· Title Created Date: 7/28/2015 8:41:17 AM

Workgroup: Immunotherapy Options for Treatment of Allergic Asthma

Addressing Disparities Program

June 30, 2015

Welcome to PCORI

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Information for Workgroup Participants

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Welcome and Introductions

Romana Hasnain-Wynia, PhD, MSProgram Director, Addressing Disparities

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Today’s webinar is open to the public and is being recorded.• Members of the public are invited to listen to this webinar.

• Topic brief, agenda, and other materials are available on the PCORI site.

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For those on the phone• If you experience any technical difficulties, please alert us via

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Housekeeping

mailto:[email protected]

Introductions: Moderator and Chair

Sandra Y. Lin, MDAssociate ProfessorJohns Hopkins School of MedicineDepartment of Otolaryngology-Head & Neck Surgery

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Welcome

• Please introduce yourself• State your name and affiliation

Introductions: Workgroup Participants

Alkis Togias, MDBranch Chief, Allergy, Asthma and Airway BiologyDivision of Allergy, Immunology, and TransplantationNational Institute of Allergy and Infectious DiseasesNational Institutes of Health

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Lynn MorrisonPresidentWashington Health Advocates

Representing the American Academy of Allergy, Asthma and Immunology

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Jonca Bull, MDAssistant Commissioner for Minority HealthU.S. Food and Drug Administration

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Bridget Smith, PhDResearch Associate Professor, PediatricsNorthwestern University Feinberg School of Medicine

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Tyra Bryant-Stephens, MDDirector and Founder, Community Asthma Prevention ProgramChildren’s Hospital of PhiladelphiaClinical Associate Professor of PediatricsUniversity of Pennsylvania School of Medicine

Representing American Academy of Pediatrics

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Lisa A. Gilmore, MBA, MSWSenior Consultant

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Peter S. Creticos, MDAssociate Professor of MedicineDivision of Allergy and Clinical ImmunologyJohns Hopkins School of MedicineDirector, Creticos Research Group

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Meryl Bloomrosen, MBI, MBASenior Vice PresidentPolicy, Advocacy and ResearchAsthma and Allergy Foundation of America

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Antonio Linares, MDRegional Vice President, Medical DirectorAnthem Blue Cross – Health and Wellness Solutions

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Kim Marie Wittenberg, MAHealth Scientist AdministratorAgency for Healthcare Research and QualityCenter for Evidence and Practice Improvement

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AgendaTime Item

10:00 AM Welcome and Introductions

10:15 AM Introduction to PCORI and Workgroup

10:30 AM Setting the Stage

11:30 AM Workgroup Participants’ Perspectives on Subcutaneous vs. Sublingual Immunotherapy

12:30 PM Lunch

1:00 PM Workgroup Discussion: Components of Comparative Effectiveness Trial(s) for Subcutaneous vs. Sublingual Immunotherapy for Allergic Asthma

2:00 PM Patient, System, and Community Factors for Conducting Trial on Subcutaneous vs. Sublingual Immunotherapy for Allergic Asthma

3:00 PM Break

3:10 PM Discussion and Consensus around Key Research Gaps

3:45 PM Identification and Refinement of Comparative Effectiveness Research Questions

4:45 PM Next Steps and Wrap-Up

5:00 PM Adjourn18

Introduction to PCORI and Workgroup


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• PCORI is an independent non-profit research organization that aims to improve the quality and relevance of evidence to help patients, clinicians, employers and others make health decisions.

• We do this by funding patient-centered comparative effectiveness research.

• Our research addresses questions most important to patientsand we involve patients and a range of stakeholders in everything we do – from topic prioritization to dissemination of our work.

About PCORI

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‘‘(c) PURPOSE—The purpose of the Institute is to assist patients, clinicians, purchasers, and policy-makers in making informed health decisions by advancing the quality and relevance of evidence…”

Patient Protection and Affordable Care Act (PPACA): Subtitle D of Title VI - Sec. 6301. (2010)

PCORI’s Mission Defined

• Be patient-centered: Is the proposed information gap of specific interest to patients, their caregivers, and clinicians?

