Transcript Diapositive 1

Infectiepreventie van de kwetsbare patiënt
Virga Jesse Ziekenhuis
24/11/2014
Vaccination of IBD patients
Tom Moreels
Cliniques Universitaires Saint-Luc
UCL Brussels
[email protected]
Jean-François Rahier
CHU Dinant Godinne
UCL Namur
Fons Van Gompel
Tropical Institute
Antwerp
= 10472 complex
situations !!
Immune mediated inflammatory diseases (IMID) in Gastroenterology
 Ulcerative colitis (UC)
 Crohn’s disease (CD)
 Indeterminate colitis
Immunomodulatory drugs commonly used in Gastroenterology
 Corticosteroids
 >2 mg/kg of body weight
 20 mg/day of prednisone or equivalent when administered for ≥2 weeks
 Budesonide > 6mg (?)
 Methotrexate (MTX)
 Azathioprine (AZA) and analogues
 Anti Tumor Necrosis Factor α agents (antiTNFα)
 infliximab, adalimumab, (certolizumab), golimumab
 Cyclosporine, Tacrolimus
 New biologicals: vedolizumab, ustekinumab, etc
IMID following vaccination... Reality or fairy tales ?
• Controversial statement: Measles-vaccination may play a role
in the development of IBD
NP Thompson et al., Lancet 1995
• No association measles, mumps and rubella
(infection/vaccination) and onset of IBD
M Feeney et al., Lancet 1997
RL Davis et al., Arch Pediatr Adolesc Med 2001
C Bernstein et al., Inflamm Bowel Dis 2007
• No link between any vaccine and IBD
T. Jess, OP UEGW 2014
Against vaccination !!
?
Against vaccination !!
Do we need vaccines in IBD patients ? - HBV
• Prevalence of HBV in IBD population = general population
BUT consequences are different !
• Numerous reports of HBV infections in IBD patients
• Risk of reactivation and hepatic failure in chronic HBV carriers
• Treatment for HBV – unfriendly for IBD
Esteve M et al, Gut 2004; Loras C et al, Am J Gastroenterol 2009; Chevaux JB et al, Inflamm Bowel Dis 2009
Do we need vaccines in IBD? - VZV
• Immunosuppression increases the risk of dissemination and
complications such as pneumonia, hepatitis, encephalitis, or
haemorrhagic disorders
• Fatal cases of primary varicella infection in young IBD
patients
Arvin AM, Clin Microbiol Rev 1996; Hambleton S, Clin Microbiol Rev 2005; Deutsch DE, J Pediatr
Gastroenterol Nutr 1995; Leung VS, Am J Gastroenterol 2004; Vergara M,Gastroenterol Hepatol 2001
Do we need vaccines in IBD? - HPV
• Probably higher incidence of abnormal Pap smears in women
with IBD
• Increased risk in patients treated with immunomodulators
Kane S et al, Am J Gastroenterol 2008; Bhatia J et al, World J Gastroenterol 2006
Zabana Y et al, Inflamm Bowel Dis 2009; Lees CW et al, Inflamm Bowel Dis 2009
Do we need vaccines in IBD? - influenza
1918 – Spanish flu
A/H1N1
40 millions deaths
WHO 2010:17000
H1N1 related deaths
88% on immunosuppressive treament
Rahier JF et al, APT 2010
Rahier JF and Moreels T , OP Gut 2012
Live and inactivated vaccines
Which vaccines for adults ?
Increased severity of infection in
immunocompromised patients ?
Routine:
Tetanus
Diphtheria
Pertussis
Polyomyelitis
Measles
No
No
No
No
Yes
Canada Communicable Disease Report (CCDR RMTC). Advisory Committee Statement (ACS) - Committee to Advise
on Tropical Medicine and Travel (CATMAT) The Immunocompromised Traveler. 04/2007
Which vaccines for adults ?
Increased severity of infection in
immunocompromised patients ?
