Targeting grossly elevated IgE: a novel therapeutic option in severe patients                                Markus Ollert...
Atopic Eczema / Dermatitis                                         • Inflammatory, chronically                            ...
Atopic Eczema / Dermatitis                                                  • Inflammatory, chronically                   ...
Total IgE levels (U/mL) of                                         >1,000 – 100,000 are                                   ...
House dust mite                                         (Encasing, SIT)                                               Food...
Targeting IgE antibodies –                  A universal therapeutic solution for                allergic atopic disorders ...
IgE and Atopic Dermatitis                                           The pathogenetic role of IgE in atopic                ...
OmalizumabPatient A: IgE = 12,534 kU/L   Klinik und Poliklinik für Dermatologie                Technische   und Allergolog...
Case Report: 15-Year-Old Patient with                Severe AsthmaKerzel et al., Klin Padiatr. 2011;223:356-359           ...
High IgE Asthma Phenotype: Therapy with            Plasmapheresis and Anti-IgE                    Table 1: Relevant labora...
High IgE Asthma Phenotype: Therapy with             Plasmapheresis and Anti-IgE          Figure 1: Dynamics of serum IgE d...
High IgE Asthma Phenotype: Therapy with       Plasmapheresis and Anti-IgE      Figure 2: Dynamics of total IgE and free Ig...
High IgE Asthma Phenotype: Therapy with       Plasmapheresis and Anti-IgE                  Figure 3: Lung function before ...
Targeting IgE antibodies –              Can we apply an IgE-directed treatment              regimen to atopic dermatitis w...
Investigator-initiated pilot study Investigator-initiated open-label clinical pilot trial, approved by ethics committee, ...
Investigator-initiated pilot studyPrimary endpoint: long-term control of free IgE levels (<150 / <1000 kU/L)Secondary endp...
Conventional plasmapheresis            Immune apheresis (Immune adsorption)                                         Ig-bin...
Immunoadsorption with TheraSorb™Tolerated very well by all patients withoutany noteworthy side effects.     Klinik und Pol...
IgE during immunoadsorption                                                              IgE during immunoadsorption      ...
IgE during omalizumab – first 12 weeks                                               Free IgE in the course of study      ...
IgE during omalizumab – first 12 weeksKlinik und Poliklinik für Dermatologie         Technischeund Allergologie           ...
Control of pruritus and visual                                   analogue scale                             (subjective pa...
Klinik und Poliklinik für Dermatologie   Technischeund Allergologie                         Universitätam Biederstein     ...
SCORAD                                         (disease activity)Klinik und Poliklinik für Dermatologie                   ...
SCORAD – first 12-25 weeks of IITKlinik und Poliklinik für Dermatologie                  Technischeund Allergologie       ...
SCORAD – first 12 weeks of IITKlinik und Poliklinik für Dermatologie                    Technischeund Allergologie        ...
SCORAD / IgE / TARC                                         (entire study period)Klinik und Poliklinik für Dermatologie   ...
SCORAD and IgE     SCORAD                                  free IgE in kU/L             fIgE                              ...
SCORAD and IgE     SCORAD                                                                           fIgE         80       ...
TARC Levels        pg/ml                                         TARC (CCL 17)       2800       2600       2400       2200...
Clinical Phenotype       week 1                              week 3     week 13   week 25         week 49Immuneapheresis  ...
Klinik und Poliklinik für Dermatologie   Technischeund Allergologie                         Universitätam Biederstein     ...
Consumption of topical medication (up to week 12) Klinik und Poliklinik für Dermatologie    Technische und Allergologie   ...
Conclusion• Immunoadsorption prior to omalizumab is suitable to    reduce highly elevated serum IgE levels and may    impr...
Future studies• Placebo-controlled,  double-blind crossover  study    Klinik und Poliklinik für Dermatologie              ...
Klinik und Poliklinik für Dermatologie   Technischeund Allergologie                         Universitätam Biederstein     ...
Muchas gracias por su atención                             OLLERT@LRZ.TUM.DEKlinik und Poliklinik für Dermatologie        ...
