Non-trough adalimumab and certolizumab drug levels associated with a therapeutic EULAR response in adherent patients with rheumatoid arthritis
Author:
Hum Ryan M123ORCID, Ho Pauline123, Nair Nisha12ORCID, Jani Meghna12ORCID, Morgan Ann W4ORCID, Isaacs John D5, Wilson Anthony G6, Hyrich Kimme L123ORCID, Plant Darren12ORCID, Barton Anne123ORCID, Gaston H, Mulherin D, Price T, Sheeran T, Chalam V, Baskar S, Emery P, Morgan AORCID, Buch M, Bingham S, O’Reilly S, Badcock L, Regan M, Ding T, Deighton C, Summers G, Raj N, Stevens R, Williams N, Isaacs J, Platt P, Walker D, Kay L, Griffiths B, Ng W -F, Peterson P, Lorenzi A, Foster H, Friswell M, Thompson B, Lee M, Griffiths I, Hassell A, Dawes P, Dowson C, Kamath S, Packham J, Shadforth M, Brownfield A, Williams R, Mukhtyar C, Harrison B, Snowden N, Naz S, Ledingham J, Hull R, McCrae F, Thomas A, Young Min S, Shaban R, Wong E, Kelly C, Heycock C, Hamilton J, Saravanan V, Wilson G, Bax D, Dunkley L, Akil M, Tattersall R, Kilding R, Till S, Boulton J, Tait T, Bukhari M, Halsey J, Ottewell L, Buckley C, Situnayake D, Carruthers D, Grindulis K, Khatack F, Elamanchi S, Raza K, Filer A, Jubb R, Abernathy R, Plant M, Pathare S, Clarke F, Tuck S, Fordham J, Paul A, Bridges M, Hakim A, O’Reilly D, Rajagopal V, Bhagat S, Edwards C, Prouse P, Moitra R, Shawe D, Bamji A, Klimiuk P, Bowden A, Mitchell W, Bruce I, Barton AORCID, Gorodkin R, Ho P, Hyrich KORCID, Dixon W, Rai A, Kitas G, Erb N, Klocke R, Douglas K, Pace A, Sandhu R, Whallett A, Birrell F, Allen M, Chaudhuri K, Chattopadhyay C, McHale J, Jones A, Gupta A, Pande I, Gaywood I, Lanyon P, Courtney P, Doherty M, Chinoy H, O’Neill T, Herrick A, Jones A, Cooper R, Bucknall R, Marguerie C, Rigby S, Dunn N, Green S, Al-Ansari A, Webber S, Hopkinson N, Dunne C, Quilty B, Szebenyi B, Green M, Quinn M, Isdale A, Brown A, Saleem B, Samanta A, Sheldon P, Hassan W, Francis J, Kinder A, Neame R, Moorthy A, Al-Allaf W, Taggart A, Fairburn K, McKenna F, Green M, Gough A, Lawson C, Piper M, Korendowych E, Jenkinson T, Sengupta R, Bhalla A, McHugh N, Bond D, Luqmani R, Bowness B, Wordsworth P, David J, Smith W, Mewar D, Tunn E, Nelson K, Kennedy T, Nixon J, Woolf A, Davis M, Hutchinson D, Endean A, Coady D, Wright D, Morley C, Raftery G, Bracewell C, Kidd L, Abbas I, Filer C, Kallarackal G,
Affiliation:
1. Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Manchester, UK 2. National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, University of Manchester , Manchester, UK 3. Kellgren Centre for Rheumatology, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, University of Manchester , Manchester, UK 4. NIHR Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital , Leeds, UK 5. Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University , Newcastle upon Tyne, UK 6. University College Dublin Centre for Arthritis Research, Conway Institute, University College Dublin , Dublin, Ireland
Abstract
Abstract
Objectives
Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients.
Methods
In a prospective observational study, 475 patients with RA were treated with certolizumab (n = 192) or adalimumab (n = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs.
Results
Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P = 0.04 and P = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive.
Conclusion
In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice.
Funder
National Institute for Health and Care Research
Publisher
Oxford University Press (OUP)
Subject
Pharmacology (medical),Rheumatology
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|