S404- Meningococcal Vaccines: Updated Policy Statement 2014

Transcription

1 S404- Meningococcal Vaccines: Updated Policy Statement 2014 Michael T. Brady, MD Associate Medical Director Nationwide Children s Hospital Columbus, Ohio

2 Disclosure of Relevant Relationship Dr. Brady (or spouse/partner) has not had (in the past 12 months) any conflicts of interest to resolve or relevant financial relationship with the manufacturers of products or services that will be discussed in this CME activity or in his presentation. Dr. Brady will support this presentation and clinical recommendations with the best available evidence from medical literature. Dr. Brady does not intend to discuss an unapproved/investigative use of a commercial product/device in this presentation.

3 Meningococcal Vaccines: Updated Policy Statement 2014 (Pediatrics 2014; 134: ) and Serogroup B Vaccines Michael T. Brady, MD Associate Medical Director Nationwide Children s Hospital

4 Neisseria meningitidis

5 Meningococcal Infections. Young boy with meningococcemia that demonstrates striking involvement of the extremities with sparing of the trunk. Committee on Infectious Diseases et al. Red Book Online Copyright American Academy of Pediatrics

6 Neisseria meningitidis (meningococcus) 13 serogroups: A, B, C, D, H, I, K, L,W, X, Y,Z and 29E (determined by antigens of polysaccharide capsule) 6 serogroups are responsible for invasive human disease: A, B, C, W, X and Y (A, W and X rare in United States) Gram-negative coccus that typically appears in pairsdiplococcus. Adjacent sides of diplococcus are flat kidney-bean shape There are non-typeable, non-invasive strains of N. meningitidis 6

7 Neisseria meningitidis: Microbiology Encapsulated gram-negative diplococcus Strictly human pathogen Asymptomatic carriage common Carrier prevalence: 5%-10% <1% of carriers become symptomatic Transmission Contact with respiratory secretions Incubation period: 2-10 days Gram stain of engulfed N. meningitidis in cerebrospinal fluid. Arrow indicates bacterial cells inside a neutrophil. van Deuren M, et al. Clin Microbiol Rev. 2000;13:144. Broome CV. J Antimicrob Chemother.1986;18:25. Dull PM, et al. J Infect Dis. 2005;191:33. WHO Fact Sheet. Available at: See safety information on Slide 40. Full prescribing information is available from your Representative 7

8 Meningococcal Disease is Challenging Persistent global health problem 1 Causes endemic and epidemic disease 1 Early disease can be easily misdiagnosed 1 May present with variable clinical manifestations 1 Signs and symptoms may be hard to distinguish from common viral illness Displays rapid onset and progression 1 High morbidity and mortality, despite effective therapy Granoff DM, et al. In: Vaccines. 2004:959 2 Rosenstein NE, et al. N Engl J Med. 2001;344: Jodar L, et al. Lancet. 2002;359:1499 8

9 Meningococcal Disease: Primary Clinical Syndromes Epiglottitis & Pericarditis <1% Otitis Media 1% Arthritis 2% Pneumonia 6% Meningitis 47% Septicemia 43% Up to 60% of infections manifest as both meningococcal septicemia and meningitis Rosenstein NE, et al. J Infect Dis. 1999;180:1894. See safety information on Slide 40. Full prescribing information is available from your Representative 9

10 Meningococcus Exposure Risk Factors Intimate contact with case/carrier Age (highest in infants, adolescents and elderly) Semi-closed populations/crowding Child care Colleges (especially freshmen in dorms) Military recruits Hajj Season - - peak late winter/early spring Upper respiratory viral illness, esp. influenza Travel to endemic area Exposure to cigarette smoke (passive or active) 10

11 Meningococcus Transmission Risk Person-to-person through droplets of respiratory secretions (e.g., coughing, sneezing, kissing, etc.) Nasopharyngeal colonization predates invasive disease 2-4% of healthy infants and children are NP (+) for meningococcus

