TETANUS

× Trismus, neck stifness, kejang

terhadap stimulus, opistotonus
× Terapi:
× Eradikasi Clostridium
tetani:antibiotik, Perawatan
luka.
× Menetralisir toksin: Anti tetanus,
Human Tetanus Imunoglobulin (
HTIG)
× Perawatan suportif dan
mempertahankan jalan nafas
dan nutrisi yang adekuat.
× Menekan efek toksin pada SSP:
Benzodiazepin
TERAPI SAAT INI (-)
 WAG Kasus Difteri ~ ketersediaan ADS

Pasien WA Group: Pengiriman

difteri Permintaan Koneksi ke WAG Kasus ADS ke Berikan ke
(klinis) ADS Dinkes Difteri & Dinkes pasien
Posko KLB
DTaP-HB-IPV/Hib
Vaccine

This slide deck is intended for Healthcare Professional Only

Brand/ Name Substitution

• Infanrix hexa : GSK DTaP Hexavalent Vaccine

• Infanrix : GSK DTaP Vaccine
Contents
GSK DTaP Hexavalent Vaccine : 17 years of experience

1 2 3
Introduction Clinical profile Real-world experience

4 5 6
Overview of safety profile Programmatic fit Summary
Contents
GSK DTaP Hexavalent Vaccine : 17 years of experience

1 2 3
Introduction Clinical profile Real-world experience

4 5 6
Overview of safety profile Programmatic fit Summary
Combination vaccines offer a range of benefits over
monovalent vaccines

Fewer injections per clinic visit1 Reduced time loss for parents and
increased efficiency for HCPs1

Minimises stress and pain associated Increased compliance, leading to

with injections for child and parent1 improved vaccine timeliness2 and
higher rates of coverage3

1. Koslap-Petraco MB et al. J Pediatr Health Care 2008;22:300–309; 2. Kalies H et al. Pediatr Infect Dis J 2006;25:507–512; 3. Marshall GS et al. Pediatr Infect Dis J
4
2007;26:496–500
What is GSK DTaP hexavalent vaccine?

GSK DTaP hexavalent vaccine is a combination vaccine

targeting six diseases* in infants and toddlers

Diphtheria
Tetanus 2+1
Pertussis
Hib†
Poliomyelitis 3+1
Hepatitis B

Helps to protect Administered as either a Can be used from 6 weeks

against six potentially 3+1 primary and of age. The safety and
serious diseases booster schedule‡1 efficacy >36 months of age
have not been established§

*Containing active substances derived from diphtheria, tetanus, pertussis and Hib bacteria, the hepatitis B virus, and inactivated polioviruses 1, 2 and 3;
†Hib is provided as a separate powder and must be reconstituted in the DTPa-HBV-IPV suspension before use;
‡Schedule dependent on locally applied/recommended schedule as per local licensing;
§No data are available

Hib, Haemophilus influenzae type b

GSK. Infanrix hexa. BPOM approval GDS14/IPI10. date of issue: 13/03/2014.

5
DTaP-HB-IPV/Hib Vaccine combines 10 antigens against
six diseases from previously licensed vaccines

– DTaP-HB-IPV/Hib Vaccine was first licensed in 2000 and is the latest step in the
development of the DTaP vaccine family1–8

DTPa/Hib DTPa-IPV/Hib
DTPa-HBV-IPV/Hib
+ Hib

Diphtheria
DTPa Tetanus
Pertussis (acellular)
+ Polio Hib*
Poliomyelitis
Hepatitis B
DTPa-IPV DTPa-HBV† DTPa-HBV-IPV
+ Hep B

19942 19961 19971 20003 20004

*Hib is provided as a separate powder and must be reconstituted in the DTPa-HBV-IPV suspension before use;
†DTPa-HBV is no longer available; ‡Previously marketed ex-US as Infanrix Penta

DTPa, diphtheria-tetanus-acellular pertussis; HBV, hepatitis B virus; Hib, Haemophilus influenzae type b; IPV, inactivated polio virus

1. André FE. Vaccine 1999;17:1620–1627; 2. Capiau C et al. Vaccine 2003;21:2273–2287; 3. Paul-Ehrlich-Institut, 2014 Vaccines against poliomyelitis; 4. European Medicines
Agency (EMA). Public Statement on Infanrix penta, 2013 (EMA/376372/2013); 5. Bogaerts H. An Pediatr 2003;58(Suppl5):41–46; 6. GSK. Hiberix US PI. FDA 2016; 7. World
Health Organization (WHO), 2010. Poliorix package insert; 8. GSK. Engerix B PI Approved BPOM GDS12/IPI08 (14 February 2017). See slide notes for full reference information.
GSK DTaP hexavalent vaccine has been extensively
evaluated in clinical trials and real-world practice

