Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response

Philippa D K Curry; Andrew P Morris; Meghna Jani; Hector Chinoy; Anne Barton; James Bluett; OUTPASS Collaborators

doi:10.1093/rap/rkae014

Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response

Rheumatol Adv Pract. 2024 Jan 30;8(1):rkae014. doi: 10.1093/rap/rkae014. eCollection 2024.

Authors

Philippa D K Curry¹, Andrew P Morris^{1

2}, Meghna Jani^{2

3

4}, Hector Chinoy^{2

4

5}, Anne Barton^{1

2}, James Bluett^{1

2}; OUTPASS Collaborators

Collaborators

OUTPASS Collaborators:
James Bluett, E G Chelliah, C Chattopadhyay, P Ho, A Barton, M Castelino, I Bruce, R Gorodkin, K Hyrich, B Parker, H Chinoy, T O'Neil, A Herrick, A Jones, R Cooper, W Dixon, B Harrison, M Jani, A Low, E Korendowych, N McHugh, W Tillett, N Goodson, S Lane, L Shand, I Pande, I Gaywood, F Rees, M Rutter, S Hayat, J F McHale, A C Jones, P Lanyon, A Gupta, P A Courtney, A Srikanth, A Abhishek, S Kyle, R Manhas, A Nandagudi, S Selvan, A Bharadwaj, N Gendi, R Alshakh, S Naz, M Ahmad, L Das, M Pattrick, A P Bowden, E E Smith, P Klimiuk, D J Speden, M Bukhari, S Kavaklieva, L Ottewell, M Massarotti, J Packham, P Watson, P Sanders, S Haque, B Pal, E Bruce, Z Karim, K Mackay, H Shiels, J Taylor, R Jeffery, P Nandi, C Filer, A Ismail, L Mercer, A Hassan, A Russell, M Durrani, W Hassan, A Samanta, P Sheldon, J Francis, A Kinder, R Neame, A Moorthy, M Bombardieri, S Kelly, J Maxwell, M Akil, S Till, L Dunkley, R Tattersall, R Kilding, T Tait, K-P Kuet, B Grant, M Kazmi, D Graham, V E Abernethy, A R Clewes, J K Dawson, G Fragoulis, D Mewar, E J Tunn, K Nelson, T D Kennedy, C Dubois, K Douglas, E Ladoyanni, C Koutsianas, N Erb, R Klocke, A J Whallett, A Pace, R Sandhu, H John, S A Young Min, A Cooper, J M Ledingham, R G Hull, F McCrae, Wong, Shaban, K Putchakayala, R Kumari, G Smith, C Marguerie, P Reynolds, C Thornton, C Gorman, C Murphy, D Roy, S Horton, M Castelino

Affiliations

¹ Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.
² NIHR Manchester BRC, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
³ Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.
⁴ Department of Rheumatology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK.
⁵ Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.

Abstract

Objective: The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA.

Methods: Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months.

Results: In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024).

Conclusion: Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures.

Keywords: TNF inhibitors; drug levels; drug response; immunogenicity; non-adherence; psoriatic arthritis.