Coste-efectividad de la vacunación universal frente a enfermedad neumocócica con las nuevas vacunas conjugadas frente a 15 y 20 serotipos / Cost-effectiveness of universal vaccination against pneumococcal disease with the new conjugate vaccines against 15 and 20 serotypes

ABSTRACT

INTRODUCCIÓN La enfermedad neumocócica (EN) es una infección bacteriana causada por Streptococcus pneumoniae, que afecta principalmente a la población pediátrica, adultos mayores de 65 años y personas con factores de riesgo. La prevención se basa en la vacunación, ya sea con vacunas conjugadas (VCN) o vacunas polisacáridas (VNP). En España se recomienda actualmente la VCN13 para niños y la VNP23 para mayores de 60 o 65 años; a los grupos de riesgo se les administra VNP23 sola o en combinación con VCN13. Las nuevas VCN frente a 15 y 20 serotipos - VCN15 y VCN20 - recientemente autorizadas por la Comisión Europea, han sido desarrolladas para abordar el aumento de casos de EN por serotipos no cubiertos por las vacunas actuales. Han demostrado su no inferioridad en inmunogenicidad respecto a VCN13, pero aún no se dispone de datos de eficacia protectora. Para la posible sustitución de la vacunación actual por las nuevas VCN se precisa de resultados de su coste-efectividad. OBJETIVOS Evaluar el coste-efectividad, describir las consi

