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
Author:
Curry Philippa D K1ORCID, Morris Andrew P12ORCID, Jani Meghna234ORCID, Chinoy Hector245ORCID, Barton Anne12ORCID, Bluett James12ORCID, , Bluett James, Chelliah E G, Chattopadhyay C, Ho P, Barton A, Castelino M, Bruce I, Gorodkin R, Hyrich K, Parker B, Chinoy H, O’Neil T, Herrick A, Jones A, Cooper R, Dixon W, Harrison B, Jani M, Low A, Korendowych E, McHugh N, Tillett W, Goodson N, Lane S, Shand L, Pande I, Gaywood I, Rees F, Rutter M, Hayat S, McHale J F, Jones A C, Lanyon P, Gupta A, Courtney P A, Srikanth A, Abhishek A, Kyle S, Manhas R, Nandagudi A, Selvan S, Bharadwaj A, Gendi N, Alshakh R, Naz S, Ahmad M, Das L, Pattrick M, Bowden A P, Smith E E, Klimiuk P, Speden D J, Bukhari M, Kavaklieva S, Ottewell L, Massarotti M, Packham J, Watson P, Sanders P, Haque S, Pal B, Bruce E, Karim Z, Mackay K, Shiels H, Taylor J, Jeffery R, Nandi P, Filer C, Ismail A, Mercer L, Hassan A, Russell A, Durrani M, Hassan W, Samanta A, Sheldon P, Francis J, Kinder A, Neame R, Moorthy A, Bombardieri M, Kelly S, Maxwell J, Akil M, Till S, Dunkley L, Tattersall R, Kilding R, Tait T, Kuet K-P, Grant B, Kazmi M, Graham D, Abernethy V E, Clewes A R, Dawson J K, Fragoulis G, Mewar D, Tunn E J, Nelson K, Kennedy T D, Dubois C, Douglas K, Ladoyanni E, Koutsianas C, Erb N, Klocke R, Whallett A J, Pace A, Sandhu R, John H, Young Min S A, Cooper A, Ledingham J M, Hull R G, McCrae F, Wong , Shaban , Putchakayala K, Kumari R, Smith G, Marguerie C, Reynolds P, Thornton C, Gorman C, Murphy C, Roy D, Horton S, Castelino M
Affiliation:
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
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.
Funder
National Institute for Health and Care Research Manchester Biomedical Research Centre Versus Arthritis NIHR
Publisher
Oxford University Press (OUP)
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