Standard-dose Trivalent Influenza Vaccine Research Articles

PIN29 PUBLIC HEALTH AND ECONOMIC IMPACT OF VACCINATION OF SENIORS WITH A HIGH DOSE TRIVALENT INFLUENZA VACCINE IN BRAZILIAN PRIVATE HEALTH CARE SYSTEM

Older adults are particularly vulnerable to influenza and are susceptible to serious complications after an influenza infection, which frequently lead to hospitalizations. Standard-dose influenza vaccines have proven to be beneficial to older patients, however presenting suboptimal efficacy due to immunosenescence. A large randomized controlled trial (FIM12) and several real world studies have shown trivalent influenza vaccine high dose (TIV-HD) to be more effective than standard dose trivalent influenza vaccine (TIV-SD) in terms of reducing influenza cases and hospitalizations, including serious cardio-respiratory events, in the elderly population. In 2018, TIV-HD has been licensed in Brazil. The objective is to assess the impact of switching from TIV-SD to TIV-HD for adults aged ≥65 years in Brazilian private health care system. A flexible age structured decision tree model was used and two classes of events were considered: cases of laboratory confirmed influenza, and hospitalizations due to conditions known to be related to influenza. Three alternative definitions of hospitalization were provided: influenza/pneumonia, any respiratory illness, or all serious cardiorespiratory events. The model was populated with clinical data from FIM12 and demographic and economic inputs appropriate to the Brazilian private setting. Switching from TIV-SD to TIV-HD for adults aged ≥65 years in Brazilian private sector was estimated to lead to an incremental annual reduction from 10,000 to 20,000 influenza-related hospitalization (where 14,000 were respiratory-related hospitalization and 6,000 were cardiovascular-related hospitalization), from 900 to 1800 influenza-related deaths, and 11,000 influenza-related general practitioner visits, corresponding to avoided costs from USD111 million (BRL454M) to USD219 million (BRL890M), depending on the hospitalization definition. Hospitalization avoided costs represented 99% of the total avoided costs. Switching to TIV-HD would significantly reduce the burden of influenza especially by reducing hospitalizations that represent the most important source of cost for private market.

PIN30 - AN ECONOMIC MODEL TO ESTIMATE THE COST-EFFECTIVENESS OF TRIVALENT INFLUENZA VACCINE HIGH DOSE FOR THE ELDERLY POPULATION IN ENGLAND AND WALES

A large RCT (FIM12) and several real world studies have shown trivalent influenza vaccine high dose (TIV HD) to be more effective than standard dose trivalent influenza vaccine (SD) in terms of reducing influenza cases and hospitalisations, including serious cardio-respiratory events (CREs), in the elderly population. The aim of this study was to estimate the public health and economic impact of switching from SD to TIV HD for adults aged ≥65 years in England and Wales using econometric modelling. An age-structured decision tree model comparing multiple vaccination strategies was designed in Microsoft Excel. Model outcomes included influenza cases, influenza-related GP consultations, hospitalisations, and deaths. Two alternative hospitalisation definitions were used; respiratory hospitalisations attributable to influenza, and CREs (possibly attributable to influenza). All analyses were conducted from the UK healthcare system perspective. The model was populated with FIM12 clinical trial data and demographic, epidemiological, and economic inputs appropriate to the UK setting. Deterministic sensitivity analysis (DSA) was performed to assess the robustness of results. In England and Wales, switching from SD to TIV HD (in adults aged ≥65 years) was associated with a reduction of 75,000 cases of confirmed influenza, 19,000 influenza-related hospitalisations, and 4,000 deaths, in an average influenza season. Using thresholds of £20,000 and £30,000/QALY, TIV HD was estimated to be cost-effective at £23.75 and £30.70 per dose, respectively. The cost-effective price at £20,000/QALY increased to £115.15 when accounting for the vaccination effect in reducing CREs. DSA showed that these results were most sensitive to relative vaccine efficacy against influenza hospitalisations whereas the remaining parameters had a low impact on model outcomes. The results suggest that the inclusion of TIV HD on the influenza vaccination schedule has the potential to be a highly cost-effective intervention for the UK healthcare system and would contribute positively to improving public health goals.

