Alina's CE Handouts- APhA Immunization June 2011 Update

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APhA Immunization Update from the June 2011 ACIP Meeting

Stephan L. Foster, Pharm.D.CAPT (Ret) U.S.P.H.S.

Professor and Vice ChairUniversity of Tennessee College of Pharmacy

Liaison MemberCDC Advisory Committee on Immunization Practices (ACIP)

AccreditationThe American Pharmacists Association is accredited by theAccreditation Council for Pharmacy Education as a provider of

continuing pharmacy education. This activity, APHA Immunization Update from the June 2011 ACIP Meeting, is approved for 1.0 hours of continuing pharmacy education credit (0.10 CEUs). The ACPE Universal Activity Number assigned by the accredited provider is: 202-000-11-106-L04-Passigned by the accredited provider is: 202-000-11-106-L04-P.To obtain continuing pharmacy education credit for this activity, participants will be required to actively participate in the entire webinar and complete an online evaluation and CPE recording form located at www.pharmacist.com/education by July 29, 2011.Initial Release Date: June 29, 2011Target Audience: PharmacistsACPE Activity Type: Knowledge-BasedLearning Level: 1Free CPE credit is brought to you by your APhA membership. Non-members will be assessed a $25 CPE activity fee for this webinar.

Copyright (C) 2011, American Pharmacists Association. All rights reserved.

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Learning ObjectivesIdentify changes to vaccine recommendations necessary for compliance with standards of practiceApply recent changes to guidelines to their vaccination programEvaluate information on new or future vaccines for potential use in their practice

DisclosuresStephan Foster, Pharm.D., serves on the Merck speakers bureau and is on an Advisory Board of both Sanofi Pasteur and GSK

APhA staff member, Mitchel Rothholz, R.Ph., declares that his spouse is an employee of Merck.

All other APhA editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria.

DisclaimerThis contains data presented at the ACIP meetingSome of this data is unpublishedIf there is a slide without a reference, then it contains

h d tsuch dataDo not quote this specific data until it is publishedACIP meeting minutes will be on the ACIP website in the near future, along with the meeting slides

www.cdc.gov/vaccines/recs/acip/default.htm


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Advisory Committee on Immunization Practices

Members15 Experts in the field of Immunization

Voting MembersEx-officio Members (9)Liaison Members (33)

MissionProvide advice and Guidance to CDCDevelop written recommendationsReduce the incidence of vaccine-preventable disease

Meets 3 times a year

More often in subcommittees

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Advisory Committee On Advisory Committee On Immunization PracticesImmunization Practices

Advisory Committee On Immunization Practices


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Herpes ZosterFDA license for adults 50-59 years (March 2011)

Herpes ZosterACIP Recommendation October 2006 for all > 60 years old

Contraindication of immunosuppressionNot recommended for persons who received varicellaNot recommended for persons who received varicella vaccine

Not intended to treat active diseaseRecommended regardless of previous zoster historyStorage frozen

Refrigerator stable version requires 50% more antigen

Disease Considerations Serious disease with pain and sufferingHigh direct and indirect costsWill never eliminate the diseaseBurden of disease increases sharply after age 50

Hospitalizations, death, pain, severityWorsens at older ages

Except work-loss costs

Only a few vaccines used where risk of disease increases with age

Influenza and pneumococcal


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Olmstead County, MN 1998-2001

Yawn BP, et al. Mayo Clin Proc 2007;82:1341-9

Shingles Prevention StudiesOxman, et al. NEJM 2005;352(22):2271-84

38,000 patientsFollowed for 3.1 years51% reduction in cases

Effectiveness reduced with ageLess likely to progress to PHN is you get shinglesBiggest effect seen in those >70 years

Tseng, et al. JAMA 2011;305(2):160-675,000 vaccinees vs. 227,300 non-vaccineesEffectiveness 55%

Effectiveness stable with age

ZEST Trial 50-59 year oldsZostavax Efficacy and Safety Trial

2007-201122,439 patients

C f Z tCases of Zoster30/11211 in vaccine group99/11228 in placebo groupEfficacy 69.8%

