RxVaccinate. Support. Objectives. Disclosures 7/8/2013. Pneumococcal Immunization Update

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1 RxVaccinate Pneumococcal Immunization Update Stephan L. Foster, Pharm.D., FAPhA, FNAP Professor and Vice-Chair College of Pharmacy University of Tennessee Health Science Center, Memphis, TN Liaison Member, CDC Advisory Committee on Immunization Practices (ACIP) This webinar is provided as part of RxVaccinate an educational research project being conducted by the American Pharmacists Association (APhA) to help pharmacists and pharmacies expand their pneumococcal immunization services. For information about how you can be part of this project, please visit: Support Supported by an independent educational grant from Pfizer Medical Education Group Disclosures Stephan L. Foster, PharmD, FAPhA, FNAP, is on the speakers bureau for Merck Vaccine. APhA s educational and 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. The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Objectives Target Audience: Pharmacists ACPE#: L01-P Activity Type: Knowledge-based At the end of this session, the participant will be able to: 1. Describe pneumococcal disease 2. Recall current CDC recommendations for pneumococcal vaccination 3. Discuss benefits and risks associated with pneumococcal vaccination 4. Answer frequently asked questions by patients and prescribers 1

2 Cases/100,000 Cases / 100,000 7/8/2013 Streptococcus pneumoniae Gram-positive coccobacillus with a polysaccharide cellular capsule Colonizes upper respiratory tract as part of normal flora Disseminated Disease Bacteremia Meningitis Arthritis Peritonitis Lower Respiratory Tract Pneumonia Upper Respiratory Tract Sinusitis Otitis Media >90 serotypes based upon polysaccharide capsules Incidence in U.S Prior to conjugate vaccine introduction Meningitis 3300 cases Invasive Disease 60,000 cases Pneumonia 100, ,000 hospitalizations Death 14% of hospitalized adults Adults - CFR 15-20% Elderly - CFR 30-40% Invasive Pneumococcal Disease (IPD) in Adults with Chronic Disease IPD IPD Changes Kyaw MH, Rose CE, Fry AM, et.al. J Infect Dis.2005;192: Hematological Cancer 2012 data unpublished from CDC HIV Immunization and Infectious Diseases IID-4 Reduce Invasive Pneumococcal Infections IID-4.1 Reduce new invasive pneumococcal infections among children under age 5 years Baseline: 20.3 cases/100,000 Goal: 12 cases/100,000 IID-4.2 Reduce new invasive pneumococcal infections among adults aged 65 years and older Baseline: 40.4 new cases/100,000 Goal: 31 new cases/100,000 All baseline date from IID-4 Reduce Invasive Pneumococcal Infections IID-4.3 Reduce invasive antibiotic-resistant pneumococcal infections among children under age 5 years Baseline: 4.3 cases/100,000 Goal: 3.0 cases/100,000 IID-4.4 Reduce invasive antibiotic-resistant pneumococcal infections among adults aged 65 years Baseline: 2.6 cases/100,000 Goal: 2 cases/100,000 2