>100 GSK-sponsored >41,000 infants received >21,000 toddlers

interventional studies1,2 primary vaccinations3 received booster doses3

>157 million doses Registered in

>100 countries7
>17 years of use
distributed worldwide8*
In clinical practice4–6
*As of September 2017

1. EU Clinical Trials Register search. https://www.clinicaltrialsregister.eu/ctr-search/search?query=Infanrix+hexa+AND+GlaxoSmithKline+Biologicals (accessed March 2018);

7
2. ClinicalTrials.gov search. https://clinicaltrials.gov/ct2/results?term=Infanrix+hexa&lead=GlaxoSmithKline (accessed March 2018); 3. GSK. Data on file, 2016N287488_00;
4. Zepp F et al. Expert Rev Vaccines 2009;8:663–678; 5. Lyseng-Williamson KA et al. Paediatr Drugs 2012;14:337–343; 6. Schmitt HJ et al. J Pediatr 2000;137:304–312;
7. GSK. Data on file, 2015N267014_00; 8. GSK. Data on file, 2017N344344_00 – Doses sold DTP vaccines from launch until Sept 2017
17 Years Clinical Experience of
DTaP-HB-IPV/Hib Vaccine: What
have we learnt?

This slide deck is intended for Healthcare Professional Only

Contents
GSK DTaP hexavalent vaccine: 17 years of experience

1 2 3
Introduction Clinical profile Real-world experience

4 5 6
Overview of safety profile Programmatic fit Summary
GSK DTaP hexavalent vaccine
clinical development programme

Objectives of the GSK DTaP hexavalent vaccine pivotal trials Additional Ph IIIb/IV studies

Primary dose Booster dose

Preterm infants13,14

3-dose primary schedule1‒4

Additional schedules
• Compare primary eg EPI, mixed,
immunisation ± HBV 2+1, 3+19,15‒17
3+1 schedule*4‒6 vaccine at birth9
Co-administration
• Assess booster with other
vaccination, immune paediatric vaccines18

2+1 schedule7,8 persistence and

immune memory4‒12
Additional
geographies9,15

*Given during the second year of life

EPI, Extended Programme of Immunisation by WHO 6-10-14 weeks of age; HBV, hepatitis B virus; Ph, Phase; WHO, World Health Organization
1. Schmitt HJ et al. J Pediatr 2000;137:304–312; 2. Arístegui J et al. Vaccine 2003;21:3593–3600; 3. Zepp F et al. Vaccine 2004;22:2226–2233; 4. Heininger U et al. Vaccine 2007;25:1055–1063;
5. GSK. Data on file: InHx03 - 2013N163277_00. 2013; 6. GSK. Data on file: InHx04 - 2013N163281_00. 2013; 7. Gabutti G et al. Scand J Infect Dis 2004;36:585–592; 8. Avdicová M et al. Eur J Pediatr 2002;161:581– 587; 9
9. Gatchalian S et al. Philipp J Pediatr 2007;56:153–161; 10. Zinke M et al. Hum Vaccin 2010;6:189–193; 11. Avdicova M et al. Vaccine 2015;33:2727−2733; 12. Behre U et al. Hum Vaccin Immunother 2016;12:2916–2920;
13. Omeñaca F et al. Pediatrics 2007;119:e179–e185; 14. Omeñaca F et al. Vaccine doi: 10.1016/j.vaccine.2018.01.005; 15. Thollot F et al. Pediatr Infect Dis J 2014;33:1246–1254; 16. Lin T-Y et al. Chang Gung Med J
2003;26:315–322; 17. Reinert P et al. Archiv Pédiatrie 2008;15:263–270; 18. Zepp F et al. Exp Rev Vaccin 2009;8:663–678. See slide notes for full reference information
High seroprotection/seropositivity rates for all antigens after
primary and booster vaccinations with a 3+1 schedule

