Non-trough serum drug levels of adalimumab and etanercept are associated with response in patients with psoriatic arthritis
Authors: Curry Philippa D K , Hum Ryan M , Morris Andrew P , Jani Meghna , Chinoy Hector , Barton Anne , Bluett James ,   for 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 , Siebert S , 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 , 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 , Siebert S , 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 , 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 , Siebert S , 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: December 2023

Abstract

Objectives
Up to 40% of 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 characteristic curves 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 1.8 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 optimize treatment response.