This slideset edited by Professors Esposito, Palmu, De Wals and Sanders for the Second WAidid Congress present some studies that compare in different countries (including Finland, Sweden, Quebec and the Netherlands) efficacy differences between PCV10 and PCV13. To learn more please visit www.waidid.org

1. Waidid CONSENSUS PAPER ON
EFFICACY DIFFERENCES BETWEEN
PCV10 AND PCV13
Susanna Esposito
Pediatric Clinic, University of Perugia
Perugia, Italy

2. PCV10 trial in Finland (FinIP)
and the Finnish NVP
Arto Palmu, MD, PhD, Research manager,
head of Clinical Research Team, Department of Public Health Solutions

3. Disclosure
• The National Institute for Health and Welfare (THL) has received
research funding
– from GlaxoSmithKline Biologicals SA for the Finnish Invasive
Pneumococcal disease vaccine trial (FinIP), a nationwide
effectiveness trial of the 10-valent PCV
– From Pfizer for non-pneumococcal research
• No outside support for NVP evaluation
• A Palmu
– Investigator in the studies
33.12.2018

4. Finnish Invasive
Pneumococcal disease
vaccine effectiveness trial
(FinIP)
”Vaccine probe analysis re.
pneumococcal disease burden”

5. Finnish Invasive Pneumococcal disease
vaccine effectiveness trial design
• Phase III/IV cluster-randomized, double-blind trial in
children <19 months of age at enrolment
• Cluster formation by geographical normal boundaries (N=78)
• Vaccines
– 10-valent PHiD-CV (GSK) in two thirds of clusters (N=52) OR
– hepatitis B or A vaccine as control in one third of clusters (N=26)
• GlaxoSmithKline as sponsor
• Conducted nationwide 2009 to 2011, follow-up until 2018
• Over 47,000 children enrolled in total
5
Palmu et. al. Lancet 2013;381:214–22
3.12.2018

6. The disease burden caused by S. pneumoniae in infants
and the vaccine preventable disease incidences (VPDI)
Outcomes
VE
3+1/2+1
95% CIs
Incidence
per 100 000
Control 3+1/2+1
VPDI
per 100 000
Contribution
of all VPDI
reduction
Contribution
of all health
care cost
reduction
IPD (invasive
pneumococcal disease) 1
94%
77 to 99
80 75 0.6% 4.3%
Non-laboratory-confirmed
IPD 2
50%
32 to 63
422 207 1.5% 11.8%
Pneumonia3 26%
8 to 41
1262 341 2.5% 13.9%
Tympanostomy tube
placement4
13%
-2 to 26
7887 1100 8.1% 31.6%
Antimicrobial
purchases 5
8%
1 to 14
154900 11800 87.3% 38.4%
3.12.2018 6
VE, Vaccine Effectiveness; CI, Confidence Interval; VPDI, Vaccine-Preventable Disease Incidence; IPD, Invasive
Pneumococcal Disease; AOM, Acute Otitis Media.
Original data published:1Palmu et al. Lancet 2013, 2Palmu et al. Lancet Resp Med 2014, 3Kilpi et al. Vaccine2018, 4Palmu et al. Pediatr Inf Dis J
2015, 5Palmu et al. Lancet Inf Dis 2014

7. 3.12.2018 7
PCV in the National Vaccination Programme (NVP)
• NVP started in Sep 2010 for children born June 2010 or later
– 2+1 schedule: 3, 5, 12 mo of age
– No catch-up, no previous PCV7
– Since 2009 for high-risk groups under 5 y of age
• A public tender process: Synflorix™ (PCV10) selected
– 70% based on price
– 30% based on the additional serotypes in PCV13 (Quality criteria)
• 2nd public tender process 2014: Synflorix™ (PCV10) selected
– based on price only
– Open process for criteria selection and discussion:
http://en.opasnet.org/w/Tendering_process_for_pneumococcal_conjug
ate_vaccine
• 3rd public tender process opening soon

8. 3.12.2018 8
PCV in the National Vaccination Programme (NVP)
• Coverage high based on national vaccination register 92 to 95%
• Results on IPD available at the public website
• THL.FI ”pneumococcal”
• Published manuscripts
– Jokinen et al PLoS One. 2015
– Palmu et al Pediatrics. 2015
– Palmu et al PLoS One. 2017
– Okasha et al Thorax. 2018
– Palmu et al Pediatr Infect Dis J. 2018
– Rinta-Kokko et al Vaccine. 2018
– Palmu et al Acta Paediatr. 2018
•