Schedule Percentage of infants with seroprotective

(months) /seropositive antibody levels (range)*

N=196 234 ≥96.4%

2 studies Seropositivity/seroprotection

N=1693 24 6 ≥96.6%
6 studies Seropositivity/seroprotection

N=1055 345 ≥96.8%

6 studies Seropositivity/seroprotection

(weeks)
N=265 6 10 14 ≥95.7%
1 study Seropositivity/seroprotection†

N=2009 2nd year of life ≥98.4%

12 studies Seropositivity/seroprotection‡

*Seroprotective thresholds: anti-diphtheria, ≥0.1 IU/mL; anti-tetanus, ≥0.1 IU/mL; anti-HBs, ≥10 mIU/mL; anti-polio, ≥1/8 dilution; anti-PRP, ≥0.15 g/mL; Seropositivity thresholds:
pertussis antigens PT, FHA, PRN ≥5 EL.U/mL;
†In a subgroup of infants not administered hepatitis B vaccine at birth, 77.7% of subjects had anti-HBs titres ≥10 mIU/mL;
‡Post-booster, 98.4% of subjects had anti-PRP concentration ≥1 µg/mL indicative of long-term protection

EL.U, enzyme-linked immunosorbent assay test units; FHA, filamentous haemagglutinin; HBs, hepatitis B surface antigen; IU, international units; PRN, pertactin; PRP, polyribosylribitol
phosphate; PT, pertussis toxoid

GSK. Infanrix hexa. BPOM approval GDS14/IPI10. Date of issue:13/03/2014.

10
Demonstrated efficacy* against pertussis following 3-
dose primary vaccination with GSK DTaP vaccine

German household contact study1

Dosing at months:
3 4 5 N=22,505
C=360
88.7% GSK
GSK DTaP
vaccine efficacy† Hexavalent
DTaP Vx
Vx

Italian randomised double-blind study2†

N=14,751¶ 83.9% Equivalence in efficacy is

Dosing at months: C=288 vaccine efficacy† based on comparison of
2 4 6 antibody titres between GSK
DTaP vaccine and GSK DTaP
5-year unblinded follow-up at age 3–6 years3‡ hexavalent vaccine4

N=9554** 86.0%
C=120 vaccine efficacy§

*Laboratory confirmed Bordetella pertussis infection, no PCR, spasmodic cough ≥21 days; †As of 1 month after dose 3; ‡During a 30-month continued follow-up in a subset of children;
§At up to 60 months since last priming dose; Number of vaccine groups subjects relevant to efficacy calculation: ¶ n=4481, c=37; ** n=4217, c=33

C, number of pertussis cases considered for evaluation as per WHO definition;* N, number of enrolled subjects; PCR, polymerase chain reaction; WHO, World Health Organization

1. Schmitt HJ et al. JAMA 1996;275:37–41; 2. Greco D et al. N Engl J Med 1996;334:341–348; 3. Salmaso S et al. Pediatrics 2001;108:E81; 4. GSK. Infanrix hexa BPOM
12
approval GDS14/IPI10. Date of issue:13/03/2014.
Documented immune persistence across vaccine antigens* for up to
7 years with a 3+1 schedule1–3

4–6 years old (n=203)1 7–9 years old (n=200)1

3, 4, 5 or 2, 3, 4 months + 12–23 months 3, 4, 5 months + 12–24 months

Diphtheria Tetanus Pertussis HBV Hib Polio

Patients with seroprotection/

100
seropositivity (%) †

80

60

40

20

0 Anti-diphtheria‡ Anti-tetanus* Anti-PT* Anti-FHA Anti-PRN Anti-HBs Anti-PRP Anti-polio type1 Anti-polio type2 Anti-polio type3

Figure created from data tables2,3 Age 4‒6 years, N=174–198 Age 7‒9 years, N=51–193

*Waning of PT and tetanus antibodies is countered by pre-school booster dose;

†Cut-off levels indicative of seroprotection/positivity: anti-diphtheria, ≥0.1 IU/mL; anti-tetanus, ≥0.1 IU/mL; anti-PT, anti-FHA, anti PRN, ≥5 EL.U/mL; anti-HBs, ≥10 mIU/mL; anti-PRP, ≥15 μg/mL; anti-

polio type1/2/3, ≥1/8 dilution; ‡Data for 4–6 years consider the neutralisation assay in addition to ELISA, if only ELISA 68.7 (61.7, 75.1)3
EL.U, enzyme-linked immunosorbent assay test units; FHA, filamentous haemagglutinin; HBs, hepatitis B surface antigen; HBV, hepatitis B virus; Hib, Haemophilus influenzae type b; IU, international
units; PRN, pertactin; PRP, polyribosylribitol phosphate; PT, pertussis toxoid

