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. 2021 Jun 19;22(1):406.
doi: 10.1186/s13063-021-05358-7.

Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid arthritis patients failing adalimumab treatment (ADDORA-switch): study protocol for a fully blinded randomised superiority test-treatment trial

Maike H M Wientjes  1 , Sadaf Atiqi  2 , Gerrit Jan Wolbink  2   3 , Michael T Nurmohamed  2   4 , Maarten Boers  4   5 , Theo Rispens  3 , Annick de Vries  3 , Ronald F van Vollenhoven  2   4   5 , Bart J F van den Bemt  6   7 , Alfons A den Broeder  8   9
Affiliations

Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid arthritis patients failing adalimumab treatment (ADDORA-switch): study protocol for a fully blinded randomised superiority test-treatment trial

Maike H M Wientjes et al. Trials. .

Abstract

Background: A substantial proportion of rheumatoid arthritis (RA) patients discontinues treatment with tumour necrosis factor inhibitors (TNFi) due to inefficacy or intolerance. After the failure of treatment with a TNFi, treatment can be switched to another TNFi or a bDMARD with a different mode of action (non-TNFi). Measurement of serum drug concentrations and/or anti-drug antibodies (therapeutic drug monitoring (TDM)) may help to inform the choice for the next step. However, the clinical utility of TDM to guide switching has not been investigated in a randomised test-treatment study.

Methods: ADDORA-switch is a 24-week, multi-centre, triple-blinded, superiority test-treatment randomised controlled trial. A total of 84 RA patients failing adalimumab treatment (treatment failure defined as DAS28-CRP > 2.9) will be randomised in a 1:1 ratio to a switching strategy to either TNFi or non-TNFi based on adalimumab serum trough level (intervention group) or random allocation (control group). The primary outcome is the between-group difference in mean time-weighted DAS28 over 24 weeks.

Discussion: The trial design differs in many aspects from previously published and ongoing TDM studies and is considered the first blinded test-treatment trial using TDM in RA. Several choices in the design of this trial are described, and overarching principles regarding test-treatment trials and clinical utility of TDM are discussed in further detail.

Trial registration: Dutch Trial Register NL8210 . Registered on 3 December 2019 (CMO NL69841.091.19).

Keywords: Adalimumab; Anti-TNF; Design; Drug concentration; Rheumatoid arthritis; Switching; Test-treatment trial; Therapeutic drug monitoring.

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Conflict of interest statement

Michael T. Nurmohamed: consulting fees from AbbVie, Celgene, Celltrion, Eli Lilly, Janssen and Sanofi; speaker’s fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Roche and Sanofi; and research funding from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Mundipharma, Novartis, Pfizer, Roche and Sanofi. Ronald F van Vollenhoven: research support (institutional grants)—BMS, GSK, Lilly and UCB; support for educational programmes (institutional grants)—Pfizer and Roche; consultancy, for which institutional and/or personal honoraria were received—AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Galapagos, Gilead, Janssen, Pfizer, Servier and UCB; speaker, for which institutional and/or personal honoraria were received—AbbVie, Galapagos, Janssen, Pfizer and UCB. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
SPIRIT figure: trial visits and assessments
Fig. 2
Fig. 2
Flow diagram of the ADDORA-switch study. *Allocation of subsequent treatment in the control group is directly based on allocation in the intervention group. In the case of randomisation allocating more patients to the control group than currently allocated to the intervention group, these patients will be randomised in a ratio of 1:2 to etanercept or a non-TNFi
See this image and copyright information in PMC

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