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WAO Global Hereditary Angioedema (HAE) Practice Parameter Timothy J. Craig, DO Professor of Medicine and Pediatrics Distinguished Educator Chief, Allergy,

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Presentation on theme: "WAO Global Hereditary Angioedema (HAE) Practice Parameter Timothy J. Craig, DO Professor of Medicine and Pediatrics Distinguished Educator Chief, Allergy,"— Presentation transcript:

1 WAO Global Hereditary Angioedema (HAE) Practice Parameter Timothy J. Craig, DO Professor of Medicine and Pediatrics Distinguished Educator Chief, Allergy, Asthma, and Immunology Program Director Director of Clinical Allergy and Respiratory Research Pennsylvania State University College of Medicine Hershey, Pennsylvania, USA

2 WAO Global Hereditary Angioedema Practice Parameter Chair: Tim Craig, USA General Advisor: Richard F. Lockey, USA  Steering Committee Members:  Konrad Bork, Germany  Tom Bowen, Canada  Henrik Boysen, Belgium  Marco Cicardi, Italy  Henriette Farkas, Hungary  Anete Grumach, Brazil (SLAAI)  Connie Katelaris, Australia (APAAACI)  Hilary Longhurst, UK  William Lumry, USA (ACAAI)  Marcus Maurer, Germany (EAACI)  Bruce Ritchie, Canada  Bruce Zuraw, USA (AAAAI)  Emel Aygören Pürsün, Germany  Inmaculada Martinez-Saguer, Germany

3 Sponsors of the WAO HAE Program CompanyFinancial Supporter CSL BehringXX DyaxXX ViropharmaXX ShireXX (via Jerini) Pharming(did not yet have a product on the market)

4 WAO Global Hereditary Angioedema Practice Parameter OBJECTIVES: 1.Produce an evidence based guideline for care of HAE patients throughout the world 2.Develop a document that would be a reference for HCP 3.To develop a document that could be used at the bedside 4.Have a document that could be utilized in all countries 5.Develop a guideline that would be approved by the global allergy community 6.Develop a power point program for use by all members of the WAO 7.Lastly, and most importantly, to improve care for the patients with Hereditary Angioedema and to improve access of therapies to all patients, in all countries around the world.

5 Is there a need for this?

6 Active Cleaved: Inactive

7 What Is C1-Inhibitor? Key regulator of four biochemical pathways 1. Complement 2. Contact 3. Fibrinolytic 4. Coagulation Human plasma protein …that mediates inflammation C1-Inhibitor deficiency can cause: –debilitating pain –disfiguring swelling –asphyxiation & death

8 Autosomal Dominant Defect Crowder JR, Crowder TR. Five generations of angioneurotic edema. Arch Inter Med 1917; 20:840-52

9 Bissler JJ, et al. Proc Assoc Am Physicians. 1997;109: Davis AE 3rd. Annu Rev Immunol. 1988;6: Verpy E, et al. Am J Hum Genet. 1996;59: Zuraw BL, Herschbach J. J Allergy Clin Immunol. 2000;105: HAE Is Caused By C1 Inhibitor Mutations

10 C1-INH involved in 3 systems → C1-INH depletion Kallikrein HMW-K Factor XII Prekallikrein Contact System C4 C2 C1 Complement System Increased vascular permeability  ANGIOEDEMA C1-INH Bradykinin Fibrinolytic System Factor XIIa Plasmin Plasminogen C1rs C1-INH

11 C1INH gene +/+ +/+ -/- -/- -/- B2BKR gene +/+ +/+ +/+ +/+ -/- Evans blue No Yes Yes Yes Yes C1INH therapy No No No Yes No C1INH Null Mice and Vascular Permeability Adapted from Han ED, et al. J Clin Invest. 2002;109:

12 In Vivo Generation of Kinins in HAE From Nussberger J, et al. J Allergy Clin Immunol. 1999;104: ; with permission.

13 Actin stress fibers VE-cadherin Nonstimulated Stimulated Increased vascular permeability From Tiruppathi C, et al. Vascul Pharmacol. 2003;39: ; with permission. How Does BK Cause Angioedema?

14 Common triggers of HAE attacks Trauma Menstruation Infection Stress Medications Angioedema Angioedem a attack

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19 Conceptually divide into three categories – Long-term prophylaxis Minimize attack frequency and severity Prevent hospitalizations and emergency room visits – Short-term prophylaxis Prevent attacks after trauma Prevent attacks during important life events – Treatment of acute attacks Terminate ongoing attack Prevent morbidity and mortality Treatment of HAE

20 PK Therapeutic Implications Adapted from Zuraw BL. Immunol Allergy Clin North Am. 2006;26:

21 DrugAdvantagesDisadvantagesBest useStatus Plasma- derived C1-INH Extensive clinical experience Corrects the fundamental defect long half-life Infectious risk Needs IV access Limited supply Acute attacks Short-term Long-term prophylaxis Prodromes Berinert P: approved in EU, USA, Canada, Argentina Cinryze: approved in EU, USA Cetor in the EU, Turkey Recombinant C1-INH Corrects the fundamental defect No human virus risk Scalable supply Needs IV access Short half-life Potential for allergic reactions Acute attacks Short prophylaxis Prodrome? Rhucin: approved in the EU Ecallantide More potent than C1-INH No infectious risk Subcutaneous administration Antibodies may cause allergic reaction or neutralization Short half-life Acute attacks in office Kalbitor: approved in the USA IcatibantNo infectious risk Stable at room temperature Subcutaneous Short half-life Local pain or irritation Home treatment of acute attacks? Firazyr: approved in EU, USA, Brazil

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26 In Summary  Global document is now being evidence based  From here it will go to the steering committee for approval  Than it will go to WAO leadership  Finally out to all the Allergy Associations for their approval  Power Point slides will go through the same process

27 Thank you. Questions?


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