Generally well toleratedMore ADEs in vaccine groups

Mostly local reactions and headacheSimilar serious ADEs to placebo


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HZV Duration of Protection

Schmader, IDSA 2008

PersistenceOnly short term studies

3-4 yearsLonger studies ongoingNo good or reliable immunological markers availableVaccine effectiveness wanes over timeCost effectiveness

Lower at younger age since disease incidence is lowerLower in older age due to more deaths

Supply IssuesRecurring shortages since Zostavax® licensed

Also affected MMRVNo effect on Varicella (Varivax ®)

Li i l d tiLive vaccine-complex productionVariability in bulk vaccine yields

Back-orders starting to get filledDelay still through first half of 2011Expect 2 million doses for rest of 2011Expect to meet demand for >60 year-olds in 2012


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ACIPOnly about 10% of >60 years are vaccinatedLimited supplies may be diverted to younger age

C ld lt i i i t diCould result in increase in zoster diseaseACIP has never recommended expansion of vaccine usage during shortage

The working group does not propose a revision of existing recommendations regarding zoster vaccine at this time

VaricellaChanged to 2 dose recommendation in 2006

Outbreaks in highly vaccinated schools1 dose – incomplete protection

Vaccination rates 85-100%Vaccination rates 85 100%A few states do not require at kindergartenRates 63-79%

2 dose vaccination safety demonstratedVaricella Active Surveillance Project

Significant decline in disease since 2006Most cases seen in unvaccinated or only having 1 dose

Meningococcal VaccineBooster dose recommended January 2011Menveo®(Novartis) indicated for 2-10 year-oldsL t ACIP t t t 2005Last ACIP statement 2005

Under revisionMenactra®(sanofi-pasteur) licensed in infants for 2 dose series in 9 – 23 months of age (3 months a part)


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Number of cases of meningococcal disease causing meningitis, pneumonia, or bacteremia, by serogroup, Active Bacterial Core surveillance sites (excluding cases from Oregon), 1998–

2007.

Cohn A C et al. Clin Infect Dis. 2010;50:184-191

Meningococcal DiseaseU.S. Serotypes 2006-2008

B – 29%C – 29%Y 33%Y – 33%W 135 – 8%

Deaths – Case Fatality Rates (CFR)W 135 – 16.3%C – 14.7%Y – 12%

Trends in meningococcal disease incidence by race, 1998–2007.

Cohn A C et al. Clin Infect Dis. 2010;50:184-191


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Menactra® (sanofi-pasteur)Safety Studies

Adverse events vs. placeboAdverse events in combinationsL l ADE d t iLocal ADE and systemic

Efficacy StudiesPhase III studiesIncluded combination with MMRV, PCV7

PCV7 serotype GMCs lower Protective levels demonstrated (titers > 1:8)

Menactra® (sanofi-pasteur)FDA Approved April 2011

2 dose series9 – 23 months with booster 3 months later

Demonstrated immune response asDemonstrated immune response as protectiveSafe alone and in combinations with MMWR and PCV7

No data with PCV13Duration of effect appears to be about 3 years

ACIPAnticipates 2 more vaccines within next year

2,4,6,12-15 month schedulesWill wait to consider adding to routine schedule

R d tiRecommendationApproved for high risk

Complement deficiency, outbreak exposures, travel to endemic areasDecided to wait for functional or anatomical asplenia

Pneumococcal more important

Approved for VFC


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Epidemics in AfricaEpidemics occur in dry seasonOccur every 5-12 years80-85% Type A1988-1997

704,000 cases>100,000 deaths

1998-2002224,000 new cases

Meningococcal VaccineCampaign in Sub-Saharan Africa began in 1996 (Meningitis Vaccine Project)

Serotype A Conjugate Vaccine produced in India$0.40 per dosep

MenAfriVac licensed in 2009Serotype A vaccineGiven to ages 2-29 years (>100% coverage)

Significant decline in meningococcal diseaseMay eliminate “Meningitis Belt” within 10 years