• Assess current options: What current guidance is available on the topic and is there ongoing research? How does this help determine whether further research is valuable?

• Have potential for new information to improve care and patient-centered outcomes: Would new information generated by research be likely to have an impact in practice?

• Provide information that is durable: Would new information on this topic remain current for several years, or would it be rendered obsolete quickly by subsequent studies?

• Compare among options: Which of two or more options lead to better outcomes for particular groups of patients?

Research Questions Should…

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• Cost effectiveness: PCORI will not answer questions related to cost-effectiveness, costs of treatments or interventions. However PCORI will consider the measurement of factors that may differentially affect patients’ adherence to the alternatives such as out-of-pocket costs.

• Medical billing: PCORI will not address questions aboutindividual insurance coverage or about coverage decisions from third party payers.

• Disease-processes and –causes: PCORI will not consider questions that pertain to risk factors, origin and mechanisms of diseases or questions related to bench science.

• Lacking comparative nature or foundation: PCORI will not consider questions that lack any comparative aspect.

Questions External to PCORI’s Mandate

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PCORI’s Process for Identifying Research Topics and Gaps

Topics/Questions proposed for further

consideration

Topics come from multiple sources

Gapconfirmation

Priority topics/questions

(Multi-stakeholderAdvisory Panels and Workgroups)

(PCORI staff in collaboration with AHRQ and others)

1:1 interactions with stakeholders

Guidelines development,

evidence syntheses

Website, staff, Advisory Panel

suggestions

Board topics

Workgroups, roundtables

• Eliminating non-comparative questions

• Aggregating similar questions

• Assessing research gaps

• Preparing topic briefs

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Addressing Disparities Program Mission Statement

Program’s Mission StatementTo reduce disparities in healthcare outcomes and advance equity

in health and health care

Program’s Guiding PrincipleTo support comparative effectiveness research that will identify

best options for eliminating disparities

PCORI’s Vision, Mission, Strategic Plan

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• Identify high-priority research questions relevant to reducing and eliminating disparities in healthcare outcomes

Identify Research Questions

• Fund comparative effectiveness research with the highest potential to reduce and eliminate healthcare disparities

Fund Research

• Disseminate and facilitate the adoption of promising/best practices to reduce and eliminate healthcare disparities

Disseminate Promising/Best

Practices

Addressing Disparities: Program Goals

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PCORI’s Investment in Asthma

• Our current cohort of asthma projects examine multi-level, multi-component interventions to improve adherence to NAEEP guidelines- Projects test a variety of strategies, many outside clinic - Think: community health workers, improving patient-

provider communication, reducing triggers in the home, projects with community roots

Optimizing PCORI’s Investment in Asthma

Where we are…

…Where we could go from here.

• Opportunity to round out current cohort with new tPFA on narrow, clinical asthma topic that would:– Shed light on important question about treatment options– Leverage future findings from existing asthma portfolio (and

vice versa)

Proposed Topic:Immunotherapy Options for Asthma Treatment

• Priority topic at NIH and AHRQ. Evidence gap identified by AHRQ Comparative Effectiveness Review:Allergen-Specific Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and/or Asthma (March 2013)

• American Academy of Allergy, Asthma and Immunology also identified topic as important gap

• Subcutaneous immunotherapy is used worldwide…• Sublingual immunotherapy used broadly in Europe, Latin

America and Asia, but 3 tablets only recently approved in US!• Meanwhile, increasing number of US docs use sublingual

immunotherapy “off-label”• Increasing interest in sublingual immunotherapy as alternative

and patient-centered approach to subcutaneous– Does not require injections– Can be administered by patients at home

Topic has BIG Potential for Influencing Practice and/or Policy in U.S. – *Important Context*

• Identify and refine clinical comparative effectiveness research question(s) on immunotherapy options (i.e., subcutaneous and sublingual) for the treatment of allergic asthma.

