Dr Gaurav Mathur (Dr G)

Vaccines Medical Director GSK Indonesia

Worked in Different geography – Indian
subcontinent, Africa, CIS countries , Singapore and
now Indonesia
MD Internal Medicine
Passionate about vaccine and vaccinology
Written chapter in Adult vaccination guidelines
India, Vaccination for high risk population -Sickle cell
, worked and collaborated with Maternal
immunization guidelines development in India and
in Singapore.
And couple of publication in vaccines cost
effectiveness and safety meta-analysis and vaccine
hesitancy.
Spoke on vaccinology in India and Singapore
Recent paper ‘Cost-effectiveness of two-dose
human papillomavirus vaccination in Singapore’
received the third prize for the SMJ Best Research
Paper Award 2018.
For Healthcare Professional Only

Pneumococcal disease vaccination

Impact of PHiD-CV on IPD pneumonia
and AOM

Dr.Gaurav Mathur
Vaccine Director GSK Indonesia

ID/SYN/0028/18a AD:05/04/19 ED:05/04/21

 Vaccination programs for pneumococcal disease:
clinical objectives
Well-tolerated vaccine1
+
Effective prevention of the disease in target group1
Young children <5 years2

Reduction in invasive Reduction in Reduction

pneumococcal pneumonia in acute
disease (IPD)1 (non-invasive)1 otitis media (AOM)1

Most serious Most frequent

disease disease

1. World Health Organization (WHO). Wkly Epidemiol Rec. 2012;87:129-44; 2. PCV10 Summary of Product Characteristics, March 2018.
Overall effectiveness and impact of PCVs:
beyond vaccine-type pneumococcal disease

Overall effectiveness1

VACCINE TYPE CROSS- REPLACEMENT

EFFECTIVENESS PROTECTION DISEASE
NET
Potential increased REDUCTION OF
Effectiveness on Effects on
individual vaccine vaccine-related
risk of disease PNEUMOCOCCAL
from serotypes not DISEASE
serotypes serotypes
included in the vaccine

“The overall impact of a given PCV formulation on IPD, AOM or

pneumonia cannot be predicted solely on the basis of its serotype
content”2

AOM, acute otitis media; IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine.
1. Castiglia P, et al. Hum Vaccin Immunother. 2017;13(10):2307-15. 2. Hausdorff WP, et al. Expert Rev Vaccines. 2015;14(3):413-28.
Other vaccination programs (e.g. rotavirus):
focus on overall effectiveness, not serotype disease

Rotavirus (RV) vaccines could be judged on the number

of serotypes they contain

Single-strain vaccine1 RV1 RV5 Five-strain vaccine1

In practice, overall vaccine effectiveness is the key measure of RV vaccine impact

– Published evidence shows similar overall vaccine effectiveness of RV1 and RV51,2

Other factors – not the number of, or exact serotypes, included

in the vaccine – are at play that dictate RV vaccine effectiveness2

RV, rotavirus; RV1, monovalent RV vaccine; RV5, pentavalent RV vaccine.

1. Kollaritsch H, et al. Clin Microbiol Infect. 2015;21:735-43. 2. World Health Organization. Wkly Epidemiol Rec. 2013;88(5):49-64.
 Overall pneumococcal disease:
proven protection with PCV101
Vaccine probe study based on FinIP (>30,000 vaccinated infants)1

Vaccine efficacy
Study outcome 3+1 and 2+1 combined (95% CI)

Laboratory-confirmed overall IPD 94% (77–99) Finland

Hospital-diagnosed pneumonia 23% (3–39)

Tympanostomy tube surgery 13% (-2 to 26)

Antimicrobial treatment (for URTI, mostly AOM) 7% (0–14)

PCV10 dramatically reduced overall IPD and also had

a major impact on pneumonia1

AOM, acute otitis media; CI, confidence interval; IPD, invasive pneumococcal disease; URTI, upper respiratory tract infection.
1. Palmu AA, et al. Vaccine. 2018;36:1816-22.
PCV10: the potential to prevent a large number
of pneumococcal-related events1
Vaccine probe study based on FinIP (>30,000 vaccinated infants)1

