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
Authors: Curry Philippa D K , Morris Andrew P , Jani Meghna , Chinoy Hector , Barton Anne , Bluett James ,   OUTPASS Collaborators, 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 
Published: January 2024

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 &lt; 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.