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Targeting grossly elevated IgE: a novel therapeutic option in severe patients

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Markus Ollert, MD. Conferencia dictada en el XVII Congreso Latinoamericano de Alergia, Asma e Inmunología, Cartagena, 2012

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Targeting grossly elevated IgE: a novel therapeutic option in severe patients

  1. 1. Targeting grossly elevated IgE: a novel therapeutic option in severe patients Markus Ollert, MD Professor of Molecular Dermatology and Immunology Department of Dermatology and Allergy Clinical Research Group of Molecular Dermatology and Immunology/ZAUM Klinikum rechts der Isar, Technische Universität München (TUM) and Helmholtz Center Munich for Environmental Health, Munich, Germany Session „Dermatitis Atopica“, XVII Congreso SLaai, Cartagena, Colombia, 25 October 2012
  2. 2. Atopic Eczema / Dermatitis • Inflammatory, chronically relapsing, non-contagious and pruritic skin disorder • Known since ancient times Robert Willan, Delineations of Cutaneous Diseases. 1817 Bieber T. N Engl J Med 2008; 358:1483-1494Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  3. 3. Atopic Eczema / Dermatitis • Inflammatory, chronically relapsing, non-contagious and pruritic skin disorder 30 Taylor, UK Ninan, UK • Known since ancient times Schultz-L, DK 25 Varonier, CH • Up to 10 % of adults in Aberg, S Eaton, UK 20 industrialized countries are Austin, UK Butland, UK Yura, J affected% 15 Heinrich, J Schäfer, D 10 5 • Especially for severe cases, no 0 satisfactory treatment option is available until today 46 58 64 68 70 71 74 79 81 85 86 89 91 92 93 94 97 99 00 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 20 Bieber T. N Engl J Med 2008; 358:1483-1494 Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  4. 4. Total IgE levels (U/mL) of >1,000 – 100,000 are common in adult patientsKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  5. 5. House dust mite (Encasing, SIT) Food allergens (Elimination: cow´s milk, hen´s egg, wheat, nuts) Inhalant allergens (SIT with pollen extract) S. aureus antigens (SEA, SEB, FN-BP) Malassezia sympodialis (Mala s 1-6) Autoallergy (Hom s 1-4)Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  6. 6. Targeting IgE antibodies – A universal therapeutic solution for allergic atopic disorders with “high IgE phenotypes” such as atopic dermatitis?Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  7. 7. IgE and Atopic Dermatitis The pathogenetic role of IgE in atopic dermatitis: a highly controversial issue Off-label use of anti-IgE antibody omalizumab in atopic dermatitis: very ambivalent results Belloni B et al. JACI 2007; 120: 1223-1225 Bieber T. N Engl J Med 2008; 358: 1483-1494 Heil PM et al. JDDG 2010; 8: 990-998Patient A: IgE = 12,534 kU/L Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  8. 8. OmalizumabPatient A: IgE = 12,534 kU/L Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  9. 9. Case Report: 15-Year-Old Patient with Severe AsthmaKerzel et al., Klin Padiatr. 2011;223:356-359 Table 2: Pharmacotherapy on first presentation in our outpatient clinic Agent Daily dose Fluticasone / salmeterol 500 µg / 50 µg bid per DPI (Diskus®) Formoterol 12 µg per pMDI Prednisolone 50 mg p.o. Omeprazole 20 mg p.o. Montelukast 10 mg p.o. Ipratropiumbromide / fenoterol 20 µg / 50 µg p.r.n per pMDI (was actually used 10 – 12 times a day) Cetirizine 10 mg p.o. NaCl 0.9% 2 ml tid per nebulizer DPI: dry powder inhaler; pMDI: pressurized metered dose inhaler. Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  10. 10. High IgE Asthma Phenotype: Therapy with Plasmapheresis and Anti-IgE Table 1: Relevant laboratory findings before plasmapheresis Actual value Reference range total IgE 4,170 kU/l [< 100 kU/l] specific IgE against 35 kU/l [< 0.35 kU/l] phleum pratense rye pollen 25 kU/l [< 0.35 kU/l] cat 209 kU/l [< 0.35 kU/l] dog 186 kU/l [< 0.35 kU/l] leukocytes 11.4 G/l [4.5 – 10 G/l] eosinophils 22% [1 – 4%]Kerzel et al., Klin Padiatr. 2011;223:356-359 Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  11. 11. High IgE Asthma Phenotype: Therapy with Plasmapheresis and Anti-IgE Figure 1: Dynamics of serum IgE during and after plasma exchange 5000 4000 plasma- plasma- plasma- pheresis pheresis pheresis 3000 IgE kU/l 2.300 kU/l free IgE 2000 1000 0 80 kU/l 0 24 48 200 700 hourKerzel et al., Klin Padiatr. 2011;223:356-359 start omalizumab Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  12. 12. High IgE Asthma Phenotype: Therapy with Plasmapheresis and Anti-IgE Figure 2: Dynamics of total IgE and free IgE during omalizumab therapy 5000 4000 total IgE free IgE 3000 kU/l 2000 400 300 200 100 0 0 100 200 300 day start omalizumab Kerzel et al., Klin Padiatr. 2011;223:356-359Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  13. 13. High IgE Asthma Phenotype: Therapy with Plasmapheresis and Anti-IgE Figure 3: Lung function before and after plasmapheresis 300 SR 250 FEV1 200 % predicted 150 100 100 80 60 omalizumab 40 -50 0 50 100 150 days Kerzel et al., Klin Padiatr. 2011;223:356-359 plasmapheresisKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  14. 