3 IID-7 Achieve and maintain effective vaccination coverage levels for universally recommended vaccines among young children IID-7.7 Achieve and maintain an effective coverage level of 4 doses of pneumococcal conjugate vaccine (PCV) among children by age 19 to 35 months Baseline: 80.1% Target: 90% IID-13 Increase the number of adults who are vaccinated against pneumococcal disease IID-13.1 Increase the percentage of noninstitutionalized adults aged 65 years and older who are vaccinated against pneumococcal disease Baseline: 60.1% (2009 data) Target 90% IID-13 Increase the number of adults who are vaccinated against pneumococcal disease IID-13.2 Increase the percentage of noninstitutionalized high-risk adults aged years who are vaccinated against pneumococcal disease Baseline: 16.6% (2009 data) Target: 60% IID-13 Increase the number of adults who are vaccinated against pneumococcal disease IID-13.2 Increase the percentage of institutionalized adults (persons aged 18 years and older in long-term or nursing homes) who are vaccinated against pneumococcal disease Baseline: 66.4% ( data) Target: 90% History 1881 Pasteur, Steinberg isolate and grow pneumococcus Gram-stain discovered % CFR for untreated pneumonia 1920 s 1930 s Antisera 18% mortality 1930 s Sulfapyridine 1941 Sulfadiazine 8% mortality 1940 s Penicillin 1970 s Penicillin resistance 1980 s 44% resistant to penicillin 1990 s Fluoroquinolone resistance Mechanism of Resistance Beta-lactams bind active enzyme needed for synthesis of cell wall Genes encoding the protein enzymes alter the affinity for penicillins, cephalosporins, lincosamides (clindamycin) Macrolides inhibit protein synthesis in ribosome Site of attachment altered to resist Efflux pump excludes macrolides Fluoroquinolones bind topoisomerase enzymes to inhibit DNA synthesis Mutations reduce binding of drugs Pneumococcus resistant increasing NEJM 2002;346:722 3

4 Strategies for Minimizing Antimicrobial Resistance Proper antibiotic use Patient Education Clinician education and guidelines Formulary management Surveillance Infection control practices Vaccination ASHP. Therapeutic position statement on strategies for identifying and preventing pneumococcal resistance. Am J Health-Syst Pharm. 2004;61: History of Pneumococcal Vaccination 1911 Gold miners in South Africa Attack rate 100/1000 persons with CFR 25% Sir Almroth Wright developer of typhoid vaccine Vaccine containing heat-killed pneumococci Left before trials completed Stated after published results the comparative statistics which have been sent forth testify in every case to a reduction in the incidence-rate and death-rate of pneumonia in the inoculated Where in comparative statistics we find the difference between the inoculated and the uninoculated is diminishing is after a certain time effaced, this does not necessarily indicate that the immunity of the inoculated is diminishing. We may be witnessing, instead of a descent of the level of the inoculated to the level of the inoculated, an assent of the uninoculated to the level of the inoculated We recommend that the prophylactic inoculation should be applied as a routine measure to every native on recruitment. History of Pneumococcal Vaccination F. Spencer Lister Left to compete work in South Africa Discovered 8 different serotypes Trials of polyvalent whole bacteria Efficacy debated due to trial flaws Suspected Wright s vaccine was not potent enough 1927 Schiemann and Casper (Germany) discovered immunogenicity of capsular polysaccharide 1930 polysaccharide vaccine with serotypes 1,2,3 Inconclusive results 1936 Type-specific antisera reduced mortality to 18% 1940 s WWII Air Force pilot training base outbreak Tetravalent vaccine types 1,2,5,7 Demonstrated Efficacy if not another serotype Effective if not a carrier Did not eliminate carrier state 1940 Penicillin Discovered Vaccination Abandoned History of Pneumococcal Polysaccharide Vaccine (PPSV) 1950 s licenses withdrawn 1970 s new studies on polysaccharide demonstrated clinical efficacy (60-70%) Increasing resistance noted valent PPSV Studies in children disappointing History of Pneumococcal Conjugate Vaccine (PCV) 1937 reported lack of responsiveness in infants 2 to 14 months of age (both PPSV and whole cell vaccine) Linked polysaccharide to horse serum was effective in rabbits Noticed lack of response to Haemophillus influenza type b (Hib) vaccine in infants 1990 studies with conjugation to protein 1993 conjugate Hib licensed Pneumococcal conjugate licensed in

