Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis.

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  • Additional Information
    • Source:
      Publisher: BMJ Country of Publication: England NLM ID: 0372355 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-2060 (Electronic) Linking ISSN: 00034967 NLM ISO Abbreviation: Ann Rheum Dis Subsets: MEDLINE
    • Publication Information:
      Publication: London : BMJ
      Original Publication: London : H.K. Lewis
    • Subject Terms:
    • Abstract:
      Objective: To evaluate the associations between (1) antidrug antibody (ADAb) and therapeutic response, (2) ADAb and serum drug trough levels and (3) serum drug levels and therapeutic responses in rheumatoid arthritis (RA) patients receiving adalimumab or etanercept. Secondarily, we aim (1) to evaluate the concordance between radioimmunoassay and bridging ELISA for ADAb assessment and to evaluate the correlation between two different ELISA methods for detecting drug levels, and (2) to determine the optimal cut-off drug levels for good European League Against Rheumatism (EULAR) response.
      Methods: ADAb levels were determined by bridging ELISA and radioimmunoassay, and drug levels evaluated using sandwich ELISA among 36 adalimumab-treated patients and 34 etanercept-treated patients at the 6th and 12th month. The optimal cut-off drug levels for EULAR responses were determined by receiver-operating characteristic curve analysis.
      Results: ADAb was detected in 10 (27.8%) and 13 (36.1%) of adalimumab-treated patients after 12-month therapy using bridging ELISA and radioimmunoassay respectively, but not detected in any of etanercept-treated patients. The presence of ADAb was associated with lower EULAR response and lower drug levels compared with those without ADAb (both p<0.001). Drug trough levels were positively associated with DAS28 decrement (ΔDAS28) (all p<0.001). The optimal cut-off trough levels for adalimumab were 1.274 μg/mL and 1.046 μg/mL, and those for etanercept were 1.242 μg/mL and 0.800 μg/mL for good EULAR response assessed at the 6th and 12th month, respectively.
      Conclusions: ADAb levels were inversely correlated with therapeutic response and drug levels. The positive correlation between drug levels and ΔDAS28 indicates that drug monitoring would be useful to evaluate therapeutic response of TNF-α inhibitors.
      (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
    • Comments:
      Comment in: Ann Rheum Dis. 2015 Aug;74(8):e42. (PMID: 25805737)
      Comment in: Ann Rheum Dis. 2015 Aug;74(8):e43. (PMID: 25841164)
    • Contributed Indexing:
      Keywords: Rheumatoid Arthritis; TNF-alpha; Treatment
    • Accession Number:
      0 (Antibodies)
      0 (Antibodies, Monoclonal, Humanized)
      0 (Antirheumatic Agents)
      0 (Immunoglobulin G)
      0 (Receptors, Tumor Necrosis Factor)
      FYS6T7F842 (Adalimumab)
      OP401G7OJC (Etanercept)
    • Publication Date:
      Date Created: 20140121 Date Completed: 20150511 Latest Revision: 20151119
    • Publication Date:
      20240829
    • Accession Number:
      10.1136/annrheumdis-2013-203893
    • Accession Number:
      24442879