Hereditary Angioedema II

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Hereditary Angioedema II

Presented by Chuleeporn Kongmeesook, MD.

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Hereditary Angioedema II

  1. 1. HEREDITARYHEREDITARYHEREDITARYHEREDITARYHEREDITARYHEREDITARYHEREDITARYHEREDITARY ANGIOEDEMAANGIOEDEMAANGIOEDEMAANGIOEDEMAANGIOEDEMAANGIOEDEMAANGIOEDEMAANGIOEDEMA CHULEEPORN KONGMEESOOK , M.D.CHULEEPORN KONGMEESOOK , M.D.
  2. 2. OutlineOutline •• TreatmentTreatment PastPast PresentPresent FutureFuture
  3. 3. HAE with normal C1INHHAE with normal C1INH •• No controlled treatment studiesNo controlled treatment studies •• Corticosteroids and antihistaminesCorticosteroids and antihistamines ineffectiveineffective TreatmentTreatment •• May respond to the same drugs as usefulMay respond to the same drugs as useful in patients with HAE due to reducedin patients with HAE due to reduced C1INHC1INH Middleton'sMiddleton's allergy:principlesallergy:principles and practice 8th editionand practice 8th edition
  4. 4. NonhistaminergicNonhistaminergic idiopathicidiopathic angioedemaangioedema •• Little is knownLittle is known TreatmentTreatment Middleton'sMiddleton's allergy:principlesallergy:principles and practice 8th editionand practice 8th edition
  5. 5. Treatment : The pastTreatment : The past Acute attacksAcute attacks •• Until late 2008, no drug approved in USUntil late 2008, no drug approved in US •• Symptomatic control of swellingSymptomatic control of swelling Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  6. 6. Treatment : The pastTreatment : The past Acute attacksAcute attacks •• Abdominal attack : Aggressive IVAbdominal attack : Aggressive IV replacement, control of pain and nauseareplacement, control of pain and nausea withwith parenteralparenteral narcotic and antiemeticnarcotic and antiemetic drugsdrugs •• Airway attack :Airway attack : IntubateIntubate or emergencyor emergency tracheotomytracheotomy •• AngioedemaAngioedema of extremities : Not requireof extremities : Not require treatmenttreatment Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  7. 7. Treatment : The pastTreatment : The past LongLong--term prophylaxisterm prophylaxis •• Goal : Decrease frequency and/orGoal : Decrease frequency and/or severity of swelling attacksseverity of swelling attacks Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  8. 8. Treatment : The pastTreatment : The past LongLong--term prophylaxisterm prophylaxis •• Anabolic androgensAnabolic androgens •• DanazolDanazol andand StanozololStanozolol (synthetic 17(synthetic 17--aa-- alkylated androgens )alkylated androgens ) 2 mg2 mg StanozololStanozolol daily or ADdaily or AD or 200 mgor 200 mg DanazolDanazol daily or ADdaily or AD •• Precise mechanism be elucidatedPrecise mechanism be elucidated Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  9. 9. Treatment : The pastTreatment : The past LongLong--term prophylaxisterm prophylaxis •• AntiAnti--fibrinolyticsfibrinolytics •• EpsilonEpsilon aminocaproicaminocaproic acid (EACA oracid (EACA or AmicarAmicar) and) and TranexamicTranexamic acidacidAmicarAmicar) and) and TranexamicTranexamic acidacid •• Reserved for not tolerate anabolicReserved for not tolerate anabolic androgensandrogens (children and pregnant women)(children and pregnant women) TranexamicTranexamic acid not available in USacid not available in US EACA 1 gm orally 3EACA 1 gm orally 3--4 times per day4 times per day Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  10. 10. Treatment : The pastTreatment : The past ShortShort--term prophylaxisterm prophylaxis •• Prevent attacks before expected trauma:Prevent attacks before expected trauma: surgery or dental proceduressurgery or dental procedures •• StanozololStanozolol 22 mg three times daily ormg three times daily or•• StanozololStanozolol 22 mg three times daily ormg three times daily or danazoldanazol 200200 mg three times daily begunmg three times daily begun 55--77 days before proceduredays before procedure •• 22 units of FFP several hours beforeunits of FFP several hours before procedureprocedure Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  11. 11. Treatment : The presentTreatment : The present •• PlasmaPlasma--derived Cderived C11INH concentratesINH concentrates Pasteurized plasmaPasteurized plasma--derived Cderived C11INHINH concentrateconcentrate NanofilteredNanofiltered and pasteurized plasmaand pasteurized plasma derived Cderived C11INH concentrateINH concentratederived Cderived C11INH concentrateINH concentrate •• PlasmaPlasma kallikreinkallikrein inhibitor:inhibitor: EcallantideEcallantide Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  12. 12. Treatment : The presentTreatment : The present Pasteurized plasmaPasteurized plasma--derived C1INHderived C1INH ConcentrateConcentrate •• BerinertBerinert (CSL Behring)(CSL Behring) •• Licensed in Europe over 20 yearsLicensed in Europe over 20 years •• Phase III study for acute attacksPhase III study for acute attacks•• Phase III study for acute attacksPhase III study for acute attacks (I.M.P.A.C.T.1)(I.M.P.A.C.T.1) Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  13. 13. TimothyTimothy J.CraigJ.Craig et alet al AllergyAllergy ClinClin ImmunolImmunol 2009;124:8012009;124:801--88