Number of cases prevented per 1000 babies vaccinated*1 Finland

1 5 22 200
IPD cases of cases of antimicrobial
pneumonia serious AOM† prescriptions‡

* Based on number needed to vaccinate (NNV) data: 671 for IPD; 185 for pneumonia; 44 for serious AOM; 5 for antimicrobial purchases.
† Requiring tympanostomy tube surgery. ‡ For upper respiratory tract infection, mostly AOM.
AOM, acute otitis media; IPD, invasive pneumococcal disease.
1. Palmu AA, et al. Vaccine. 2018;36:1816-22.
 Sweden childhood PCV program: IPD Impact Study
A unique opportunity to compare the impact of PCVs

PCV used June 2010 - Dec 2016

• Study of PCV impact in the Swedish

childhood immunisation program

• Mandatory reporting of IPD cases

from clinicians/hospitals and
laboratories

• Comparison of IPD episodes by type

*
of vaccine, pre-vaccination versus
* post-vaccination, and by age

IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine.

Naucler P, et al. Clin Infect Dis 2017;65(11):1780–90. Jonkopin county (grey) not included in analysis. Mixed: Switch PCV-13/PCV10 between 2010-2016
the map has been independently created by GSK from the original data
Serotype distribution in IPD 0-2 years of age:
PCV10 vs PCV13
30 Rate ratio: 0.27 (0.12-0.58) 30 Rate ratio: 0.30 (0.16,0.56)

25 25

20 20

Incidence*
Incidence*

15 15 NVT
3, 6A, 19A
10 10
1, 5, 7F
5 5 PCV7 ST

0 0

No statistical difference between vaccines on overall IPD impact despite some

difference on IPD serotype distribution
¨*Incidence per 100,000 population in a year
Naucler P, et al. Clin Infect Dis 2017;65(11):1780–90. the graphs have been independently created by GSK from the original data
Serotype distribution in IPD >65 years of age:
PCV10 vs PCV13
60 60
Rate ratio: 0.86 (0.73-1.01) Rate ratio: 1.07 (0.89-1.29)
50 50

40 40
Incidence*

Incidence*
30 30 NVT
3, 6A, 19A
20 20 1, 5, 7F
10 PCV7 ST
10

0 0

No statistical difference between vaccines on overall IPD impact despite some

difference on IPD serotype distribution
¨*Incidence per 100,000 population in a year
Naucler P, et al. Clin Infect Dis 2017;65(11):1780–90. the graphs have been independently created by GSK from the original data
 Conclusions – Sweden IPD Impact Study

• 13 counties using PCV10 and 8 using PCV13 in 2016, with up to 97%

vaccination coverage

• Childhood immunisation program can impact IPD incidence across ages with
the main impact in 0-4 year old children

• The overall impact of IPD incidences were not statistically different

irrespective of vaccine used.
• The dominance of NVTs limited the effect of current paediatric PCVs against
IPD in the elderly.

Naucler P, et al. Clin Infect Dis 2017; 65(11): 1780–90.

Trends in otitis media incidence after conjugate
pneumococcal vaccination: a national observational study1
Outpatient AOM Ventilation tube insertions
PCV use in studied
Last reported Last reported counties (2014)
Pre-PCV PCV7 PCV years Pre-PCV PCV7 PCV years
5500 1000
Incidence/100,000

5000 900
4500 800
4000
700
3500
600
3000
500
2500
400
2000
300
2007 2008 2009 2013 2014
2007 2008 2009 2013 2014

PCV10 counties RR=0.78 (0.72-0.83)

RR=0.75 (0.73-0.78)
PCV13 counties P<0.001 P<0.001
in favour of PCV10 in favour of PCV10

