Non-trough serum drug levels of adalimumab and etanercept are associated with response in patients with psoriatic arthritis

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Abstract

Objectives. Up to 40% of psoriatic arthritis (PsA) patients experience first-line Tumour Necrosis Factor inhibitors (TNF-i) failure. Lower serum drug levels (SDL) have been associated with lower response in autoimmune conditions. This study aimed to: (i) establish the relationship between adalimumab (ADL) and etanercept (ETN) SDL and 3-month response; and (ii) identify optimal non-trough SDL thresholds in PsA.

Methods. PsA patients commencing ADL or ETN were recruited to the UK observational study OUTPASS. Patients were seen pre-TNF-i and at 3 months when response was measured, and non-trough serum samples collected. Response was defined according to the PsARC or EULAR criteria. Descriptive statistics and concentration-effect curves established differences in SDL based on response. Receiver operating characteristics and regression identified optimal SDL thresholds.

Results. PsA ETN (n=97) PsARC and EULAR good responders had significantly higher 3-month SDL compared to non-responders (p=0.006 and p=0.020 respectively). Non-trough 3-month ETN SDL discriminated PsARC responders from non-responders (AUC=0.70), with a threshold of 1.8µg/ml being 63% specific and 69% sensitive. EULAR good and non-/moderate responders were discriminated with an AUC of 0.65 with a threshold of 2.0µg/ml being 57%
specific and 69% sensitive. ADL prescribed (n=104) EULAR good responders had significantly higher 3-month SDL (p=0.049). Non-trough 3-month ADL SDL discriminated EULAR good and non-/moderate responders (AUC=0.63) with a threshold of 3.6µg/ml being 48% specific and 81% sensitive.

Conclusion. Higher 3-month SDL were detected in responders. Interventions to optimise SDL may improve treatment response earlier. This study suggests 3-month SDL thresholds which may be useful in clinical practice to optimise treatment response.
Original languageEnglish
Article numberkead666
JournalRheumatology
Early online date9 Dec 2023
DOIs
Publication statusE-pub ahead of print - 9 Dec 2023

Keywords

  • PsA
  • serum drug levels
  • therapeutic response
  • adalimumab
  • etanercept
  • TNF-i
  • pharmacokinetics

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