Prediction of successful dose reduction or discontinuation of adalimumab, etanercept, or infliximab in rheumatoid arthritis patients using serum drug levels and antidrug antibody measurement

ABSTRACT

Background: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug antibodies (ADAb) can predict successful dose reduction (in patients with high DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid arthritis (RA) patients.

Research design and methods: RA patients that were using adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing well, were tapered until discontinuation or flare (1–1.5 year follow up). Random timed DL for adalimumab and etanercept and trough DL for infliximab were measured before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut-off DL were determined.

Results: No predictive value of adalimumab and infliximab DL for all outcomes were found, except for an inverse association of lower etanercept DL and higher chance for successful dose reduction (Area Under the Curve (AUC) 0.36, 95% CI 0.23–0.49; cut-off <2.6 mg/l). In sub analyses, higher adalimumab trough DL predicted successful dose reduction (AUC 0.86, 0.58–1.00; cut-off >7.8). ADAb were infrequent and not predictive of successful discontinuation.

Conclusions: No predictive value of baseline adalimumab, etanercept and infliximab DL or ADAb for successful dose reduction or discontinuation in RA was found in this context, with the possible exception of high adalimumab trough levels for successful dose reduction.

KEYWORDS:

• Antibodies
• rheumatoid arthritis
• tapering
• therapeutic drug monitoring
• tumor necrosis factor inhibitor

Acknowledgments

Etanercept and adalimumab data have been published previously as a letter (Van Herwaarden et al. ARD 2015 Dec;74(12):2260-1) and have been presented as posters at the NVR (Dutch Association of Rheumatology, The Netherlands) 2014, ACR (American College of Rheumatology, USA) 2014, and NVZA/NVPV (Dutch Association of Hospital Pharmacology, The Netherlands) 2014 annual meetings. Infliximab data have been presented as a poster at the ACR 2013 annual meeting. Dutch clinical trial registration number: NTR 3216.

Declaration of interest

A den Broeder reports having received congress invitations from ABBVIE, ROCHE and Celltrion, and expert witness fees from AMGEN and Bl, all external to this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Additional information

Funding

This manuscript was funded by the Sint Maartenskliniek, Nijmegen, The Netherlands.