PCV10

“A greater decrease in outpatient AOM and ventilation tube insertions was seen in the counties
that used PCV10, however, geographical differences were large also before vaccine introduction”
RR: Risk Ratio 1. Gisselsson-Solen M. Pediatr Infect Dis J. 2017 Nov;36(11):1027-1031.
 Real-world impact on overall IPD: no notable
difference between higher-valent PCVs1,2
Number of notified cases of IPD (all ages) by quarter reported,
New Zealand
January 2010–December 20171
250 PCV7 PCV10 PCV13 PCV10
Number of notified cases

200

150

100

50
2018
PCV10
0 reinstated in
1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 New Zealand
2010 2011 2012 2013 2014 2015 2016 2017
Year (quarters’)

No substantial differences in the seasonal pattern of overall IPD cases

were observed with PCV10 and PCV131,2
The graph has been independently created by GSK from the original data.
IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine.
1. Roos R, Heffernan H. Invasive Pneumococcal Disease Quarterly Report, July–December 2017. Available at: https://surv.esr.cri.nz/PDF_surveillance/IPD/2017/2017Q4_IPDReport.pdf
[accessed June 2018]. 2. Deceuninck G, et al. Vaccine. 2015;33:2684-9.
 PCV10 has an acceptable safety profile
and is generally well tolerated

PCV10 is generally well tolerated. Most common adverse reactions:

pain at the injection site, redness, swelling, drowsiness, appetite lost,
irritability and fever; mostly mild to moderate severity
and not long-lasting.
PCV10 must not be used in children hypersensitive to the active
substances or any other ingredients contained in the vaccine.
In children with acute severe febrile illness, vaccination should be
postponed; presence of a mild infection e.g. a cold, should not result
in the deferral of vaccination.

PCV10 Summary of Product Characteristics, March 2018.

PCV10 helps you transform your policy
into possibilities

1. The public health benefit of PCV is the impact on overall burden of

pneumococcal disease
2. PCV10 effectively helps prevent pneumococcal disease as demonstrated by
real-world evidence
3. Currently available PCVs have comparable impact on overall pneumococcal
disease
4. The use of PCV10 is supported by recommendations of trusted, independent
international bodies (e.g. the WHO SAGE and PAHO TAG) and an increasing
number of national and local public health authorities
5. Given the existence of highly effective vaccines with acceptable safety profiles,
the key determinant of protection is immunization coverage

PAHO, Pan American Health Organization; SAGE, Strategic Advisory Group of Experts on Immunization; TAG, Technical Advisory Group; UMV, universal mass vaccination; WHO, World Health Organization.
THANK YOU !

ID/SYN/0028/18a AD:05/04/19 ED:05/04/21

Safety, Prescribing Information,
Adverse Event Reporting Procedure
PCV10 has an acceptable safety profile
and is generally well tolerated

PCV10 should be given with caution to individuals with

thrombocytopenia or any coagulation disorder.
In common with other vaccines, serious adverse events such as
apnea in premature infants, syncope, convulsions and hypotonic-
hyporesponsive episodes have been reported infrequently.
Ringkasan Informasi Produk

