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

Philippa D K Curry; Ryan M Hum; Andrew P Morris; Meghna Jani; Hector Chinoy; Anne Barton; James Bluett; for OUTPASS collaborators

doi:10.1093/rheumatology/kead666

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

Rheumatology (Oxford). 2023 Dec 9:kead666. doi: 10.1093/rheumatology/kead666. Online ahead of print.

Authors

Philippa D K Curry¹, Ryan M Hum^{1

2}, Andrew P Morris^{1

2}, Meghna Jani^{3

2

4}, Hector Chinoy^{2

4}, Anne Barton^{1

2}, James Bluett^{1

2}; for OUTPASS collaborators

Affiliations

¹ Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, United Kingdom.
² NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
³ Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, United Kingdom.
⁴ Department of Rheumatology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, United Kingdom.

PMID: 38070158
DOI: 10.1093/rheumatology/kead666

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 with 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 1.8 µg/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 2.0 µg/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 3.6 µg/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.

Keywords: PsA; TNF-i; adalimumab; etanercept; pharmacokinetics; serum drug levels; therapeutic response.