Immunization Update 2017

Tamara Sheffield, MD, MPA, MPH

November 10, 2017

• I have no conflicts of interest to disclose

• I will be discussing “off label” use

• I will be discussing an unlicensed vaccine

DISCLOSURE:

LEARNING OBJECTIVES: PHARMACIST

At the conclusion of this activity, pharmacists should be able to successfully:

• Employ the latest ACIP Immunization Recommendations when delivering services to their clients

• Describe common errors in vaccine delivery and implement strategies to avoid these errors

• Locate tools developed to assist Intermountain vaccine providers in administering vaccines in a clinically appropriate manner

Impact of Vaccines

Hepatitis B Hep B infections have decreased by 90.6% in US since vaccination initiated in 1982

• Locally contracted – mainly due to injection drug use

• 95% of new cases are imported

• Current focus on diabetics age 19-59 years (only 25% completion of series) – they are coming to your pharmacies for their meds and insulin

Schille S, Presentation at ACIP Oct 19, 2016

Impact of Vaccines

Community Immunity

Successes

Pneumococcal – PCV7• Vaccinating children protects adults comparing

1997-1999 with 2007-2009Overall 168,000 fewer hospitalizations all ages

• 555/100,000 fewer for children

• 360/100,000 fewer for ages 75-84

• 1300/100,000 fewer for ages 85+

Pneumococcal – PCV13 (approved 2010)• Invasive pneumococcal disease (IPD) rates 33-62%

lower in post vaccination period than in pre-PCV13 child vaccine years (2007-2009) in all age groups

• Rates in seniors have been stable even after introduction of PCV13 in that age group

Griffin MR, NEJM 2013;369:155-63https://idsa.confex.com/idsa/2017/webprogram/Paper64222.html (accessed 10/11/17)

H= Herd

Immunity

Threshold

IMMUNIZATION RATES

DM: Diabetes Mellitus; HR: high risk; y/o: years old

Vaccine Group2013 data

(%)2014 data (%) 2015 data (%) % diff from 2014

PneumococcalHR, age 19-64 21.2 20.2 23 2.8

Age ≥ 65 59.7 61.3 63.6 2.3

Tetanus (any)

Age 19-49 62.9 62.6 62.1 -0.5

Age 50-64 64 64.7 64.1 -0.6

Age ≥ 65 56.4 57.7 56.9 -0.9

Tdap ≥ 19 y/o, total 17.2 20.1 23.1 3.1

≥ 65 y/o 11.9 14 16.5 2.5

Hepatitis B

(3 doses)

19-59 y/o, DM 26.3 23.5 24.4 0.8

19-59 y/o, liver

disease29.8 27.4 -2.4

Herpes Zoster ≥ 60 y/o 24.2 27.9 30.6 2.7

MMWR Surveillance Summaries/ February 5, 2016 /Vol. 65 / No. 16. MMWR/ February 6, 2015 / Vol. 64 / No. 4, 95-102. MMWR Surveillance Summaries/ May 5, 2017 / Vol. 66/ No 11, 1–28.

Slide courtesy of Kathy Povilus, Pharm D, BCACP - modified

Highlighted Topics

• Influenza• Vaccine Errors• 2-Dose HPV• Meningococcal• Future Recs• Zoster

• Yellow fever vaccine access• Intermountain protocols

and resources

INFLUENZA

2016-2017 Season

• A:H3N2 predominant

• Had the typical second wave of Type B

• Vaccine well matched to all 4 strains

2017-2018 Season - Trivalent

• A/Michigan/45/2015 (H1N1) pdm09-like –NEW (used in 2017 Southern hemisphere)

• A/Hong Kong/4801/2014 (H3N2)-like

• B/Brisbane/60/2008-like (B/Victoria lineage)

2017-2018 Season – Quadrivalent

• B/Phuket/3073/2013

(B/Yamagata lineage)

Influenza

2016-2017 Season

Chart presented at June 2017 ACIP Meeting

You have a 75 year old client wishing to receive an influenza vaccine from you. Which vaccine will potentially provide the greatest protection against contracting influenza?

1. Trivalent High-dose

2. Quadrivalent regular dose

You have a 75 year old client wishing to receive an influenza vaccine from you. Which vaccine will potentially provide the greatest protection against contracting influenza?

