TY - JOUR
T1 - 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
T2 - study protocol for a fully blinded randomised superiority test-treatment trial
AU - Wientjes, Maike H. M.
AU - Atiqi, Sadaf
AU - Wolbink, Gerrit Jan
AU - Nurmohamed, Michael T.
AU - Boers, Maarten
AU - Rispens, Theo
AU - de Vries, Annick
AU - van Vollenhoven, Ronald F.
AU - van den Bemt, Bart J. F.
AU - den Broeder, Alfons A.
N1 - Funding Information: The study is funded by ZonMw (grant number 8481 01 006) and Sanquin Diagnostics. The study protocol was peer reviewed by external reviewers in the course of the grant application for ZonMw. There are no other financial or non-financial conflicts of interest other than specified. Funding Information: 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. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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).
AB - 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).
KW - Adalimumab
KW - Adalimumab/adverse effects
KW - Anti-TNF
KW - Antirheumatic Agents/adverse effects
KW - Arthritis, Rheumatoid/diagnosis
KW - Design
KW - Drug Monitoring
KW - Drug concentration
KW - Etanercept/therapeutic use
KW - Humans
KW - Multicenter Studies as Topic
KW - Randomized Controlled Trials as Topic
KW - Rheumatoid arthritis
KW - Switching
KW - Test-treatment trial
KW - Therapeutic drug monitoring
KW - Treatment Outcome
KW - Tumor Necrosis Factor Inhibitors
KW - Tumor Necrosis Factor-alpha
UR - http://www.scopus.com/inward/record.url?scp=85108162714&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85108162714&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34147123
U2 - https://doi.org/10.1186/s13063-021-05358-7
DO - https://doi.org/10.1186/s13063-021-05358-7
M3 - Article
C2 - 34147123
SN - 1745-6215
VL - 22
SP - 406
JO - Trials
JF - Trials
IS - 1
M1 - 406
ER -