No registrations found.
ID
Source
Brief title
Health condition
- Psoriatic arthritis, Axial Spondyloarthritis, Dose reduction, TNF inhibitors
- Artritis psoriatica, Axiale Spondylartritis, Dosis reductie, TNF remmers
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in proportion of patients between T2T strategy with or without tapering attempt who are in LDA state (PASDAS ≤ 3.2 and modified BSA ≤ 3% of the skin (PsA), ASDAS < 2.1 (axSpA) and an absence of active extra-axial symptoms) at 12 months follow-up, compared to the prespecified non-inferiority margin of 0.2 (20%).
Secondary outcome
- To assess the proportion of patients in the intervention group able to reduce their TNFi dose, able to discontinue TNFi altogether, or not able to reduce TNFi dose without an increase in disease activity, respectively,
- To compare the differences in efficacy between the intervention versus control group with TNFi measured by change in PASDAS and BSA of the skin and/or ASDAS at 3, 6, 9 and 12 months follow-up,
- To assess the difference in the change from baseline in functioning measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and Bath Ankylosing Spondylitis Functional Index (BASFI - axSpA only) between both groups with TNFi at 3, 6, 9, and 12 months follow-up,
- To estimate cost-effectiveness ratio of the T2T strategy with tapering attempt of TNFi compared to the T2T strategy without tapering attempt,
- To compare (dosage and) proportion of patients using NSAID, corticosteroid’s or cs/b/tsDMARDs between intervention and control group at 12 months follow up,
- To predict in the intervention group which baseline factors (including [change in] serum drug levels and antidrug antibody levels) are associated with successful and maintained dose reduction,
- To compare the difference in cumulative incidence of flare between the intervention and control group at 12 months follow up,
- To assess the safety of this strategy with respect to proportion of patients developing adverse events with special attention to allergic (injection) reactions and infections
Background summary
Spondyloarthritis, notably psoriatic arthritis (PsA) and axial SpA (axSpA) can successfully be treated with Tumour Necrosis Factor inhibitors (TNFi) therapy. When patients are in low disease activity (LDA), the question arises whether patients may be able to maintain LDA with a lower dose or without TNFi, as overtreatment with TNFi is associated with risk for infections and higher costs. A few non-randomised studies have previously explored the possibility of disease activity guided dose reduction in PsA and axSpA, but data is scarce and evidence from randomised trials is lacking. Also, no cost-effectiveness analysis has been performed to provide insight into the potential cost savings of effective dose reduction of TNFi. In contrast, the safety and efficacy of disease activity guided dose reduction of TNFi have already been shown in Rheumatoid Arthritis (RA), and similar strategy trials in Crohns’ disease and psoriasis are ongoing in the Netherlands. The aim of this study is therefore to investigate whether a treat-to-target (T2T) strategy with tapering attempt of TNFi is non-inferior to a T2T strategy without tapering attempt in PsA and axSpA patients having LDA for at least 6 months. In addition, a cost-effectiveness analysis will be performed to assess the cost effectiveness between both groups.
Study objective
The aim of the study is to compare the proportion of patients (for PsA and axSpA together) having LDA at 12 months between a T2T strategy with versus without tapering attempt against a pre-set non-inferiority margin of 20%.
Study design
3, 6, 9 and 12 months
Intervention
The following dose reduction strategy will be adviced to rheumatologists: For patients allocated to the T2T strategy group with tapering attempt the TNFi dose will be reduced about one third by extending the interval every 3 months from 14 to 21 to 28 days for adalimumab and certolizumab, from 7 to 10 to 14 days for etanercept, from 4 to 6 to 8 weeks for golimumab, after which the TNFi will be stopped For infliximab, the interval will remain 8 weeks but the dose will be reduced every 3 months from 3 to 2.25 to 1.5 mg/kg bodyweight after which infliximab will be stopped When a persistent loss of response/flare occurs, the treatment is intensified to the last effective interval/dose. Patients allocated to the T2T strategy group without tapering attempt will continue treatment following a standardized protocol that is aimed to maintain LDA, at the discretion of the rheumatologist and patiënt. Patients will have a 12 month follow-up period, which will be extended by an additional 12 months observational period (total 24 months of follow-up).
Inclusion criteria
- Eligible patients are ≥ 16 years of age at the time of signing the informed consent form AND
1) have peripheral SpA of the psoriatic arthritis subtype diagnosed clinically by the rheumatologist , supported by the Classification Criteria for Psoriatic Arthritis (CASPAR) and/or
2) have axial SpA of the axial spondyloarthritis subtype, supported by the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, AND
- Are using full dose, or at least > 50% of the authorized defined daily dose (DDD), of an originator or biosimilar TNFi (adalimumab, certolizumab, etanercept, golimumab, infliximab);
- Patients have to have stable LDA, Psoriatic Arthritis Disease Activity Score (PASDAS) ≤ 3.2 and a skin measure of body surface area involvement (modified BSA) using a target of 3% as used by rheumatologists in clinical practice for PsA and/or Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and an absence of active extra-axial symptoms such as Crohn’s disease, uveitis, colitis or psoriasis for axSpA, for at least 6 months, or when formal measurements are not available, judgement of physician and patient.
Exclusion criteria
- Previous recorded unsuccessful dose reduction of TNFi in the previous 24 months,
- Comorbidities expected to hamper successful dose reduction (e g Crohns disease, Ulcerative colitis, Psoriasis, Uveitis),
- Not able to have 12 months follow-up (life expectancy, planned relocation),
- Not able to measure outcome (language, other limitations)
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL6771 |
| NTR-old | NTR7640 |
| CCMO | NL66181.091.18 |
| OMON | NL-OMON49692 |