1. Zinke M et al. Hum Vaccin 2010;6:189–93; 2. GSK. Infanrix hexa BPOM approval GDS14/IPI10. Date of issue:13/03/2014. 3. GSK. Data on file, 2014N203547_00 – Infanrix 17
hexa persistence data graphed in Zinke et al. 2010
 Hepatitis B
Quick Key Fact

 Disebabkan oleh virus Hepatitis B (HBV), suatu virus DNA

dari Hepadnaviridae family1
 Infeksi pada hati/ liver yang sangat menular
– 50–100 lebih infeksius dibanding HIV2
 HBV ditularkan melalui kontak dengan darah atau cairan tubuh
yang terinfeksi 1–3
 WHO memperkirakan sekitar 600 000 orang meninggal tiap tahun
disebabkan kondisi yang berhubungan dengan HBV2,4
 Infeksi HBV hanya menyerang manusia1,4
– Carriers dapat asymptomatic atau symptomatic1
 Infeksi hati kronik dapat terjadi, yang dalam waktu yang
(Image sourced from
lama dapat menjadi cirrhosis hati dan hepatocellular fotolia.com, royalty-free image)

carcinoma1–3 Hepatitis is a serious infection of

the liver, causing chronic
– Hepatitis B diperkirakan menjadi penyebab sampai 80% inflammation and cirrhosis
kasus hepatocellular carcinoma1
 Pencegahan: Vaksinasi
HBcAg, hepatitis B core antigen; HBsAg, hepatitis surface antigen; WHO, World Health Organization 18
1. CDC. In: Epidemiology and Prevention of Vaccine-Preventable Diseases [Pink Book]. 2012:115–138;
2. WHO. Hepatitis B. Fact sheet No. 204. 2008; 3. CDC. In: CDC Health Information for International Travel [Yellow Book]. 2012;
4. WHO. Wkly Epidemiol Rec 2009;84(40):405–420; 5. World Bank. World Development Indicators. Global population data 2010. June 2012
Long-term immune memory to HBV using a 3+1 schedule
Immune persistence to HBV documented for up to 12 years

234 11–14

At 12–13 years of age,

administration of challenge
dose to mimic HBV exposure2
1 month after
booster dose
(12–15 months)* 60.5% remained seroprotected prior
(54.6–66.1) to challenge (n=291)†

98.4%
97.6% overall produced an
had seroprotective anamnestic response (n=289)
(95.1–99.0)
antibody titres against
hepatitis B†1
initially seronegative subjects
92.1% (anti-HBs <6.2 mIU/mL) produced
(84.5–96.8) an anamnestic response (n=89)

*Pooled across different primary vaccination schedules; †Defined as subjects with an anti-HBs titre ≥10 mIU/mL
HBs, hepatitis B surface antigen; HBV, hepatitis B vaccine; IU, international units

1. GSK. Infanrix hexa BPOM approval GDS14/IPI10. Date of issue:13/03/2014. 2. Behre U et al. Hum Vaccin Immunother 2016;12:2916–2920
15
Preterm infants are at increased risk of acquiring
pertussis and having severe outcomes1–3

5x 2x
Increased risk of severe disease Increased risk of hospitalisation
with a history of prematurity in preterm vs full term infants
(OR: 5.00; 95% CI: 1.27, 19.71)1 (IRR: 1.99, 95% CI: 1.47, 2.71)2

4.5x ~4x
Increased risk of disease Increased risk of death
in infants born at 23–27 weeks vs full term in infants born at <36 vs ≥36 weeks
(IRR: 4.49, 95% CI: 2.33, 8.67)2 (OR: 3.8; 95% CI: 2.0, 7.0)3

Despite the elevated risk of pertussis and associated complications in preterms,

vaccination is often delayed due to concerns about effectiveness and safety4

IRR, incidence rate ratio; OR, odds ratio

1. Marshall H et al. Pediatr Infect Dis 2015;34:339–345; 2. Riise OR et al. Pediatr Infect Dis 2017;36:e151–e156; 3. Haberling DL et al. Pediatr Infect Dis J 2009;28:194–198;
20
4. Tozzi AE et al. Vaccine 2014;32:793–799
High immunogenicity against pertussis in preterms was
observed with GSK DTaP hexavalent vaccine1,2
2 4 6 months 2 4 6 18–24 months
Primary vaccination1 1 month after
booster vaccination1