Prevent 123,000 deathsPrevent disability to 287,000


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http://www.meningvax.org/

Measles UpdateJan 1– June 17, 2011 United States

156 cases measles (largest since 1996) 12 outbreaks3-21 cases per outbreakp

89% US residents85% unvaccinated or unknown status34% hospitalized87% import associated

From all over globeMost from Europe

Outbreaks in France, Spain, and BelgiumNext largest from India

PertussisRecommendation in previous ACIP meetings

All adults need 1 dose TdapExcluded pregnancy at that time

Gi Td if d d (Td t t i di t d)Give Td if needed (Tdap not contraindicated)Give TDAP post partumCocooning of family members

Usually inactive vaccines safe in pregnancyVaccines indicated in pregnancy

Influenza and tetanus toxoidNo evidence of toxicity


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Tdap in PregnancySafety

VAERS – no signalsTd and TT used for years

N id f t t i itNo evidence of teratogenicitySimilar evidence seen in post marketing surveillance by sanofi-pasteur with Adacel®

Cost EffectivenessTdap in pregnancy more cost effective than cocooning

Cost per QALY calculations18 variables used in calculations

Cost-Effectiveness ModelsQuality-Adjusted Life Year (QALY)

1 year in perfect health = 1 QALYDeath = 0 QALY1 year in less than perfect health between 0 and 1y p

Cost per QALY(Vaccine + admin cost)-(cost of illness averted by vaccination)

Number of QALYs gained by vaccination

Threshold for cost effectivessNo concensusUS: $50,000-$100,000 often citedWHO: < 3 times per capita GDP (US per-capita GDP=$50,000)

Cost per Outcome GainedChildhood

DTAP, Hib, MMR, Polio, Varicella <$0 per QALYCost saving

Influenza (LAIV) ~ $10 000Influenza (LAIV) ~ $10,000Rotavirus ~ $135,000-$225,000

AdolescentsMeningococcal

11-17 y/o ~$105,00011 y/o (routine) ~$140,000

Influenza Healthy ~$140,000High-risk ~$10,000

Tdap ~$25,000

http://www.cdc.gov/vaccines/recs/acip/slides-oct10.htm#evidence


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Tdap in PregnancyImmune Interference

Transplacental antibody transmission to infant? Cause blunting of infant response to vaccinationShift i k f di f t ld i f tShifts risks of disease from younger to older infants

Reduce disease and death in <4 months of age (period of most infant deathsPossibly shifts higher risk to older infants

Tdap in PregnancyCanadian study underway

Double blinded, randomized control (Td or Tdap)Passive protection

T l t l b t ilkTransplacental or breast milkImmunization of infant with DTaPStill blinded

Elevated Ab levels at birth and 2 months in 1 groupLower antibody levels in same group at 1 month after 3rd

DTaPComparable antibody levels at 4-6 monthBoth groups increasing levels at 6-7 months

Tdap in PregnancyCocooning

Limited dataInitial evidence of effectivenessNo success at national level

Poor uptake by fathers and family membersPoor uptake by fathers and family membersConclusion

Continue to recommendInsufficient national strategy

VaccinationMost experts consider safeProgrammatic cost are equal

Tdap recommended postpartum

Protects both mother and infant


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ACIP VoteRecommend Tdap vaccination preferably during the late second or third trimester of pregnancy (after 20 weeks) if they have never received a previous Tdap If it is notreceived a previous Tdap. If it is not administered during pregnancy, the Tdap should be administered immediately postpartum. Cocooning of family members is still encouraged.

Vaccine SupplyHepatitis B Vaccine

Merck – no supply except dialysis vaccineGSK OK

Hepatitis AHepatitis AMerck – Available in 2012GSK OK

MMRV – No timing details availableZoster – Previously covered (2-3 month wait)Cervarix (HPV)

Vials discontinued (Syringes available)

http://www.cdc.gov/vaccines/vac-gen/shortages/default.htm

Estimated Percentage of Cancers Associated with HPV

CANCER ANY HPV % HPV 16/18 %EstimatedAnnually

2004-2006

Cervical 96 76 9000

Vaginal 64 56 400

Vulvar 51 44 1,350

Anal 93 872,590 (F)1,410 (M)

Penile 36 31 310

Oropharyngeal 63 601,380 (F)5,360 (M)


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National, State, and Local Area Vaccination Coverage among Adolescent Females Aged 13-17 Years – U.S.

