Influenza Vaccines: Giving the Right Dose at the Right Time Wednesday, December 9, 2015 12:00 PM ET Agenda Agenda Welcome and Introduction William Schaffner, MD, NFID Medical Director Influenza Vaccines: Giving the Right Dose at the Right Time Kathleen M. Neuzil, MD, MPH, Professor, Department of Medicine, Director, Center for Vaccine Development, University of Maryland School of Medicine Open Discussion/Questions and Comments 1
General Information Please note that today s webinar is being recorded All phone lines will be placed on mute throughout the program To hear audio: Computer: Follow directions Phone: 303-248-0285; Access Code 6560003 After the presentations, there will be a Question and Answer period Use the Chat box on the lower left side of your screen to type your question At the end of the webinar, participants will be directed to an online evaluation CME Credit/Webinar Evaluation The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. NFID designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit TM. Online evaluation and post-test will be available following the webinar at: http://bit.ly/flu-webinar Certificate will be available for print or download following successful completion of online evaluation and post-test. 2
Disclosures Marla Dalton (NFID staff, content reviewer) owns stock, stock options, or bonds from Merck & Co., Inc. William Schaffner (NFID medical director, content reviewer) served as an advisor or consultant for Merck & Co., Inc., Pfizer Inc., and Novavax; and served as a speaker or member of a speaker s bureau for Merck & Co., Inc. All other faculty, activity planners/reviewers, and staff for this activity have no relevant financial relationships to disclose Learning Objectives At the conclusion of this webinar, participants will be able to: Evaluate the characteristics of influenza vaccines and the appropriateness of each for different populations Develop strategies to increase immunization coverage in clinical practice Provide patient education on the prevention and control of influenza 3
About NFID Non-profit 501(c)(3) organization dedicated to educating the public and healthcare professionals about causes, treatment, and prevention of infectious diseases across the lifespan Reaches consumers, health professionals, and media through: Coalition-building activities Public and professional educational program Scientific meetings, research, and training Longstanding partnerships to facilitate rapid program initiation and increase programming impact Flexible and nimble organization Influenza Vaccine: New Options, New Opportunities Kathleen M. Neuzil, MD, MPH Professor, Department of Medicine Director, Center for Vaccine Development University of Maryland School of Medicine December 9, 2015 4
Influenza Vaccine: New Options, New Opportunities To review the characteristics of currently available influenza vaccines To provide the evidence and rationale for the current influenza vaccine recommendations To describe future directions for influenza vaccines and vaccination strategies Influenza A Virus Hemagglutinin (H) 17 subtypes (attachment, penetration) Neuraminidase (N) 10 subtypes (release) 8 viral genes (assembly, replication) M2 Protein (replication) Source: AS Fauci 5/13/2013 5
Reassortment of Influenza A Viruses Alpha 2,3 receptors in respiratory tract Alpha 2,6 receptors Non-human virus Alpha 2,6 & Alpha 2,3 receptors in respiratory tract Page 11 Reassortant virus 5/13/2013 Human Influenza - Clinical Acute febrile respiratory illness - Many influenza-like illness definitions - Fever or feverish - Cough and/or sore throat or other manifestations (otitis) - More serious pulmonary manifestations - Primary or secondary pneumonia, croup, bronchiolitis - Non-specific febrile illness - Extra-pulmonary manifestations - Neurologic Encephalitis, seizures - Myositis - Cardiac You will find what you look for! Page 12 5/13/2013 6
38-yo Fever, cough, myalgias 56 yo s/p BMT - primary influenza pneumonia 73 yo woman with primary influenza pneumonia 43 yo man S. aureus pneumonia Influenza Burden in US Infection rates are highest among children, with complications, hospitalizations, and deaths from seasonal influenza being greatest among persons aged 65 years, children aged <2 years, and persons of any age who have medical conditions that confer increased risk for complications from influenza Highly variable from year-to-year From 1976-77 through 2005-06, deaths ranged from 3,000 to 49,000 annually From 1979 80 through 2000 01, the estimated annual overall number of influenza-associated hospitalizations in the United States ranged from approximately 55,000 to 431,000 per annual epidemic (mean: 226,000) 7
