamic effects: Efficacy and effectiveness: The efficacy of GlaxoSmithKline (GSK)'s Oka/RIT varicella vaccines in preventing confirmed varicella disease (by polymerase chain reaction {PCR} or exposure to a varicella case) has been evaluated in a large active controlled clinical trial in which children aged 12-22 months received one dose of VARILRIX or two doses of combined measles, mumps, rubella and varicella (Oka/RIT) vaccine. Vaccine efficacy against confirmed varicella of any severity and against moderate or severe confirmed varicella observed after a primary follow-up period of 2 years (median duration 3.2 years) and after an extended follow-up period of 6 years (median duration 6.4 years) are presented in the Table as follows. (See Table 1.)
Click on icon to see table/diagram/imageIn another randomised placeo-controlled trial conducted in children (n=327) 12 - 30 months of age one dose of VARILRIX vaccine was administered and followed up for an average of 29.3 months. The protective efficacy against common clinical cases of varicella was 100% and against clinical varicella of any severity was calculated as 88% (95% CI 72-96). The median number of vesicles in breakthrough cases in children was 2 (placebo group median = 30).
In a randomised placeo-controlled trial conducted in adults (n=233) two doses of VARILRIX vaccine were administered at an interval of 2 months and then followed up for an average of 18 months. Efficacy against clinical varicella of any severity was conservatively estimated at 75.9% (95% CI 43.8-89.7); errors in the methodology used in this trial imply that efficacy cannot be accurately determined. Of the 11 vaccinees with breakthrough disease, only 2 had >200 vesicles, compared with 57% of the unvaccinated subjects.
In both trials, subjects who responded to vaccination and who later developed breakthrough varicella had fewer lesions than unvaccinated individuals, demonstrating attenuation of varicella infection for those subjects who were not protected completely.
In a 3 year follow-up study, lower incidences of varicella breakthrough cases were reported in the group receiving two-doses of PRIORIX-TETRA (1 case, 0.44%) than in the group receiving only one dose of VARILRIX (4 cases, 5.06%), however the number of breakthrough cases were too small to make any conclusion about comparative vaccine efficacy. No cases of measles, mumps or rubella breakthrough disease were reported in any group during this 3 years follow-up.
Effectiveness studies: Effectiveness data suggest a higher level of protection and a decrease in breakthrough varicella following two doses of vaccine than following one dose.
The effectiveness of one dose of VARILRIX was estimated in different settings (outbreaks, case-control and database studies) and ranged from 20%-92% against any varicella disease and from 86%-100% against moderate or severe disease.
The impact of one dose of VARILRIX in reducing varicella hospitalizations and ambulatory visits among children in a study performed in Uruguay were respectively 81% and 87% overall.
Immune response: Healthy subjects: In children aged 9 months to 12 years, the overall seroconversion rate was >98% when measured at 6 weeks after vaccination with one dose. In children 12-15 months of age, antibodies persisted for at least 7 years after vaccination with one dose.
In children aged 9 months to 6 years, the seroconversion rate was 100% when measured 6 weeks after vaccination with a second dose. A marked increase of antibody titres was observed following the administration of a second dose (5 to 26-fold GMT increase).
In subjects aged 13 years and above the seroconversion rate was 100% when measured 6 weeks after the second dose. One year after vaccination, all subjects tested were still seropositive.
In clinical trials, the majority of vaccinated subjects who were subsequently exposed to wild-type virus were either completely protected from clinical chickenpox or developed a milder form of the disease (i.e. low number of vesicles, absence of fever).
There are insufficient data to assess the rate of protection against complications of chickenpox such as encephalitis, hepatitis or pneumonia.
High-risk patients: There are only very limited data from clinical trials available in patients at high risk of varicella. The overall seroconversion rate in these patients was found to be ≥ 80%.
In high-risk patients, periodic measurement of varicella antibodies after immunisation may be indicated in order to identify those who may benefit from re-immunisation.
Clinical studies: See Pharmacodynamic effects.
Pharmacokinetics: Evaluation of pharmacokinetic properties is not required for vaccines.