35404550

05

1015202530

2007 2008 2009

> 1 Dose3 doses

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5932a3.htmhttp://www.cdc.gov/mmwr/preview/mmwrhtml/mm5836a2.htm

HPV Duration of ProtectionNordic Study – 7 years out

Original Phase IIICancer RegistriesV i Eff ti (VE)Vaccine Effectiveness (VE)

HPV 16/18 CIN 2 or worse = 100%HPV other types = 3 cases/1217

Serological Titers (Anti-HPV - % seropositive)Compared at 7 and 72 monthsTiters similar for types 6, 11, and 16Lower in type 18 but no breakthrough cases

Follow up continues

Human Papillomavirus VaccinesUse in males

Permissive recommendation in Oct 2009New FDA approval for anal cancerA i t d ith h lAssociated with oropharyngeal cancerVaccine Efficacy Males

89% Genital Wart75% Anal Intraepithelial Neoplasia 2/3


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Vaccination of Males with HPV Vaccine

Cost Effectiveness - Published studies$24,000 – $62,000 (Cost effective if vaccination of girls is low)Male vaccination less cost-effective as female coverage increasesAt current female coverage, male vaccination could be cost-effectiveCost of vaccine plays most important part of calculation

October ACIP MeetingConsider policy change to include routine for malesStronger recommendation for MSMWill Catch-up schedule be recommended?

Oropharyngeal Cancer (OP)HPV 16 causes cancer on OP

Distinctly different from HPV – negative tumors

Oral HPV 16 rare in healthy personsOP cancer increasing in U SOP cancer increasing in U.S.Risk Factors for oral HPV infection

Age and GenderSexual behavior

Number of partnersKissing and other oral sexual behaviorsTobacco useHIV infection

Evidence for HPV vaccine protection is lacking

Vaccines and Febrile Seizures2-5% of children aged 6-60 monthsMentioned in most PI of vaccinesReported most commonly with:

DTwP (no increase with DTaP)MMR

2010 Australia InfluenzaSlight increase with TIV and PCV13 given together


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Febrile SeizuresFever is common and can lead to febrile seizuresSimple febrile seizure

97%Last less than 15 minutes No recurrence

Complex febrile seizuresFocalLast longer than 15 minutesRecurrent within 24 hours

Risk of epilepsy same as general populationSlight increase (2.4%)

If multiple, first before age 12 months, family historyGood prognosis but frightening to parentsExpensive to work-up

Vaccines and Febrile SeizuresVaccine Safety Data Link (continued)

Looked at PCV, PCV + TIV, TIV aloneOnly increase seen in TIV + PCV13O l i ifi t i hild 12 23 th ldOnly significant in children 12-23 month old group1 case/2375 vaccinees (42/100,000)

Feb ACIP - 1 case/1,640 doses (61/100,000 doses)May have received other vaccinesOnly increase in 2010-2011 season

Risk of DiseaseInfluenza

Age 12-23 monthsHospitalizations 3-11/10,000

Seizures reported in 8%Seizures reported in 8%0.77 deaths/100,000

Pediatric Deaths282 in 2009-10106 in 2010-11

Pneumococcal Children <5 years

42,000 Hospitalizations1 million episodes of illness


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Febrile Seizure DiscussionsRisk 1/1641

One every 7 years in pediatric clinicOne every 28 years in family medicine clinic

HHowever…..Risk with MMRV was 1/2000Recommendation not to give on first dose

Again seizures, while benign, are frighteningRecommend education of patients, but not to change ACIP recommendation

Hepatitis BCases in 2009-2010 Behavioral Risk Factor Surveillance System Survey (NYC)

Acute hepatitis B – 331 casesThose with diabetes 49Those with diabetes – 49

Total diabetics17.2 million total8.4 million aged 20-59

Estimates of protection with vaccineAge 29-59 years

5071 infections prevented304 chronic cases prevented

Hepatitis B VaccinationCost effectiveness

More diabetics with hepatitis B than non-diabeticsVaccination efficacy decreases with ageCost