14. Targeting IgE antibodies – Can we apply an IgE-directed treatment regimen to atopic dermatitis with “high IgE phenotype”?Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  15. 15. Investigator-initiated pilot study Investigator-initiated open-label clinical pilot trial, approved by ethics committee, government agencies and European Medicines Agency (EMA) (EudraCT #2009- 014582-51) 10 patients with severe therapy refractory atopic dermatitis and grossly elevated total IgE-levels ranging from 3,728 kU/L to 69,972 kU/L Initial immunoadsorption prior to administration of anti-IgE-antibody omalizumab for 6 months and a 6 months follow-upIg-Apheresis Tx with Anti-IgE (Omalizumab) Control period/Follow-up 2-4 days 450 mg s.c. bi-weekly 24 weeks 24 weeks Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  16. 16. Investigator-initiated pilot studyPrimary endpoint: long-term control of free IgE levels (<150 / <1000 kU/L)Secondary endpoints: - severity of AD (rated by SCORAD) - TARC (CCL 17) levels in serum - patient’s personal evaluation on severity and pruritus scale - standardized photographySponsor: Klinikum rechts der Isar/TUMSupport: Miltenyi Biotec (supply and materials for Therasorb Ig-apheresis)Ig-Apheresis Tx with Anti-IgE (Omalizumab) Control period/Follow-up 2-4 days 450 mg s.c. bi-weekly 24 weeks 24 weeks Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  17. 17. Conventional plasmapheresis Immune apheresis (Immune adsorption) Ig-binding specificity/capacity of the TheraSorb system: IgG > IgM > IgE Ig-binding specificity/capacity of other available systems: IgG > IgM >>> IgEKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  18. 18. Immunoadsorption with TheraSorb™Tolerated very well by all patients withoutany noteworthy side effects. Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  19. 19. IgE during immunoadsorption IgE during immunoadsorption 120% 100% Patient 1 Patient 2 80% Patient 3 Patient 4 IgE 60% Patient 5 Patient 6 40% Patient 7 Patient 8 Paitent 9 20% Patient 10 0% beofore IA1 IA1 IA2 IA3 IA4Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  20. 20. IgE during omalizumab – first 12 weeks Free IgE in the course of study 15000 14000 Free IgE levels 13000 continued to drop 12000 during OMZ therapy 11000 Patient 1 reaching free IgE- 10000 Patient 2 levels offree IgE in IU/ml 9000 Patient 3 8000 <150 kU/L in 5/10 Patient 4 7000 and Patient 5 6000 Patient 6 <1,000 kU/L in 9/10 5000 Patient 7 patients during the 4000 3000 Patient 8 entire treatment 2000 Patient 9 period of 24 weeks 1000 Patient 10 0 1 3 5 7 9 11 13 = nach IA week Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  21. 21. IgE during omalizumab – first 12 weeksKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  22. 22. Control of pruritus and visual analogue scale (subjective patient score)Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  23. 23. Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  24. 24. SCORAD (disease activity)Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  25. 25. SCORAD – first 12-25 weeks of IITKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  26. 26. SCORAD – first 12 weeks of IITKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  27. 27. SCORAD / IgE / TARC (entire study period)Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  28. 28. SCORAD and IgE SCORAD free IgE in kU/L fIgE 14000 free IgE in kU/L 12000 10000 8000 6000 Immune apheresis 4000 2000 0 End of OMZ TxKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  29. 29. SCORAD and IgE SCORAD fIgE 80 14000 SCORAD 70 12000 free IgE in kU/L 60 10000 50 8000 40 6000 30 Immune apheresis 4000 20 10 2000 0 0 week 1 week 3 week 13 week 25 week 49Klinik und Poliklinik für Dermatologie Technischeund Allergologie End of OMZ Tx Universitätam Biederstein München
  30. 30. TARC Levels pg/ml TARC (CCL 17) 2800 2600 2400 2200 2000 1800 Immune 1600 apheresis 1400 1200 1000 week 1 week 3 week 13 week 25 week 49Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein End of OMZ Tx München
  31. 31. Clinical Phenotype week 1 week 3 week 13 week 25 week 49Immuneapheresis End of OMZ Tx Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  32. 32. Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  33. 33. Consumption of topical medication (up to week 12) Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  34. 34. Conclusion• Immunoadsorption prior to omalizumab is suitable to reduce highly elevated serum IgE levels and may improve clinical symptoms of atopic dermatitis• Further studies regarding IgE control in atopic dermatitis are justified and needed due to the given limitations of our pilot study• Targeting IgE by apheresis: a promising treatment option in severely diseased patients with „high IgE phenotype“ Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  35. 35. Future studies• Placebo-controlled, double-blind crossover study Klinik und Poliklinik für Dermatologie Technische und Allergologie Universität am Biederstein München
  36. 36. Klinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München
  37. 37. Muchas gracias por su atención OLLERT@LRZ.TUM.DEKlinik und Poliklinik für Dermatologie Technischeund Allergologie Universitätam Biederstein München

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