5 Cases per 100,000 7/8/ Serotype Pneumococcal Polysaccharide Vaccine Licensed Vaccines Introduced 1977 Products Pneumovax 14 (Merck & Co.) Pnu-Imune 14 (Lederle, Inc.) 14 Serotypes 1, 2, 3, 4, 5,6A, 7F, 8, 9N, 12F, 18C, 19F, 23F, 25F 68-80% that cause invasive disease Included 1 serotypes that cause most drugresistant infections Replaced in Serotype Pneumococcal Polysaccharide Vaccine Introduced 1983 Products Pneumovax 23 (Merck & Co.) Pnu-Imune 23 (Lederle, Inc.) ended production Serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F 85-90% that cause invasive disease 7 Serotype Pneumococcal Conjugate vaccine Licensed in 2000 Product Prevnar 7 (Wyeth) 7 serotypes 4, 6B, 9V, 14,18C, 19F, 23F When introduced, covered 80% of serotypes causing invasive pneumococcal disease (IPD) in children 50-60% older children and adults 13 Serotype Pneumococcal Conjugate vaccine Rates of Pneumococcal Disease are Decreasing ABC Surveillance Licensed in 2010 Product Prevnar 13 (Pfizer) 13 serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F, 23F Additional serotypes caused 61% of IPD cases in children <5 years (before introduction of vaccine) Approved based upon safety and noninferiority immunogenicity data compared to these serotypes in PPSV < > 65 Age in years

6 Not Optimal CDC National Estimates (ABC Surveillance) 36,850 cases per year 4,250 deaths per year Pneumococcal Vaccination Rate Months (PCV) 93.6% (3 doses) 84.4% (4 doses) years high-risk (PPSV) 20.1% (18.5% in 2010) > 65 years (PPSV) 62.3% (59.7% in 2010) Vaccines are underused! Non-influenza Vaccination Rates 2011 Vaccine % 2010 % PPSV23 (19-64 y/o high-risk) PPSV23 (>65 y/o) Tetanus in past 5 years (19-49 years) Tdap in past 6 years (19-64 years) Tdap living with infants <1 y/o (19-49 years) Tdap in past 5 years (HCP) not including unknown 37.3 Hepatitis A (19-49 years) Hepatitis B (19-49 years) Hepatitis B with Diabetes (19-49 years) Zoster (>60 years) HPV Females (19-26 years) HPV Males (19-21 years) Changes in invasive pneumococcal disease (IPD) incidence by serotype group among children aged <5 years (A) and adults aged 65 years (B) *Seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the United States for routine use among young children and infants in the second half of by the Infectious Diseases Society of America Pilishvili T et al. J Infect Dis. 2010;201:32-41 Trends due to PCV7 Decrease in IPD in children by 79% Overall rates leveled off all ages IPD by Penicillin resistant strains decreased 57% overall 81% children IPD by non-pcv7 serotypes increased Mostly type 19A Hospitalizations for pneumonia in children decreased 35% Decrease in otitis media Herd Effects of PCV7 Rates/ incidence of IPD in older children and adults have decreased: 34% age years 14% age years 37% age > 65 years IPD due to 7 serotypes decreased 90-93% Decrease in all-cause pneumonia hospitalizations among young adults No benefit for adults with high-risk conditions MMWR 2010;59 (RR-11):1-19 Comparison of Serotypes Pneumovax 23 (Merck) B 7F 8 9N 9V 10A 11A 12F 14 15B 17F 18C 19A 19F 20 22F 23F 33F Prevnar 13 (Pfizer) A 6B 7F Red indicates serotypes unique to vaccine 9V 14 18C 19A 19F 23F 6

