June 2016 ACIP Immunization Update

June 2016 ACIP Immunization Update Stephan L. Foster, PharmD, FAPhA CAPT (Ret) USPHS Professor, University of Tennessee College of Pharmacy Liaison Member, CDC Advisory Committee on Immunization Practices (ACIP) Disclosures Stephan L. Foster, PharmD, FAPhA, serves on speakers bureaus for Merck, Pfizer, and Sanofi Pasteur; he is also on the advisory boards for Seqirus and Pfizer. APhA s 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. For complete staff disclosures, visit www.pharmacist.com/education Conflicts of interest have been resolved through content review by Helen Sairany, PharmD, BCACP, Associate Director of Content Development at the American Pharmacists Association. Accreditation Information The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). This activity, June 2016 ACIP Immunization Update HOME STUDY, is approved for 1 hour of CPE credit (0.10 CEUs). The ACPE Universal Activity Numbers assigned by the accredited provider are: 0202-0000-16-128-H04-P (pharmacists) 0202-0000-16-128-H04-T (pharmacy technicians) To obtain CPE credit for this activity, participants are required to complete the assessment and evaluation questions by July 27, 2019. Initial Release Date: August 10, 2016 Target Audience: Pharmacists and pharmacy technicians Activity Type: Knowledge-based Learning Level: 2 Fee: There is no fee for this activity. 2016 by the American Pharmacists Association. All rights reserved. 1

Development This recording of the July 27 webinar entitled, June 2016 ACIP Immunization Update, is an online continuing education activity for pharmacists and pharmacy technicians developed by the American Pharmacists Association. Learning Objectives At the completion of this knowledge-based activity, participants will be able to: Identify how the proposed changes to vaccine recommendations will impact the immunization schedules for children, adolescents, and adults Explain how recent changes to vaccine recommendations will impact their vaccination programs Discuss information on new or future vaccines for potential use in their practices Self-Assessment Question #1 The FDA has approved meningococcal B vaccination with Trumenba: A. As single dose B. As a 2-dose series given at 0 and 1-2 months under certain circumstances C. As a 2-dose series given at 0 and 6 months under certain circumstances D. That must always be given as a 3-dose series at 0, 1-2 months, and 6 months 2016 by the American Pharmacists Association. All rights reserved. 2

Self-Assessment Question #2 The ACIP has recommended that vaccination with LAIV (FluMist) in the 2016-17 influenza season: A. Is preferred in children over IIV B. Has no preference from the ACIP over IIV C. Should not be given to anyone D. Should be given to all age-eligible patients, aged 2-49 years Self-Assessment Question #3 The ACIP is discussing vaccination with a 2-dose series of HPV9 in a 0-6 month schedule for: A. Patients aged 11-26 years B. Patients aged 9-14 years C. Patients aged 15-26 years D. Is not recommended for any age June 2016 ACIP Immunization Update 2016 by the American Pharmacists Association. All rights reserved. 3

Dr. Thomas Frieden, Director, CDC Cholera Vibrio cholerae Type O1 (99% of global infections) Type O139 Rare in U.S. Most are in travelers Watery diarrhea Can be severe or fatal Endemic in over 50 countries Treatment rehydration Prevention Safe food and water Personal hygiene High Risk Travelers Visiting friends and relatives Long-term Not following safe water, food, personal hygiene Healthcare workers and response workers Populations at risk for poor outcomes No access to rehydration or medical care Conditions Blood type O (cholera gravis) Pregnancy Immune deficiency CV or renal disease Low gastric acidity 2016 by the American Pharmacists Association. All rights reserved. 4

Vaxchora (CVD 103-HgR) PaxVax Hamilton, Bermuda FDA approved June 10, 2016 Fast tracked and priority review Live-attenuated, oral Not absorbed Several different formulations have been tried Redeveloped as Vaxchora Efficacy based upon immunogenicity and oral cholera challenge One Study 90% efficacy at 10 days and 80% at 3 months Vaxchora Single oral dose given 10 days before travel Approved for persons aged 18-64 years Adverse effects Tiredness, headache, abdominal pain, N/V, lack of appetite, diarrhea No data on this vaccine Pregnancy, breastfeeding, immunocompromised, children, shedding/household transmission Limited data on older formulations No effectiveness data Persons living in cholera areas Persons with pre-existing immunity to cholera Vaxchora Does not protect against other strains of cholera Duration of protection No efficacy data beyond 3 to 6 months Seroconversion studies up to 6 months (90.4%) No revaccination studies 2016 by the American Pharmacists Association. All rights reserved. 5