Our Goal for Today

The Plan

• Step 1: Perspectives and insight from around the table» Each workgroup participant will have a few minutes to share

perspective on this research topic

• Step 2: Discuss key considerations for trial» Discuss trial design and implementation: methods, intervention,

population(s) and recruitment, cost and feasibility

» Discuss patient, system, and community factors (e.g., clinical settings, community involvement)

» Achieve consensus on most important evidence gaps

• Step 3: Identify and refine research question(s)» Identify specific populations, setting, outcomes, etc. (PICOTS

framework)

» Consideration of PCORI criteria for research topics32

• Participants in this workgroup will be eligible to apply for funding if PCORI decides to produce a funding announcement.

• The Chair(s) of the workgroup will be eligible to apply for funding should they not participate in any subsequent discussions with PCORI following the workgroup.

• Input received during the workgroup deliberations are broadcast via webinar, and the webinar is then archived and available to other researchers, patients, or stakeholders on the website.

• PCORI does not have subsequent discussions with the participants after this workgroup.

• Participants are expected to address a set of questions we’ve asked – not to tell us about their research.

• There should be no “influence advantage” to being a workgroup member, or any knowledge advantage by participating in the workgroup.

How PCORI Manages the Potential for Conflict of Interest

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Immunotherapy for the Treatment of Allergic Asthma: Setting the Stage

Sandra Y. Lin, MD

Johns Hopkins School of MedicineDepartment of Otolaryngology – Head and Neck Surgery

• Allergic rhinitis is an inflammatory, IgE-mediated, disease characterized by nasal congestion, rhinorrhea (nasal drainage), sneezing, and/or nasal itching.

• Asthma is a chronic lung disease that inflames/narrows the airways. Symptoms can include wheezing, chest tightness, shortness of breath, and coughing.

• Allergic asthma is asthma that can have an allergic trigger.

Definitions

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• 9% of Americans suffer from asthma, 230 million worldwide• Asthma is the leading chronic disease in children and reason for

missed school days• Cause for 2 million ER visits annually• 62% of asthmatics show evidence of allergy (1 or more positive

allergy tests)

Healthcare Burden: Allergic Asthma

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ImmunotherapyOnly true hope of “cure”

Disease Modulation

Avoidance Pharmacotherapy

Treatment Options for AR and Allergic Asthma

KAS 11: Immunotherapy

• Diagnosis is confirmed with specific IgE testing (skin testing or blood testing).

• Inadequate response to environmental controls/pharmacotherapy

• Patient preference• Adherence to therapy• Medication requirements/adverse effects• Allergic asthma• Prevention of asthma/new sensitivities

AAO-HNS Allergy Rhinitis CPG: Candidates for Immunotherapy

Otolaryngology -- Head and Neck Surgery February 2015 152: S1-S43, doi:10.1177/0194599814561600

• Allergen specific immunotherapy (IT)– recognized as effective since early 1900’s– subcutaneous route most common in U.S.– immune system “modulation” to develop “tolerance” to

environmental allergens

Allergen Immunotherapy

KAS 11: Immunotherapy

Subcutaneous Immunotherapy-injections

Immunotherapy in the US

Sublingual Immunotherapy-Aqueous-Tablet

-Ragweed-Timothy-Grass Mix

• Dosed in physicians office– Once/week first year

• Typical duration: 3-5 years of treatment• Continued benefit after discontinuation of therapy• How effective is SCIT?

Subcutaneous Immunotherapy (SCIT)

Allergen-Specific Immunotherapy for theTreatment of Allergic Rhinoconjunctivitisand/or Asthma: ComparativeEffectiveness Review

Lin SY, Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Ward D, Chelladuria Y, Segal JB.

AHRQ Grant HHSA 290 2007 10061AHRQ Publication No. 13-EHC061-EF. Rockville, MD: Agency forHealthcare Research and Quality. March 2013.http://effectivehealthcare.ahrq.gov/ehc/products/270/1427/allergy-asthma-immunotherapy-130802.pdf

This report was based on research conducted by the Johns Hopkins University Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10061-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

Disclaimer:

437/28/2015

• Objective: Systematically review the effectiveness and safety of SCIT for allergic rhinitis and asthma

• Methods: RCTs comparing SCIT to placebo, medication, or other SCIT– English language– Adults and Children– Similar formulation must be available in the U.S.– Must contain direct clinical outcomes

Systematic Review: SCIT Effectiveness

44

Literature SearchM

edlin

e, E

mba

se, L

ilacs

, Co

chra

ne Search from database inception to Dec 2012

abst

ract

s 7,746

Full

artic

le 1804

Fina

l inc

lude

d 74 RCTs

4,350participants

45

Grading the Evidence

Category DefinitionsConsistency Overall consistency of the direction of

change

Directness Does this measure a direct clinical outcome (symptoms, medication use)?