7 IPD Caused by Vaccine Serotypes, 2008 MMWR 2010;59 (RR-11):1-19 Differences between PPSV23 and PCV13 Immune Response PPSV23 T-independent antigen Stimulates mature B lymphocytes Not T lymphocytes Response is not long lasting nor creates an anamnestic (memory) response to rechallenge No boosting effect Infants and small children respond poorly PCV13 T-dependent antigen Changed due to protein conjugate Stimulates a T helper cell response Strong memory response on rechallenge Good response in infants and small children. Decreases nasopharyngeal carriage Differences between PPSV23 and PCV13 Adverse reactions Similar in both Mostly local (redness, induration, pain) Mild and self limiting PPSV23 more local effects with revaccination Difficult to evaluate due to variety of vaccines given at the same time. Systemic Myalgia and fever infrequent Febrile seizures with PCV and TIV in season Risk: 1 in 1640 vaccinees Serious rare (similar to other vaccines) Hyporesponsiveness Repeated doses of bacterial polysaccharide vaccines may induce immune tolerance Most data from meningococcal polysaccharide vaccines (serotype C) Antibody concentrations lower than primary immunization Lower immune (antibody) response May relate to existing memory B cells overwhelmed by large dose of antigen May depend upon existing antibody concentration Limited number of studies on pneumococcal vaccines have shown varied results. Many are short-term studies Many different variables involved (i.e. serotypes, measurement of immunogenicity, base-line titers) ACIP Decision PCV13 not for routine use in adults Awaiting more evidence High risk groups Pneumococcal vaccine-naïve person Give PCV13 first Give PPSV23 at least 8 weeks later Repeat PPSV23 5 years later Previous vaccination with PPSV23 Give PCV13 8 weeks after last PPSV23. If second dose of PPSV23 is needed No sooner than 8 weeks after PCV13 No sooner than 5 years after PPSV23 Over 65 One additional dose of PPSV23 If 5 years since last PPSV23 If 8 weeks after PCV13 ACIP.MMWR 2012;61(40):

8 Footnotes Childhood Indications Routine for all Children (PCV13) Ages 2,4,6 months booster months Ages months who completed PCV7 series, single dose High-risk children months, 1 dose if 3 PCV13 doses previously given 2 doses 8 weeks apart if fewer doses given 6-18 years, single dose PCV13 to previously unvaccinated children 2 years or older, PPSV 8 weeks after last PCV13 Additional PPSV after 5 years to patients with asplenia and immunocompromising conditions High-Risk Conditions MMWR 2010;59 (RR-11):1-19 8

9 Footnotes 1.Pneumococcal polysaccharide (PPSV23) vaccination 1. Vaccinate all persons with the following indications: 1. all adults aged 65 years and older; 2. adults younger than age 65 years with chronic lung disease (including chronic obstructive pulmonary disease, emphysema, and asthma); chronic cardiovascular diseases; diabetes mellitus; chronic renal failure; nephrotic syndrome; chronic liver disease (including cirrhosis); alcoholism; cochlear implants; cerebrospinal fluid leaks; immunocompromising conditions; and functional or anatomic asplenia (e.g., sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, splenic dysfunction, or splenectomy [if elective splenectomy is planned, vaccinate at least 2 weeks before surgery]); 3. residents of nursing homes or long-term care facilities; and 4. adults who smoke cigarettes. 2. Persons with immunocompromising conditions and other selected conditions are recommended to receive PCV13 and PPSV23 vaccines. See footnote #10 for information on timing of PCV13 and PPSV23 vaccinations. 3. Persons with asymptomatic or symptomatic HIV infection should be vaccinated as soon as possible after their diagnosis. 4. When cancer chemotherapy or other immunosuppressive therapy is being considered, the interval between vaccination and initiation of immunosuppressive therapy should be at least 2 weeks. Vaccination during chemotherapy or radiation therapy should be avoided. 5. Routine use of PPSV23 is not recommended for American Indians/Alaska Natives or other persons younger than age 65 years unless they have underlying medical conditions that are PPSV23 indications. However, public health authorities may consider recommending PPSV23 for American Indians/Alaska Natives who are living in areas where the risk for invasive pneumococcal disease is increased. 6. When indicated, PPSV23 should be administered to patients who are uncertain of their vaccination status and there is no record of previous vaccination. When PCV13 is also indicated, a dose of PCV13 should be given first (see footnote #10). Adult Indications (PPSV23) All adults aged 65 years and older Only one dose.do not repeat All adults younger than 65 years with highrisk conditions (immunocompetent) One time revaccination 5 years after the first dose with the following conditions: Chronic renal failure or nephrotic syndrome Functional or anatomic asplenia Immunosuppressed One dose after age 65 if one or two doses were received before and it has been at least 5 years since the last dose. Adult High-Risk Conditions Adult Indications (PCV13) Approved for adults 50 years and older for the prevention of pneumococcal pneumonia and invasive disease caused by the 13 vaccine strains PPSV23 and PCV13 Contraindications Severe allergic reaction after previous dose Precautions Moderate or severe acute illness with or without fever PPSV23 Vaccine Effectiveness Cochrane Collaboration Review 25 studies met inclusion criteria 18 RCTs with 64,852 participants Strong evidence of efficacy against IPD (reduced disease by 74%) Efficacy against all cause pneumonia in low income countries (46%) No reduction in all-cause mortality Efficacy poorer in adults with chronic illness 7 non-rcts with 62,294 participants Protection against IPD (reduced disease by 52%) Moberley s, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults.cochrane Database of Systematic Reviews