1. Trivalent High-dose

2. Quadrivalent regular dose

Study of high-dose efficacy & Estimation of IIV4 v. IIV3

IIV3-HD compared to IIV3-SD

Age 65 years and older

Lab confirmed influenza of any subtype

24.2% relative efficacy

NEJM 2014; 371:635-645

Quadrivalent Vaccine

• Adds 1 more B type than IIV3

• Type B (0-40% - most years 20-25% of circulating virus)

• Each year 30/70 split of TypeBs circulating

• Then multiply by vaccine efficacy (40-60%)

You have a 75 year old client wishing to receive an influenza vaccine from you. Which vaccine will potentially provide the greatest protection against contracting influenza?

1. Trivalent high-dose

2. Trivalent adjuvanted

3. Quadrivalent Recombinant

You have a 75 year old client wishing to receive an influenza vaccine from you. Which vaccine will potentially provide the greatest protection against contracting influenza?

1. Trivalent high-dose

2. Trivalent adjuvanted – Don’t know

3. Quadrivalent Recombinant –Interesting new study

Study of Recombinant Influenza Vaccine (RIV4)

RIV4-HD compared to IIV4 (standard dose)

Age 50 years and older

PCR lab-confirmed influenza of any subtype during a mismatch season

RIV4 attack rate = 2.2% IIV attack rate = 3.2%

30% lower probability of influenza like illness with RIV4 than with IIV4

Sanofi has purchased Protein Sciences – maker of RIV (Flublok)

NEJM 2017; 376:2427-36

How about Egg Allergy?

ACIP 2016-2017 Recs• Remove egg allergy chart• 30 minute wait down to 15

minute• All products can be used

including LAIV**• Be able to recognize and treat

severe allergic reactions (all allergy symptoms except hives)

**CDC has recommended against providing LAIV (FluMist®) for the 2017-2018 season

MMWR; August 26, 2016;65(5);1-54

Influenza Vaccines

Available Products

Age Type Trade Name Manufacturer

6 mo + IIV4 Fluzone® Sanofi

6 mo + IIV4 FluLaval® GSK/ID BIo

2-49 years LAIV FluMist®** AstraZeneca

3 years + IIV4 Fluarix® GSK

4 years + ccIIV4 Flucelvax® Seqirus

5 years + IIV3 Afluria® Seqirus

5 years + IIV4 Afluria® Seqirus

18 years + RIV4 FluBlok® Protein Science

18-64 years IIV4 Fluzone®

IntradermalSanofi

65 years + IIV3 Fluzone® High-dose

Sanofi

**CDC has recommended against providing LAIV (FluMist®) for the 2017-2018 season

MMWR; August 26, 2016;65(5);1-54Updated for 2017 - unpublished

FluLaval for Infants

Approved by FDA

FluLaval QuadrivalentTM (IIV4)

New age indication, 6 through 35 months

Different dose than pediatric Fluzone

• FluLaval = 0.5 mL

• Fluzone = 0.25 mL

2017 CPT code determined by dose, not age

• 90686 0.5mL syringe (all ages)

• 90688 0.5mL MVD (all ages)

• 90685 0.25 mL syringe (6-35 mo)

• 90687 0.25 mL MVD (6-35 mo)

FluLaval Package Insert

Afluria QIV

Approved by FDA

as safe and effective

Indicated for age 5+ years (as of 8/31/17)

Studies on going for age 6 months to 5 years

Concerns about fevers and febrile seizures in young children in the TIV formulation (Australia)

Resolved fever concern with change in manufacturing process

• Increased use of TDOC (deoxycholate) splitting agent in both QIV and TIV

• Reduce lipids connected to mRNA fragments

• Lipids = fevers

Afluria TIV also approved by ACIP down to 5 years

• Previously ACIP limited it to ages 9 years + because of fevers

• FDA approval has always been 5 years +Grohskopf presentation, ACIP June 2017

FluMist (LAIV)

Concerns of Efficacy

• Heat stability

• HA activation pH

• Replicability

Grohskopf presentation, ACIP June 2016

Documents to assist vaccine providers

Influenza Immunization Plan

Plan Summary (1pg. 2 side)

• Table of start and stop times

National Vaccine Administration Errors

https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-02/errors-01-shimabukuro.pdf

Vaccine Errors Wrong dose or vaccine for age• Influenza (0.25mL/0.5mL)

