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Biologika bei Kollagenosen und Vaskulitiden

Biologics for connective tissue diseases and vasculitides

  • Schwerpunkt: Biologika in der Inneren Medizin
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Zusammenfassung

Basierend auf neuen Erkenntnissen zur Pathogenese werden seit wenigen Jahren Biologika und „small molecules“ als zielgerichtete Therapeutika bei Kollagenosen und Vaskulitiden untersucht. Belimumab, ein Antagonist des B‑Lymphozyten-stimulierenden Faktors (BLyS), wird seit einigen Jahren zur Behandlung des systemischen Lupus erythematodes (SLE) eingesetzt und wurde kürzlich auch für die Add-on-Therapie der Lupusnephritis zugelassen. Auch Anifrolumab, ein Antikörper gegen den Typ-I-Interferon-Rezeptor, erwies sich in Phase-III-Studien zur Therapie des SLE als wirksam. Der Interleukin(IL)-6-Antagonist Tocilizumab zeigte bei der systemischen Sklerose (SSc) zumindest an der Lunge eine Effektivität und ist in den USA von der US Food and Drug Administration (FDA) zugelassen. In Europa steht uns mit Nintedanib ein Tyrosinkinaseinhibitor für die interstitielle Lungenerkrankung bei Kollagenosen zur Verfügung, insbesondere bei der SSc. Tocilizumab ist zur Therapie der Riesenzellarteriitis zugelassen und reduziert sowohl das Rezidivrisiko als auch den kumulativen Glukokortikoid(GC)-Bedarf. Der B‑Lymphozyten-depletierende Antikörper Rituximab ist zur Induktions- und Erhaltungstherapie der Granulomatose mit Polyangiitis (GPA) und der mikroskopischen Polyangiitis (MPA) zugelassen. Bei Patienten mit eosinophiler GPA führt der IL-5-Antikörper Mepolizumab zu einer verbesserten Krankheitskontrolle und reduziert den GC-Bedarf. Eine Phase-III-Studie zum Einsatz des gegen den Komplement-C5a-Rezeptor gerichteten „small molecule“ Avacopan als Ersatz von hoch dosierten GC in der Induktionstherapie der GPA und MPA erreichte ihre primären Endpunkte. Diverse andere Biologika und antagonistische „small molecules“ befinden sich derzeit bei verschiedenen Kollagenosen und Vaskulitiden in teils fortgeschrittenen Stadien der klinischen Entwicklung.

Abstract

Despite therapy with glucocorticoids (GC) and conventional immunosuppressants, patients with connective tissue diseases and vasculitides often develop functionally relevant and prognostically unfavourable internal organ damage. Based on new pathogenetic insights, biologics and small molecules have recently been studied as targeted therapies for collagen vascular diseases and vasculitides. The B lymphocyte stimulator antagonist belimumab has been used for the treatment of systemic lupus erythematosus (SLE) for several years and has recently also been approved as an add-on therapy for lupus nephritis. Anifrolumab, an antibody against the type‑1 interferon receptor, has also been shown to be effective in phase III trials for the treatment of SLE. The interleukin (IL)-6-antagonist tocilizumab showed efficacy in the treatment of interstitial lung disease (ILD) in systemic sclerosis (SSc) and thus has been approved in the USA, although the phase III trial had a negative primary endpoint. In Europe the tyrosine inhibitor nintedanib is approved for progressive ILD in SSc. Tocilizumab is approved for the treatment of giant cell arteritis and reduces both the risk of recurrence and the cumulative GC requirement. The B‑lymphocyte depleting antibody rituximab is approved for induction and maintenance therapy of granulomatosis with polyangiitis and microscopic polyangiitis (MPA) and is currently also being investigated for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). In patients with EGPA, the IL‑5 antibody mepolizumab leads to improved disease control and reduces GC requirements. A phase III trial of the small molecule antagonist avacopan targeting the complement C5a receptor as a replacement for high-dose GC in induction therapy of GPA and MPA met its primary endpoints. Various other biologics and small molecule antagonists are currently in clinical development for several type of vasculitis and collagen vascular diseases, some of them at advanced stages.

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Authors and Affiliations

  1. Klinik für Innere Medizin, Rheumatologie und Immunologie, medius Kliniken, Akademisches Lehrkrankenhaus, Universität Tübingen, Eugenstr. 3, 73230, Kirchheim u. Teck, Deutschland

    Bernhard Hellmich

  2. Zentrum für Interdisziplinäre Klinische Immunologie, Rheumatologie und Autoimmunerkrankungen (INDIRA), Universitätsklinikum Tübingen, Tübingen, Deutschland

    Joerg C. Henes

  3. Medizinische Klinik II (Onkologie, Hämatologie, Klinische Immunologie und Rheumatologie), Universitätsklinikum Tübingen, Tübingen, Deutschland

    Joerg C. Henes

  4. Vaskulitiszentrum-Süd, Tübingen & Kirchheim-Teck, Deutschland

    Bernhard Hellmich & Joerg C. Henes

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Correspondence to Bernhard Hellmich.

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B. Hellmich: Honorare für Beratung von Boehringer-Ingelheim, GSK, InflaRx, Roche und Vifor, Honorare für Referententätigkeit von AbbVie, BMS, Celgene, Chugai, GSK, MSD, Novartis, Pfizer, UCB, Roche; ehrenamtliche nicht vergütete Koordination von Leitlinien zu Großgefäßvaskulitiden: European Alliance of Associations for Rheumatology (EULAR), Deutsche Gesellschaft für Rheumatologie (DGRh). J.C. Henes Honorare für Beratungs- und Vortragstätigkeiten von Abbvie, Boehringer-Ingelheim, GSK, Roche, MSD, Novartis, Pfizer, SOBI, UCB.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Michael Hallek, Köln

Elisabeth Märker-Hermann, Wiesbaden

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Hellmich, B., Henes, J.C. Biologika bei Kollagenosen und Vaskulitiden. Internist 63, 143–154 (2022). https://doi.org/10.1007/s00108-021-01249-w

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