9. Experience in Sweden
• Differences between countries but not
between counties?
• In Sweden, different counties use either
PCV10 or PCV13
– Parallel (=at the same calendar time)
comparison within one country!
3.12.2018 9

10. Experience in Sweden, Naucler et al CID2017
• The overall impact on IPD was similar between the vaccines, despite
higher reduction in PCV13 counties for serotypes 6A and 19A (and 6C)
• Similar results have also been
reported for pneumonia and otitis
• Note: Correction of the article
published 09 October 2018
3.12.2018 10

11. Rationale for changes in the
PCV program for children in
Quebec
11
Philippe De Wals, MD, PhD
Department of Social and Preventive
Medicine, Laval University
Quebec National Public Health Institute

12. 12
PCV Program in Quebec
 October 2002: PCV7 offered to high-risk infants
(3+1 doses) and children  5 years.
 December 2004: PCV7 offered to all infants
(2+1doses) + catch-up for children  5 years
 June 2009: switch from PCV7 to PCV10 (no
catch-up)
 January 2011: switch from PCV10 to PCV13
(no catch-up)
 September 2018: switch from PCV13 to PCV10

13. Incidence rate of invasive pneumococcal disease
(per 100 000 person-years) among individuals less
than 5 years of age in Quebec, 2000-2016
13
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
PCV13 types Other types Total
PCV7 PCV10 PCV13
Incidence rate of invasive pneumococcal disease
(per 100 000 person-years) among individuals less
than 5 years of age in Quebec, 2000-2016
4
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
PCV13 types Other types Total
PCV7 PCV10 PCV13
Overall IPD rate reduction = 86%

14. Incidence rate of invasive pneumococcal disease
(per 100 000 person-years) among individuals > 5
years of age in Quebec, 2000-2016
14
PCV7 PCV10 PCV13
0
5
10
15
20
25
30
35
40
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
PCV13 types Other types Total
Overall IPD rate reduction = nope

15. PCV effectiveness against serotype 19A IPD,
Case-control study in Quebec, 2005-2016
15
Deceuninck et al. Poster 0300 ISPPD
PCV10 PCV13 PCV 10+13
≥ 1 dose 52% 61% -
=2 doses 42% 33% 100%
=3 doses 60% 83% 58%
≤365 days after last dose
• ≥ 1 dose
73% 69% 82%
>365 days after last dose
• ≥ 1 dose -211% 23% 8%

16. 16
 A 2+1 PCV13 schedule would be the most
effective but also the most expensive option
for IPD prevention
 A mixed 2 PCV10 + 1 PCV13 schedule
would be the most cost-effective option
 A 2+10 schedule would be acceptable if a
mixed schedule is impossible to negotiate

17. Seotype 19A IPD rates (per 100 000 p-y)
among children less than 5 years of age in
PCV10 and PCV10 countries in Sweden
(Nauclair et al., CID 2017, corrected 2018)
Counties Pre PCV10 or
PCV13
Post PCV10
or PCV13
Difference/
100 000
PCV10 0.7 1.1 0.4
PCV13 1.6 0.0 (1.6)
PCV10 vs
PCV13
2.0
17

18.  With a price differential of 25 CAD
per dose between PCV10 and
PCV13, a 2+1 PCV10 schedule
would be more cost effective than
a 2+1 PCV13 schedule in almost
all plausible scenarios
18

19. References
 Avis sur le calendrier optimal de vaccination des
enfants contre les infections à pneumocoque au
Québec:
 https://www.inspq.qc.ca/publications/2334
 Scientific advisory on the optimal schedule for
childhood immunization against pneumococcal
disease in Québec
 https://www.inspq.qc.ca/en/publications/2379
19

20. PCV7 FOLLOWED BY PCV10: DUTCH
DATA ON IPD AND PNEUMONIA
Lieke Sanders
The Neherlands

21. 18C
PCV-7
CRM197
PCV-10
PD
4 4
6B 6B
9V 9V
14 14
18C 18C T
19F 19F D
23F 23F
Pfizer 1
5
7F
GSK
• 2006: PCV-7 as 3+1 schedule
No catch-up
• 2011: PCV-10 (PHiD-CV),
3+1 schedule
• 2013: PCV-10 as 2+1 schedule
(2, 4 -11 months)
• PPV23: restricted to high risk groups
uptake <5% of ≥ 65+ years
IPD in the Netherlands following PCV-7 and PHiD-CV10