  14. 14. TimothyTimothy J.CraigJ.Craig et alet al AllergyAllergy ClinClin ImmunolImmunol 2009;124:8012009;124:801--88
  15. 15. TimothyTimothy J.CraigJ.Craig et alet al AllergyAllergy ClinClin ImmunolImmunol 2009;124:8012009;124:801--88
  16. 16. Treatment : The presentTreatment : The present Pasteurized plasmaPasteurized plasma--derived C1INHderived C1INH ConcentrateConcentrate •• BerinertBerinert received approval from FDA forreceived approval from FDA for use in treatment of acuteuse in treatment of acute angioedemaangioedema attacks in adolescent and adult HAEattacks in adolescent and adult HAEattacks in adolescent and adult HAEattacks in adolescent and adult HAE patientspatients Bruce LBruce L ZurawZuraw et al J Allergyet al J Allergy ClinClin ImmunolImmunol 20132013;;131131::14911491--33 Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 20102010;; 66::11--88
  17. 17. Treatment : The presentTreatment : The present NanofilteredNanofiltered and pasteurizedand pasteurized plasma derived Cplasma derived C11INH concentrateINH concentrate •• CinryzeCinryze ((ViroPharmaViroPharma Incorporated)Incorporated) •• Two separate randomized doubleTwo separate randomized double--blindblind placebo controlled studies ofplacebo controlled studies of CinryzeCinryzeplacebo controlled studies ofplacebo controlled studies of CinryzeCinryze performed in USperformed in US Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 20102010;; 66::11--88
  18. 18. Bruce LBruce L ZurawZuraw et al Net al N EnglEngl J Med 2010;363:513J Med 2010;363:513--2222
  19. 19. Bruce LBruce L ZurawZuraw et al Net al N EnglEngl J Med 2010;363:513J Med 2010;363:513--2222
  20. 20. Treatment : The presentTreatment : The present NanofilteredNanofiltered and pasteurizedand pasteurized plasma derived C1INH concentrateplasma derived C1INH concentrate •• CinryzeCinryze received FDA approval forreceived FDA approval for prophylactic treatment in adolescentprophylactic treatment in adolescent and adult HAE patientsand adult HAE patientsand adult HAE patientsand adult HAE patients •• Application for use ofApplication for use of CinryzeCinryze to treatto treat acute attacks ofacute attacks of angioedemaangioedema is stillis still pendingpending Bruce LBruce L ZurawZuraw et al J Allergyet al J Allergy ClinClin ImmunolImmunol 2013;131:14912013;131:1491--33 Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  21. 21. Treatment : The presentTreatment : The present PlasmaPlasma kallikreinkallikrein inhibitorinhibitor •• EcallantideEcallantide •• Recommended dose to treatRecommended dose to treat angioedemaangioedema attack :attack : 3030 mg,mg, administered as threeadministered as three 11 ml SCml SCadministered as threeadministered as three 11 ml SCml SC •• 22 separate RDBPC phase III studiesseparate RDBPC phase III studies EDEMAEDEMA 33 EDEMAEDEMA 44 Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  22. 22. MarcoMarco CicardiCicardi et alet al NN EnglEngl J Med 2010;363:523J Med 2010;363:523--3131
  23. 23. MarcoMarco CicardiCicardi et alet al NN EnglEngl J Med 2010;363:523J Med 2010;363:523--3131
  24. 24. MarcoMarco CicardiCicardi et alet al NN EnglEngl J MedJ Med 20102010;;363363::523523--3131
  25. 25. Treatment : The presentTreatment : The present PlasmaPlasma kallikreinkallikrein inhibitor :inhibitor : EcallantideEcallantide •• Based on data from both Phase IIIBased on data from both Phase III studies, approval for use ofstudies, approval for use of ecallantideecallantide to treat acute HAE attacks in patientsto treat acute HAE attacks in patients aged >aged >1616 ((granted on Decembergranted on December 2 20092 2009)) •• Black box warning on anaphylacticBlack box warning on anaphylactic potential and requiring that the drug bepotential and requiring that the drug be administered by health care provideradministered by health care provider Bruce LBruce L ZurawZuraw et al J Allergyet al J Allergy ClinClin ImmunolImmunol 2013;131:14912013;131:1491--33 Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  26. 26. Treatment : The futureTreatment : The future •• Recombinant human CRecombinant human C11INHINH •• IcatibantIcatibant •• Other future directionsOther future directions Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  27. 27. Recombinant human CRecombinant human C11INHINH •• RhucinRhucin ((PharmingPharming NV)NV) •• Two separate phase III studiesTwo separate phase III studies Treatment : The futureTreatment : The future Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 20102010;; 66::11--88