Magnitude of Effect Percent difference pre/post to comparator:-weak <15%-moderate 15-40%-strong >40%

Risk of Bias -Random Allocation-Allocation Concealment-Inadequate Blinding-Incomplete Data Reporting-Sponsor Participation in Study Design*from GRADE Working Group

Guide for CER

Grading the EvidenceEvidence Grade Definition Criteria

High High confidence that evidence reflects true effect; further research unlikely to change confidence

-At least 2 low ROB, one with strong MOE-Overall evidence consistent

Moderate Moderate confidence that evidence reflects true effect; further research may change estimate

-1 low ROB with Strong MOE, or-2 or more medium ROB with strong MOE, or-1 low ROB with mod MOE plus 1 medium ROB plus strong MOE

Low Low confidence that evidence reflects true effect; further research likely to change estimate

-Does not meet the above

Insufficient Evidence unavailable

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• Age Range: 3-72 years• Children only studies: • Risk of Bias Moderate (52%)• Comparator groups

– Placebo 73%– Meds 9%

Results

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SCIT Results

Outcome No. Studies No. Participants Strength of Evidence

Asthma symptoms 16 1,178 High

Asthma symptoms(children only)

6 550 Moderate

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• Strong to moderate evidence supports the effectiveness of SCIT for AR and allergic asthma

SCIT SR Conclusion

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• Safety data reported in 45/74 studies• No consistent reporting system for adverse events—

cannot pool• Local reactions: 5-58% patients/0.6-54% injections

– mild

• Systemic reactions: in 15% of injections– Most commonly respiratory– Most mild

• Anaphylaxis: 13 reactions• Deaths: none

SR: SCIT Safety

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• Dosed at home• Aqueous “Drops” FDA off label• Tablets: FDA Approval April 2014

Sublingual Immunotherapy in the United States

Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma: A Systematic Review

Lin SY, Erekosima N, Kim JM, Ramanathan M, Suarez-Cuervo C, Chelladurai Y, Ward D, Segal JB.JAMA.2013;309(12):1278-88.

AHRQ Grant HHSA 290 2007 10061

• Objective: Systematically review the effectiveness and safety of aqueous SLIT for allergic rhinitis and asthma

• Methods: RCTs comparing SLIT to placebo, medication, or other SLIT– English language– Adult and Children– Similar formulation must be available in the U.S.– Must contain direct clinical outcomes

SLIT Aqueous SR Results

54

Literature SearchM

edlin

e, E

mba

se, L

ilacs

, Co

chra

ne Search from database inception to Dec 2012

abst

ract

s 8,156

Full

artic

le 1827

Fina

l inc

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d 63 RCTs

5131 participants

55

• Age range 4-74• Children only 20 studies (n=1814)• Risk of Bias Moderate (68%)• Comparator groups

– Placebo 73%– Other SLIT 14%– Meds 13%

SLIT Results

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SLIT Results

Outcome No. Studies No. Participants Strength of Evidence

Asthma Symptoms

13 625 High

Asthma Symptoms*

9 471 High

*Kim JM, Lin SY, Suarez-Cuervo C, Chelladurai Y, Ramanathan M, Segal JB, Erekosima N. Allergen-specific immunotherapy for pediatric asthma and rhinoconjunctivitis: a systematic review.Pediatrics. 2013 Jun;131(6):1155-67

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• “The overall evidence provides a moderate grade level of evidence to support effectiveness of SLIT for AR and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review.”