Preterm VLBW (600–1490 g; n=79) Preterm VLBW (600–1490 g; n=62)

Preterm LBW (1500–1990 g; n=82) Preterm LBW (1500–1990 g; n=57)

Participants with titre above

Participants with titre above

100 100

cut-off, % ( 95% CI)

cut-off, % ( 95% CI)

80 80

60 60

40 40

20 20

0 0
Anti-PT Anti-FHA Anti-PRN Anti-PT Anti-FHA Anti-PRN
Vaccine response Vaccine response

Booster vaccination in the second year of life

Seropositivity was demonstrated for ≥92% of
induced increased antibody titres indicating
infants against pertussis antigens1
effective priming1

1. Vazquez L et al. Acta Pædiatrica 2008;97:1243–1249; 2. Omeñaca F et al. Vaccine doi: 10.1016/j.vaccine.2018.01.005
21
The graphs have been independently created by GSK using data from the source
Contents
GSK DTaP hexavalent vaccine: 17 years of experience

1 2 3
Introduction Clinical profile Real-world experience

4 5 6
Overview of safety profile Programmatic fit Summary
Pertussis
Quick Key Fact

Cause
• Respiratory infection
caused by the Gram-
negative bacterium
Bordetella pertussis1
Contagiousness
• One case can lead
to up to 17 cases in
an unvaccinated
population4
• Asymptomatic carriers,
particularly adults and
adolescents, are one of the main
sources of infection1,2
• Three-quarters of infants
0‒3 months of age catch the
infection from family members,
primarily from their mothers5
Symptoms
Prevention
• Not all patients present with • Vaccination is the most
the characteristic ‘whoop’ important preventative
when coughing; they may strategy against
present with vomiting, sleep pertussis1,2
problems and exhaustion2,3 • As vaccination does not
• Young children may turn blue provide lifelong immunity
against pertussis, booster
from a lack of air while
coughing2,3 vaccinations are needed to
maintain protection at an
• Initial symptoms are similar individual and community
to those of the common cold,
level2
including a runny nose, slight
fever and a sore throat2,3 • Every infection prevented is
one that needs no treatment
(lowering the need for
antibiotic use)3

1. World Health Organization (WHO). Wkly Epidemiol Rec 2015;35:433–460; 2. Centers for Disease Control and Prevention (CDC), 2018. Pertussis. In: The Pink Book:
23
Epidemiology and Prevention of Vaccine-Preventable Diseases. https://www.cdc.gov/vaccines/pubs/pinkbook/pert.html (accessed August 2018); 3. National Health Service (NHS)
Choices, 2016. Whooping cough. http://www.nhs.uk/Conditions/Whooping-cough/Pages/Introduction.aspx (accessed August 2018); 4. Kilgore PE et al. Clin Microbiol Rev
2016;29:449–486; 5. Bisgard KM et al. Pediatr Infect Dis 2004;23:985–989
Pertussis disease control: real-world evidence
Disease reduction with DTPa vaccination 2+1 schedule in Italy and Sweden*

Exclusive use of GSK DTaP

Italy1 National pertussis immunisation
recommendation issued
hexavalent vaccine
since 20063†
100
DTPw vaccination DTPa vaccination
Pertussis incidence

80 Low coverage High coverage

(per 100,000)

60

40

20

0
1925 1940 1955 1961 1970 1985 1995 2000 2012
Figure is reproduced with modifications from a royalty-free source (Eurosurveillance): Gonfiantini MV et al.
Epidemiology of pertussis in Italy: Disease trends over the last century. Euro Surveill 2014;19(40):pii=20921

Sweden2 DTPa immunisation

DTPa vaccination with GSK DTaP vaccine and SP-MSD Pa2c
introduced
160
Pertussis incidence

140
(per 100,000)

120
100 Mainly GSK DTaP vaccine used
80 from 1996–1998 (except
60 Gothenburg area)
40
20
0
1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015

*Since pertussis immunisation recommendations were issued in 1961, Italy has always used a 2+1 vaccination schedule, while in Sweden, DTPa has been administered in a 2+1
schedule since 1996; †GSK market knowledge: Infanrix hexa has been used exclusively from 2006–2015
DTPa, diphtheria-tetanus-acellular pertussis; DTPw, diphtheria-tetanus-whole-cell pertussis; SP-MSD Pa2c, Sanofi Pasteur-MSD two-component acellular pertussis vaccine