22. IPD surveillance June 2004 - June 2018
• Sentinel laboratory surveillance
– Nine sentinel labs
– Covering 25% of the Netherlands
• (population 17 million)
• Positive isolates from blood and/or CSF
• Hospitalized cases
• Serotyped
• Age, sex, date of material taken, hospital

23. IPD surveillance acoording to vaccine groups in The
Netherlands, May 2004- May 2018
Children < 5 yrs
0.0
5.0
10.0
15.0
20.0
25.0
04-05 05-06 06-07 07-08 08-09 09-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 17-18
Pre Post-PCV7 Post-PCV10
Incidenceper100,000
Epidemiological year
<5 years
PCV7 PCV10 extra PCV13 extra nonPCV13 all
M.Knol et al, 2018, unpublished
2004-2006 vs 2016-18
Overall impact -69%

24. 0.0
1.0
2.0
3.0
4.0
5.0
6.0
04-05 05-06 06-07 07-08 08-09 09-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 17-18
Pre Post-PCV7 Post-PCV10
Incidenceper100,000
Epidemiological year
5-49 years
PCV7 PCV10 extra PCV13 extra nonPCV13 all
IPD surveillance acoording to vaccine groups in The
Netherlands, May 2004- May 2018
Age 5-49 yrs
M.Knol et al, 2018, unpublished
2004-06 vs 2016-18
Overall impact -31%

25. 0
5
10
15
20
25
04-05 05-06 06-07 07-08 08-09 09-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 17-18
Pre Post-PCV7 Post-PCV10
Incidenceper100,000
Epidemiological year
50-64 years
PCV7 PCV10 extra PCV13 extra nonPCV13 all
2004-06 vs 2016-18
Overall impact
+ 6%
IPD surveillance acoording to vaccine groups in The
Netherlands, May 2004- May 2018
Age 50-64 yrs
M.Knol et al, 2018, unpublished

26. 0
10
20
30
40
50
60
70
04-05 05-06 06-07 07-08 08-09 09-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 17-18
Pre Post-PCV7 Post-PCV10
Incidenceper100,000
Epidemiological year
65+ years
PCV7 PCV10-7 PCV13-10 non-PCV13 all serotypes
2004-06 vs 2016-18
Overall impact -19%
IPD surveillance acoording to vaccine groups in The
Netherlands, May 2004- May 2018
Age 65+ years
M.Knol et al, 2018, unpublished

27. 0
10
20
30
40
50
60
70
04-05 05-06 06-07 07-08 08-09 09-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 17-18
Pre Post-PCV7 Post-PCV10
Incidenceper100,000
Epidemiological year
65+ years
PCV7 PCV10-7 PCV13-10 non-PCV13 all serotypes
Emerging serotypes
8, 12F, 9N
2004-06 vs 2016-18
Overall impact -19%
IPD surveillance acoording to vaccine groups in The
Netherlands, May 2004- May 2018
Age 65+ years
M.Knol et al, 2018, unpublished
Serotypes 19A and 3

28. Post-PCV10 IPD summary in the Netherlands
• PCV7 followed by PCV-10 resulted in substantial reduction in IPD in
• children <5 yrs (69%)
• 18-49 yrs (31%)
• 65+ yrs (19%)
• After the switch from PCV7 to PCV10, a (non-significant) additional reduction in
IPD was observed in childen < 5 yrs of age (RR 0.68, 0.42-1.11)
• No additional reduction following PCV10 in older adults (50+ yrs) and elderly (65+
yrs) due to emergence of non PCV-13 serotypes
• No additional reduction in IPD incidence across all ages was observed after the
switch from PCV7 to PCV10 (2016-18 vs 2009-2011 RR 1.05, 95% CI 0.97-1.14)

29. Acknowledgements
NRLBM, AMC/RIVM
• Arie van der Ende
RIVM
• Mirjam Knol
• Hester de Melker
UMCU
• Elisabeth Sanders
• Krystof Trzcinski
• Annemarie van Deursen
Antonius Ziekenhuis
• Gert Jan Wagenaar
• Stefan Vestjens

