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Evidenz der Therapie chronisch-entzündlicher Erkrankungen in Kindheit und Adoleszenz mit Biologika

Evidence of treatment of chronic inflammation in childhood and adolescence with biologics

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Zusammenfassung

Hintergrund

Biologika, meist monoklonale Antikörper oder Fusionsproteine, sollen spezifisch in die Immunpathogenese chronisch-entzündlicher Erkrankungen eingreifen. Um diese Substanzen auch bei Kindern und Jugendlichen mit chronisch-entzündlichen Erkrankungen zu testen, wurden finanzielle Anreize für die Hersteller geschaffen und Klassifikationen sowie Definitionen von Krankheitsaktivität, Besserung, Verschlechterung und Remission etabliert und große internationale Forschungsverbünde gegründet.

Methoden

Selektive Literaturrecherche zur Therapie chronisch-entzündlicher Erkrankungen bei Kindern und Jugendlichen mit Biologika unter Einbeziehung aktueller Leitlinien.

Ergebnisse

Nur 7 von 18 eingesetzten Biologika besitzen eine meist eingeschränkte Zulassung für Kinder. Die Evidenz ihrer Wirksamkeit beruht auf 4 doppelblind randomisierten, placebokontrollierten Studien, 7 Absetzstudien und 7 Beobachtungsstudien. Trotz der im Vergleich zum Einsatz bei Erwachsenen geringen Evidenz werden die Substanzen weltweit breit eingesetzt und haben zu einer Erweiterung und deutlichen Verbesserung der therapeutischen Möglichkeiten geführt, wenn die konventionelle Therapie keine ausreichende Besserung oder inakzeptable Nebenwirkungen mit sich bringt. Schwerwiegende Nebenwirkungen wie Infektionen treten gelegentlich auf (0,01–0,03 Ereignisse pro Patientenjahr). Die Malignomrate wird offenbar nicht erhöht. Allerdings sprechen nur etwa 2/3 auf die Therapie an. Das Ansprechen ist oft nicht von einer vollständigen Normalisierung begleitet. Der Zustand mancher Patienten verschlechtert sich wieder und ein vollständiges Absetzen der Medikamente ist nur selten möglich.

Schlussfolgerung

Da der Einsatz der Biologika zu einem wesentlichen Teil der Therapie geworden ist, aber nur auf einer unzureichenden Evidenz beruht, sind weitere Studien bei Kindern und Jugendlichen mit Erkrankungen wie juveniler idiopathischer Arthritis, M. Crohn, Colitis ulcerosa und genetischen Fiebersyndromen zu fordern. Bei der Vielzahl vorhandener Substanzen können diese Studien gegen Verum durchgeführt werden.

Abstract

Background

Biologics, usually monoclonal antibodies or fusion proteins, are thought to specifically interfere with immunopathogenesis of chronic inflammatory diseases. In order to test these substances also in children and adolescents, financial incentives for manufacturers were created and classification of chronic inflammatory diseases and definition of disease activity, improvement, relapse and remission were established and large international research cooperation projects were founded.

Methods

A selective literature search was carried out for treatment of chronic inflammatory diseases in children and adolescents with biologics including current guidelines.

Results

Only 7 out of 18 prescribed biologics have been approved for children and mostly within narrow limits. The evidence for efficacy is based on four randomized double blind placebo-controlled studies, seven withdrawal studies and seven observational studies. In spite of the limited evidence in comparison to their use in adult patients these substances are broadly used worldwide and have enlarged and substantially improved the therapeutic choices in children when conventional treatment failed or proved to be toxic. Severe adverse events including infections occasionally occur (0.01–0.03 events per patient year) but the rate of malignancies is not obviously increased; however, only two thirds of patients respond to treatment. Improvement is often incomplete, some patients deteriorate and definite termination of drug treatment is possible in only a few patients.

Conclusion

As the prescription of biologics has become an important issue of treatment but is based on insufficient evidence data, further studies are necessary in children and adolescents with diseases, such as juvenile idiopathic arthritis, Crohn’s disease, ulcerative colitis and inherited fever syndromes. As many drugs are available these studies can be conducted against verum.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. H.-I. Huppertz hat im Rahmen von Vorträgen und Beratertätigkeiten Honorare der Firmen Abbott, Chugai, Pfizer, Roche, Swedish Orphan erhalten. Die Firmen Abbott, Chugai, Novartis und Pfizer haben von ihm organisierte Fortbildungen unterstützt. H.W. Lehmann hat im Rahmen von Vorträgen Honorare der Firmen Abbott, Novartis, Pfizer, Roche, Wyeth erhalten. Für die Vorbereitung von wissenschaftlichen Fortbildungsveranstaltungen erhielt er Honorare der Firmen Abbott, Novatis, Pfizer und Wyeth. Ebenso erhielt er von der Firma Wyeth Gelder für ein von ihm initiiertes Forschungsvorhaben. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Prof.-Hess-Kinderklinik, Klinikum Bremen-Mitte, Sankt-Jürgen-Str. 1, 28177, Bremen, Deutschland

    H.-I. Huppertz

  2. Zentrum für Kinderheilkunde, Universität Giessen, Giessen, Deutschland

    H.W. Lehmann

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Huppertz, HI., Lehmann, H. Evidenz der Therapie chronisch-entzündlicher Erkrankungen in Kindheit und Adoleszenz mit Biologika. Z. Rheumatol. 73, 907–916 (2014). https://doi.org/10.1007/s00393-014-1398-8

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