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Entwicklung der subkutanen Allergen-Immuntherapie (Teil 1): von den Anfängen zu immunologisch orientierten Therapiekonzepten

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Zusammenfassung

Hintergrund

Die Allergen-Immuntherapie durch subkutane Injektionen (SCIT) des relevanten Allergens ist die klassische kausale Behandlungsmethode IgE-vermittelter allergischer Atemwegserkrankungen, und wird bereits seit über 100 Jahren erfolgreich eingesetzt. Das wachsende Verständnis immunologischer Grundlagen erweitert fortlaufend das Wissen über Wirkmechanismen der SCIT. Hinsichtlich verwendeter Therapieschemata und Art der Therapieextrakte finden ständig Weiterentwicklungen statt. Derzeit sind zur SCIT in Deutschland nicht modifizierte Allergenpräparate als wässrige oder physikalisch gekoppelte (Semidepot-)Extrakte sowie chemisch modifizierte Extrakte (Allergoide) als Semidepotextrakte kommerziell verfügbar. Für die Vielfalt an Allergenen sind Daten zur Wirksamkeit aus klinischen Studien in unterschiedlicher Anzahl und Qualität vorhanden.

Methoden

Für die vorliegende Publikation wurde eine selektive Literaturrecherche in Pubmed und Medline durchgeführt, und zusätzlich wurden die aktuellen Publikationen nicht in Literaturdatenbanken verfügbarer deutschsprachiger Zeitschriften analysiert. Diese Literaturrecherche erfasste Original- und Reviewarbeiten in deutscher oder englischer Sprache.

Ergebnisse

Die SCIT ist ein langjährig etabliertes und außerordentlich gut dokumentiertes Therapieverfahren für Inhalations- und Insektengiftallergien mit guter Wirksamkeits- und Sicherheitsdokumentation sowohl bei Erwachsenen, als auch im Kindes- und Jugendalter. Am Markt befindliche Präparate werden kontinuierlich weiterentwickelt und vor allem im Rahmen der Therapieallergeneverordnung klinisch evaluiert. Sie können in kontinuierlich ganzjährig (perennialen), präsaisonalen und kombiniert prä-/kosaisonalen Therapieschemata als Standard-, Cluster-, Rush- und Boostertherapieverfahren angewendet werden. Die SCIT ist vor allem gut etabliert für häufig vorkommende Inhalationsallergene wie Pollen aus der Familie der Süßgräser, Betula sp. (Birke, Erle, Hasel), Dermatophagoides sp. (Arten der Gattung Hausstaubmilbe) und für Insektengifte (Bienen- und Wespengift). Jedoch existieren auch für einige andere Therapieallergene gute Daten: zum Beispiel Kräuterpollen („Ragweed“, Beifuß etc.), Schimmelpilze (u. a. Alternaria, Cladosporium etc.), Vorratsmilben und Tierepithelien (u. a. Katze). Klinische Untersuchungen in weiteren Indikationen wie dem oralen Allergiesyndrom und der atopischen Dermatitis werden durchgeführt.

Schlussfolgerung

SCIT-Präparate sind bei sachgerechter Applikation durch allergologisch erfahrene Ärzte sicher sowie gut verträglich anwendbar und hinsichtlich vielfältiger Indikationen gut dokumentiert.

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Abbreviations

AIT:

Allergen-Immuntherapie

AD:

Atopische Dermatitis

APC:

Antigenpräsentierende Zelle

AR:

Allergische Rhinitis

ARIA:

Allergic rhinitis and its impact on asthma

AU:

Allergy unit

CI:

Konfidenzintervall

OAS:

Orales Allergiesyndrom

ODN:

Oligodesoxynukleotide

DBPC:

Doppelblind placebokontrolliert

DC:

Dendritic cell

EAACI:

European Academy of Allergy and Clinical Immunology

IFN:

Interferon

IL:

Interleukin

LZ:

Langerhans-Zelle

LPS:

Lipopolysaccharide

MCT:

Mikrokristallines Tyrosin

MPL:

Monophosphoryl lipid A

MS:

Medikationsscore

OR:

Odds ratio

PAMP:

Pathogen associated molecular patterns

PEI:

Paul-Ehrlich-Institut

PRR:

Pattern recognition receptors

QoL:

Quality of Life

RQLQ:

Rhinoconjunctitivis Quality-of-Life Questionnaire

RR:

Relatives Risiko

SCORAD:

Scoring Atopic Dermatitis

SCIT:

Subkutane Immuntherapie

SLIT:

Sublinguale Immuntherapie

SMS:

Symptom- und Medikationsscore

SQ-U:

Standard quality unit

SS:

Symptomscore

TAV:

Therapieallergene-Verordnung

TGF:

Transforming growth factor

TLR:

Toll-like receptor

Treg:

Regulatorische T-Zelle

TU:

Transducing unit

VlPs:

Virus-like particles

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Authors and Affiliations

  1. Zentrum für Rhinologie und Allergologie, Wiesbaden, Deutschland

    Ludger Klimek &  Oliver Pfaar

  2. Klinik für Hautkrankheiten, Universitätsklinikum Münster, Münster, Deutschland

    Randolf Brehler

  3. Klinik für Kinder- und Jugendmedizin, Evangelisches Klinikum Bethel (EvKB), Bielefeld, Deutschland

    Eckard Hamelmann

  4. Allergie Centrum Ruhr (ACR), Universitätsklinikum, Ruhr-Universität Bochum, Bochum, Deutschland

    Eckard Hamelmann

  5. Sektion Pädiatrische Pneumologie und Allergologie, Kinder- und Jugendmedizin, Universitätsklinikum Schleswig-Holstein, Lübeck, Deutschland

    Matthias Kopp

  6. Airway Research Center North (ARCN), Mitglied des Deutschen Zentrum für Lungenforschung (DZL), Borstel, Deutschland

    Matthias Kopp

  7. Haut- und Allergieklinik am Biederstein, Technische Universität München, München, Deutschland

    Johannes Ring

  8. Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Leipzig, Leipzig, Deutschland

    Regina Treudler

  9. Leipziger Interdisziplinäres Centrum für Allergologie (LICA), Universitätsklinikum Leipzig, Leipzig, Deutschland

    Regina Treudler

  10. Klinik für Dermatologie und Allergologie, Universitätsklinikum Gießen, UKGM, Justus-Liebig Universität Gießen, Gießen, Deutschland

    Thilo Jakob

  11. Klinik für Dermatologie, Venerologie und Allergologie, Charité — Universitätsmedizin Berlin, Campus Mitte, Berlin, Deutschland

    Margitta Worm

  12. Universitäts-HNO-Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Deutschland

    Oliver Pfaar

  13. Klinik für Hals-, Nasen-und Ohrenheilkunde, Sektion Rhinologie und Allergologie, Universitätsklinikum Gießen und Marburg GmbH, Philipps-Universität Marburg, Marburg, Deutschland

    Oliver Pfaar

  14. Klinik für Hals-, Nasen-und Ohrenheilkunde Sektion Rhinologie und Allergologie, Universitätsklinikum Gießen und Marburg GmbH Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland

    Oliver Pfaar

Authors
  1. Ludger Klimek
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  2. Randolf Brehler
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  3. Eckard Hamelmann
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  4. Matthias Kopp
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  5. Johannes Ring
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  6. Regina Treudler
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  7. Thilo Jakob
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  8. Margitta Worm
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  9. Oliver Pfaar
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Corresponding author

Correspondence to Oliver Pfaar.

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Anmerkung

Die Entwicklung dieser Publikation wurde von Allergopharma, Reinbek, durch einen unabhängigen Medical Writing Grant finanziell unterstützt. Die Ansichten und Meinungen, die in dieser Veröffentlichung beschrieben werden, spiegeln nicht unbedingt die Ansichten des Zuschussgebers wider.

Interessenkonflikt

Ludger Klimek hat Forschungsgelder von folgenden Unternehmen erhalten: ALK-Abelló, Dänemark; Allergopharma, Deutschland; Bionorica, Deutschland; Biomay, Österreich; Boehringer Ingelheim, Deutschland; Circassia, USA; Stallergenes, Frankreich; HAL, Niederlande; Allergy Therapeutics/Bencard, Großbritannien/Deutschland; Hartington, Spanien; Lofarma, Italien sowie von MEDA Schweden; MSD, USA; Novartis, Schweiz; Leti, Spanien; ROXALL, Deutschland; GlaxoSmithKline, Großbritannien; Cytos, Schweiz und Curalogic, Dänemark. Darüber hinaus war er als Referent der oben genannten Pharmaunternehmen tätig. Ferner ist Ludger Klimek Berater für AllergyTherapeutics/Bencard, Großbritannien/Deutschland; HAL, Niederlande; MEDA, Deutschland und Boehringer Ingelheim, Deutschland.

Randolf Brehler hat Forschungsgelder von folgenden Unternehmen in Anspruch genommen: Allergopharma, Bencard, Biotech Tools sowie Genentech, Leti, Novartis und Circassia. Des Weiteren war er als Referent für ALK-Abelló, Allergopharma, Almirall, Astra Zeneca, Bencard, die Gesellschaft zur Förderung der Dermatologischen Forschung und Fortbildung, Gesellschaft für Information und Organisation sowie GlaxoSmithKline, Dr. Pfleger, HAL, Leti, MedUpdate, Merck, Novartis, Oto-Rhino-Laryngologischer Verein, Pierre Fabre, Pohl Boskamp, Stallergenes und Thermo-Fischer tätig. Beratend arbeitete Randolf Brehler für: Allergopharma, Bencard, HAL, Leti, Novartis.