In selected groups:
Invasive Pneumococcal Disease
Yes
Influenza
Yes
Others:
Human Papilloma virus
Varicella /Zoster
Hepatitis B
Yes
Yes
Yes
Canada Communicable Disease Report (CCDR RMTC). Advisory Committee Statement (ACS) - Committee to Advise
on Tropical Medicine and Travel (CATMAT) The Immunocompromised Traveler. 04/2007
Which vaccines for adults ?
Travel related
vaccine:
Increased severity of infection in
immunocompromised patients ?
Hepatitis A
Typhoid fever
Yellow fever
Japanese encephalitis
Meningococcal meningitis
Tick born encephalitis
Rage
No
?
?
No
?
?
No
(TBC/BCG)
Cholera
Yes
?
Canada Communicable Disease Report (CCDR RMTC). Advisory Committee Statement (ACS) - Committee to Advise
on Tropical Medicine and Travel (CATMAT) The Immunocompromised Traveler. 04/2007
Basic vaccinations in Flanders in 2014
leeftijd
IPV-DTPa-Hib-HBV
Pnc-13
8 weken
X
X
12 weken
X
16 weken
X
12 maand
MenC
IPV-DTPa
HPV
dTpa
X
X
15 maand
MBR
X
X
X
6 jaar
X
10 jaar
X
12 jaar*
XX
14 jaar
X
gebruikte symbolen voor vaccins
IPV
geïnactiveerd injecteerbaar vaccin tegen polio
D
vaccin tegen difterie (d: verlaagde dosis)
T
vaccin tegen tetanus
Pa
vaccins gratis beschikbaar in Vlaanderen - 2014
vaccinatie
merknaam
IPV-DTPa-Hib-HBV
Hexyon
Pnc-13
Prevenar 13
acellulair vaccin tegen pertussis (pa verlaagde dosis)
MBR
Priorix
Hib
vaccin tegen Haemophilus influenzae type b
MenC
NeisVac-C
HBV
vaccin tegen hepatitis B
IPV-DTPa
Infanrix-IPV
MBR
vaccin tegen mazelen, bof en rubella
HBV
Engerix B 20 (volwassenen)
Pnc-13
geconjugeerd vaccin tegen pneumokokken
HPV
Cervarix (enkel meisjes 1ste jaar S.O.)
MenC
vaccin tegen meningokokken van serogroep C
dTpa
Boostrix (enkel 3de jaar secundair)
dT
Tedivax pro adulto
IPV
Imovax polio
HPV
vaccin tegen Humaan Papillomavirus
Recommended vaccine in IMID patients ?
Basic vaccines:
Tetanus
Diphtheria
Pertussis
Polio
(every 10 yrs)
(every 10 yrs)
(1x)
(1x)
HP Brezinschek et al., Curr Opin Rheumatol 2008 ; B Sands et al., Inflamm Bowel Dis 2004; JF Rahier et al., JCC
2014 ; M Lebwohl et al., J Am Acad Dermatol 2008; British Society for Rheumatology 2002, Van Assen Ann Rheum
Dis 2011 http://rheumatology.org.uk/guidelines/guidelines_other/vaccinations/view
Superior Health Council www.health.fgov.be/CSS_HGR
CDC http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm
Wasan AJG
Recommended vaccine in IMID patients ?
IMID Patients
Vaccine
Impact
disease
in IC
patients ?
Influenza Increased
mortality
Pneumo
Belgian
Superior
Health
Council
CDC
RA
Association
European
Crohn &
Colitis
Org.
Am.
Psoriasis
Found.
YES
YES
YES
YES
YES
YES
YES
YES
Increased subgroups
mortality
HP Brezinschek et al., Curr Opin Rheumatol 2008 ; B Sands et al., Inflamm Bowel Dis 2004; JF Rahier et al., JCC
2014 ; M Lebwohl et al., J Am Acad Dermatol 2008; British Society for Rheumatology 2002, Van Assen Ann Rheum
Dis 2011 http://rheumatology.org.uk/guidelines/guidelines_other/vaccinations/view
Superior Health Council www.health.fgov.be/CSS_HGR
CDC http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm
Wasan AJG 2009
4. Recommended vaccine in IMID patients
? Patients
IMID
Vaccine
Impact
Belgian
disease
Superior
in IC
Health
patients ? Council
HPV
Increased subgroups
morbidity
Varicella
/Zoster
HBV
Increased
mortality
CDC
YES
Increased subgroups Sub
morbidity
groups
RA
European
Association Crohn &
Colitis
Org.
