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

Trials

Theo Rispens¹  Annick de Vries¹  Maarten Boers²  Bart J. F. van den Bemt³  Sadaf Atiqi⁴  Gerrit Jan Wolbink⁵  Michael T. Nurmohamed⁶  Ronald F. van Vollenhoven⁷  Maike H. M. Wientjes⁸  Alfons A. den Broeder⁹ 

[1]Biologics Lab, Sanquin Diagnostic Services, Sanquin, Amsterdam, the Netherlands

[2]Department of Epidemiology and Data Science, Amsterdam Rheumatology and Immunology Center, UMC Amsterdam, Vrije Universiteit, Amsterdam, the Netherlands

[3]Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, UMC/Academic Medical Center, Amsterdam, the Netherlands

[4]Department of Pharmacy, Sint Maartenskliniek, Nijmegen, the Netherlands

[5]Department of Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands

[6]Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, the Netherlands

[7]Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, the Netherlands

[8]Biologics Lab, Sanquin Diagnostic Services, Sanquin, Amsterdam, the Netherlands

[9]Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, the Netherlands

[10]Department of Epidemiology and Data Science, Amsterdam Rheumatology and Immunology Center, UMC Amsterdam, Vrije Universiteit, Amsterdam, the Netherlands

[11]Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, the Netherlands

[12]Department of Epidemiology and Data Science, Amsterdam Rheumatology and Immunology Center, UMC Amsterdam, Vrije Universiteit, Amsterdam, the Netherlands

[13]Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, UMC/Academic Medical Center, Amsterdam, the Netherlands

[14]Department of Rheumatology, Sint Maartenskliniek, PO box 9011, 6500 GM, Nijmegen, the Netherlands

[15]Department of Rheumatology, Sint Maartenskliniek, PO box 9011, 6500 GM, Nijmegen, the Netherlands

[16]Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands

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

DOI  :  10.1186/s13063-021-05358-7

来源: Springer

【 摘 要 】

BackgroundA 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.MethodsADDORA-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.DiscussionThe 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 registrationDutch Trial Register NL8210. Registered on 3 December 2019 (CMO NL69841.091.19).

【 授权许可】

CC BY