12

13 Incidence per 100,000 Incidence by Serogroup* and Age-Group, United States, Serogroup B Serogroup A, C, W, Y 0 <1 year 1-4 years 5-10 years years years years Age group (years) years years 65+ years *NNDSS data with additional serogroup data from ABCs and state health departments. Unknown serogroup excluded (23%) 13

14 Rate per 100,000 Meningococcal Disease Incidence in Children <5 years, Serogroup C Serogroup Y Other* Serogroup B < Age (years) *Other includes: serogroups W-135, nongroupables, other, and unknown ABCs cases from and estimated to the U.S. population (2010 data provisional)

15 Meningococcal Incidence in All Ages by Serogroup and Adolescent MenACWY Vaccine Coverage, Serogroup B Serogroup C Serogroup Y 100 Incidence per 100, : 564 cases 3 (0.18/100,000) 2013 MenACWY coverage, NIS-Teen 2 : 1 dose: 77.8% (range by state, 40.4%-93.7%) 2 doses: 29.6% % Coverage with 1 MenACWY among year olds 2 1 Source: Active Bacterial Core surveillance (ABCs) cases from estimated to the U.S. population with 18% correction for nonculture confirmed cases. In 2010, estimated case counts from ABCs were lower than cases reported to the National Notifiable Diseases Surveillance System (NNDSS) and might not be representative. 2 National Immunization Survey Teen; NNDSS 2013 final case count 15

16 Incidence per 100,000 Incidence per 100,000 Incidence of Meningococcal Disease by Age and Serogroup, United States, Age (years) Serogroup B Serogroup C Serogroup Y 0 < Age (years) 16

17 Number of cases Sporadic and Cluster-Associated Cases in the United States by Month, Cluster-associated cases Sporadic cases Month and Year

18 Outline of meningitis belt in Africa showing average annual attack rates F. Marc LaForce, Neil Ravenscroft, Mamoudou Djingarey, Simonetta Viviani Vaccine Volume 27, Supplement B13 - B19 18

19 Persons at Increased Risk for Meningococcal Disease Persons with persistent complement component deficiencies (Inherited or chronic deficiencies in C#, CJ-9, properdin factor D, factor H, or taking eculizumab {Soliris}) Persons with anatomic or functional asplenia (including sickle cell disease) Persons in the population identified to be at increased risk in a meningococcal disease outbreak Unvaccinated or incompletely vaccinated first year colege students living in residence halls Military recruits Persons who travel to or reside in countries in which meningococcal disease is hyperndemic or epidemic Microbiologist routinely exposed to isolators of Neisseria meningitis

20 Risk for Meningococcal Disease Group Estimated persons aged 10 years Persistent complement Prevalence of 0.03% 1 component deficiencies ~80,000 persons Anatomic or Functional Asplenia (including sickle cell) Sickle cell ~90, ,000 (all ages) 3 Microbiologists ~100,000 clinical; 400 research Outbreak at-risk populations 60,000 in 5 serogroup B university outbreaks 5 Risk Up to 10,000 fold increased risk 2 High risk of recurrent disease 2 Risk not well defined 2 Higher risk of mortality (40-70%) 4 13/100,000 2 Higher risk of mortality 2 Up to 1400 fold increased risk 5 1 P Densen. Complement deficiencies and meningococcal disease. Clin Exp Immunol. Oct 1991; 86(Suppl 1): Cohn et al. Prevention and Control of Meningococcal Disease. MMWR. March 22, 2013; 62 (RR-2) Updated recommendations for the use of meningococcal conjugate vaccines. MMWR. January 28,2011; 60(3): CDC unpublished data 20

21 Eculizumab (Soliris ) Monoclonal antibody approved for treatment of atypical hemolytic uremic syndrome (ahus) and paroxysmal nocturnal hemoglobinuria (PNH) Binds to C5 and inhibits the terminal portion of the complement cascade 5/326 subjects in a clinical trial developed meningococcal disease despite prior vaccination with MenACWY Not explicitly included in MenACWY conjugate vaccine recommendations 21

