To assess the effect of adding a tapering decision aid on a dynamic flare prediction model to disease-activity-guided dose optimisation (DGDO) on the incidence of flares and medication use.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
- Medical device
N.a.
Outcome measures
Primary outcome
<p>Primary endpoint: the number of flares per patient over 18 months. </p>
Secondary outcome
<p>Main secondary endpoint: dose reduction (expressed as percentage of full-dose)<br />
over 18 months.</p>
Background summary
Biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) are effective in
the treatment of rheumatoid arthritis, but they have several sometimes
dose-dependent drawbacks. These include the patient*s need for self-injection,
increased risk of infection and malignancy, and high costs. Thus, the question
arises whether this adequate level of disease control can be maintained with
less medication. Recent studies have shown that disease activity guided dose
optimisation (DGDO) of bDMARDS, with trial and error dose reduction or even
discontinuation in RA, is non-inferior to usual care. Results showed no
difference in functional status, quality of life, relevant radiographic
progression or adverse events between DGDO and usual care, although long-term
effects are not fully clear. DGDO does however inherently increase the risk of
short-lived flares, estimates in the DRESS study being 73% vs 27%. This can
make doctors and patients hesitant to start the DGDO process. Therefore, the
need arises to better predict and prevent flares during tapering.
We previously developed and externally validated a dynamic prediction model to
predict the probability of a flare occurring within 3 months. By predicting a
flare, tapering may be halted in time to prevent a flare. Our dynamic
prediction model performed moderately well with an area under the ROC curve
after cross-validation of 0.76 (95% CI 0.69-0.83). Using dynamic predictions
added to DGDO to guide tapering reduced the number of flares and retained most
of the reduction in bDMARD dose compared to DGDO alone. These promising
simulation results should however be confirmed in a controlled study.
Study objective
To assess the effect of adding a tapering decision aid on a dynamic flare
prediction model to disease-activity-guided dose optimisation (DGDO) on the
incidence of flares and medication use.
Study design
Pragmatic, open, randomized, superiority, multi-centre strategy trial with 18
months follow-up.
Intervention
A tapering decision aid based on a dynamic flare prediction model in addition
to disease-activity-guided dose optimisation (DGDO) in regular patient care.
Study burden and risks
In the control group RA patients with stable low disease activity will taper
their bDMARD according to disease-activity guided dose optimisation. This has
been shown to be non-inferior to full-dose treatment and is in line with the
advice of a review of 45 tapering studies and a recent Cochrane review.
However, because this strategy may increase the risk of short-lived flares, the
tapering in the intervention group will be assisted by a tapering decision aid
aiming to halt tapering before a flare occurs. Thus, by definition there will
be less flares in the intervention group. When a flare occurs (or when a flare
is predicted in the intervention group), tapering will be halted in both
groups, and no further tapering attempts will be taken. The treating
rheumatologist is free to deviate from the protocol if he/she deems this
medically necessary. Participation in the trial requires only very limited
extra work for patients, as the 3-monthly visits with assessment of disease
activity are standard in regular care. In addition, patients will be asked to
fill out a limited set of questionnaires at regular intervals.
P.M.J. Welsing
Heidelberglaan 100
Utrecht 3584 CX
Netherlands
088-7550459
reumatologie-research@umcutrecht.nl
P.M.J. Welsing
Heidelberglaan 100
Utrecht 3584 CX
Netherlands
088-7550459
reumatologie-research@umcutrecht.nl
Trial sites in the Netherlands
Listed location countries
Age
Inclusion criteria
• A clinical diagnosis of rheumatoid arthritis as assessed by the treating
rheumatologist.
It will be registered if patients meet ACR 1987 or EULAR/ACR 2010 criteria. If
these criteria are not met, the separate components of the criteria will be
registered.
• Treatment of their RA with one of the following bDMARDs that are registered
for RA in >=66% of the standard dose (i.e. maximally one dose reduction step
previously taken): adalimumab, certolizumab, golimumab, infliximab, etanercept,
sarilumab, tocilizumab or abatacept).
• Patient is eligible to taper bDMARD according to treating physician (i.e. no
other indication for bDMARD such as psoriasis or IBD, i.e. no recent relevant
radiographic progression).
• Stable low disease activity with current bDMARD for >= 6 months according to
treating physician
• Current DAS28-CRP <= 2.9 (low disease activity)
or
Current stable low disease activity according to treating physician and patient
with a maximum DAS28-CRP <=3.5 (i.e. 2.9 + measurement error in DAS28
(~0.6)(33)).
• Patient is willing to taper (and if possible, stop) his/her bDMARD as well as
to continue his/her current bDMARD dose.
• At least 18 years of age
Exclusion criteria
• Recent earlier (<6 months) tapering attempt(s) with the same bDMARD that
failed according to treating physician
• Inability to comply with protocol, e.g. no possibility to measure outcome
over 18 months, e.g. insufficient knowledge of the Dutch language
Design
Recruitment
Medical products/devices used
IPD sharing statement
Plan description
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 |
|---|---|
| CCMO | NL74537.041.21 |
| Research portal | NL-008028 |