Cutaneous Adverse Events During Treatment of Chronic Inflammatory Rheumatic Conditions With Tumor Necrosis Factor Antagonists: Study Using the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases

Authors

  • Mª Victoria Hernández,

    Corresponding author
    1. Hospital Clínic, Barcelona, Spain
    • Arthritis Unit, Rheumatology Department, Hospital Clínic of Barcelona, Villarroel 170, Stairway 11, Second Floor, 08036 Barcelona, Spain. E-mail: mvhernan@clinic.ub.es

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  • Raimon Sanmartí,

    1. Hospital Clínic, Barcelona, Spain
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  • Juan D. Cañete,

    1. Hospital Clínic, Barcelona, Spain
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  • Miguel A. Descalzo,

    1. Spanish Society of Rheumatology, Madrid, Spain
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  • Mercè Alsina,

    1. Hospital Clínic, Barcelona, Spain
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  • Loreto Carmona,

    1. Universidad Camilo José Cela, Madrid, Spain
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    • Dr. Carmona has received speaking fees (less than $10,000) from Pfizer and has received research grants from Abbott, MSD, and Roche.

  • Juan J. Gomez-Reino,

    1. Hospital Clínico Universitario and Universidad de Santiago de Compostela, Santiago de Compostela, Spain
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    • Dr. Gomez-Reino has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, BMS, MSD, Pfizer, Roche, Schering-Plough, and Wyeth; has received research grants from Roche and Schering-Plough; and serves on the advisory boards for Abbott, BMS, Pfizer, Roche, Schering-Plough, and UCB.

  • on behalf of the BIOBADASER 2.0 Study Group


Abstract

Objective

To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists.

Methods

We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE.

Results

A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50–57) for CAE, 28 (95% CI 25–30) for infection, 15 (95% CI 13–17) for infusion reactions, 5 (95% CI 4–6) for autoimmune skin diseases, and 3 (95% CI 2–4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids.

Conclusion

The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases.

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