Highlights from

ERS 2019

The ERS International Congress 2019

Madrid, Spain 28 September - 2 October 2019

Pneumococcal vaccines: an effective way to reduce COPD hospitalisations

Although there is increasing evidence of the protection offered by vaccination for pneumococcal disease, the majority of patients at risk in Europe are not vaccinated.

“Pneumonia is still a major health problem and a significant cause of mortality and morbidity worldwide,” said Prof. Antoni Torres (University Hospital Clinic Barcelona, Catalonia, Spain) [1]. Streptococcus pneumoniae was the main cause of morbidity and mortality in the Global Burden of Disease Study [2]. It contributed to more deaths than all other aetiologies combined in 2016 (1,189,937 deaths) [2].

Currently, two approved types of pneumococcal vaccines are available for adults: the pneumococcal polysaccharide vaccine (PPV)23 that contains a polysaccharide antigen and conjugate vaccines that contain polysaccharide antigens covariantly linked to a carrier protein. Pneumococcal conjugate vaccine (PCV)13, 10, and 7 belong to this group. The conjugate vaccines provide improved immunological responses.

People with chronic obstructive pulmonary disease (COPD) are at an increased risk of pneumococcal disease, especially pneumonia, as well as acute exacerbations. In a Cochrane review of COPD patients, the efficacy of injectable PPV or PCV versus a control or alternative vaccine type were compared. There were no differences between the vaccines, but 1 in 21 vaccinated patients avoided an episode of community-acquired pneumonia (CAP) [13]. In addition, 1 in 8 avoided an acute COPD exacerbation due to the vaccination. However, according to this review, no hospital admissions were prevented, and there was no influence of the vaccination on all-cause mortality [13]. On the other hand, no harm was reported. “Taken together, vaccines against Streptococcus pneumoniae offer the possibility of striking reductions in invasive disease,” said Prof. Torres.

In the Dutch CAPiTA study, the efficacy and clinical benefit was assessed of the 13-valent PCV13 in preventing first episodes of vaccine-type strains of pneumococcal CAP, nonbacteraemic and non-invasive pneumococcal CAP, and invasive pneumococcal disease [14]. The trial included 84,496 vaccine-naïve subjects aged >65 year. The vaccine was able to prevent vaccine-type pneumococcal CAP (both invasive and non-invasive forms). In the per-protocol analysis of first episodes of infections due to vaccine-type strains, CAP occurred in 49 persons in the PCV13 group compared with 90 persons in the placebo group, which translates into a vaccine efficacy of 45.6%. Nonbacteraemic and non-invasive CAP occurred in 33 persons in the PCV13 group and 60 persons in the placebo group. The most striking difference was seen in invasive pneumococcal disease, that occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy 75.0%). The efficacy of the vaccination persisted throughout the trial with a mean follow-up of 3.97 years.

Overall, the vaccine was well tolerated, and the adverse event profile was consistent with those of prior studies in adults. “Since only 63% of hospitalised CAP episodes were captured in the CAPiTA trial, the vaccine-preventable disease incidence is probably underestimated,” said Prof. Torres.

PCV also effective in real-life setting

It is important to assess not only the clinical efficacy and safety but also the real-world effectiveness of vaccination following routine introduction into a broader population. Patients seen in daily practice differ considerably of participants included in a randomised clinical trial. Therefore, the effectiveness of PCV13 against hospitalised vaccine-type CAP was measured in a US population, the Louisville pneumonia cohort [5]. In this case control study, a subset of CAP patients was assessed who were aged ≥65 years and consented to have their pneumococcal vaccination history confirmed by health insurance records. All cases were defined as hospitalised CAP patients with PCV13 serotype identified via culture or serotype-specific urinary antigen detection assay. The remaining CAP patients served as test-negative controls. Hospitalised patients were less likely to have received the vaccine compared with controls (4.4% vs 14.5%). This translated into an unadjusted vaccine effectiveness of 72.8% [5]. According to Prof. Torres, this trial shows that the PCV13 vaccine is equally effective under real-life conditions.

In another trial, the indirect effect of the childhood PCV10/13 vaccination programme on the incidence of invasive pulmonal disease in older adults across 13 sites in 10 European countries was assessed [6]. Five-year data showed that there was indeed a large decline in invasive pulmonal disease due to vaccine serotypes, which was partly countered by increases in non-PCV13 serotypes, resulting in a limited net effect on overall invasive pulmonal disease. Thus, the potential benefit of a PCV13 programme in older adults may progressively reduce over time due to the gradual rise in non-PCV13 serotypes. Vaccines targeting older adults should include other, or at least more, serotypes to provide a wider mechanism of protection against pneumococcal disease.

Both smokers and COPD patients are a high-risk group that benefit most from vaccination. The ERS president Prof. Tobias Welte (Hannover Medical School, Germany), who chaired the symposium, commented that less than 10% of at-risk populations in Germany are vaccinated against pneumococcal infections because they have to pay for the vaccine and many of them do not realise the importance of the vaccine.

Keywords: Vaccination; CAPiTA; Pneumococcal Infections; COPD; Pneumococcal Vaccines

Top image: @ iStockPhoto: sudok1

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.