PIN33 - A DYNAMIC TRANSMISSION MODEL TO ESTIMATE THE PUBLIC HEALTH IMPACT AND COST-EFFECTIVENESS OF TRIVALENT INFLUENZA VACCINE HIGH DOSE FOR THE ELDERLY POPULATION IN ENGLAND AND WALES

Influenza vaccination is a critical public health intervention supporting the UK’s NHS winter planning. The aim of this study was to estimate the public health impact and the cost-effectiveness of switching from standard dose trivalent influenza vaccine (SD) to trivalent influenza vaccine high dose (TIV HD) in adults ≥65 year olds in England and Wales using econometric modelling. A dynamic compartmental transmission model was used to replicate the annual number of influenza cases in all ages over an eight-year period (2000-2008) under two vaccination programmes. A decision tree model (economic module) was interfaced with the transmission model to estimate incremental costs and quality adjusted life years (QALYs) associated with replacing SD with TIV HD for individuals aged ≥65 years. This approach accounted for B-strain cross-protection, population immunity and herd protection effects. Outcomes included influenza cases, GP consultations, hospitalisations (respiratory hospitalisations attributable to influenza or serious cardio-respiratory events [CREs]), and deaths. The model was populated with FIM12 clinical trial data and demographic, epidemiological, and economic inputs appropriate to the UK setting. Probabilistic sensitivity analyses (PSA) were performed on the economic module. Using conservative epidemiological assumptions, the switch to TIV HD was associated with a reduction of 8,500 GP consultations, 800 influenza-related hospitalisations, and 600 deaths in an average annual season. We estimated TIV HD economically justifiable prices (EJP) of £27.00 and £36.80 per dose for ICER thresholds of £20,000/QALY and £30,000/QALY, respectively. The EJP at £20,000/QALY increased to £94.27 when accounting for the vaccine impact on CREs. In the PSA, 90% of simulations fell below the £20,000/QALY threshold for a price £24.54 per dose for TIV HD. Vaccination of elderly individuals with TIV HD in the UK is likely to be a highly cost-effective vaccination strategy compared to SD TIV. This benefit would largely be driven by reduction in influenza-related hospitalisations.

Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection

BackgroundApproaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. MethodsChildren and young adults (3–21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. ResultsEighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). ConclusionHD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV.

Safety of high dose trivalent inactivated influenza vaccine in pediatric patients with acute lymphoblastic leukemia

BackgroundAlthough children with acute lymphoblastic leukemia (ALL) mount immune responses after vaccination with the trivalent influenza vaccine (TIV), these responses are lower compared to controls. Recently, a high dose (HD) TIV was found to increase the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized that the HD TIV would be well‐tolerated and more immunogenic compared to the SD TIV in pediatric subjects with ALL.ProcedureThis was a randomized, double‐blind, phase I safety trial comparing the HD to the SD TIV in children with ALL. Our secondary objective was immunogenicity. Subjects were randomized 2:1 to receive either the HD (60 µg) or the SD (15 µg) TIV. Local and systemic reactions were solicited, hemagglutinin inhibition titers to influenza virus antigens were measured, and monitoring labs were collected prior to and/or after each vaccination.ResultsFifty subjects were enrolled (34 HD, 16 SD). Mean age was 8.5 years; 63% were male, and 80% were in maintenance therapy. There were no significant differences reported in local or systemic symptoms. No severe adverse events were attributed to vaccination. No significant differences between the HD and SD TIV groups were noted for immune responses.ConclusionsNo differences were noted between the HD and SD TIV groups for solicited systemic and local reactions. Since this study was not powered for immunogenicity, a phase II trial is needed to determine the immunogenicity of HD versus SD TIV in the pediatric ALL population. Pediatr Blood Cancer 2014;61:815–820. © 2013 Wiley Periodicals, Inc.