Systematic Review Conclusions

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• 45 (75%) reported safety data• Lack of standardized reporting • Local reactions:

– SLIT 0.2-97% – Comparator 3-38.5%

• Systemic reactions rare• No anaphylaxis or deaths

Lin SY, Erekosima N, Kim JM, Ramanathan M, Suarez-Cuervo C, Chelladurai Y, Ward D, Segal JB.JAMA.2013;309(12):1278-88.

SR: Safety Aqueous SLIT

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SLIT Tablet Efficacy: United States Studies

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SLIT Tablets: US Ragweed RCTs

Study N Age DoseAmb 1-U

Duration OutcomeAsthma

Creticos P2013

784 Adults 12 1 year 27%Asthma SxScore, Entire Season(p=.022)

Nolte HS2013

565 Adults 12 1 year Not reported

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SLIT Tablets: US Timothy RCTs

Study N Age DoseMicrogramsPhl p 5

Duration Outcome:Asthma

Blaiss M2011

345 Children5-17

15 Pre/co-seasonal

23 weeks

No significant improvementwell controlled and allowed asthma meds

Nelson HS 2011

439 Adults 15 Pre/co-seasonal

23 weeks

24%TASS(p=.004)

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SLIT Tablets: US Grass Mix RCTsStudy N Age Dose Duration Outcome:

Asthma

Wahn U2009

278 Children5-17

300IR Pre/co-seasonal Not reported

Didier A2011

633 Adults 300IR 4 mo pre/co-seasonal

Not reported

Cox LS2012


Not reported

Didier A2007


Not reported

Effectiveness of Subcutaneous Versus SublingualImmunotherapy for the Treatment of AllergicRhinoconjunctivitis and Asthma: A Systematic Review

Yohalakshmi Chelladurai, MBBS, MPH, Catalina Suarez-Cuervo, MD, Nkiruka Erekosima, MD, MPH,Julia M. Kim, MD, MPH, Murugappan Ramanathan, MD, Jodi B. Segal, MD, MPH, and Sandra Y. Lin, MDJ Allergy Clin Immunol Pract. 2013 Jul-Aug;1(4):361-9.

Which is more effective: SLIT vs SCIT?

• Systematic review of studies with head to head comparison of SCIT and SLIT

• English language RCTs• Results:

– 8 studies– 4 studies: allergic asthma outcomes– 6 studies: allergic rhinitis outcomes

SCIT vs SLIT SR

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SLIT vs SCIT Results

Outcome No. Studies

No. Participants

Strength of Evidence

Asthma 4 171 Low favoring subcutaneous

Rhinoconjunctivitis 6 412 Moderate favoring subcutaneous

Medication Use 5 219 Low minimal difference

CombinedMed Sx

2 65 Low favoring subcutaneous

QOL 1 48 Insufficient

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• Heterogeneous symptom scoring– Sx-med scores primary outcome

• Lack of standardization for adverse event reporting– WHO standards

• Lack of consistent statistical reporting• Dosing units varied—how to translate?• Comparison of US and European allergens

Studies– Challenges for Systematic Review

67

What are the knowledge gaps and challenges in SLIT facing US practitioners?

68

• Need for U.S. studies

Effectiveness of SLIT tablets for allergic asthma?

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• Majority of SLIT efficacy studies done in Europe– JAMA 7/63 studies N. America– Units not standardized around world

• Lack of Ag standardization: US vs. Europe– Definitions & units vary– Translation to US dosing difficult

• Lack of large scale US studies

What dose should we give in the US for Aqueous SLIT?

Calderon MA, Simons FER, Malling HJ et al. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67:302-311.

• JAMA 2013:– Dust mite – Conversion to micrograms/month– Highest dose 50x greater than lowest effective dose

What dose should we give in the US for Aqueous SLIT?

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• Aqueous SLIT (Marogna 2010)– DM 3, 4, 5 year– All lasting effects after d/c, up to 8 years– 4 years recommended as equivalent to 5

• Timothy SLIT Tab (Durham 2012)– 3 yrs– 2 yr f/u continued effect

• Pre/coseasonal vs Year Round – Need further follow up on pre/coseasonal

How long to treat?

