Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis

J. Hiltunen, P. Parmanne, T. Sokka, T. Lamberg, P. Isomäki, O. Kaipiainen-Seppänen, R. Peltomaa, T. Uutela, L. Pirilä, K. Taimen, M. J. Kauppi, T. Yli-Kerttula, R. Tuompo, H. Relas, S. Kortelainen, K. Paalanen, J. Asikainen, P. Ekman, A. Santisteban, K. L. VidqvistK. Tadesse, M. Romu, J. Borodina, P. Elfving, H. Valleala, M. Leirisalo-Repo, V. Rantalaiho, H. Kautiainen, T. S. Jokiranta, K. K. Eklund, for the FinADASpA Study Group

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    Abstract

    Key messages: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Abstract: Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1–2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

    Original languageEnglish
    JournalRHEUMATOLOGY INTERNATIONAL
    Volume42
    Issue number6
    Early online dateAug 2021
    DOIs
    Publication statusPublished - 2022
    Publication typeA1 Journal article-refereed

    Keywords

    • Ankylosing spondylitis
    • Anti-drug antibodies
    • Biological therapy
    • Disease activity
    • Spondyloarthritis
    • Therapeutic drug monitoring

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Rheumatology
    • Immunology

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