(yes )
Selected
YES
YES
YES
(yes)
At risk
YES
Am.
Psoriasis
Found.
HP Brezinschek et al., Curr Opin Rheumatol 2008 ; B Sands et al., Inflamm Bowel Dis 2004; JF Rahier et al., JCC
2014 ; M Lebwohl et al., J Am Acad Dermatol 2008; British Society for Rheumatology 2002, Van Assen Ann Rheum
Dis 2011 http://rheumatology.org.uk/guidelines/guidelines_other/vaccinations/view
Superior Health Council www.health.fgov.be/CSS_HGR
CDC http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm
Wasan AJG 2009
Is efficacy and/or safety of vaccines influenced by the IMID itself or by
the underlying immunocompromised status ?
IMID driving a generalized immunocompromised status?
• IBD : NO (defective innate immunity ?)
Immunomodulatory drugs may influence E/S of vaccines
in IMID patients
MF Doran et al. Arthritis Rheum 2002
Safety of a vaccine
in terms of
• Adverse events
• Risk for flare of IBD
• Risk for infection by the vaccine itself (live vaccines)
Safety of a vaccine – adverse events
When evaluating the safety of a vaccine,
consider “safety” of the disease !
Idiopathic thrombocytopenia following MMR vaccination:
1/ 30000 vaccinated children
Risk of thrombocytopenia after natural rubella or measles infection:
1/3000 and 1/6000 respectively
DC Wraith et al,. Lancet 2003;362:1659-66
Efficacy of a vaccine
1/ demonstration of field efficacy
• preferably trough well-conducted and well-controlled vaccine
efficacy trials
• different possible end points (infection, disease, hospitalization,
death)
• in different settings and populations
not always possible or feasible…
SA Plotkin, CID 2008
Efficacy of a vaccine
2/ immunological markers (adaptive immune system)
• used as “correlate” and/or “surrogate” of protection (against
infection and/or disease)
MOST OFTEN :
• demonstration of B cell–generated antibodies
- seroconversion / geometric mean titers / peak titers
- quality (e.g. avidity; bactericidal / opsonic / neutralizing
antibodies; etc)
- rapidity of decline of titers or long term persistence
ALSO : effector T cells / memory B & T cells
SA Plotkin, CID 2008
Efficacy of a vaccine
• No vaccine is completely effective
• Heterogeneous studies (various and combination of therapies)
Brezinschek HP, Curr Opin Rheumatol 2008
Efficacy and safety of a vaccine in IBD: influenza
• Decreased response in patients with IM+biologicals
compared to IM alone or
IBD without IM: similar to healthy controls
• Proportion of seroprotected patients and geometric mean titers
at post-vaccination were similar between non-
immunocompromised and immunocompromised groups for all
three strains
Mamula P CGH 2007; Lu Y Am J Gastro 2009; Debruyn JC , IBD 2011;
Efficacy of a vaccine in IBD: influenza
Cullen G, Gut 2011
Safety of a vaccine – flare of IBD
Evolution of clinical IBD score 4 weeks after H1N1 vaccination (n= 557)
Rahier JF et al, Gut 2011
Efficacy of a vaccine in IBD: Pneumococcal polysaccharide
(Pneumo 23)
Patients
IBD IM+biologicals
IBD no IM Healthy
controls
Vaccine response
40%
80%
AZA: 79%
Biologics: 58%
Combination: 63%
88%
85%
Melmed GY Am J Gastro 2010 ; Fiorino G, IBD 2011
Efficacy of a vaccine in IBD: Prevenar 13
?