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• Europe-Single• US-Multiple• Most studies monotherapy• Yet unanswered question as

inconsistent results

To treat with single or multi-allergen SLIT?

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• Elderly• Pregnant women• Minorities• Inner-city and rural residents• Patients with severe asthma

Is safety/effectiveness of immunotherapy different in distinct subpopulations?

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• SLIT aqueous– No CPT dosing– Limited publications on U.S. dosing

• SLIT tablets– Limited number of allergens available

Other Concerns

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KAS 11: ImmunotherapySCIT SLITEffectiveness for allergic rhinitis Supported by systematic reviews of

randomized, controlled trialsSupported by systematic reviews of randomized, controlled trials

SafetyDeaths: 1 per 2.5 million injections

No reported deaths

Rate of systemic reactions0.06%-0.9% 0.056%

DosingAdministered in physician’s office Administered at home

SLIT aqueous dosing not standardized

First dose of SLIT tablet should be administered in physician’s office, epiautoinjector

FDA status FDA approvedSLIT aqueous FDA “off-label” use

SLIT tablets approved by FDA in April 2014; limited number of allergens available for treatment

Socioeconomic CPT code exists for SCIT vial preparation and injections

Covered by most insurance plans

No CPT code exists for SLIT aqueous preparation. SLIT aqueous not covered by most insurance plans.

SLIT tablet insurance coverage to be determined by individual insurance carriers.

• Moderate to high grade evidence supports use of both SCIT and SLIT for allergic rhinitis and asthma.

• Low grade evidence supports SCIT more effective for allergic asthma

• Clinical choice of therapy dependant on patient-physician decision making

Conclusions

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Questions

Immunotherapy for the Treatment of Allergic Asthma:NIAID Research Programs

Alkis Togias, MDBranch ChiefAllergy, Asthma, and Airway BiologyDivision of Allergy, Immunology and TransplantationNational Institute of Allergy and Infectious DiseasesNational Institutes of Health

• Long-term effects after therapy is discontinued

• Potential for asthma prevention

• Conduit to understand immune tolerance– Fundamental immune alterations of “allergy”

– Insights into other immune-mediated diseases (autoimmunity)

Allergen Immunotherapy: Reasons for NIAID’s Interest

• Efficacy well-demonstrated

However,• Magnitude and duration of the clinical effect require

improvement

• Risks must be reduced

• Duration of treatment must be reduced

• Mechanism of action must be elucidated

Allergen Immunotherapy for Allergic Rhinitis and Asthma: Needs (A)

Goals and New Directions in Allergen Immunotherapy

Sublingual Epicutaneous

• Increase immunogenicity • Decrease allergenicity• Promote particular types of immune responses

Alternative routes ofadministration

OralIntranodal Immunodominant

peptides

Alternative forms ofallergen

Allergen modification

Allergen “plus”

ImmunomodulatorsAdjuvantsChemical Molecular

• Questions raised by the AHRQ review

– SCIT vs SLIT

– Mono vs multi-allergen therapy

– Effects on disease progression (rhinitis to asthma)

– Optimization of the dosing and duration of currently available forms of therapy

Allergen Immunotherapy for Allergic Rhinitis and Asthma: Needs (B)

• Biomarker development

• Development of immunotherapy for allergens important to populations with increased morbidity

Allergen Immunotherapy for Allergic Rhinitis and Asthma: Needs (C)

• Cockroach allergen immunotherapy program (Inner City Asthma Consortium)

• Development of new forms of allergen immunotherapy and investigations of the mechanisms of immune tolerance by allergen immunotherapy (Immune Tolerance Network)

• Individual grant support

NIAID Programs on Allergen Immunotherapy for Allergic Rhinitis and Asthma

The Importance of Cockroach Allergy in Inner-City Asthma

Asthma phenotyping

ICAC II2009-2014

ICAC I2002-2008anti-IgE trial

Stronger benefits in cockroach allergic

and exposed

ICAS1996-2001Environmental

Intervention Study

Stronger benefits in cockroach allergic and

exposed

NCICAS1991-1995

Observational Study

Cockroach allergy: Major risk factor for asthma morbidity

Probability of“D

ifficult-to-control”