  28. 28. Bruce LBruce L ZurawZuraw et alet al J AllergyJ Allergy ClinClin ImmunolImmunol 2010;126:8212010;126:821--77
  29. 29. Bruce LBruce L ZurawZuraw et alet al J AllergyJ Allergy ClinClin ImmunolImmunol 2010;126:8212010;126:821--77
  30. 30. Bruce LBruce L ZurawZuraw et alet al J AllergyJ Allergy ClinClin ImmunolImmunol 2010;126:8212010;126:821--77
  31. 31. IcatibantIcatibant ((FirazyrFirazyr, Shire), Shire) •• Administered subcutaneously as aAdministered subcutaneously as a singlesingle 3030 mg injectionmg injection •• Two RDBPC phase III studyTwo RDBPC phase III study FASTFAST--11 Treatment : The futureTreatment : The future FASTFAST--11 FASTFAST--22 Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  32. 32. M.M. CicardiCicardi et alet al NN EnglEngl J MedJ Med 20102010;;363363::532532--4141
  33. 33. M.M. CicardiCicardi et alet al NN EnglEngl J MedJ Med 20102010;;363363::532532--4141
  34. 34. M.M. CicardiCicardi et alet al NN EnglEngl J Med 2010;363:532J Med 2010;363:532--4141
  35. 35. IcatibantIcatibant •• Approved for use for acute attacks inApproved for use for acute attacks in the European Unionthe European Union •• The FDA disapproved the application forThe FDA disapproved the application for Treatment : The futureTreatment : The future •• The FDA disapproved the application forThe FDA disapproved the application for licensure, and new RDBPC phase III triallicensure, and new RDBPC phase III trial (FAST(FAST33) is ongoing) is ongoing Bruce LBruce L ZurawZuraw et al J Allergyet al J Allergy ClinClin ImmunolImmunol 2013;131:14912013;131:1491--33 Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  36. 36. Other future directionsOther future directions •• Administering CAdministering C11INH concentrate byINH concentrate by subsub--cutaneouscutaneous infusioninfusion •• Inhibition of factor XII activity mightInhibition of factor XII activity might Treatment : The futureTreatment : The future •• Inhibition of factor XII activity mightInhibition of factor XII activity might preventprevent bradykininbradykinin generationgeneration •• Orally availableOrally available bradykininbradykinin receptorreceptor antagonistsantagonists Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  37. 37. Other future directionsOther future directions •• CombinedCombined bradykininbradykinin BB22 and Band B11 receptor antagonismreceptor antagonism •• Gene repair or intracellular traffickingGene repair or intracellular trafficking Treatment : The futureTreatment : The future •• Gene repair or intracellular traffickingGene repair or intracellular trafficking for molecular correction of defects infor molecular correction of defects in HAEHAE Bruce LBruce L ZurawZuraw AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 20102010;; 66::11--88
  38. 38. Larisa V.Larisa V. BuyantsevaBuyantseva et alet al AsainAsain PacPac JJ AllergyAllergy ImmunolImmunol 20122012;; 3030::8989--9898
  39. 39. TreatmentTreatment Middleton'sMiddleton's allergy:principlesallergy:principles and practiceand practice 88th editionth edition
  40. 40. TreatmentTreatment Middleton'sMiddleton's allergy:principlesallergy:principles and practice 8th editionand practice 8th edition
  41. 41. TreatmentTreatment Middleton'sMiddleton's allergy:principlesallergy:principles and practiceand practice 88th editionth edition
  42. 42. Timothy Craig et al WAO JournalTimothy Craig et al WAO Journal 20122012;; 55::182182––199199
  43. 43. Tom Bowen et alTom Bowen et al AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 20102010;; 66::11--88
  44. 44. Tom Bowen et alTom Bowen et al AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  45. 45. Tom Bowen et alTom Bowen et al AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 20102010;; 66::11--88
  46. 46. KonradKonrad BorkBork AllergyAllergy,, AsthmaAsthma && ClinicalClinical ImmunologyImmunology 2010; 6:12010; 6:1--88
  47. 47. THANK YOUTHANK YOUTHANK YOUTHANK YOUTHANK YOUTHANK YOUTHANK YOUTHANK YOU
  48. 48. Middleton'sMiddleton's allergy:principlesallergy:principles and practiceand practice 88th editionth edition
  49. 49. Middleton'sMiddleton's allergy:principlesallergy:principles and practice 8th editionand practice 8th edition

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