ACIP Recommendation Safe food and water precautions Evaluation of risk of infection for everyone Not recommended for travelers at low risk of exposure Consider risk factors Recommended: Travelers to areas of active cholera transmission Meningococcal B Vaccine Revised dose schedule for Trumenba (Pfizer) approved by FDA (April 4, 2016) 0, 6 months 0, 1-2, 6 months Choice depends upon risk of exposure and patient s susceptibility to MenB disease Based upon reanalysis of earlier studies used for initial approval Current ACIP Recommendations Persons aged >10 years who are at increased risk for meningococcal disease should receive MenB vaccine (Category A) MenB series may be administered to adolescents and young adults aged 16-23 years to provide short-term protection against most strains of serogroup B meningococcal disease (Category B) 2016 by the American Pharmacists Association. All rights reserved. 6

Meningococcal Vaccines in U.S. Men ACWY Vaccines Menomune Sanofi Pasteur (MPSV4) Menactra Sanofi Pasteur (MenACYW135-D) Menveo Novartis (MenACYW-135-CRM) MenHibrix GSK (HibMenCY-TT) CDC-ACIP recommendations Routine in adolescents High-risk >2 months of age MenB Vaccines Both licensed by FDA for persons aged 10 25 years Trumenba (Pfizer) 3-dose series (0, 2, 6 months) Components: fhbp subfamily A/v2,3; subfamily B/v1 Bexsero (Novartis) 2-dose series (0, 1 6 months) Components: fhbp subfamily B/v1, NhbA, NadA, Por A1.4 ACIP, October 30, 2014 (http://www.cdc.gov/vaccines/acip/meetings/slides-2014-10.html) Trumenba Dosing Schedules Studied 3-dose schedule 0,2,6 months 0,1,6 months 2-dose schedule 0-6 months 0-4 months 0-2 months 0-1 month 2016 by the American Pharmacists Association. All rights reserved. 7

Percentage with >4-fold Increase in hsba Titer (From PI) Trumenba 3-dose (0,1,6 months) 74.1-91.2% Composite Response 80.3% 3-dose (0,2,6 months) 78.3-93.8% Composite Response 81.8% 2-dose (0,6 months) 64.5-90.1% Composite response 72.9% Bexsero (0,1 month) Composite response 63-88% (2 studies) Workgroup Conclusions 2-dose series Best schedule is 0-6 months Lower hsba titers than 3 dose GMTs are lower compared with 3 dose Data not presented Antibody persistence not presented Will be in October No safety issues Issues to discuss hsba data for outbreaks Impact on carriage Discussion Workgroup prefers 3 dose for persons at increased risk (including outbreaks) Workgroup prefers 3 dose for adolescents Maximizes protection Both schedules require 3 months to complete Perhaps if someone receives first dose and returns for second at 6 months, then consider only 2 doses Committee wants more data No vote More to come Possible vote October 2016 Start discussing booster doses next year 2016 by the American Pharmacists Association. All rights reserved. 8

MenACYW-135 The risk of meningococcal disease increases in patients with HIV Vaccination not currently recommended in U.S. $732,000/QALY estimated $212,000/QALY for vaccinating all adolescents Grade analysis showed evidence of benefit was low Seroresponse in persons aged 2-10 years with HIV is low and rapidly wanes Deliberations Only MenACYW, Not MenB Increased risk is lifelong in HIV patients Booster doses would be needed Suggests adding HIV to high-risk group Differing opinion on age of vaccination 2 months vs 11 years Small numbers, aligns with asplenia recommendation Vote Passed Human Immunodeficiency Virus (HIV)-infected persons aged >2 months should routinely receive MenACYW vaccine Hepatitis Vaccines Recommendations old Hepatitis A 2006 Hepatitis B 2005 and 2006 Changes since Twinrix Hepatitis B in DM Post-exposure management for HCP Hepatitis B infected mothers Workgroup to start working on new recommendations 2016 by the American Pharmacists Association. All rights reserved. 9

FluLaval Quadrivalent (GSK) FDA approved August 2013 for ages >3 years Submitted Biologics License Application to include ages 6-35 months Expect FDA response November 2016 Utilize same dose (15 mcg each strain) Currently Fluzone only vaccine available for this age group 7.5 mcg each strain Other vaccines not studied or too reactogenic Safety and immunogenicity similar to Fluzone More discussion in future meetings Flucelvax Quadrivalent (Seqirus) FDA approved May 23, 2016 for persons aged >4 years Prepared in canine kidney cells Safety and efficacy Immunogenicity non-inferior to cciiv3 Similar safety profile Vaccine Safety Monitoring 2015-16 Influenza Season VAERS No safety concerns Will add new vaccines for next review Guillain-Barré syndrome (GBS) FDA real-time monitoring with CMS of Medicare patients 7.25 cases/million reported (15.4 million doses given) 5.45 cases/million for past 3 seasons Vaccine Safety Datalink (VSD) Relative Risk (RR) 3-3.67 (3.1 million doses) RR 1.1.38 last year 2.6 additional GBS cases per million doses Similar to some previous seasons Change from ICD-9 to ICD-10 limited data available 2016 by the American Pharmacists Association. All rights reserved. 10