Allergen levels in house dust (µg/g)

The Importance of Cockroach Allergy in Inner-City Asthma

• Development of a successful german cockroach immunotherapy regimen for the treatment (and prevention) of asthma and rhinitis in inner city populations

– Stepwise approach

• Step 1: extract evaluation

• Step 2: SLIT safety

• Step 3: SLIT and SCIT immunologic activity (3 studies)

Cockroach Allergen Immunotherapy Program

Cockroach Allergen Immunotherapy Program

Wood et al J Allergy Clin Immunol 2014;133:846

N=54 N=99 N=10

• Step 4: Efficacy evaluation of cockroach SCIT – Study 1: Development of a nasal cockroach challenge model

(10 adults followed by 25 children)

– Study 2: Utilization of the nasal cockroach challenge as the primary outcome in a Phase IIa trial (children)

• 2 maintenance doses vs placebo

• 1 year duration

• Include secondary clinical outcomes of asthma and rhinitis

• Assess confounders (allergen exposure)

Cockroach Allergen Immunotherapy Program (ICAC 2015-2021)

• Development of a successful mouse immunotherapy regimen for the treatment (and prevention) of asthma and rhinitis in inner city populations

– Study 1: SCIT safety and immunologic activity

Mouse Allergen Immunotherapy

• The ITN is focused on the development of therapeutic approaches for asthma and allergy, autoimmune diseases, type 1 diabetes and solid organ transplantation that lead to immune tolerance

Immune Tolerance Network (ITN)

• Pioneering the concept of “allergen plus” where allergen immunotherapy is delivered in combination with immunomodulators– Anti-cytokine agents– T-cell depletion– Immune deviation– T-reg induction

• Modified allergens

• Alternative routes of allergen administration

Allergen Immunotherapy for Allergic Rhinitis and Asthma: ITN

Allergen Immunotherapy for Allergic Rhinitis and Asthma: ITN

Gauging the Response in Allergic rhinitis to Sublingual and Subcutaneous immunotherapy

GRASS Design

Year 1 assessment

Random allocation

Year 2 assessment

Year 3 assessment

Subcutaneous immunotherapy Sublingual immunotherapy Placebo (double dummy)

Oct 2011-Feb 2012 Start Rx

Jan 2013

Dec 2013 End Rx

Jan 2015 Tolerance?

Baseline assessment

Mar-Sept 2011

Recruit/ screen

GRASS Design

Year 1 assessment

Random allocation

Year 2 assessment

Year 3 assessment



Jan 2013

Dec 2013 End Rx

Jan 2015 Tolerance?

Baseline assessment

Mar-Sept 2011

Recruit/ screen

GRASS Design

Year 1 assessment

Random allocation

Year 2 assessment

Year 3 assessment



Jan 2013

Dec 2013 End Rx

Jan 2015 Tolerance?

Baseline assessment

Mar-Sept 2011

Recruit/ screen

106 randomized, 92 completed the study

GRASS Design

2 sprays100mcL each nostril

10-10,000 BU/ml Phleum Pratense

Nasal challenge device

GRASS Design

Sneezing 0-3

Nose running 0-3

Blockage 0-3

Itch 0-3

TOTAL 0-12

Modified from Bousquet et al 1987and Lent et al 2006

Symptom score (TNSS)Peak nasal inspiratory

flow

2 sprays100mcL each nostril

10-10,000 BU/ml Phleum Pratense

Nasal challenge device

GRASS Results - Symptoms

OnTreatment

OnTreatment

OffTreatment

GRASS Results - Symptoms

SLIT-Placebo

SCIT-Placebo

SCIT-SLIT

Year 1 14.7 34.0% 29.2%

Year 2 27.0% 41.6% 25.1%

Year 3 (off treatment) 5.6% 17.8% 14.9%

Treatment Percent Differences by Assessment Year

Shaded areas: p<0.05 comparing mean diameters adjusting for baseline year

(ANCOVA)