22 Meningococcal Vaccines Quadravalent polysaccharid vaccine (A,C,W;Y) -MPSV4 (Menomung sanofi pasteur)->2years of age Conjugate vaccines -Men ACWY-D (menactra, Sanofi pasteur)-9mos-55ys -Men A CWY-CRM (Menveo, Novartis)-2mos-55yrs -Hib Men CY-TT (Men Hib Rix, Glaxo)-2mos-18mos Group B Vaccines -Trumenba (Pfizer) yrs -Bexsero (Novartis) yrs

23 Meningococcal Vaccination Recommendations Adolescents should be routinely immunized at 11 through 12 years of age and given a booster dose at 16 years of age; Adolescents who received their first dose at age 13 through 15 years should receive a booster at age 16 through 18 years or up to 5 years after their first dose; Adolescents who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose; Unvaccinated or incompletely vaccinated first year college students living in residence halls should receive a single dose of meningococcal conjugate vaccine;

24 Meningococcal Vaccination Recommendations A 2-dose primary series should be administered 2 months apart for those who are at increased risk of invasive meningococcal disease because of persistent complement component (e.g. C5-C9, properdin, factor H, or factor D) deficiency (2 months through 54 years of age) or functional or anatomic asplenia (2 months 54 years of age) and for adolescents with HIV infection; For the pediatric population, an age-appropriate meningococcal conjugate vaccine is preferred to the meningococcal polysaccharide vaccine, unless there is a contraindication for the meningococcal conjugate vaccine.

25 Average Annual Cases of Meningococcal Diseases in Children <5 years, Age Serogroup B Serogroup C Serogroup Y Serogroup C + Y (Incidence) 0-2 months (1.3) 3-5 months (1.4) 6-8 months (1.3) 9-11 months (0.9) 1 year (0.3) 2 years (0.3) 3 years (0.2) 4 years (0.2) Total (0.40) 58 of 251 (23%) of cases prevented ABCs cases from and estimated to the U.S. population (2010 data provisional)

26 Meningococcal Vaccines for Infants and Toddlers MCV4-D (Menactra Sanofi) -2 dose series at 9 & mos (FDA approved April 2011) -Co-administration with pneumococcal conjugate vaccine decreased antibody responses to some pneumococcal serotypes HibMenCY-TT (GSK) - 3 dose primary (2,4,6m) mo booster (FDA approved June 2012) MCV4-CRM (Menveo Novartis) -3 dose primary (2,4,6m) month booster (FDA approved June 2013)

27 Recommended Meningococcal Vaccines by Age Group Age group MenACWY-D (Menactra) MenACWY-CRM (Menveo) HibMenCY-TT (MenHibrix) 2 months 10 years Not routinely recommended in this age group Not routinely recommended in this age group Not routinely recommended in this age group Recommended for persons at increased risk starting at age 9 months Recommended for persons at increased risk Recommended for persons at increased risk up to age 18 months For children with asplenia this vaccine should be postponed until pneumococcal vaccine series is complete Not appropriate if protection for serogroups A or W- 135 is warranted.

28 Recommended Meningococcal Vaccines by Age Group Age group MenACWY-D (Menactra) years Routinely recommended MenACWY-CRM (Menveo) Routinely recommended HibMenCY-TT (MenHibrix) Not approved in this age group

29 Schedule for booster doses in individuals with persistent increased risk for invasive meningococcal disease Age at last MCV dose Duration until next booster dose 2 mos-6y 3 yᵃ > 6y 5 y ᵃIf the last dose was HIBMenCY-TT, the booster dose should be MenACWY-D or MenACWY-CRM

30 Incidence per 100,000 Meningococcal Incidence in Adolescents and Young Adults by Serogroup, Serogroup B Serogroups C & Y Age (years) *NNDSS data with additional serogroup data from ABCs and state health departments. Unknown serogroup (19%) and other serogroups (8%) excluded 30