Nama produk: PCV10 (Pneumococcal polysaccharide and Non-Typeable Haemophilus influenzae (NTHi) protein D conjugate
vaccine). KOMPOSISI: satu dosis (0.5 mL) mengandung 1 mcg polisakarida dari serotipe 11,2, 51,2, 6B1,2, 7F1,2, 9V1,2, 141,2 and
23F1,2, dan 3 mcg dari serotipe 41,2, 18C1,3 dan 19F1,4.
absorbed on aluminium fosfat: 0.5 milligram Al3+;
terkonjugasi ke protein D dari Non-Typeable Haemophilus influenzae ~13 mcg
terkonjugasi ke carrier protein tetanus toksoid ~8 mcg;
terkonjugasi ke carrier protein difteria toxoid ~5 mcg.
Indikasi: imunisasi aktif terhadap penyakit invasive (termasuk sepsis, meningitis, dan bacteremia) dan otitis media akut yang
disebabkan oleh Streptokokus pneumonia serotipe 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F dan 23F pada bayi dan anak dari usia 2
bulan sampai 5 tahun.
Dosis dan cara pemakaian: Bayi usia 2-6 bulan: 3 dosis primer + 1 dosis booster. Dosis pertama pada usia 2 bulan, dan
interval antar dosis paling tidak 1 bulan. Dosis booster direkomendasikan paling tidak 6 bulan setelah dosis primer terakhir.
Alternatif lain: 2 dosis primer + 1 dosis booster. Alternatif ini dipakai ketika PCV10 merupakan bagian dari program imunisasi
bayi rutin. Dosis pertama pada usia 2 bulan, dosis kedua 2 bulan berikutnya. Booster direkomendaikan paling tidak 6 bulan
setelah dosis primer terakhir. Pada bayi preterm yang lahir setelah usia gestasional 27 minggu, jadwal imunisasi yang
direkomendasikan adalah 3 dosis primer + 1 dosis booster.
Bayi dan anak yang belum divaksinasi: Bayi usia 7-11 bulan: jadwal vaksinasi terdiri atas 2 dosis primer dengan interval antar
dosis paling tidak 1 bulan. Dosis ke-3 (booster) direkomendasikan paling pada usia 1 tahun dengan interval paling tidak 2 bulan.
Anak usia 12-23 bulan: jadwal vaksinasi terdiri atas 2 dosis dengan interval antar dosis paling tidak 2 bulan. Kebutuhan akan
booster belum dipastikan. Anak usia 24 bulan-5 tahun: jadwal vaksinasi terdiri atas 2 dosis dengan interval antar dosis paling
tidak 2 bulan.
Sangat dianjurkan bahwa anak yang menerima dosis pertama PCV10 untuk melengkapi vaksinasinya dengan PCV10. Vaksin
ini harus diberikan secara suntikan intramuskular. Lokasi suntikan yang dianjurkan adalah di paha sisi anterolateral pada bayi
dan bagian atas otot deltoid pada anak.
Kontraindikasi: PCV10 tidak boleh diberikan kepada bayi/anak yang diketahui hipersensitif terhadap
salah satu komponen vaksin. Sama seperti vaksin yang lain, pada subjek yang mengalami demam akut
berat, pemakaian PCV10 harus ditunda. Tetapi, adanya infeksi yang minor (seperti common cold) tidak
menghalangi pemberian vaksin. Peringatan dan Perhatian: PCV10 tidak boleh diberikan secara IV
atau intradermal. Tidak ada data tentang pemberian secara subkutan. Kejadian tidak diinginkan:
sangat umum (≥1/10): hilang nafsu makan, iritabilitas, mengantuk, nyeri, kemerahan, pembengkakan di
tempat injeksi, demam dengan suhu rektal 38°C (usia <2 tahun). Umum (≥1/100 to <1/10): reaksi di
lokasi suntik seperti indurasi, demam dengan suhu rektal >39°C rectally (usia <2 tahun). Interaksi:
PCV10 dapat diberikan bersamaan dengan vaksin monovalen ataupun kombinasi [seperti DTPa-HBV-
IPV/Hib dan DTPw-HBV/Hib]: diphtheria-tetanus-acellular pertussis vaccine (DTPa), HBV, IPV, Hib,
DTPw, MMR, vaksin varicella, vaksin meningokokal serogroup C konjugasi (CRM197 dan TT), OPV dan
vaksin rotavirus. Vaksin injeksi yang berbeda harus disuntik di tempat yang berbeda. Kehamilan dan
