Use of 13-valent Pneumococcal Conjugate Vaccine and 23-valent Polysaccharide Vaccine in Adults with Immunocompromising Conditions

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1 Use of 13-valent Pneumococcal Conjugate Vaccine and 23-valent Polysaccharide Vaccine in Adults with Immunocompromising Conditions Tamara Pilishvili, MPH Respiratory Diseases Branch National Center for Immunization & Respiratory Diseases, CDC 5 th Regional Pneumococcal Symposium March 5-6, 2013

2 ACIP Recommendations for Use of Pneumococcal Polysaccharide Vaccine (PPSV23) in Adults All adults 65 yrs and older Adults years old with the following conditions Advisory Committee on Immunization Practices (ACIP), MMWR 2010

3 Timeline for pneumococcal conjugate vaccines in the U.S. Recommendations for PCV7 ACIP Recommendations for PCV13 ACIP Recommendations for PCV13 among immunocompromised adults ACIP Feb 2000 Oct 2000 Feb 2010 Dec 2011 Jun 2012 Jan 2013 PCV7 licensed for infants and young children FDA PCV13 licensed (replaced PCV7) FDA PCV13 licensed for adults 50 years or older FDA PCV13 licensed for children 6 through 17 years old FDA FDA= Food and Drug Administration ACIP=Advisory Committee on Immunization Practices

4 13-valent Pneumococcal Conjugate Vaccine (PCV13) for Adults Licensed for use among adults >50 years old on 12/30/11 FDA approved under the Accelerated Approval Pathway Based on non-inferior immunogenicity compared to PPSV23 Indications Prevention of pneumococcal disease (including pneumonia and invasive disease) in adults 50 years of age and older Prevention of disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Post-approval condition of licensure: Randomized controlled trial of PCV13 against pneumococcal pneumonia among adults >65 years old in the Netherlands

5 Cases per 100,000 persons Incidence of Invasive Pneumococcal Disease among all adults, U.S., Age, years CDC, ABCs, unpublished, 2012

6 Estimated number of IPD cases and deaths in the U.S., ,296 Cases 4,506 1,873 < or older Deaths , ,847 Total cases=~44,000 Total deaths=~4,800 CDC unpublished data ABCs 2010 incidence data; US 2009 post-census population estimates 6

7 Incidence of Invasive Pneumococcal Disease Among Adults >65 Years by Serotype, PCV7 introduced PCV7 PCV13 introduced PCV13/non-PCV ABCs unpublished data, continuous sites

8 Percent of invasive cases Rank order of IPD serotypes among Adults >65 years of age, Other types PPV23 / NonPCV13 types PCV13 types 19A 7F 3 22F 6C 23A 9N 35B 11A 16F 15A Serotype CDC, unpublished,

9 PCV13 age-based recommendations: U.S. ACIP Decision At this time, the available evidence is insufficient to recommend routine use of PCV13 among older adults Critical data elements for the ACIP recommendation to be made are not available at this time the indirect effects of PCV13 use in children on adult disease incidence results from the CAPITA trial Clinical relevance of immunogenicity data unclear without defined correlate of protection Cost-effectiveness data relies heavily on assumptions of efficacy against pneumonia and potential indirect effects

10 Policy question considered by ACIP Pneumococcal Working Group: Should ACIP recommend PCV13 for immunocompromised adults?

11 Cases per 100,000 persons Incidence of IPD in adults aged years with selected underlying conditions, United States, fold increased risk fold increased risk HEALTHY CVD DIABETES PULMONARY KIDNEY LIVER ALCOHOL HIV/AIDS HEMATOLGICAL CANCER Kyaw, JID 2005;192:377-86

12 Trends in IPD rates among adults yrs old with & without HIV-infection, before and after PCV7 introduction, Adults with HIV infection Adults without HIV infection 6-8/ 100K 64 / 100K Cohen, AIDS 2010;24(14):

13 Efficacy against Invasive Pneumococcal Disease (IPD) IPD = isolation of pneumococcus from a normally sterile site Double-blind, randomized, placebo-controlled Efficacy trial among HIV-Infected Adults in Malawi (N=496) All enrolled subjects had recovered from documented IPD 2 doses of PCV7 given 4 weeks apart Endpoint Vaccine Efficacy (95% CI) PCV7-serotype IPD 74% (30%, 90%) French N, et.al. N Engl J Med 2010;362:

