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Prävalenz und Therapie von rheumatologischen Nebenwirkungen bei Immun-Checkpoint-Inhibitor-Therapie

Prevalence and treatment of rheumatological adverse events due to immune checkpoint inhibitor therapy

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Zusammenfassung

Hintergrund

Immun-Checkpoint-Inhibitoren (ICIs) haben die Behandlungsmöglichkeiten von verschiedenen malignen Erkrankungen wesentlich verändert, indem sie Einfluss auf das Immunsystem nehmen und Tumorzellen sich nicht mehr der Immunüberwachung entziehen können. Neben diesem erwünschten Effekt können immunvermittelte Nebenwirkungen (irAE) in fast jedem Organsystem und damit auch rheumatologische-irAE (rh-irAE) auftreten.

Fragestellung

Rh-irAE sind bisher in verschiedenen Veröffentlichungen beschrieben und anhand dieses Reviews erstmals untersucht worden. Ziel ist es, einen Überblick über die Prävalenzen, Schweregerade, Therapiemöglichkeiten und das Tumoransprechen bei Patienten mit rh-irAE zu geben.

Material und Methoden

Wir führten bis Januar 2020 eine Literaturrecherche nach dem PICO-Modell in PubMed durch, in der Studien und Fallberichte zu rh-irAE unter ICI-Therapie beschrieben wurden.

Ergebnisse

Es wurden 18 Originalarbeiten eingeschlossen, größtenteils klinische Studien (n = 13) und wichtige Fallberichte (n = 5). Rh-irAE treten in verschiedenen Erscheinungsformen auf, wobei es am häufigsten zu Arthralgien, Arthritiden und Myositiden kommt. Vaskulitiden, Sarkoidose oder Kollagenosen werden seltener beschrieben. Die publizierte Prävalenz von rh-irAE variiert, es werden Prävalenzen zwischen 2,3 und 6,6 % angegeben Die Therapie richtet sich primär nach dem Schweregrad der Nebenwirkung und beinhaltet in den meisten Fällen nichtsteroidale Antirheumatika und Kortikosteroide, in wenigen Fällen auch konventionelle DMARDs wie MTX oder biologische DMARDs. Das Tumoransprechen ist bei Patienten mit rheumatologischen Nebenwirkungen höher im Vergleich zu Patienten ohne Nebenwirkungen.

Diskussion

Eine frühzeitige Erkennung von rh-irAE ist wichtig, um diese rechtzeitig zu behandeln. Weitere prospektive Untersuchungen sind nötig um rh-irAE systematisch zu untersuchen.

Abstract

Background

Immune checkpoint inhibitors (ICI) have essentially improved the treatment options for various malignant diseases. They lead to an activation of the immune system and subsequent attack of tumor cells by affecting the immune system and preventing tumor cells from avoiding detection. In addition to this desired effect, immune-related adverse events (irAE) can occur in nearly all organ systems and therefore also rheumatological irAE (rh-irAE).

Objective

The occurrence of rh-irAE has been described in various publications and is specifically investigated in this review. The aim is to provide an overview on the prevalence, severity, treatment options and altered tumor response in patients with rh-irAE.

Material and methods

We conducted a literature search for studies and case reports on rh-irAE under ICI therapy in PubMed up to January 2020 using the PICO model.

Results

A total of 18 publications were included, most of which were clinical studies (n = 13) and the rest case reports (n = 5). Several rh-irAE can occur with a wide variety of manifestations of which arthralgia, arthritis and myositis were the most common. Other rheumatic diseases, such as vasculitis, connective tissue diseases and sarcoidosis were less frequently described. The published prevalence of rh-irAE varied with a prevalence between 2.3% and 6.6%. Treatment of rh-irAE depends on the severity and most patients receive nonsteroidal anti-inflammatory drugs and glucocorticosteroids. In some cases, conventional DMARDs, such as methotrexate and biological DMARDs, were administered. Patients with rh-irAE in general had a higher tumor response rate compared to patients without side effects.

Conclusion

A close observation of patients and early detection of rh-irAE are important in order to treat these side effects in time. Further prospective studies are necessary to systematically investigate rh-irAE.

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  1. Medizinische Klinik und Poliklinik III, Klinik für Hämatologie, Onkologie, Rheumatologie und klinische Immunologie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland

    S. H. Verspohl, A. Heine & V. S. Schäfer

  2. Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, München, Deutschland

    H. Schulze-Koops

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Verspohl, S.H., Schulze-Koops, H., Heine, A. et al. Prävalenz und Therapie von rheumatologischen Nebenwirkungen bei Immun-Checkpoint-Inhibitor-Therapie. Z Rheumatol 79, 797–808 (2020). https://doi.org/10.1007/s00393-020-00873-5

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