Efficacy of a vaccine in IBD: HBV
• Various regimens (0, 1 and 2 months or - 0,1 and 6)
• Various cut-off points for adequate immunity
(>10 mUI/ml or 100 mUI/ml)
• Response rate lower for patients on anti-TNFa
• Overall response rate in 60% patients
Gisbert JP, APT 2012; Gisbert JP AmJ Gastro 2012
Efficacy of a vaccine in IBD: HPV
HPV vaccine (Gardasil ®; HPV6-11-16-18)
• 17/34 (50%) on immunomodulator therapy and 17/34 on
anti-TNFa therapy; majority of subjects had inactive disease
throughout the study
• No serious adverse events
• Immune response to each serotype of the vaccine was strong
and comparable to healthy controls
Jacobson DL, IBD 2013
Vaccines in IBD patients
Stop
IS / anti TNF
Diagnosis of IBD
3 weeks
Attenuated
3 months*
NO
live vaccines
MMR / VZV / Yellow fever
Typhoid Ty21a, Vaccinia, live attenuated influenza vaccine, oral polio, BCG
Non live
Vaccines
DTP / Recombinant Hepatitis B vaccines / Influenza / Pneumococcal
polysaccharide
HPV / Hepatitis A
* This delay may be reduced to 1 month in case of use of corticosteroids alone
Vaccinating IBD patients: 3 scenarios
For optimal immunological response: vaccinate prior to administering any
immunomodulator.
Scenario 1: What should be done at diagnosis?
1. Check with the GPs the routine vaccination scheme and
immunization history (serologies: HBV, VZV and possibly measles).
2. Update if necessary:
A) ROUTINE VACCINATIONS (NON-LIVE)
❍ Diphtheria
(every 10 years)
❍ Tetanus
(every 10 years)
❍ Pertussis
(one boost in adulthood)
❍ Poliomyelitis
(one boost in adulthood)
❍ Human papilloma virus
(for female patients 10-26 years)
Belgian Superior Health Council Advisory report 8561 regarding the vaccination of immunocompromised children and adults - 19/10/2011 (http://tinyurl.com/HGR-8561-vacc-immuno = Dutch;
http://tinyurl.com/CSS-8561-vacc-immuno = French; http://tinyurl.com/SHC-8561-vacc-immuno =English).
Scenario 1: What should be done at diagnosis?
Update if necessary:
B) IBD SPECIFIC NON-LIVE VACCINATIONS
❍ Influenza
(every year for patient > 65 years)
❍ Pneumococcal diseases
(for patient > 65 years)
❍ Hepatitis B
(Engerix B®, HBvaxpro®, Fendrix®, Twinrix®*):
Serological response should be measured 4 to 8 weeks after the completion of
vaccination, and higher doses of immunising antigen may be necessary to achieve
success.
* Twinrix is a combination vaccine for hepatitis A en B and only contains half a dose of hepatitis A.
Belgian Superior Health Council Advisory report 8561 regarding the vaccination of immunocompromised children and adults - 19/10/2011 (http://tinyurl.com/HGR-8561-vacc-immuno = Dutch;
http://tinyurl.com/CSS-8561-vacc-immuno = French; http://tinyurl.com/SHC-8561-vacc-immuno =English).
Scenario 1: What should be done at diagnosis?
Update if necessary:
C) IBD SPECIFIC LIVE VACCINATIONS 2 injections at least 4 weeks apart.
❍ Varicella zoster virus (Provarivax®, Varilrix®):
Verify serology if no clear history of:
chickenpox or shingles, or
varicella zoster virus vaccine
 If seronegative, immunization should be performed when possible.
❍ Measles, Mumps and Rubella (M.M.R. VaxPro®, Priorix®):
Verify serology if no clear history of :
measles, or
MMR vaccine
 If seronegative, consider vaccination.
Consider the risk to be infected and the urgency to start an immunosuppressive therapy.
Vaccination is at physician discretion. Attention for patients with high risk contact,
e.g. teachers, patients working at a crèche, etc.
Scenario 2: What should be done before start of
immunosuppressive therapy?
1.
Patients that are likely to receive immunosuppressive therapy in the future:
update according to scenario 1.