Safety and Immunogenicity of High Dose Trivalent Inactivated Influenza Vaccine in Pediatric Patients with Acute Lymphoblastic Leukemia

AbstractAbstract 3531 Background:Influenza is an important cause of morbidity and mortality worldwide. Most deaths outside the elderly population are seen in other high risk groups, such as immunocompromised individuals. Compared to the general population, children with cancer have a higher frequency of influenza infections, have symptoms lasting twice as long and are more likely to require hospitalization, all of which may lead to delays in their chemotherapy. It is recommended that children with cancer receive a yearly trivalent influenza vaccine (TIV) and studies show that children with acute lymphoblastic leukemia (ALL) do mount an immune response to the TIV, although they often have lower titers and seroresponse rates compared to healthy controls. Recently, a high dose (HD) TIV was found to provide a statistically significant increase in the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized that the HD TIV would be well tolerated and more immunogenic compared to the SD TIV in pediatric patients with ALL. Methods:This was a randomized, double-blind, phase I safety and immunogenicity trial comparing HD to SD TIV in children with ALL aged 3–17 years, at least one month into chemotherapy and in 1stcomplete remission. Subjects were randomized 2:1 to receive either 0.5mL of HD (60ug per antigen) or SD (15ug per antigen) 2010–11 or 2011–12 TIV. Local and systemic reactions were collected for 7 days after each vaccination. HAI titers to influenza virus antigens as well as complete blood count, quantitative CD4, CD8, CD19 and serum IgG levels were measured before and 28–35 days after vaccination. In year 1, no blood was drawn before dose 2 if a second dose was required. Results:50 subjects were enrolled (20 in year 1, 30 in year 2). Mean age was 8.25 years (range 4.7 – 12.3 years) and 62% were male. The majority of patients (78%) were in the maintenance phase of therapy. 34 subjects received the HD TIV and 16 subjects received the SD TIV (mean age 7.8 vs. 9.3 years), with 11 subjects receiving 2 doses (9 in HD and 2 in SD groups). The only significant difference noted between the HD and SD TIV group was mean total CD19 count (29 vs. 56, p=0.027). There were no significant differences reported in local or systemic symptoms, except fatigue/malaise and headaches were reported more frequently in the SD TIV group (p=0.008 and p=0.03, respectively). No severe adverse events were attributed to vaccination. The immune response measured by a ≥ 4-fold rise in titers for each vaccine antigen were similar in both the HD and SD TIV groups after 1 or 2 vaccines, respectively (A/California: p=0.12, p=0.46; A/Perth: p=0.35, p=0.34; B/Brisbane: p=0.42, p=0.89). Please see refer to tables 1 and 2 for further immunogenicity results. Conclusion:No differences were noted between the HD and SD TIV groups for solicited systemic and local reactions. The immune response appeared similar in both vaccine groups. A phase 3 trial is planned to determine the immunogenicity of HD versus SD TIV in the pediatric ALL population.Table 1Immunogenicity results in high dose and standard dose vaccine patientsAntigenTitersHAIHD VaccineSD VaccineVaccine #1 (N=28)Vaccine #2 (N=9)Vaccine #1 (N=15)Vaccine #2 (N=2)A/California/7/09 H1N1≥4-fold rise, % (n/N)100% (28/28)100% (9/9)100% (15/15)100% (2/2)Titer ≥40, % (n/N)32% (9/28)78% (7/9)57% (8/14)100% (2/2)A/Perth/16/2009 H3N2≥4-fold rise, % (n/N)96% (27/28)100% (9/9)87% (13/15)50% (1/2)Titer ≥40, % (n/N)11% (3/28)33% (3/9)21% (3/14)0% (0/2)B/Brisbane/60/2008≥4-fold rise, % (n/N)100% (28/28)100% (9/9)100% (15/15)100% (2/2)Titer ≥40, % (n/N)25% (7/28)56% (5/9)14% (2/14)50% (1/2)Table 2Geometric Mean Titer results in high dose and standard dose vaccine patientsAntigenVisit 1Visit 2Visit 3HDSDHDSDHDSDA/California/7/09 H1N1533 [361, 785]611 [341, 1096]780 [568, 1072]1940 [1256, 2997]1613 [712, 3651]5120 [905,28981]A/Perth/16/2009 H3N2192 [96.8, 383]231 [146, 365]149 [82.5, 267]221 [99, 494]56.6 [2.7, 1175]691.2 [165, 2889]B/Brisbane/60/2008168 [106, 265]170 [126, 230]244 [155, 383]306 [165, 566]508 [189, 1361]640 [79.1, 5178] Disclosures:No relevant conflicts of interest to declare.