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Observational Study
. 2023 Jun 1;62(6):2090-2097.
doi: 10.1093/rheumatology/keac564.

Non-trough adalimumab and certolizumab drug levels associated with a therapeutic EULAR response in adherent patients with rheumatoid arthritis

Ryan M Hum  1   2   3 , Pauline Ho  1   2   3 , Nisha Nair  1   2 , Meghna Jani  1   2 , Ann W Morgan  4 , John D Isaacs  5 , Anthony G Wilson  6 , Kimme L Hyrich  1   2   3 , Darren Plant  1   2 , Anne Barton  1   2   3 ; BRAGGSS Collaborators
Collaborators, Affiliations
Observational Study

Non-trough adalimumab and certolizumab drug levels associated with a therapeutic EULAR response in adherent patients with rheumatoid arthritis

Ryan M Hum et al. Rheumatology (Oxford). .

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.

Keywords: RA; TNF-α; adalimumab; adherence; certolizumab; inhibitors; serum drug levels; therapeutic response.

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Figures

Figure 1.
Figure 1.
Schematic illustrating a potential clinical paradigm involving the use of SDLs and therapeutic thresholds based on fully adherent patients achieving a good treatment response
Figure 2.
Figure 2.
Box and whisker plots comparing SDLs of fully adherent RA patients with EULAR non-/moderate response (red) vs good response (blue) after treatment with (A) adalimumab or (B) certolizumab. Colour version can be viewed online
Figure 3.
Figure 3.
ROC curve analysis. Fully adherent RA patients with EULAR good response vs non-/moderate response with SDLs at 3 months after treatment with (A) adalimumab or (B) certolizumab
See this image and copyright information in PMC

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