2.
Additionally, consider vaccinating for:
❍ Influenza with inactivated vaccine (α-Rix®, Agrippal®, Inflexal V®, Influvac S®, Intanza®, Vaxigrip®):
vaccinate every year during the seasonal period.
❍ Pneumococcal diseases (Pneumo 23®, Prevenar 13®). Pneumococcal disease vaccination scheme for
IBD patients:
MMWR Morb Mortal Wkly Rep. 2012 Oct 12;61(40):816-9. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising
conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP).
Scenario 3: What should be done during
immunosuppressive therapy?
A) NON-LIVE VACCINE
Can be given to patients on immunosuppressive therapy  However efficacy of vaccine may
be suboptimal and in some cases booster injections are needed.
The vaccination scheme of immunosuppressed patients should be updated for the following
diseases in addition to the other routine vaccinations:
❍ Influenza with inactivated vaccine (seasonal)
❍ Pneumococcal diseases
❍ Hepatitis B
❍ Human papilloma virus
Scenario 3: What should be done during
immunosuppressive therapy?
B) LIVE VACCINE
Live vaccines are contraindicated during immunosuppressive therapy. In Belgium available
live vaccines are:
❍ Varicella zoster virus
❍ Measles, Mumps and Rubella
❍ Yellow fever and typhoid fever*
❍ (BCG)
If live vaccine is required during immunosuppressive therapy:
 Stop therapy 3 months before vaccination, and withhold for 3 to 4 weeks after live-vaccine
injection.
* For typhoid fever, both a live and non-live vaccine are available.
Casus 1
• 28 years old female CD patient, she is a teacher
• Ileal disease 2008 (10 cm)
• At diagnosis, VZV+, HBV+
• 5 ASA and budesonide in 2008, doing well
• 5 ASA in 2009-2010, doing well
• Endoscopy in 2010: aphtoid ileal lesions, continue on 5 ASA
• Any additional test ? Vaccine ?
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Casus 1
• 28 years old female CD patient, she is a teacher
• Ileal disease 2008 (10 cm)
• At diagnosis, VZV+, HBV+
• 5 ASA and budesonide in 2008, doing well
• 5 ASA in 2009-2010, doing well
• Endoscopy in 2010: aphtoid ileal lesions, continue on 5 ASA
• Any additional test ? Vacccine ?
• MMR status ? Teacher !!
• Would like to travel to yellow fever endemic area ? Problem ?
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Casus 2
• 78 years old men with left sided UC, newly diagnosed
• Born in Hasselt, lives in Hasselt and probably will die in Hasselt…
• At diagnosis HBV -, Measles +, VZV +
• Not responding to 5 ASA
• Start clipper 5 mg, doing well
• Additional test ? Vaccine ?
Cycle Meeting Gastro 24 04 2014
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Casus 2
• 78 years old men with left sided UC
• Born in Hasselt, lives in Hasselt and probably will die in Hasselt…
• At diagnosis HBV -, Measles +, VZV +
• Not responding to 5 ASA
• Start clipper 5 mg, doing well
• Additional test ? Vaccine ?
• Pneumococcus YES
• Influenza YES
• HBV ? Probably no if no intention to travel
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Casus 3
• 17 years old, severe ileocaecal CD in 2013 (pain +++, diarrhea ++)
• Deep ulcers on endoscopy, 30 cm ileum
• At diagnosis : HBV + , MMR+, VZV neg
• What to do ? Vacccinate or treat ?
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Casus 3
• 17 years old, ileocaecal severe CD in 2013 (pain +++, diarrhea ++)
• Deep ulcers on endoscopy, 30 cm ileum
• At diagnosis : HBV + , MMR+, VZV neg
• What to do ? Vacccinate or treat ?
• Start immunosuppressive treatment ! Anti-TNFa and AZA
• Check co-habitants for varicella; inform the patient
• 1 month later: 2 ileal abscesses treated with antibiotics
• Right hemicolectomy and stop treatment
• Opportunity for vaccination against VZV !
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