31

32 Epidemiology of Serogroup B Meningococcal Disease in Adolescents With widespread use of conjugate vaccines in adolescents and young adults, serogroup B now causes nearly half of all meningococcal disease cases in this age group Approximately 50 cases annually among year olds Approximately one third of cases among year olds occur in college students Recent outbreaks on college campuses have been due to serogroup B 32

33 Outbreaks of Meningococcal Disease Meningococcal outbreaks are rare, historically causing ~2-3% of US cases 1 Five serogroup B meningococcal disease clusters/outbreaks on college campuses Princeton: 1400 fold increased risk; 5,800 recommended vaccine UCSB: 200 fold increased risk; 20,000 recommended vaccine Threshold for vaccination for serogroup B outbreaks in institutional settings 2 2 cases in population <5,000 persons 3 cases in population 5,000 persons 1 National Notifiable Diseases Surveillance System

34 Meningococcal Serogroup B Vaccine The polysaccharide capsule of N. meningitidis serogroup B is poorly Immunogenic Antibodies directed against the polysaccharide capsule of N. meningitidis serogroup B react with glycoproteins isolated from human brains The polysaccharide capsule of N. meningitides serogroup B has a similar immunochemical structure to intracellular adhesion molecules (Human immune system may see N. meningitidis serogroup B polysaccharide capsule as self ) 34

35 FHbp: Factor H binding protein subfamily A (variant 2,3) or subfamily B (variant 1) NhbA: Neisserial heparin binding antigen NadA: Neisserial adhesin A Vaccine 30S:B87,2012

36 Serogroup B Meningococcal Vaccines Two MenB vaccines are now licensed in the United States for persons years of age Trumenba (Pfizer) was licensed on October 29, 2014 Bexsero (Novartis) was licensed on January 23, 2015 Both vaccines were licensed under an accelerated pathway MenB vaccines are distinct from MenACWY conjugate vaccines because they are based on immunity to proteins rather than capsular polysaccharides

37 Meningococcal Serogroup B Vaccines Trumenba (Pfizer)-FDA approved Oct different recombinant lapidated factor H binding (FHBP) variants - 3 dose primary series Bexsero (Novartis)-FDA approval pending - 3 recombinant proteins from N.meningitidis serogroup B (neisserial adhesion A, factor H binding protein; and neisserial heparin binding antigen) - Outer membrane vesicles (New Zealand epidemic strain N298/254) - 2 dose primary series 37

38 Solicited Adverse Reactions for MenB Vaccines in Clinical Trials Local Adverse Reactions: Trumenba Bexsero Pain (severe) 5-8% 20-29% Systemic Reactions: Fever ( 38 o C) 2-8% 1-5% Headache (severe) 1% 4-6% Fatigue (severe) 1-4% 4-6% Muscle pain (severe) 1-3% 12-13% Joint pain (severe) 1% 2% Use of Antipyretic medication 17-26% NA From package inserts for Trumenba and Bexsero Trumenba : percentage of participants reporting adverse reactions following dose 1, dose 2, or dose 3 Bexsero : percentage of participants reporting adverse reactions following dose 1 or dose 2 38

39 Safety Summary Majority of local & systemic reactions are mild to moderate in severity and transient Most common AE was pain at injection site Serious AE are rare and similar between vaccine recipients and controls in clinical trials Safety data not currently available in groups at increased risk Theoretical concerns from mouse models about autoimmune disorders; will be monitored through postlicensure safety surveillance Potentially serious adverse reactions may occur following any type of vaccine 39

40 Meningococcal Serogroup B Vaccine Potential Candidates Groups at high-risk for meningococcal disease Healthy individuals? A or B recommendation Meningococcal serogroup B outbreaks Pregnant women to protect infants??? - 40

41 ACIP/AAP Men B Recommendations Recommendations pending Anticipated ACIP Discussions/vote -High risk populations - February Healthy Individual - June Outbreaks (revised) - October

42 Category A vs. B Recommendation Category A routine recommendations are made for all persons in an age- or risk-factor-based group Category B recommendations are made for individual clinical decision making (permissive) Both Category A and B recommendations are covered (financially) under the Affordable Care Act and VFC 42