2016 by the American Pharmacists Association. All rights reserved. 11

Vaccine Effectiveness 2015-16 U.S. Flu VE Network All Ages Any Vaccine Overall Adjusted VE 47% A/H1N1pdm09 41% A/H3N2 45% B/Yamagata 55% B/Victoria 55% IIV Overall Adjusted VE 49% A/H1N1pdm09 44% A/H3N2 43% B/Yamagata 59% B/Victoria 58% Vaccine Effectiveness Ages 2-17 Any Virus A/H1N1pdm01 B-Yamagata B-Victoria IIV 63 65 64 56 LAIV 3-21 -4 31 Ages 2-8 Any Virus A/H1N1pdm01 B IIV 58 62 47 LAIV -3-48 36 Ages 9-17 Any Virus A/H1N1pdm01 B IIV 71 66 69 LAIV 20 33 17 2016 by the American Pharmacists Association. All rights reserved. 12

Vaccine Effectiveness DOD Military Dependents Aged 2-17 years Any Virus A/H1N1pdm01 A/H3N2 All B IIV 66 68 82 63 LAIV 53 15 47 84 AstraZeneca ICICLE Study Ages 2-17 years Any Virus A/H1N1pdm01 All B IIV 65 71 56 LAIV 46 50 47 AstraZeneca Other studies presented Finland National Institute for Health and Welfare Comparison throughout season Comparison over years Conclusions No explanation for differences ICICLE and Finland studies showed good VE Limitations of observational study designs Sample size limitations Results of VE since 2009 2-17 years (U.S. Flu Network) Any Flu A or B 2010-11 Mixed 2011-12 H3N2 2012-13 H3N2 2013-14 H1N1 2014-15 H3N2 2015-16 H1N2 IIV 71 55 45 60 15 63 LAIV3 71 67 46 LAIV4-1 3 3 DOD 18 years+ Any Flu A or B 2010-11 Mixed 2011-12 H3N2 2012-13 H3N2 IIV 53 75 35 28 LAIV3-13 74 34 LAIV4-17 2013-14 H1N1 2016 by the American Pharmacists Association. All rights reserved. 13

Possible Explanations Suboptimal performance of A/H1N1 vaccine strain Interference among virus when additional B strain added to quadrivalent Reduce immunogenicity of LAIV as a result of more highly vaccinated population in later years; more children were vaccine naïve in earlier years Recommendations for LAIV Potential Issues Decreased effectiveness against A/H1N1pdm09 Unknown effectiveness against A/H3N2 and B Possible shortages Impact on school programs No alternative for those who refuse injections Communication difficulties How to predict effectiveness in future seasons if not used Vote In light of the evidence for poor effectiveness of LAIV in the United States over the last three influenza seasons (2013-2016), for the 2016-17 season, the ACIP makes the interim recommendation that LAIV should not be used. Recommendations for 2016-17 Influenza Season No LAIV Reiteration of vaccination of all persons 6 months and older Minor change in wording of vaccination timing Healthcare providers should offer vaccination by October, if possible. Vaccination should continue to be offered as long as influenza viruses are circulating. Changes to egg allergy recommendations New vaccines 2016 by the American Pharmacists Association. All rights reserved. 14

Respiratory Syncytial Virus (RSV) Humans only source Spread by direct or close contact Incubation 4-6 days Viral shedding 3-8 days (up to 4 weeks) Major cause of lower respiratory disease Infants and children 50% infected in 1 st year of life 150,000 hospitalizations/year Bronchiolitis, pneumonia, or apnea Adults Substantial outpatient burden Repeated yearly infections Most upper respiratory worse than common cold 177,000 hospitalizations of persons aged 65 years and older 14,000 deaths yearly RSV Vaccine No vaccine over last 59 years since virus discovery Monoclonal antibodies for high-risk infants First vaccine 1966 Formalin Inactivated More severe RSV disease than unvaccinated Infants need replicating vaccine Subunit vaccines (+ adjuvants for adults) RSV Vaccine Needs Neonates Maternal antibodies prevent live vaccines Older infants and children Live-attenuated vaccines (Phase 1 trials) Pregnant women Transfer of maternal antibodies Prevent infection from mother to infant Subunit vaccines (Phase 1-3 trials) Older adults Subunit inactivated vaccines RSV F subunit nanoparticle vaccine first before FDA ACIP to consider over next 2 years 2016 by the American Pharmacists Association. All rights reserved. 15

