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.
Adalimumab
Anti-TNF
Design
Drug concentration
Rheumatoid arthritis
Switching
Test-treatment trial
Therapeutic drug monitoring
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
19 Jun 2021
19 Jun 2021
Historique:
received:
02
04
2021
accepted:
04
06
2021
entrez:
20
6
2021
pubmed:
21
6
2021
medline:
23
6
2021
Statut:
epublish
Résumé
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. 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. 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. Dutch Trial Register NL8210 . Registered on 3 December 2019 (CMO NL69841.091.19).
Sections du résumé
BACKGROUND
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
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
CONCLUSIONS
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
BACKGROUND
Dutch Trial Register NL8210 . Registered on 3 December 2019 (CMO NL69841.091.19).
Identifiants
pubmed: 34147123
doi: 10.1186/s13063-021-05358-7
pii: 10.1186/s13063-021-05358-7
pmc: PMC8214249
doi:
Substances chimiques
Antirheumatic Agents
0
Tumor Necrosis Factor Inhibitors
0
Tumor Necrosis Factor-alpha
0
Adalimumab
FYS6T7F842
Etanercept
OP401G7OJC
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
406Subventions
Organisme : ZonMw
ID : 8481 01 006
Pays : Netherlands
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