GRASS Results – Nasal Airflow

On Treatment On Treatment Off Treatment







SLIT versus SCIT

Efficacy ++ Safety +

Efficacy +Safety ++

SCIT SLIT

Workgroup Participants’ Perspectives on Subcutaneous vs. Sublingual Immunotherapy for Allergic Asthma

Workgroup Participants’ Perspectives

Antonio Linares, MDRegional Vice President, Medical DirectorAnthem Blue Cross – Health and Wellness Solutions

108


Meryl Bloomrosen, MBI, MBASenior Vice PresidentPolicy, Advocacy and ResearchAsthma and Allergy Foundation of America

109


Peter S. Creticos, MDAssociate Professor of MedicineDivision of Allergy and Clinical ImmunologyJohns Hopkins School of MedicineDirector, Creticos Research Group

110


Lisa A. Gilmore, MBA, MSWSenior Consultant

111


Tyra Bryant-Stephens, MDDirector and Founder, Community Asthma Prevention ProgramChildren’s Hospital of PhiladelphiaClinical Associate Professor of PediatricsUniversity of Pennsylvania School of Medicine

Representing American Academy of Pediatrics

112


Bridget Smith, PhDResearch Associate Professor, PediatricsNorthwestern University Feinberg School of Medicine

113


Jonca Bull, MDAssistant Commissioner for Minority HealthU.S. Food and Drug Administration

114


Lynn MorrisonPresidentWashington Health Advocates

Representing the American Academy of Allergy, Asthma and Immunology

115


Alkis Togias, MDBranch Chief, Allergy, Asthma and Airway BiologyDivision of Allergy, Immunology, and TransplantationNational Institute of Allergy and Infectious DiseasesNational Institutes of Health

116


Kim Marie Wittenberg, MAHealth Scientist AdministratorAgency for Healthcare Research and QualityCenter for Evidence and Practice Improvement

117

Lunch

• Visit us at www.pcori.org• Submit comments via Chat

http://www.pcori.org/

Workgroup Discussion: Components of Comparative Effectiveness Trial(s) for Subcutaneous vs. Sublingual Immunotherapy for Allergic Asthma

• Study design• Active intervention and comparator(s)

– Allergen• Restricted to FDA approved extract tablets?• Other considerations: season variability, geography, populations

sensitized

– Dosing

• Population(s) and recruitment• Cost and feasibility of trials

Discussion: Components of Comparative Effectiveness Trial(s) for Subcutaneous vs. Sublingual Immunotherapy for Allergic Asthma

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Patient, System, and Community Factors for Conducting Trial on Subcutaneous vs. Sublingual Immunotherapy for Allergic Asthma

• Patient factors (e.g., engagement, education)• Optimizing access (e.g., rural vs. urban)• Clinical settings (e.g., PCP vs. specialty setting)• Availability of information for PCPs and specialists• Community involvement

Patient, System, and Community Factors for Conducting Trial on Subcutaneous vs. Sublingual Immunotherapy for Allergic Asthma

Discussion and Consensus around Key Research Gaps

Identification and Refinement of Comparative Effectiveness Research Questions

• Population• Intervention• Comparator• Outcomes• Time of observation• Setting

How to describe a research question: PICOTS

PCORI Research Topic Criteria

• Patient-Centeredness: is the comparison relevant to patients, their caregivers, clinicians or other key stakeholders and are the outcomes relevant to patients?

• Impact of the Condition on the Health of Individuals and Populations: Is the condition or disease associated with a significant burden in the US population, in terms of disease prevalence, costs to society, loss of productivity or individual suffering?

• Assessment of Current Options: Does the topic reflect an important evidence gap related to current options that is not being addressed by ongoing research.

• Likelihood of Implementation in Practice: Would new information generated by research be likely to have an impact in practice? (E.g. do one or more major stakeholder groups endorse the question?)

• Durability of Information: Would new information on this topic remain current for several years, or would it be rendered obsolete quickly by new technologies or subsequent studies?

Prioritized questions and deliberations from workgroup will be shared with PCORI leadership.

Determination regarding funding announcements on specified topics made by PCORI Board of Governors by August 2015.

What happens next?

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· Title Created Date: 7/28/2015 8:41:17 AM