30. WAidid Consensus Paper
The impact of PCV10 and
PCV13 on pneumococcal
infections

31. Methods – Literature Search
• Conducted using pre-defined keywords,
also including useful suggestions received
during and after the conference call
• Conducted using PubMed/Medline and
Web of Science
• Search for additional (missed) articles by
checking the lists of references, reviews,
and Google Scholar findings

32. Methods – Search strings
• In PubMed/Medline: (pneumococcal OR
pneumococcus OR streptococcus pneumoniae)
AND (pcv10 OR pcv13 OR pcv-10 OR pcv-13 OR
phid-cv OR 13vpcv OR 10vpcv OR 10-valent OR
13-valent)
• In WoS: TS=((pneumococcal OR pneumococcus
OR streptococcus pneumoniae) AND (pcv10 OR
pcv13 OR pcv-10 OR pcv-13 OR phid-cv OR 13vpcv
OR 10vpcv OR 10-valent OR 13-valent))
• Limits: papers published from 2010 onwards

33. Methods – Search results
• In PubMed/Medline: 1252 papers
• In WoS: 1132 papers
(Search period: February 2017)
In a preliminary analysis, an important proportion (20-
25%) of those papers could include relevant data to
the purpose of this investigation
 Too wide: restrict the inclusion criteria and focus
on the central question only

34. WAidid Consensus Paper – Main Aim (2)
• Focus the investigation on the impact and
effectiveness of PCV10 and PCV13 in
children ≤5 years in the following
conditions:
 IPD
 Pneumonia
 Otitis media
 Reference paper: de Oliveira et al, PlosOne 2016

35. Flow-chart for
search & selection
of relevant articles

37. Methods – Search results (2)
• More than 10% of papers were maintained
after 1st selection
• About half of them were excluded after the
2nd (full-text) examination
• A total of 81 papers reported data relevant
to the investigation

38. Papers included (1)
(continues)
Claudio Pelucchi WAidid Consensus Paper meeting Rome, 6 April 2017
Disease-vaccine No. papers No. papers by country
IPD-PCV10 14 (from 12
studies)
4 Canada
4 Finland (2 studies)
2 Brazil
1 each: Spain, Netherlands, Czech
Republic, Chile
IPD-PCV13 40 (from 39
studies)
10 USA
5 Spain
3 Canada, UK, Germany (2 studies)
2 South Africa, Taiwan, Italy
1 Australia, Uruguay, Gambia,
Norway, Czech Republic, Denmark,
Portugal, Israel, France, Sweden

39. Papers included (2)
Claudio Pelucchi WAidid Consensus Paper meeting Rome, 6 April 2017
Disease-vaccine No. papers No. papers by country
Pneumonia-PCV10 9 6 Brazil
2 Chile
1 Sweden
Pneumonia-PCV13 18 (from 15
studies)
3 USA (2 studies), Sweden (2
studies)
2 Argentina, Scotland, France,
Spain, Israel (1 study)
1 Nicaragua, Rwanda
Otitis media-PCV10 2 1 each: Australia, Finland
Otitis media-PCV13 4 (3 studies) 2 Israel (1 study)
1 each: UK, Australia

40. Figure 1 (a)
Range:
2%-93%

41. Figure 1 (b)
Range: -3%-89%

42. Figure 1 (c)
Range: 22%-87%

43. Figure 2 (a)
Range: 4%-56%

44. Figure 2 (b)
Range: 1%-63%

45. Figure 3 (a)
Range: 6%-42%

46. Figure 3 (b)
Range: 6%-75%

47. Conclusions – (1)
• Both PCV10 and PCV13 had a major impact
against IPD in children ≤5 years
• Effectiveness was comparable in
studies/countries that adopted PCV10 and
PCV13

48. Conclusions – (2)
• Both PCV10 and PCV13 had an impact
against pneumonia in children ≤5 years
• The size of the impact was lower than for
IPD
• Effectiveness against pneumonia of PCV13
might be slightly higher than PCV10 – but
the issue is difficult to ascertain

49. Conclusions – (3)
• Few studies focused on otitis media, with
heterogeneous results
• Both PCV10 and PCV13 have an impact
against OM in children ≤5 years
• One study compared PCV10 and PCV13
effectiveness against OM, and found no
significant difference

50. Conclusions – (4)
• In general, results were highly
heterogeneous between studies/countries,
due to a number of factors such as:
 Design and methods of the study
 Periods examined (of PCV use and
comparison period)
 Age group considered