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Influenza: An epidemic respiratory disease associated with excess deaths Selwyn Collins, USA 9
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Influenza Vaccine Recommendations, US, 2015 Routine annual influenza vaccination of all persons aged 6 months continues to be recommended No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one product is otherwise appropriate MMWR. August 7, 2015. Vol 64. No 30. 818-821. However it is most important for people at increased risk of complications and for those who care for them Highest risk Children 6 through 59 months Adults 65 years and over Persons of all ages with underlying conditions that predispose them to more severe disease Including pregnant women Healthcare workers and persons in close contact with any of the above 11
73-year-old retired professor presents for his annual influenza vaccine. He has heard that the flu shot may not work in older people. He knows that his grandson just received a nasal spray vaccine. After discussion and providing education to your patient, what influenza vaccine would you administer? Page 23 January 10, 2014 Influenza Vaccines, US, 2015-2016 Type of Vaccine Trade Name Manufacturer Age Indications Route IIV3: Inactivated influenza vaccine; Trivalent Afluria Flucelvax CSL Limited Novartis Vaccines 9 years 18 years IM and needle-free jet injector IM Note: One vaccine is produced in cell culture; this is referred to as cciiv IIV4: Inactivated influenza vaccine; Quadrivalent Fluvirin Novartis Vaccines 4 years IM Fluzone Sanofi Pasteur 6 months IM Fluzone High-Dose (60mcg HA/strain/dose Sanofi Pasteur 65 years IM Fluarix Quadrivalent GlaxoSmithKline 3 years IM Fluzone Quadrivalent Sanofi Pasteur 6 months IM FluLaval ID Biomedical 3 years IM RIV3: Recombinant HA; Trivalent Fluzone Intradermal (9mcg HA/strain/dose) FluBlok (45mcg HA/strain/dose) Sanofi Pasteur 18 through 64 years Intradermal Protein Sciences > 18 years IM LAIV4: Live attenuated influenza vaccine; Quadrivalent FluMist Quadrivalent MedImmune 2 through 49 years Intranasal 12
Live Attenuated Standard Inactiv High dose Inactivated Recomb Inactiv. intradermal Route Intranasal IM IM IM ID Frequency Annual Annual Annual Annual Annual Approved risk groups and ages Healthy, 2 thru 49 yrs All, 6 months All,>65 years All, > 18 years All, 18 thru 64 years HA (mcg/strain) 15 15 60 45 9 Common side effects Pregnant women? Use in close contacts of high risk/pregnant/ Immune compromised Sore throat nasal congest. Injection site rxn More injection site rxn Injection site rxns Erythema at inject site NO YES YES YES YES YES* YES YES YES YES * Except persons requiring a protected environment (e.g., hematopoietic stem cell transplant recipient). Influenza Vaccines for Older Persons While post-licensure observational studies are important tools for monitoring vaccine effectiveness, such studies relating to influenza vaccine in the elderly are particularly challenging to perform and interpret Confounding Inadequate adjustment for medical co-morbidities can affect effectiveness estimates Difficult to adjust for other characteristics of vaccinees versus non-vaccinees (vaccine-seeking behavior) Non-specific and limited outcome measures Influenza causes a range of non-specific clinical syndromes Many of the early observational studies did not include laboratory-confirmed outcomes Jackson LA, Jackson ML, Nelson JC, Neuzil KM, Weiss NS. Evidence of bias in estimates of influenza vaccine effectiveness in seniors. Int J Epidemiol 2006; 35: 337-344. 5/13/2013 13
Re-analysis of randomized, controlled trial of influenza vaccine in persons 60 years and older Mortality benefits of influenza vaccination in elderly people. The Lancet. August 2008, Volume 8, page 460. 5/13/2013 14
B. Flannery ACIP June 24, 2015 B. Flannery ACIP June 24, 2015 15