Eckard Hamelmann hat Forschungsgelder vom Bundesministerium für Bildung und Forschung (BMBF), dem Landesforschungsministerium Nordrhein-Westfalen und der Deutschen Forschungsgemeinschaft (DFG) erhalten. Zudem hat er Vorträge gehalten, und war beratend für Allergy Therapeutics/Bencard, Großbritannien/Deutschland; ALK-Abelló, Dänemark; Allergopharma, Deutschland; Boehringer Ingelheim, Deutschland; GlaxoSmithKline, Großbritannien; HAL Allergy, Niederlande; Leti, Spanien; Lofarma, Italien; Novartis, Schweiz und Stallergenes, Frankreich tätig.

Matthias Kopp hat im Zeitraum der vorliegenden Studie Honorare von ALK-Abelló, Allergopharma, Leti und Novartis sowie von Boehringer Ingelheim, Chiesi, GlaxoSmithKline und Infectopharm erhalten.

Johannes Ring war in Beiräten für ALK-Abelló , Allergopharma, Bencard, HAL und Novartis tätig.

Regina Treudler erklärt, im Zeitraum der vorliegenden Studie Honorare von ALK-Abelló und Leti erhalten zu haben. Außerhalb der vorliegenden Arbeit hat sie Honorare von Sanofi Aventis und Novartis erhalten.

Thilo Jakob hat außerhalb der eingereichten Arbeit folgende Zuwendungen erhalten: Forschungsgelder und Honorare von ALK-Abelló, Deutschland; Honorare und nicht finanzielle Unterstützung von Bencard/Allergy Therapeutics, Deutschland; Forschungsgelder, Honorare und nicht finanzielle Unterstützung von Thermo Fisher Scientific, Schweden sowie Honorare von Stallergenes, Deutschland; Forschungsgelder, Honorare und nicht finanzielle Unterstützung von Allergopharma, Deutschland und Forschungsgelder und Honorare von Novartis, Deutschland. Außerdem hat Thilo Jakob Honorare von Springer Nature sowie nicht finanzielle Unterstützung von der Deutschen Gesellschaft für Allergie und klinische Immunologie erhalten.

Margitta Worm gibt Honorare an für Beiratstätigkeiten und Vorträge von Allergopharma GmbH & Co. KG, ALK-Abelló Arzneimittel GmbH, Meda Pharma GmbH & Co. KG, HAL Allergie GmbH, Stallergenes GmbH, Bencard Allergie GmbH und LETI Pharma GmbH — alle außerhalb der vorliegenden Arbeit.

Oliver Pfaar gibt Forschungsgelder sowie Honorare an von ALK-Abelló, Forschungsgelder sowie Honorare von Allergopharma, Forschungsgelder sowie Honorare von Stallergenes Greer, Forschungsgelder sowie Honorare von HAL Allergy Holding B.V./HAL Allergie GmbH, Forschungsgelder sowie Honorare von Bencard Allergie GmbH/Allergy Therapeutics, Forschungsgelder sowie Honorare von Lofarma, Forschungsgelder von Biomay, Forschungsgelder von Nuvo, Forschungsgelder von Circassia, Forschungsgelder sowie Honorare von ASIT Biotech Tools S.A., Forschungsgelder sowie Honorare von Laboratorios LETI/LETI Pharma, Honorare von Novartis Pharma, Honorare von MEDA Pharma, Forschungsgelder sowie Honorare von Anergis S.A., Honorare von Mobile Chamber Experts (a GA2LEN Partner), Honorar von Pohl-Boskamp, Honorar von Indoor Biotechnologies, Forschungsgelder von Glaxo Smith Kline, Honorar von Astellas Pharma Global, alle außerhalb der vorliegenden Arbeit.

Der Verlag erklärt, dass die inhaltliche Qualität des Beitrags von zwei unabhängigen Gutachtern geprüft wurde. Werbung in dieser Zeitschriftenausgabe hat keinen Bezug zur CME-Fortbildung. Der Verlag garantiert, dass die CME-Fragen frei sind von werblichen Aussagen und keinerlei Produktempfehlungen enthalten. Dies gilt insbesondere für Präparate, die zur Therapie des dargestellten Krankheitsbildes geeignet sind.

Zitierweise

Klimek L, Brehler R, Hamelmann E, Kopp M, Ring J, Treudler R, Jakob T, Worm M, Pfaar O. Evolution of subcutaneous allergen immunotherapy (part 1): from first developments to mechanism-driven therapy concepts. Allergo J Int 2019;28:78—95 https://doi.org/10.1007/s40629-019-0092-4

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Klimek, L., Brehler, R., Hamelmann, E. et al. Entwicklung der subkutanen Allergen-Immuntherapie (Teil 1): von den Anfängen zu immunologisch orientierten Therapiekonzepten. Allergo J 28, 26–48 (2019). https://doi.org/10.1007/s15007-019-1819-8

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