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%.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
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
Spondyloarthritis (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. Both PsA/axSpA
treatment strategy studies as well as specifically TNFi tapering studies have
been identified in the most recent 2017 European research agenda on PsA/axSpA.
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
This study is a pragmatic, open-label, randomised controlled, non-inferiority
strategy trial. 95 (PsA and AxSpA together) patients already receiving TNFi and
having LDA for at least 6 months will be randomised to a T2T strategy with
versus without tapering attempt of TNFi therapy using a concealed randomisation
procedure, stratified for PsA and axSpA and csDMARDs. Follow up duration will
be 12 months for all patients. The control arm will receive a T2T strategy
without tapering attempt and the intervention arm will receive aT2T strategy
with tapering attempt following a dose reduction strategy for each TNFi in
which the dose interval will be increased every 3 months when disease activity
remains low. As the final step of dose reduction, TNFi therapy is discontinued.
When a persistent loss of response/flare occurs, the treatment is intensified
to the last effective interval/dose.
Intervention
The following T2T strategy will be adviced to rheumatologists: For patients
allocated to the T2T strategy with tapering attempt group 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 without tapering attempt group will continue
treatment following a standardized protocol that is aimed to maintain LDA, at
the discretion of the rheumatologist and patient.
Study burden and risks
In daily practice, rheumatologists monitor their patients on a ongoing basis
once every three or six months. Normally, disease activity is measured and
blood samples are collected during regular visits. In this study patients will
be scheduled to a visit once every three months. At the baseline visit,
patients are asked for baseline characteristics. Radiographs will be made of
the hands, feet and cervical, lumbar spine and SI-joints at baseline and the
last visit. If necessary, radiographs will be taken of other joints. During all
visits two blood samples will be collected. Several short questionnaires will
be completed HAQ-DI, BASFI, EUROQOL-5D-3L, SF-12, ASAS-HI, transition scale and
PASS question during all visits. The extra time required for this study is
estimated to be approximately 1 hour for the first visit and 15 minutes for the
other visits. This results in a total of 2,15 hours of extra time required for
a patient to take part in the study (excluding travel time). Risks of
participation in this study includes the chance of a temporary increase in
disease activity in the patients receiving a lower dose than they used to.
However, if this happens, the increase in disease activity will be short-lived
as the rheumatologist will immediately act. On the other hand, patients
receiving a lower dose of TNFi will have a reduced chance on TNFi related side
effects
Hengstdal 3
Ubbergen 6574 NA
NL
Hengstdal 3
Ubbergen 6574 NA
NL
Listed location countries
Age
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
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003432-72-NL |
| CCMO | NL66181.091.18 |
| OMON | NL-OMON29006 |