Non-trough serum drug levels of adalimumab and etanercept are associated with response in patients with psoriatic arthritis
Author:
Curry Philippa D K1ORCID, Hum Ryan M12ORCID, Morris Andrew P12ORCID, Jani Meghna234ORCID, Chinoy Hector24ORCID, 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, 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,
Affiliation:
1. Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester , Manchester, UK 2. NIHR Manchester Biomedical Research Centre, 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
Abstract
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.
Funder
National Institute for Health and Care Research Manchester Biomedical Research Centre
Publisher
Oxford University Press (OUP)
Subject
Pharmacology (medical),Rheumatology
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