High-Dose Influenza Vaccine in Adults 65 Years and Over A multicenter, randomized, double-blind controlled study was conducted to compare HD vaccine (which contains 60 mcg of HA per strain) with the licensed standard-dose (SD) vaccine (which contains 15 mcg HA per strain) in adults 65 years of age HD vaccine was administered to 2575 subjects, and SD vaccine was administered to 1262 subjects The immunogenicity of HD vaccine was assessed in terms of rates of seroconversion and ratio of GMTs for each virus strain, relative to the values obtained for the SD vaccine 5/13/2013 Falsey et al. JID 2009:200 (15 July). 5/13/2013 16
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Randomized, Controlled Trial of High- Dose vs. Standard Dose Influenza Vaccine Presented at ACIP, October, 2013 www.cdc.gov Randomized, Controlled Trial of High-Dose vs. Standard Dose IIV Presented at ACIP, October, 2013 www.cdc.gov 18
Presented at ACIP, October, 2013 www.cdc.gov 19
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Used data from the FIM12 head-to-head randomized controlled trial High dose cost US $31.82, standard dose $12.04 Incremental cost-effectiveness ratios (ICERs) Per-participant Costs by Resource Item (in US$ per vaccine) 21
Adjuvanted Influenza Vaccines Widely studied with pre-pandemic vaccines to enhance immunogenicity Increased cross-protection Enhanced antibody and cellular responses Seasonal MF-59 adjuvanted (FluAd) approved for 65+ in Europe since 1997 MF-59 and ASO3 used in monovalent vaccines during the pandemic Generally safe (Some countries have identified possible link between ASO3 and narcolepsy) Higher regulatory hurdles in the US Page 43 5/13/2013 22
Recombinant Influenza Vaccines Benefits (compared with current egg-based): Production not reliant on or limited by production in eggs Potentially shorter cycle from strain identification to vaccine availability Potential for closer match with circulating strains Challenges Market share and price 23
Many Unanswered Questions What is the effect of priming (original antigenic sin?) on future vaccine responses? What is the effect of vaccination over multiple years? What is the duration of vaccine protection? Will effects differ by type of vaccine (nonreplicating vs live attenuated?) How do we best measure indirect protection in different settings/environments? What are we looking for in a better vaccine? 24
What are we looking for in a better vaccine? More effective at preventing influenza illness? What are we looking for in a better vaccine? More effective at preventing influenza illness? More effective at preventing severe infection? 25
What are we looking for in a better vaccine? More effective at preventing influenza illness? More effective at preventing severe infection? More broadly protective? What are we looking for in a better vaccine? More effective at preventing influenza illness? More effective at preventing severe infection? More broadly protective? Longer lasting immunity? 26
What are we looking for in a better vaccine? More effective at preventing influenza illness? More effective at preventing severe infection? More broadly protective? Longer lasting immunity? Safer? What are we looking for in a better vaccine? More effective at preventing influenza illness? More effective at preventing severe infection? More broadly protective? Longer lasting immunity? Safer? Easier, more efficient manufacturing? 27
What are we looking for in a better vaccine? More effective at preventing influenza illness? More effective at preventing severe infection? More broadly protective? Longer lasting immunity? Safer? Easier, more efficient manufacturing? How much are we willing to pay for these improvements? 12/9/2015 Page 56 28
> 65 years: 66.7 % 29
Influenza Common respiratory illness accounting for substantial morbidity, mortality, lost productivity annually Influenza vaccines are safe and effective how effective varies by year and influenced by virus, vaccine, host Vaccination schedules will become more nuanced in regard to the use of specific vaccines for specific age and risk groups 30
Questions & Answers CME Credit/Webinar Evaluation The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. NFID designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit TM. Online evaluation and post-test will be available following the webinar at: http://bit.ly/flu-webinar Certificate will be available for print or download following successful completion of online evaluation and post-test 31
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