• DTaP/Tdap

• Hep A – adult and ped

• Kinrix/ProQuad

Wrong interval between doses

Wrong diluent

Temperature excursions

Keeping up with guidelines: New ACIP recommendations 3X per year

Storage: Multiple products, diluent not with vaccine, labels,

Similar names and colors

Vaccine ErrorsOne dose for Influenza vaccine (0.5mL)

Use single dose syringes rather than multi-dose vials

Scan vaccine bar code prior to administering – iCentra prompts

Refer to USIIS forecast before administering

“Registry Import” button

Keep diluent connected to vaccine

iCentra removed “General” influenza choice when ordering

Strategies to avoid errors

9vHPV 2-Dose

Original 3-dose recommendation

Originally recommended as 3-dose series

Any product (2valent, 4valent, 9valent)

Interval = 0, 2 months, 6 months

For the prevention of cervical, vulvar, vaginal, and anal cancers, precancerous or dysplastic lesions (HPV Types 16, 18, 31, 33, 45, 52, 58) and genital warts (HPV Types 6, 11)

MMWR, August 29, 2014, Vo1 63, #RR05

9vHPV 2-Dose

New ACIP Rec

Evidence

1 trial of 9vHPV (girls and boys 9-14 v. females 16-26 yo)

• >97.9% seroconverted to all 9 serotypes

• Non-inferiority criteria met for seroconversion and GMTs

• GMTs significantly higher for all 9 serotypes in 2-dose 9-14 yo than 3 dose 16-26 yo

6 additional trials of 4vHPV, 2vHPV –immunogenicity non-inferior in 9-14 yo

MMWR 2016;65(49);1405-8.

9vHPV 2-Dose

New Recommendation

A 2-dose series of HPV vaccine will be appropriate if:

• Initiate first dose before age 15 years

• If patient is healthy (not immunocompromised)

• If separation of doses is 6 months (5 months minimum interval)

Series can include doses of 2vHPV, 4vHPV or 9vHPV

HPV recommended for females 9 to 26 years, males 9-21 years, high risk males 22-26

MeningococcalACYW

Menomune MPSV has been discontinued

Give high-risk adults age 56 years and older MenACYWconjugate vaccine

High risk:• Complement component deficient• Anatomic or functional asplenia• Microbiologists exposed• HIV• Outbreaks• Travel

MMWR, March 22, 2013 Vol 62. #RR02 – addresses off-label use

Meningococcal B New 2-Dose

Approved for low risk, BUT----

Still not a general recommendation (Category B)

2 doses for both products• Bexero – (0, 1 month)• Trumenba (0, 6 month)

Category B - Individual shared clinical decision, allows for insurance coverage (ACA)

• Series may be administered to age 16 through 23 years for short-term protection against most strains of serogroup B meningococcal disease

Not Category A because of low incidence of disease, lack of efficacy and safety data

No herd protection----

High risk and outbreak – still need 3 doses of Trumenba (0, 1-2 mo, 6 mo)

Meningococcal B

High Risk, age 10 years and older

Category A recommendation

Those at high-risk may receive 2 doses of

• Bexero – (0, 1 month)

But must still receive 3 doses of

• Trumenba (0, 1-2 months, 6 month)

High risk includes:

• Asplenia (anatomic)

• Asplenia (functional, such as sickle cell)

• Complement component deficiency

• Microbiologists exposed

• Outbreak

MMWR May 19, 2017:66(19);509-513

SHINGLES- HERPES ZOSTER

Background:• Caused by varicella zoster virus (VZV)o Exclusively human pathogen that affects approx. 98% of US adult population

o Reactivation of Chickenpox infection

• Herpes Zoster (“shingles”) is a localized and painful cutaneous eruptiono Vesicular rash across dermatomes of the involved sensory nerve roots

o 1 in 3 persons will develop shingles in their lifetime

• Post Herpetic Neuralgia (PHN) is a common complication of zoster o Can occur up to 6 months after rash and can last months to years

o Impacts quality of life (sleep, work, activity), contributes to social withdrawal and depression

“SHINGRIX” – HERPES ZOSTER SUBUNIT VACCINE (HZ/su)

Investigational herpes zoster subunit vaccine for prevention of herpes zoster and post herpetic neuralgia in adults ≥ 50 years

• Unique ingredient components designed to enhance CD4+ T-cell-mediated immune responses and improve vaccine efficacy:

oAntigen: varicella zoster virus (VZV) glycoprotein E

oAdjuvant system: AS01B adjuvant

• Two dose series, separated by 2 months

• Manufactured by GlaxoSmithKline

Lal H, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. NEJM 2015;372:2087-96 Cunningham AL, et al. Efficacy of the herpes zoster subunit vaccine in adults ≥70 years of age. NEJM 2016;375:1019-1032

Colindros R. Investigational Herpes Zoster Adjuvanted Subunit (HZ/su) Vaccine: Efficacy in People 70 years and Older. Presented at: ACIP 2016. 2016 Oct 19.