1. Gonfiantini MV et al. Euro Surveill 2014;19:pii=20921; 2. Swedish Institute for Communicable Disease Control, 2017. Pertussis surveillance in Sweden – Nineteen year report.
18
https://www.folkhalsomyndigheten.se/contentassets/65ed8f6dbdab4999bc358fcd9b657e77/pertussis-sweden-nineteen-year-report.pdf (accessed March 2018); 3. Sanofi Pasteur
MSD. Hexavac EPAR – scientific conclusion. EMA, 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Scientific_Conclusion/human/000298/WC500074684.pdf (accessed March 2018)
 Haemophillus Influenzae Type B
Quick Key Fact

 Penyebab bakteri Gram-negatif, Haemophilus

influenzae type b1,2
 H. influenzae terbagi atas strain berkapsul dan
tidak berkapsul 1,2

 Lapis luar kapsul H. influenzae mengandung PRP,

suatu polisakarida yang menyebabkan virulensi dan Haemophilus influenzae
respon imunitas2
(Photo courtesy of Dr Tony Brain/
– Terdapat 6 seroypte (a–f)2 Science Photo Library)
– Serotype b (Hib) adalah penyebab~95% penyakit
invasive1,2
 Transmisi terutama melalui sekresi saluran napas
dari orang yang terinfeksi1,3
 Penyakit invasive yang disebabkan oleh Hib dapat
mengenai banyak sistem2
 Tiap tahun, Hib diperkirakan Hib menyebabkan:3,4
– 3 juta penyakit serius di dunia
– 386 000 kematian di dunia
 Komplikasi: Meningitis, epiglositis, pneumonia,
arthritis, bacteremia, dll
 Reservoir: Hib secara asimptomatis berkoloni di
saluran napas bagian atas2
 Pecegahan: Vaksinasi

Hib, H. influenzae type b; PRP, polyribosylribitol phosphate 25

1. Chandran A et al. In: Vaccines. 2008:157–176; 2. CDC. In: Epidemiology and Prevention of Vaccine-Preventable Diseases [Pink Book].
2012:87–100; 3. WHO. Haemophilus influenzae type B (Hib). Fact sheet No. 294. 2005; 4. WHO. Wkly Epidemiol Rec 2006;81(47):445–452
Post-marketing studies in Germany showed high effectiveness
of GSK DTaP hexavalent vaccine against invasive Hib disease

Follow-up Vaccine Number of doses Vaccine effectiveness % (95% CI)

1–2 68.4 (19.0–87.6)

Two hexavalent
5 years1
vaccines (including 3 90.4 (70.6–96.8)
(N=2893)
GSK DTaP
hexavalent
vaccine) 3+1 100.0 (52.7–100.0)

3 89.6
Two hexavalent
7 years2 vaccines (including
GSK DTaP 3+1 100.0
hexavalent
vaccine)

Hib, Haemophilus influenzae type b

1. Kalies H et al. Vaccine 2008;26:2545–2552; 2. GSK. Infanrix hexa BPOM approval GDS14/IPI10. Date of issue:13/03/2014.
22
Contents
GSK DTaP hexavalent vaccine: 17 years of experience

1 2 3
Introduction Clinical profile Real-world experience

4 5 6
Overview of safety profile Programmatic fit Summary
In clinical trials, GSK DTaP hexavalent vaccine was
generally well tolerated in children <2 years of age1–8*

• GSK DTaP hexavalent vaccine administered as a 2+1 or 3+1 schedule (aggregated

data)
• Not co-administered with other vaccines

100
Doses followed by a reaction (%, ± 95% CI)†

Reactions to primary immunisation9 Reactions to booster immunisation9 Grade 3 reactions*9

24 studies‡ 19 studies‡ or fever >39.5C
N=15,095 doses‡ N≤7719 doses‡
80

Solicited local
60 injection-site reactions Solicited systemic reactions

40

20

0
Pain Redness Swelling Drowsiness Irritability/ Loss of Fever Diarrhoea Vomiting Restlessness Unusual
fussiness appetite crying

*Grade 3 reactions defined as: pain, crying when a limb was moved, or spontaneously painful; redness and swelling, diameter >20 mm;
†Symptoms reported during the 4-day post-vaccination period (Days 0–3); ‡Pooled analysis of GSK-sponsored interventional studies