laktasi : PCV10 tidak untuk digunakan oleh orang dewasa. Tidak ada data yang adekuat untuk
penggunaan selama kehamilan dan laktasi pada manusia serta reproduksi hewan Ringkasan PI
(Abbreviated Product Information) berdasarkan PI PCV10 yang disetujui BPOM versi nomor:
GDS016/IPI016 (25 Jan 2017)
Sebelum meresepkan, harap merujuk kepada Informasi Produk yang tersedia berdasarkan permintaan. Laporkan
Kejadian Tidak Diinginkan (KTD) ke GlaxoSmithKline Indonesia melalui telp +6221 2553 2350 ( jam kerja 08.30 –
17.30 ) atau email ke yqq68540@gsk.com
Kontraindikasi: PCV10 tidak boleh diberikan kepada bayi/anak yang diketahui hipersensitif terhadap
salah satu komponen vaksin. Sama seperti vaksin yang lain, pada subjek yang mengalami demam akut
berat, pemakaian PCV10 harus ditunda. Tetapi, adanya infeksi yang minor (seperti common cold) tidak
menghalangi pemberian vaksin. Peringatan dan Perhatian: PCV10 tidak boleh diberikan secara IV
atau intradermal. Tidak ada data tentang pemberian secara subkutan. Kejadian tidak diinginkan:
sangat umum (≥1/10): hilang nafsu makan, iritabilitas, mengantuk, nyeri, kemerahan, pembengkakan di
tempat injeksi, demam dengan suhu rektal 38°C (usia <2 tahun). Umum (≥1/100 to <1/10): reaksi di
lokasi suntik seperti indurasi, demam dengan suhu rektal >39°C rectally (usia <2 tahun). Interaksi:
PCV10 dapat diberikan bersamaan dengan vaksin monovalen ataupun kombinasi [seperti DTPa-HBV-
IPV/Hib dan DTPw-HBV/Hib]: diphtheria-tetanus-acellular pertussis vaccine (DTPa), HBV, IPV, Hib,
DTPw, MMR, vaksin varicella, vaksin meningokokal serogroup C konjugasi (CRM197 dan TT), OPV dan
vaksin rotavirus. Vaksin injeksi yang berbeda harus disuntik di tempat yang berbeda. Kehamilan dan
laktasi : PCV10 tidak untuk digunakan oleh orang dewasa. Tidak ada data yang adekuat untuk
penggunaan selama kehamilan dan laktasi pada manusia serta reproduksi hewan Ringkasan PI
(Abbreviated Product Information) berdasarkan PI PCV10 yang disetujui BPOM versi nomor:
GDS016/IPI016 (25 Jan 2017)
Sebelum meresepkan, harap merujuk kepada Informasi Produk yang tersedia berdasarkan permintaan. Laporkan
Kejadian Tidak Diinginkan (KTD) ke GlaxoSmithKline Indonesia melalui telp +6221 2553 2350 ( jam kerja 08.30 –
17.30 ) atau email ke yqq68540@gsk.com
Safety Information PCV10TM:

Frequency Adverse reactions

Clinical trials
Very common Appetite lost, irritability, drowsiness, pain, redness, swelling at the injection
site, fever 38°C rectally (age < 2 years)
Common Injection site reactions like injection site induration, fever >39°C rectally (age < 2 years)
Uncommon Crying abnormal, apnoea in very premature infants (≤28 weeks of gestation)
(see Warnings and Precautions), diarrhoea, vomiting, rash, injection site reactions like
injection site haematoma, haemorrhage and nodule
Rare Allergic reactions (such as allergic dermatitis, atopic dermatitis, eczema), convulsions
(including febrile convulsions), urticaria(1)
Very rare Angioedema, Kawasaki disease

Adverse reactions additionally reported after booster vaccination of primary series and/or catch-up vaccination:

Common Fever ≥38°C rectally (age 2 to 5 years)

Uncommon Injection site reactions(2) like pruritus, diffuse swelling of the injected limb, sometimes
involving the adjacent joint; age < 2 years: fever > 40°C rectally; age 2 to 5 years:
headache, nausea and fever >39°C rectally
Post-marketing experience
Rare Hypotonic-hyporesponsive episode
Very rare Anaphylaxis