ZostavaxEfficacy

Merck

ZOE-50 TrialHZ/su

NEJM May 28 2015

ZOE-70 Trial HZ/su

NEJM Sept 15 2016

13,900 participants, mean age 75.6 years

Efficacy

• Age 70-79 (90.0%)

• Age 80 + (89.1%)

• All (89.8%)

Pooled ZOE-50 and ZOE-70 (91.3% efficacy)

• Postherpetic neuralgia (88.8%)

Zoster CandidateHZ/su

Safety• No difference from placebo in Severe Adverse

Events• Local reaction – pain, redness, swelling – 9.1%

Of those who had a first dose Grade 3 reaction • 91.4 % received 2nd dose (local reaction)

• 89.2% received 2nd dose (systemic reaction)

Efficacy and persistence of protection out to 9 years so far• Cellular and humoral immune responses:

3.4 fold titers sustained from years 4 to 9

Safety and Duration of Protection

Colindres, R Presentation at ACIP Feb 2017

COMPARISONZostavax® Shingrix®

Live vaccine Inactivated vaccine

Indication Recommended for prevention of

shingles in patients ≥ 50 YOAApplied for FDA-approval for prevention

of shingles in patients ≥ 50 YOA

Dosing schedule 1 injection 2 injections, 2-6 months apart

Efficacy for HZ 51.3% 91.3%

Efficacy for PHN 66.5% 91.2%

Duration of HZ efficacy 31.9% after 7 year follow up 87.9% at 4 year follow up

Other notes2 doses may decrease compliance and

increase site reactions

Manufacturer Merck & Co., Inc. GlaxoSmithKline Inc.

Professional Resource, Shingles Vaccine: FAQs. Pharmacist’s Letter/Prescriber’s Letter. Dec 2016. | CDC. Update on Recommendation for Use of Herpes Zoster Vaccine: Recommendations of the ACIP. MMWR 2014; 63(33): 729-731 .Lal H, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. NEJM 2015;372:2087-96 | Cunningham AL, et al. Efficacy of the herpes zoster subunit vaccine in adults ≥70 years of age. NEJM 2016;375:1019-1032

HZ = Herpes zoster; PHN = Post herpetic neuralgia; YOA = Years of age;

Slide courtesy of Kathy Povlius, Pharm D, BCACP

Zoster CandidateHZ/su

Submitted to FDA for approval

ACIP recommendation planned for October 2017

• Age 50 and above

• Good efficacy and safety when given 5 years after Zostavax

• Refrigerate, not frozen

• Not a live vaccine – may recommend giving to immunocompromised

• Preferential recommendation?

Summary

Yellow Fever Vaccine

Access limited during manufacturing plant reconstruction

YF-VAX ® (Sanofi) unavailable until mid-2018

To find sites providing Stamaril® (Sanofi) under IND Protocol:

https://wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics

Utah: Davis County HD, Passport Health-Midvale, SLCounty HD, University of Utah Travel Clinic,Utah County HD, BYU)

Intermountain Healthcare Immunization Resources

Located on the Medical Group’s Clinical Resources Webpage:

Type: IMG in the URL line

Also located in the Primary Care Clinical Program Webpage in the topics on the left sidebar

Not at Intermountain? Go to www.immunize.org or www.cdc.gov/vaccines (hcp page)

Intermountain Healthcare Immunization Resources

Located on the Medical Group’s Clinical Resources Webpage:

Type: IMG in the URL line

Go to Clinical Resources, then Immunizations

• Policies, Procedures

• Vaccine Protocols

• Links to immunization programs/resources

• Tools

Questions?

Tamara Sheffield, MD, MPA, MPH

Medical Director, Community Health and Prevention

Intermountain Healthcare

36 S State Street, 21st Floor

Salt Lake City, UT 84111

(801) 442-3946

Tamara.Sheffield@imail.org