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Incident psoriasis under treatment with tumor necrosis factor-α inhibitors in juvenile idiopathic arthritis patients—analysis of the BiKeR registry

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Abstract

The efficacy of tumor necrosis factor inhibitors (TNFi) for the treatment of psoriasis is well established, but patients may develop psoriasis for the first time while on TNFi as a paradoxical effect. Limited data on this association in patients with juvenile idiopathic arthritis (JIA) are available. Safety data from patients registered to the German Biologics registry (BiKeR) were analyzed. Patients were grouped by treatment regime: single TNFi, multiple TNFi, non-TNFi biologics or bDMARD-naïve control group receiving methotrexate. TNFi-associated psoriasis was defined as incident diagnosis of psoriasis after starting TNFi treatment. Patients with a history of psoriasis or psoriasis arthritis prior to TNFi therapy were excluded. Event rates using AEs reported after first dose were compared by Wald’s test. A total of 4149 patients were treated with a TNFi (etanercept, adalimumab, golimumab, infliximab), 676 with a non-TNFi biologic (tocilizumab, abatacept, anakinra, canakinumab) and 1692 with methotrexate only. A total of 31 patients were diagnosed with incident psoriasis while on one of the above treatments. Compared with methotrexate, psoriasis was more frequent in the TNFi cohorts (RR 10.8, p = 0.019), specifically in the subgroup of TNF antibodies (RR 29.8, p = 0.0009), whereas no significant signal was observed with etanercept. Also, non-TNFi-treated patients presented high incident psoriasis rates (RR 25.0, p = 0.003). Our findings indicate a higher rate of incident psoriasis in JIA patients treated with TNFi monoclonal antibodies or non-TNFi biologic treatment. JIA patients receiving monoclonal antibody TNFi or non-TNFi bDMARD should be monitored for incident psoriasis. Medication change, if topical skin treatment remains insufficient, may be considered.

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Open Data Sharing has not been approved by all patients of their legal guardians/parents, therefore we cannot publicly share individual data.

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Acknowledgements

We would like to thank our colleagues K. Minden, D. Windschall, I. Foeldvari, T. Schwarz, B. Huegle, M. Borte, C. Rietschel, F. Weller-Heinemann, P. Oommen, H. Kössel, J. Grulich-Henn, JP. Haas, R. Trauzeddel, all other contributing doctors, nurses and patients/families for supporting the BiKeR registry.

Funding

The BiKeR registry was temporarily supported by unrestricted grants from AbbVie, Chugai, MSD, Novartis, Pfizer and Roche. The data accumulation, analysis and publication are not influenced by the sponsors and lay in the full and only responsibility of the authors. F. Dressler has received speaker’s fees from AbbVie, Novartis and Pfizer and is a member of advisory boards for Novartis and Mylan; D. Foell has received a speaker honorarium (speakers bureau) from Novartis, Sobi, Biontech and Werfen, was a consultant of Novartis, Sobi and Boehringer and has received grant/research support from Novartis, Sobi and Boehringer; T. Hospach has received consulting fees from Novartis and Sobi; M. Hufnagel has been advisory speaker for Novartis; G. Horneff has been advisory speaker for Pfizer, Novartis and Sobi and a consultant of MSD and Lilly and has received grants from Novartis, MSD and Roche.

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Authors and Affiliations

  1. Asklepios Clinic Sankt Augustin, Kinderrheumatologie, Arnold-Janssen-Str. 29, 53757, Sankt Augustin, Germany

    Angela Zimmer, Ariane Klein & Gerd Horneff

  2. Pädiatrische Rheumatologie and Autoinflammation Reference Center Tübingen, Klinik für Kinder- und Jugendmedizin, Member of ERN-RITA, Universitätsklinikum Tübingen, 72076, Tübingen, Germany

    Jasmin B. Kuemmerle-Deschner

  3. Kinderklinik der Medizinischen Hochschule Hannover, Kinderrheumatologische Ambulanz, 30625, Hannover, Germany

    Frank Dressler

  4. Kinder- und Jugendärztliche Gemeinschaftspraxis, 21337, Lüneburg, Germany

    Nils Onken

  5. Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Normi Brueck

  6. Städt. Klinikum St. Georg, Klinik für Kinder- und Jugendmedizin, 04129, Leipzig, Germany

    Maria Fasshauer

  7. Olgahospital, Kinderrheumatologie, 70174, Stuttgart, Germany

    Toni Hospach

  8. Division of Pediatric Infectious Diseases and Rheumatology, Department of Pediatrics and Adolescent Medicine, Medical Faculty, University Medical Center Freiburg, University of Freiburg, 79106, Freiburg, Germany

    Markus Hufnagel

  9. Universitätsklinikum Münster, Klinik für Pädiatrische Rheumatologie und Immunologie, 48149, Munster, Germany

    Dirk Foell

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  1. Angela Zimmer
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  2. Ariane Klein
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Contributions

All co-authors take full responsibility for the integrity and accuracy of all aspects of the work. All authors contributed to the study conception and design. Material preparation and data collection/data acquisition were performed by AZ, AK, JK-D, FD, NO, NB, MF, TH, MH, DF and GH. Data analysis was performed by AZ and GH. The first draft of the manuscript was written by AZ and GH. The first review of the manuscript was conducted by AZ, AK and GH. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Angela Zimmer.

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Zimmer, A., Klein, A., Kuemmerle-Deschner, J.B. et al. Incident psoriasis under treatment with tumor necrosis factor-α inhibitors in juvenile idiopathic arthritis patients—analysis of the BiKeR registry. Rheumatol Int 43, 1675–1684 (2023). https://doi.org/10.1007/s00296-023-05352-z

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