Tdap in Pregnant Women Current recommendations 27-36 weeks New data on 2 nd trimester and 28-32 weeks Higher maternal antibody concentrations Higher pertussis toxin in mothers early No apparent differences in neonatal titers More to discuss at October ACIP meeting Safety monitoring No increase in birth defects More injection site reactions but still within expected rates Laboratory Confinement of Poliovirus Last cases WPV2 October 1999 India WPV3 November 2012 Nigeria WPV1 2016 (16 cases) 11 Pakistan 5 Afghanistan WHO Action Plan Containment Destroy Transfer to Essential Laboratory Contain become an Essential Laboratory U.S. Action Plan National survey Last done in 2002-2003 Completion of survey July 31, 2016 Containment Phase 1 WPV2 Completion 2016 Phase 2 all WPV Completion 2019 Many challenges Labs concerned about future research Academic labs with frequent turnover Some labs unaware of containment Absolute containment not possible Excretion of virus Synthetic biology production possible 2016 by the American Pharmacists Association. All rights reserved. 16

HPV Vaccine Application to FDA Merck 2-dose schedule HPV9 WHO recommended for HPV2 and HPV4 Administered before age 15 years Immunogenicity data presented at February ACIP Higher titers with vaccination than natural infections Non-inferior antibody response in 9-14 year olds Compared with 3 doses in 16-26 year olds 0 6 months or 0 12 months schedule Higher seroconversion in younger ages HPV2 (GSK) to withdraw from U.S. November 2016 HPV4 (Merck) to withdraw by end of 2016 2-Dose Schedules Persistence No evidence of waning antibodies after 3 dose HPV2 and HPV4 10 years (some studies ongoing) Immune memory demonstrated by anamnestic response to additional doses No data from 2-dose studies Cost effectiveness Many factors (efficacy, increased coverage) Must protect at least 20 years 2-Dose Schedules Review of studies in other countries No studies of HPV9 13 studies reviewed 3 post-hoc analyses of clinical trials Similar outcomes of 3-dose series 10 evaluating uncompleted series Most looked at 0-1 month or 0-2 month 0-6 months showed good effectiveness data Post-licensure effectiveness studies have many issues GRADE Analysis Compare ages 9-14 years with 15-26 years Non-inferior immunogenicity Decreased adverse effects 2016 by the American Pharmacists Association. All rights reserved. 17

Draft Proposal 2-dose schedule at age 11-12 years Second dose 6-12 months after first If interval less than 6 months, give 3rd dose 6 months from first 3-dose schedule after 15th birthday 0,1-2,6 months Immunocompromised 3-dose series Discuss again at October Meeting Summary and Conclusions Next ACIP Meeting October 19-20, 2016 in Atlanta If questions, please contact: Stephan L. Foster, PharmD E-mail: sfoster@uthsc.edu Reminder ACIP recommendations are not final. The director of the CDC makes the final decision. Not official until published in MMWR. Do not incorporate these discussions/decisions into practice until published. 2016 by the American Pharmacists Association. All rights reserved. 18

Self-Assessment Question #1 The FDA has approved meningococcal B vaccination with Trumenba: A. As a single dose B. As a 2-dose series given at 0 and 1-2 months under certain circumstances C. As a 2-dose series given at 0 and 6 months under certain circumstances D. That must always be given as a 3-dose series at 0, 1-2 months, and 6 months Self-Assessment Question #2 The ACIP has recommended that vaccination with LAIV (FluMist) in the 2016-17 influenza season: A. Is preferred in children over IIV B. Has no preference from the ACIP over IIV C. Should not be given to anyone D. Should be given to all age eligible patients aged 2-49 years Self-Assessment Question #3 The ACIP is discussing vaccination with a 2-dose series of HPV9 in a 0-6 month schedule for: A. Patients aged 11-26 years B. Patients aged 9-14 years C. Patients aged 15-26 years D. Is not recommended for any age 2016 by the American Pharmacists Association. All rights reserved. 19

AUDIENCE QUESTIONS How to Obtain CPE Credit (Webinar) 1. At the conclusion of this activity, log in to pharmacist.com 2. Click LEARN, MY TRAINING. Under ENROLLMENTS, click on activity, June 2016 ACIP Immunization Update 3. Complete assessment and evaluation questions 4. Claim credit Deadline to claim credit for this online activity is July 27, 2019. No credit will be issued after this date. ACPE Universal Activity Numbers to claim credit: 0202-0000-16-128-H04-P (pharmacists) 0202-0000-16-128-H04-T (pharmacy technicians) APhA members may claim CPE credit for either the live webinar or home-study (webinar recording); you may not claim credit for both. A supplemental clinical case challenge will become available after participants have completed either live webinar OR home-study. 2016 by the American Pharmacists Association. All rights reserved. 20