ABSTRACT

INTRODUCTION Pneumococcal disease is a bacterial infection caused by Streptococcus Pneumoniae, which mainly affects children, older adults above 65 years old and people with underlying conditions. Prevention consists of vaccination, with either conjugate vaccines (PCV) or polysaccharide vaccines (PPSV). In Spain, PCV13 is recommended for children and PPSV23 for adults older than 60 or 65 years, while populations with underlying conditions are vaccinated with PPSV23 alone or in combination with PCV13. New PCVs against 15 and 20 serotypes - PCV15 and PCV20 - recently authorized by the European Commission, have been developed in order to address the increase of cases of Pneumococcal disease caused by serotypes not covered by current vaccine options. These new options have proven their non-inferiority regarding immunogenicity of PCV13, but data on their protective efficiency is not available. In order to explore the possibility of substituting current vaccination options for the new PCV options, results on their cost-effectiveness are needed. OBJECTIVES Evaluate cost-effectiveness, describe ethical, legal, organizational, social and environmental considerations, and identify research needs regarding universal vaccination against pneumococcal disease with the new PCV against 15 and 20 serotypes. METHOD Systematic review of economic evaluations A systematic review was conducted in order to identify scientific evidence regarding cost-effectiveness of universal vaccination against Pneumococcal Disease with PCV15 or PCV20 in the paediatric population, population over 65 years old or population with underlying conditions. Studies published until 31/8/2023 were eligible. Methodological quality was valued following the criteria proposed by Drummond et al. Cost-effectiveness analysis A complete economic evaluation was carried out, in which costs and health outcomes for universal vaccination against pneumococcal disease were evaluated for three populations children younger than 5 years old, immunocompetent population older than 65 years of age and immunocompromised population older than 18 years of age. This analysis was based on a decision model which synthesizes Spain's epidemiologic data (2022 incidence), vaccine efficiency and costs, as well as consequences and/or side effects of the diseases of interest (in terms of costs and quality-adjusted life years (QALY) gained). Three Markov models with annual cycles were developed. A 3% discount rate was applied to both costs and effects. For each vaccination strategy considered the incremental cost-effectiveness ratio (ICER) was calculated and it was compared with the cost-effectiveness threshold of 25 000€/QALY. In addition, probabilistic and deterministic sensitivity analyses were carried out. Budget impact analysis A budget impact analysis for a period of 5 years was conducted in order to inform about the cost that the implantation of the new vaccination strategies would have for the Spanish National Health System. RESULTS Systematic review of economic evaluations After conducting a systematic search in four electronic databases, 16 economic evaluations that evaluated at least one of the new PCV were identified. • Children Six studies evaluated paediatric vaccination, only one of them without conflict of interest. Results were homogeneous, finding the new PCVs cost-effective or dominant compared to PCV13 for different European countries, USA and Japan. In the economic evaluation identified for Spain and funded by PCV15 manufacturer, it is concluded that this new vaccine is cost-effective compared to PCV13, with an ICER of € 3582 per QALY. • Elderly Ten economic evaluations were identified in Europe, USA and Japan, only two of them without conflict of interest. Nine studies concluded that the new PCV is dominant or cost-effective compared to the current strategy of the country. Four studies compared the new PCVs with one another, including one study in Spain, and results allowed the conclusion in favour of the PCV20, regardless of the funding. • Population with underlying conditions Evaluated in five studies conducted in Europe, all of them being funded by one of the manufacturers. All the studies conclude in favour of the new PCV evaluated, when compared to the current strategy of each country. Comparison between PCV15 and PCV20 benefits PCV20, regardless of the funding. Cost-effectiveness analysis • Paediatric population New PCVs would avoid more cases of illness caused by Streptococcus Pneumoniae than the current strategy (PCV13). The strategy of replacing PCV13 for the PCV15 would be dominant (more effective and less costly), while its substitution for the PCV20 would not be cost-effective (ICER € 169,335 per QALY). Results are sensitive to vaccine coverage (if it decreases, ICER increases) and to vaccine price (PCV20 would be cost-effective if its price would drop by 22%, from € 47.2 to € 36.6). Lowering PCV13's price, new PCVs become not cost-effective. • Immunocompetent population over 65 years New vaccines are also more beneficial than the current strategy (PPSV23). Strategies that include PCV20 (combined with PPSV23 or alone) are dominant compared to the current strategy, being the PCV20+PPSV23 dominant when compared to the rest of strategies. PCV15 in sequence with PPSV23 would be cost-effective (ICER € 1561 per QALY) and PCV15 alone would not be cost-effective (ICER € 36,792 per QALY). These results change if the indirect effects of paediatric vaccination with the new PCVs are taken into consideration (only sequential strategies would be cost-effective), or if the PCV15's price would drop by 13% (from € 45 to € 39). • Immunocompromised adult population The two most effective strategies are the new PCVs in combination with PPSV23, being both of them dominant against current strategy (PCV13+PPSV23). The sequential strategy involving PCV20+PPSV23 is dominant over the rest of evaluated alternatives. Budget impact analysis • Paediatric population Vaccination with PCV15 instead of with PCV13 would save 4.2 million euros in the following 5 years. As for PCV20, the impact would be of 92.2 million euros in the following 5 years. • Immunocompetent population over 65 years Substituting PPSV23 with PCV20 would have a net budget impact of 53 million euros in 5 years; the strategy involving PCV20+PPSV23 would have an impact of 91.2 million euros in 5 years. Both strategies with PCV15 would have an impact of 56.8 and 93.1 million euros in the following 5 years, respectively. • Immunocompromised adult population Strategies involving PCV20 (alone or with PPSV23) and PCV15 alone would generate savings for the NHS of 207.8 million, 39.3 million and 154.4 million euros, respectively, while the strategy with PCV15+PPSV23 would have an insignificant impact in the following 5 years. CONCLUSIONS Available evidence in scientific literature is limited and comes from studies developed in Europe, USA and Japan, mainly funded by the new PCVs' manufacturers. Most of the published economic evaluations conclude that the vaccination strategies which include new PCVs are cost-effective or dominant • In the paediatric population new PCVs are cost-effective or dominant (more effective and less costly) compared to PCV13. Specifically, the economic evaluation identified for Spain concludes that PCV15 is cost-effective. • For the population of older adults (≥65 years old), the majority of studies conclude that the new PCV evaluated (PCV15 or PCV20) is dominant or cost-effective against the current strategy of each country. Comparisons between new PCVs with one another, including the Spanish study, conclude in favour of PCV20, regardless of the funding. • For the population with underlying conditions, all the economic evaluations conclude in favour of the new PCVs compared to the current recommendations for each country, and in favour of the PCV20 when compared with PCV15, regardless of the funding. Results of the cost-effectiveness model developed for this report, suggest that in Spain • In the paediatric population vaccination with PCV15 is a more effective and less costly strategy (dominant) when compared to the current strategy with PCV13. Vaccination with PCV20, apart from requiring an additional dose, is not cost-effective and it only would be if the vaccine price drops by 22%. • In immunocompetent older adults above 65 years old, vaccination with PCV20 alone or in combination with PPSV23 are dominant strategies. PCV15 is only cost-effective if combined with PPSV23. PCV15 alone could be considered cost-effective if its price drops by 13%. • Regarding immunocompromised adult population, PCV15+PPSV23 and PCV20+PPSV23 strategies are dominant and this last one (PCV20+PPSV23) is dominant compared to the rest of alternatives. • Results are sensitive to variations in some parameters such as vaccine price, effectiveness, vaccination coverage or the indirect effects of paediatric vaccination. The net budget impact in 5 years established • Savings (4.2 million euros) from vaccination with PCV15 in the paediatric population. • Additional costs (53-91.2 million euros) from vaccination with PCV20, administering only PCV20 or in combination with PPSV23 in populations older than 65 years. • Savings (39.3 million euros) with PCV20+PPSV23 vaccination in immunocompromised population. It would be recommendable to update this report in 5 years because of the epidemiologic changes that can occur, the possibility of serotype replacement as a consequence of vaccination and the publication of new data regarding effectiveness of new vacines.