1. GSK. Infanrix hexa EU SmPC. EMA, 2018. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000296/WC500032505.pdf (accessed March 2018);
2. Arístegui J et al. Vaccine 2003;21:3593–600; 3. Zepp F et al. Vaccine 2004;22:2226–2233; 4. Schmitt HJ et al. J Pediatr 2000;137:304–312; 5. Avdicová M et al. Eur J Pediatr 2002;161:581–587; 24
6. Gatchalian S et al. Philipp J Pediatr 2007;56:153–161; 7. Tichmann I et al. Hum Vaccin 2006;2:249–254; 8. Heininger U et al. Vaccine 2007;25:1055–1063; 9. GSK. Data on file, 2016N295531_00 – Pooled
safety analyses Infanrix hexa as reflected in SmPC since 2008 (GDS 8.0)
More than 17 years of post-marketing safety surveillance
Safety profile of GSK DTaP hexavalent vaccine administered as a 2+1 or 3+1
schedule

>157 million doses delivered

Frequency per 100,000 doses
globally as of September 20171
Fever 2.30
Crying <1.00

The 10 most frequently Floppiness <0.50

Pallor
spontaneously reported events Vomiting
occurred at a frequency of
Redness <0.25
≤2.3 per 100,000 doses2† Itching
Rash
Cyanosis ≤0.20
No vaccination programmes Convulsion
reported interruption due to
safety issues*

*Information correct to the knowledge of GSK;

†Reported to OCEANS, GSK’s worldwide safety database, in a 2+1 schedule with pneumococcal conjugate vaccine co-administration, over a distribution of 15 million doses

OCEANS, Operating Companies Event Accession and Notification System

1. GSK. Data on file, 2017N344344_00 – Doses sold DTP vaccines from launch until Sept 2017; 2. Baldo V et al. Hum Vaccin Immunother 2014;10:129–137
26
Contents
GSK DTaP hexavalent vaccine: 17 years of experience

1 2 3
Introduction Clinical profile Real-world experience

4 5 6
Overview of safety profile Programmatic fit Summary
GSK DTaP hexavalent vaccine has the widest documented
co-administration options of any 6-in-1* vaccine1‒3

Studies have demonstrated immunogenicity and tolerability

+
of co-administration of GSK DTaP hexavalent vaccine
with:

Pneumococcal MMRV
Rotavirus vaccines
vaccines vaccines

 GSK PCV10 Vaccine4  HRV7  GSK MMRV§9

 PCV 13†5  HBRV8  MSD MMRV§10
 PCV13‡6

*Containing active substances derived from diphtheria, tetanus, pertussis and Haemophilus influenzae type b bacteria, the hepatitis B virus, and inactivated polioviruses;
†A potential increased risk of fever or convulsion (with or without fever) has been observed when Infanrix hexa is co-administered with Prevnar or Prevnar131;
‡Due to an increased risk of fever, tenderness at the injection site, change in eating habits and irritability when Bexsero is co-administered with other vaccines, separate vaccinations

can be considered where possible1;

§When co-administered with MMRV vaccine, the rate of febrile reactions is higher compared to administration of Infanrix hexa alone and similar to that occurring following the

administration of MMRV vaccine alone1

MMRV, measles-mumps-rubella-varicella

1. GSK. Infanrix hexa BPOM approval GDS14/IPI10. Date of issue:13/03/2014. ; 2. Sanofi Pasteur SA. Hexyon SmPC, 2018; 3. MCM Vaccine BV. Vaxelis SmPC, 2017; 4. Chevallier B et al. Pediatr Infect
Dis J 2009;28:S109–18; 5. Tichmann-Schumann I et al. Pediatr Infect Dis J 2005;24:70–77; 6. Gimenez-Sanchez F et al. Vaccine 2011;29:6042–6048 7. Vesikari T et al. Vaccine 2010;28:5272–5279; 8. 28
Ciarlet M et al. Pediatr Infect Dis J 2009;28:177–181; 9. Zepp F et al. Eur J Pediatr 2007;166:857–64; 10. Deichmann KA et al. Vaccine 2015;33:2379–86.
GSK DTaP hexavalent vaccine can be used in a
range of standard vaccination schedules1

GSK DTaP hexavalent vaccine was highly immunogenic and well tolerated
when evaluated in different vaccination schedules2–7