10 Studies in HIV patients PPSV23 No effect on infection or death All-cause pneumonia higher in vaccine group French N, et al. 23-valent polysaccharide vaccine in HIV-1 infected Ugandan adults:doubleblind, randomised and placebo controlled trial. Lancet 2000;355: PCV7 Vaccine efficacy of 74% against serotypes in vaccine French, et al. A trial of 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010;362; Herd Effect of PCV7 Reduction in IPD Mortality still high (40 times higher than non-hiv) Need more intervention in this population Cohen,et al. Prevention of invasive pneumococcal disease among HIV-infected adults in the era of childhood pneumococcal infection. AIDS 2010;24: PCV13 for use in adults PCV 13 (Prevnar Pfizer) FDA approval in Adults > 50 years (December 30, 2011) Accelerated Approval Pathway Approved based upon immunogenicity data Indication Prevention of disease against types in vaccine Approval based upon immunogenicity data Evidence not available Efficacy against pneumonia Study in Netherlands to be completed 2013 No evidence of indirect (herd) effect due to use in children ACIP recommendations for PCV13 in adults High-Risk Conditions June 2012 ACIP meeting PPSV23 Limited efficacy in immunocompromised Safe and covers 70% of serotypes of IPD Continue use (2 or 3 doses in very high risk) PCV13 No recommendation for routine use in adults Potential benefit seen in previous studies Herd effect in children unlikely to contribute Add one dose to high-risk adults PCV 1 year after PPSV PPSV 8 weeks after PCV NOTE: The dose recommendations for PCV-13 noted on this slide are correct MMWR.2012;61(40) accessed at Pneumococcal Vaccine Decision Tree for Adults Years Old with Select Conditions Pneumococcal Vaccine Decision Tree for Adults 65 Years Old with Select Conditions ACIP. MMWR. 2012; 61 (40): ACIP. MMWR. 2012; 61 (40):

11 Roles of Health-care Providers Get vaccinated yourself! Dispel myths and educate the public Screen patients Keep records - document Have all immunizations available Use Immunization Information Systems Registries Communicate with other providers Participate in health fairs and community events Develop policies/procedures Involve all personnel in your practice Addressing Concerns Discussion with patient / parent or guardian Factual Appropriate language Simple, easy to understand Communicate with empathy Use strong language You should get this vaccine today! Reinforce key points Safety Risks for disease State laws Show where patient can get good information Immunization resources Communication Tips Talk about impact of pneumococcal disease Explain methods of payments available Use Vaccine Information Statement (VIS) If refused, offer at next visit. If one vaccine refused, give others if acceptable Talking Points Vaccination can help protect against a serious disease Pneumococcal infection can be deadly You are at increased risk Over 65 years High-risk medical conditions Smoker Vaccination is safe May I administer this vaccine to you today?...any questions? 11