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      Okuläre Nebenwirkungen von biologischen Anti-TNF-Medikamenten – eine Übersicht

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          Abstract

          Die kürzlich erfolgte Einführung biologischer Wirkstoffe hat die Behandlung chronischer immuninflammatorischer Erkrankungen revolutioniert, doch ist diese neue Therapie mit erheblichen Nebenwirkungen verbunden. Durch groß angelegte kontrollierte Studien, in denen sich ein Rückgang der Uveitis-Schübe zeigte, hat die Therapie mit Tumornekrosefaktor (TNF)-Hemmern bei nicht infektiöser Uveitis weiter an Bedeutung gewonnen. Es liegen Berichte vor, denen zufolge diese Medikamente paradoxerweise entgegen ihrer therapeutischen Wirkung mit dem Auftreten oder Wiederauftreten von entzündlichen Augenerkrankungen assoziiert sind. Etliche Studien deuten darauf hin, dass Anti-TNF-α-Wirkstoffe bei der Auslösung oder Verschlimmerung eines zugrunde liegenden Entzündungsprozesses eine Rolle spielen könnten, darunter auch die Hypothese eines gestörten Zytokingleichgewichts; die Mechanismen, die für diese Nebenwirkungen verantwortlich sind, sind jedoch noch nicht vollständig geklärt. Es erfolgte eine Literatursuche in PubMed anhand folgender Begriffe: ophthalmologische Komplikationen, Uveitis, entzündliche Augenerkrankung, Optikusneuritis, Neuropathie, Nebenwirkungen, Anti-TNF, TNF-alpha-Inhibitor, Infliximab, Etanercept, Adalimumab, Golimumab, Certolizumab und Biologika. Die in der vorliegenden Studie vorgestellten Daten stammen überwiegend aus der Anwendung von TNF-Inhibitoren in der Rheumatologie, was vor allem daran liegt, dass diese Medikamente in diesem Fachgebiet schon seit längerer Zeit eingesetzt werden. Viele der in dieser Übersichtsarbeit berichteten okulären Nebenwirkungen können möglicherweise als paradoxe Wirkung der Anti-TNF-Therapie betrachtet werden. Wir fanden eine Vielzahl von Daten, nach denen eine Anti-TNF-Therapie bei rheumatischen Erkrankungen mit einer neu auftretenden Uveitis assoziiert war, insbesondere unter Etanercept. Insgesamt lässt sich sagen, dass zwar zunehmend Daten zu okulären Nebenwirkungen vorliegen, doch bleibt abzuwarten, ob der vermutete Zusammenhang zwischen TNF-Inhibitoren und dem Auftreten von Augenentzündungen durch weitere qualitativ hochwertige Daten untermauert wird. Gleichwohl soll das Bewusstsein für mögliche Nebenwirkungen der Anti-TNF-Therapie erhöht werden.

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          Most cited references98

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          Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen.

          Propionibacterium acnes is known primarily as a skin commensal. However, it can present as an opportunistic pathogen via bacterial seeding to cause invasive infections such as implant-associated infections. These infections have gained more attention due to improved diagnostic procedures, such as sonication of explanted foreign materials and prolonged cultivation time of up to 14 days for periprosthetic biopsy specimens, and improved molecular methods, such as broad-range 16S rRNA gene PCR. Implant-associated infections caused by P. acnes are most often described for shoulder prosthetic joint infections as well as cerebrovascular shunt infections, fibrosis of breast implants, and infections of cardiovascular devices. P. acnes causes disease through a number of virulence factors, such as biofilm formation. P. acnes is highly susceptible to a wide range of antibiotics, including beta-lactams, quinolones, clindamycin, and rifampin, although resistance to clindamycin is increasing. Treatment requires a combination of surgery and a prolonged antibiotic treatment regimen to successfully eliminate the remaining bacteria. Most authors suggest a course of 3 to 6 months of antibiotic treatment, including 2 to 6 weeks of intravenous treatment with a beta-lactam. While recently reported data showed a good efficacy of rifampin against P. acnes biofilms, prospective, randomized, controlled studies are needed to confirm evidence for combination treatment with rifampin, as has been performed for staphylococcal implant-associated infections.
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            Adalimumab in Patients with Active Noninfectious Uveitis

            Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.
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              Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases.

              Tumor necrosis factor (TNF)-targeted therapies are increasingly used for a rapidly expanding number of rheumatic and autoimmune diseases. With this use and longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. We have analyzed the clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy found through a MEDLINE search of articles published between January 1990 and December 2006. We identified 233 cases of autoimmune diseases (vasculitis in 113, lupus in 92, interstitial lung diseases in 24, and other diseases in 4) secondary to TNF-targeted therapies in 226 patients. The anti-TNF agents were administered for rheumatoid arthritis (RA) in 187 (83%) patients, Crohn disease in 17, ankylosing spondylitis in 7, psoriatic arthritis in 6, juvenile RA in 5, and other diseases in 3. The anti-TNF agents administered were infliximab in 105 patients, etanercept in 96, adalimumab in 21, and other anti-TNF agents in 3. We found 92 reported cases of lupus following anti-TNF therapy (infliximab in 40 cases, etanercept in 37, and adalimumab in 15). Nearly half the cases fulfilled 4 or more classification criteria for systemic lupus erythematosus (SLE), which fell to one-third after discarding preexisting lupus-like features. One hundred thirteen patients developed vasculitis after receiving anti-TNF agents (etanercept in 59 cases, infliximab in 47, adalimumab in 5, and other agents in 2). Leukocytoclastic vasculitis was the most frequent type of vasculitis, and purpura was the most frequent cutaneous lesion. A significant finding was that one-quarter of patients with vasculitis related to anti-TNF agents had extracutaneous involvement. Twenty-four cases of interstitial lung disease associated with the use of anti-TNF agents were reported. In these patients, 2 specific characteristics should be highlighted: the poor prognosis in spite of cessation of anti-TNF therapy, and the possible adjuvant role of concomitant methotrexate. In conclusion, the use of anti-TNF agents has been associated with an increasing number of cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, SLE, and interstitial lung disease.
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                Author and article information

                Journal
                KOP
                10.1159/issn.2297-0118
                Karger Kompass Ophthalmologie
                S. Karger AG
                2297-0118
                2297-0045
                2020
                September 2020
                18 August 2020
                : 6
                : 3
                : 120-126
                Affiliations
                [_a] aMedicine School, University of São Paulo, São Paulo, Brasilien
                [_b] bMoorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
                Author notes
                *Fernanda Nicolela Susanna, Medicine School, University of São Paulo, São Paulo, Brasilien, fernanda.susanna@fm.usp.br
                Article
                509813 Kompass Ophthalmol 2020;6:120–126
                10.1159/000509813
                d39498dd-9a9f-44e3-b2f2-5254d5b13f0c
                © 2020 S. Karger GmbH, Freiburg

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Tables: 1, Pages: 7
                Categories
                Übersichtsarbeit

                Vision sciences,Ophthalmology & Optometry,Pathology
                Optikusneuritis,Biologika,entzündliche Augenerkrankung,Uveitis,Anti-TNF,okuläre Nebenwirkung

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