Primary vaccination (months) Booster

≥ 6 months
1 2 3 4 5 6

Preferably
3-dose <18 months of age
schedule

Preferably
2-dose between 11 and
schedule 13 months of age

Preferably
EPI*
<2 years of age1,8

*A birth dose of HBV vaccine must be given; recommended vaccine schedule is at 6, 10, 14 weeks
EPI, Expanded Program on Immunization; HBV, hepatitis B vaccine

1. GSK. Infanrix hexa BPOM approval GDS14/IPI10. Date of issue:13/03/2014. ;

2. Arístegui J et al. Vaccine 2003;21:3593–3600; 3. Zepp F et al. Vaccine 2004;22:2226–2233; 4. Schmitt HJ et al. J Pediatr 2000;137:304–312; 5. Avdicová M et al. Eur J Pediatr 2002;161:581–587; 31
6. Thollot F et al. Pediatr Infect Dis J 2014;33:1246–1254; 7. Gatchalian S et al. Philipp J Pediatr 2007;56:153–161
GSK DTaP hexavalent vaccine can substitute for any HBV
dose in infants ≥6 weeks of age to complete the HBV
priming series1
HBV GSK DTaP hexavalent vaccine GSK DTaP-IPV/Hib

Birth Primary vaccination† ≥ 6 months Booster Ref

(0, 1 mo) 2

3
3x
4
HBV
5

6
4x
HBV
7

5x 7,8
HBV

GSK DTaP hexavalent vaccine can be given regardless of whether infants received an HBV
vaccine at birth*
*In the EPI schedule, a birth dose of HBV vaccine must be given when no HBV booster vaccination is provided;1
†
From 6 weeks to 6 months of age
EPI, Expanded Program on Immunization; HBV, hepatitis B vaccine

1. GSK. Infanrix hexa BPOM approval GDS14/IPI10. Date of issue:13/03/2014. ; 2. Lim FS et al. Ann Acad Med Singapore 2007;36:801–806; 3. Tejedor JC et al. Pediatr Infect
Dis J 2006;25:713–720; 4. Reinert P et al. Arch Pediatr 2008;15:263–270; 5. Avdicová M et al. Eur J Pediatr 2002;161:581–587; 6. Pichichero ME et al. Pediatr Infect Dis J 32
2002;21:854–859; 7. Gatchalian S et al. Philipp J Pediatr 2007;56:153–161; 8. Cheng HK et al. Southeast Asian J Trop Med Public Health 2004;35:685–692
Contents
GSK DTaP hexavalent vaccine: 17 years of experience

1 2 3
Introduction Clinical profile Real-world experience

4 5 6
Overview of safety profile Programmatic fit Summary
Summary: GSK DTaP hexavalent vaccine

Immune persistence observed for up to

The only 6-in-1* vaccine with more than
7 years against all antigens, and up to
17 years of use in clinical practice1–3*
12 years against hepatitis B1†

The only 6-in-1 vaccine supported by Widest documented

safety and immunogenicity data from co-administration options
prospective trials in preterm infants1–3 of any hexavalent vaccine1–5

Extensive post-marketing surveillance Highly immunogenic and well

shows acceptable tolerability in tolerated across a range of standard
full-term and preterm infants1,6 vaccination schedules6–12

*Containing active substances derived from diphtheria, tetanus, pertussis and Haemophilus influenzae type b bacteria, the hepatitis B virus, and inactivated polioviruses 1, 2 and 3;
†Immune persistence to 3+1 schedule

1.GSK. Infanrix hexa BPOM approval GDS14/IPI10. Date of issue:13/03/2014. ;

2.Sanofi Pasteur SA. Hexyon SmPC, 2018; 3. MCM Vaccine BV. Vaxelis SmPC, 2017; 4. Gossger N et al. JAMA 2012;307:573–582; 5. Vesikari T et al. Lancet 2013;381:825–835; 6. Omeñaca F et al. 34
Vaccine doi: 10.1016/j.vaccine.2018.01.005; 7. Schmitt HJ et al. J Pediatr 2000;137:304–312; 8. Arístegui J et al. Vaccine 2003;21:3593–3600; 9. Zepp F et al. Vaccine 2004;22:2226–2233; 10. Avdicová M
et al. Eur J Pediatr 2002;161:581–587; 11. Thollot F et al. Pediatr Infect Dis J 2014;33:1246–1254; 12. Gatchalian S et al. Philipp J Pediatr 2007;56:153–161
TERIMA KASIH