We aim to estimate the difference in effectiveness of DAS28CRP low disease activity and SDAI remission as treatment targets in RA treat to target strategies with regard to RA outcome.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome of this trial is the proportion of patients that score
positive for the dichotomous composite outcome for clinical and radiological
remission. This composite measure includes:
- radiographic progression <= 1 SENS score point
- <=1 swollen joints detected during joint count
- Positive patient acceptable symptom state (PASS)
Secondary outcome
Secondary outcomes in this study are defined as:
1. All individual parts of the composite primary endpoint including
radiographic progression, number of swollen joints and proportion of patients
being in PASS at 18 months follow-up
2. The proportion of patients who reach the predefined target for each
treatment arm (DAS28CRP-LDA or SDAI remission)
3. Percentage of patients that reach LDA or remission, using DAS28CRP- and
SDAI-based definitions, in each treatment arm
4. Number of flares that occur in each treatment arm over 18-months follow-up
5. Daily functioning, measured by HAQ DI
6. Physician T2T/Ta2T protocol adherence
7. Drug use of the patients, consisting of the type and volume of antirheumatic
drugs (GC, DMARDS, NSAIDs) used over the 18 months period, and at 18 months
visit
8. Safety ((serious) adverse events, according to CTCAE criteria version 5.0)
9. Quality of life (QoL) as defined by the EQ5-D-5L questionnaire
10. Costs: volumes of medical costs and productivity loss
Background summary
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by
inflammation of synovial joints. RA patients present with pain, stiffness and
swelling of the affected joints. Due to high direct and indirect medical costs,
RA is associated with a great economic burden for both patients and society.
There is currently no cure for RA, but many treatment options are available.
The central aim of RA treatment is lowering disease activity. The proactive
treatment strategy called treat to target (T2T) includes measuring disease
activity, setting a target and adjusting treatment accordingly until the goal
is reached. Additionally, the strategy can be implied in the phase when stable
disease or remission is reached to taper the drug, also called *taper to
target* (Ta2T). T2T has proven to be superior to usual care, but there is much
debate regarding the most optimal treatment measure and target. The Disease
Activity Score with 28-joint counts and c-reactive protein (DAS28CRP)
low-disease activity (LDA) target and the more stringent Simplified Disease
Activity Index (SDAI) remission target are the best validated targets.
Especially the DAS28CPR is the most commonly used in research and practice,
whereas the SDAI remission target is most recommended. The EULAR recommends to
strive for remission, whereas the ACR recommends to strive for LDA.
In patients with new and established RA, the (cost)effectiveness of aiming for
remission compared to LDA when starting and tapering antirheumatic drugs has
not been directly compared. This study therefore aims to directly compare two
T2T strategies, aiming at DAS28CRP-LDA and SDAI remission, in patients with
established RA.
Study objective
We aim to estimate the difference in effectiveness of DAS28CRP low disease
activity and SDAI remission as treatment targets in RA treat to target
strategies with regard to RA outcome.
Study design
A multi-centre, randomized strategy trial in 340 patients with an existing
diagnosis of RA. Patients are randomised towards a treatment target of :
1. Disease Activity Score with 28-joint counts and c-reactive protein
(DAS28CRP), low-disease activity target
2. Simplified Disease Activity Index (SDAI), remission target
A follow-up period of 18 months is chosen to facilitate assessment of the full
difference between the two arms, as some time is needed in T2T for each drug to
show its effect (3-6 months). Several iterative cycles might be necessary to
arrive at the desired effect, with another six months until any changes in
radiological progression can be seen. Both strategies are already implemented
in clinical practice and all drugs used are already authorised for RA.
Intervention
Patients are randomised towards a treatment target of :
1. Disease Activity Score with 28-joint counts and c-reactive protein
(DAS28CRP), low-disease activity target
2. Simplified Disease Activity Index (SDAI), remission target
Study burden and risks
During the trial period, patients are asked to fill in different questionnaires
at different points in time. It is estimated that the questionnaires take less
than 30 minutes to complete. The remainder of the data will be measured and
collected by a trained nurse at different points in time during the trial.
In the literature, it has been established that T2T strategies are more
effective compared to usual care in newly diagnosed RA. There is a risk for the
patients that one of the T2T strategies might be less effective than the other.
However, it is thought to still be more effective than usual care. Therefore,
there is limited additional risk for the patients that participate in this
study.
Hengstdal 3
Ubbergen 6574 NA
NL
Hengstdal 3
Ubbergen 6574 NA
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of RA (according to the 2010 ACR/ EULAR classification criteria
and/or clinical diagnosis)
- Aged 16 years or older
- At most low disease activity, operationalised as DAS28-CRP <3.5 (DAS28 CRP
2.9 cut off for low disease activity with measurement error 0.6) or SDAI < 19
(SDAI 11 cut off for low disease activity with measurement error 8) or the
rheumatologist*s opinion. A state of low disease activity is required at
inclusion, as for RA patients in moderate or high disease activity there is no
equipoise on the best course of action (treatment needs to be escalated, both
in case of aiming for remission or LDA).
- Fluency of Dutch or English, both written and verbally; able to fill in
questionnaires
- Provided informed consent
Exclusion criteria
- Clinical deep remission, operationalised as SDAI <3.3 or DAS28-CRP
<2.4, AND a taper attempt in the past 2 years that was discontinued due to
occurrence of flare.
- Fewer than 3 DMARD treatment options left for this patient (severe
difficult-to-treat or refractory RA)
- Current severe comorbidity or other serious life-shortening conditions
hampering trial participation
- Inability to comply with the study protocol or to provide informed consent
with regard to intervention control and measuring outcomes
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrial.gov nummer volgt |
| CCMO | NL84995.091.23 |