14 Summary: Immunogenicity of PCV in immunocompromised adults PCV does elicit an immune response in HIV+ and cancer patients 1,2,3,4,5,6 Response following a single dose of PCV is as good or better than PPV23 (both in vaccine naive or previously vaccinated) 1,2,3 Studies with sequential vaccination show similar or improved immune response if PCV given first 1,2,3 Revaccination with PCV show similar immunogenicity compared to the first dose 4 1. Feikin Diag Lab Immunology 2004, 2. Lesprit AIDS 2007, 3. Penaranda AIDS Miro JID, Chan JID, Crum JID, 2010

15 In adults with immunocompromising conditions, should we use PCV13, PPSV23 or Both? Proportion of IPD by vaccine serotype, 2010 Immunocompromised 29% 50% 21% 21% of disease due to serotypes in PPSV23 not covered by PCV13 Opportunity for broader serotype protection through use of BOTH vaccines PCV13 PPV23/NonPCV13 Other CDC, ABCs, unpublished, 2011

16 Conclusions for PCV13 among Immunocompromised Adults Extremely high burden of disease among immunocompromised adults Indirect effects of PCV13 use in children unlikely to eliminate PCV13 serotypes from immunocompromised adults Benefits of PCV13 use in this group outweigh the harms PCV13 alone may not provide adequate coverage of serotypes causing disease Combined regimen of PCV13 and PPSV23 likely better than either vaccine alone ACIP Decision: Benefits likely outweigh harms and both PCV13 and PPSV23 should be recommended for adults with immunocomromising conditions

17 PCV13 and PPSV23: Vaccination Sequence Data for PCV followed by PPSV 3 studies in HIV+ show that antibodies non-inferior or superior when PCV given prior to PPSV Phase III studies in immunocompetent show that PCV13 + PPSV23 > PPSV23 + PCV for 11/12 serotypes Data for PPSV followed by PCV In 1 study in HIV+ in Uganda, PPSV 5 yrs prior did not affect response to PCV In 1 study in HIV+ in US, there was no difference in immunogenicity between PCV and PPSV given 3-8 years after PPSV Data support use of PCV13 followed by PPSV23

18 PCV13 and PPSV23: Interval between vaccines What is the optimal interval between PCV and PPSV? 1 & 2 month intervals Immunocompetent older 6 and 12 month intervals All intervals showed significant increases in antibody as well as non-inferior or superior response compared to PPSV alone What is the optimal interval between PPSV and PCV? Studies in immunocompetent suggest blunting of immune response <5 years after PPSV No evidence of reduced immunogenicity in HIV+ with PCV 5 years after PPSV No studies have been designed to evaluate the optimal interval

19 Recommendation for PCV13 and PPSV23 Vaccine naïve adults: PCV13 dose is recommended to be given before PPSV23, whenever possible PPSV23 should be given at least 8 weeks after a dose of PCV13 Recommendations for 2 nd dose of PPSV and a dose at age 65 years or older remain unchanged PPSV23-immunized adults A dose of PCV13 is recommended to be given to adults with immunocompromising conditions who received 1 or more doses of PPSV23 1 or more years after the last PPSV23 dose Total number and interval between PPSV23 doses unchanged from current recommendations 19

20 Indications for PCV13 and PPSV23 Advisory Committee on Immunization Practices, MMWR 2012

21 Prevention of pneumococcal disease among adults with immunocompromising conditions Recommendation for PPSV23-naïve adults PCV PPSV PPSV* >8 weeks >5 years + PPSV (@ 65 years or later) Integrating new PCV13 recommendation for adults previously vaccinated with PPSV23 >5 years 1) PPSV PCV PPSV* + PPSV (@ 65 years or later) >1 year >8 weeks 2) PPSV PPSV*- PCV + PPSV (@ 65 years or later) >5 years >1 year >1 year 3) PPSV PPSV* + PPSV (@ 65 +) PCV >5 years *Second PPSV dose before age 65 years NOT recommended for adults with CSF leaks or those with cochlear implants 21

22 ACIP members Nancy Bennett (Chair) Wendy Keitel Jeffrey Duchin Michael Marcy Ex Officio members Mark Grabowsky Kristin Nichol Lucia Lee Acknowledgements CDC Tamara Pilishvili Cynthia Whitney Matt Moore Kathleen Dooling Tom Hennessy Sandra Steiner Gina Mootrey William Atkinson Jorge Arana Maria Cano Erin Kennedy Carolyn Bridges Charles LeBaron Liaison representatives Lorry Rubin Rick Zimmerman William Schaffner Caroline Quach Ken Gershman Daniel Musher Mary Glode Jane Zucker Lisa Jackson Monica Farley Kathy Neuzil Julie Morita Anthony Brenneman Sandra Fryhofer The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Immunization & Respiratory Diseases Division of Bacterial Diseases