A 20 59 $58 762 QALYAge 20-59 = $58,762 per QALYAll ages = $159,000

Options for ACIP vote in OctoberAll diabetics at time of diagnosisAll diabetics <60 years of age

Consideration of risk factors

ConsiderationsEfficacy at what age groupCatch-up


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13-Valent Pneumococcal Conjugate Vaccine

PCV 13 anticipated FDA approval in Adults >50 years (October 2011)Public Health and economic impact

P t d b PfiPresented by PfizerBased assumptions on limited dataExtrapolated to all adultsModel with minimal clinical dataModel with many assumptions

Pneumococcal Disease and VaccinationEpidemiology

Large herd effect from PVC7Expectations from PCV13 unknown

Pneumococcal disease high among adults >50 yearsVariable efficacy data for PCV 23

Considerations for PVC13Considerations for PVC13Published immunogenicity studies non-inferior for select serotypes in vaccineEfficacy in HIV adult adults

74% for vaccine serotypes vs 25% for all cause pneumoniasApproximately 20-30% disease in adults from Non-PVC13 serotypes

Cost Effectiveness – Possibly!Many assumptions

PVC13 effectiveness against noninvasive pneumoniaPPSV23 effectiveness against IPDHerd Immunity of PCV13

Working group waiting for more data

InfluenzaEpidemiology2010-2011 vaccine coverage2010-2011 vaccine effectivenessFluzone High doseIntradermal VaccineInfluenza and egg allergies


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2010-3

2010-3

Pediatric Deaths 2010-11106 Total (110 latest)

27 (26%) A(H1N1)18 (17%) A(H3N2)20 (19%) A k t20 (19%) A unknown type40 (38%) B


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InfluenzaActivity currently lowStrains matched vaccine well last yearVaccine effectiveness estimated at ~60%No evidence of antigenic driftTotal Vaccine Distributed – 163 million

http://www.cdc.gov/mmwr/PDF/wk/mm6022.pdf

Seasonal Vaccination Coverage 2010-2011

Group 2009-2010 (%) 2010-2011 (%)Overall (>6 Months) 41.3 42.8Children 6 Months-17 years 42.3 49.0Persons > 18 years 40.5 40.9

18-49 yrs 30.3 30.250-64 years 44.8 45.6> 65 years 68.9 68.6

Pregnant Women 32-51 44-49Healthcare Providers 62 56-65

http://www.cdc.gov/mmwr/PDF/wk/mm6022.pdf


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Fluzone® High-DoseLicensed December 2009Available 2010-2011 Season10% of persons >65 years immunizedHigher rates of nausea, vomiting and diarrhea than regular Fluzone®

Clinical trial to begin in Fall 2011

Intradermal Influenza Vaccine

Intradermal Influenza VaccineSkin plays major role in immune functionRich in immune cellsGreat blood vasculature and lymphatic

tsystemDendritic cells contibute to immune memory and long-lasting B cell response


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Micro-Injection system

ID Administration

Intradermal Influenza Vaccination90% smaller needle (1.5mm)27 mcg antigen (45 mcg in regular dose)/ 0.1mlI di t d 18 64Indicated 18-64 yearsGood immune responseMore injection site reactionsHigh level of provider and patient acceptance


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Influenza Vaccine and Egg AllergyReview of data

Risk of allergy much lower than risk of influenzaNo reported serious reactions to 2700 egg allergic patientsSkin testing not predictive of reaction

ACIP voteNot a contraindication but a precautionIf problem with eggs is hive

Receive TIV and not LAIVLow ovalbumin product (all 2011 products are)Observe for 30 minutes

Persons with risk for more serious reactionsReferred for further work-up

Summary and ConclusionsNext ACIP Meeting October 25-26, 2011 in Atlanta, GA

Next Webinar scheduled for November 9, 2011

If you have questions please contact:Stephan L. Foster, Pharm.D.E-mail: [email protected]

Questions/comments


Alina's CE Handouts- APhA Immunization June 2011 Update

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