|- candidate number||10712|
|- NTR Number||NTR3216|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||21-dec-2011|
|- Secondary IDs||NL37704.091.11 CMO|
|- Public Title||Onderzoek naar non inferioriteit van afbouw en stop behandelstrategieŽn van adalimumab of etanercept bij patiŽnten met reumatoÔde artritis: Kosten besparen tegen welke prijs?|
|- Scientific Title||Randomised controlled non-inferiority study of dose reduction and withdrawal strategies of adalimumab and etanercept in rheumatoid arthritis: Saving costs at what expense?|
|- ACRONYM||DRESS (Dose REduction Strategies of Subcutaneous TNF inhibitors)|
|- hypothesis||Dose reduction and withdrawal is feasible in a proportion of RA patients without increase in disease activity.|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis, Etanercept, Adalimumab, Dosis reduction|
|- Inclusion criteria||1. Rheumatoid arthritis (either 2010 ACR RA20 and/or 1987 RA21 criteria and/or clinical diagnosis of the treating rheumatologist, fulfilled at any time point between start of the disease and inclusion);|
2. Using either adalimumab or etanercept (all dose/interval regimens, all background medication including DMARDs and corticosteroids up to 5 mg, higher doses of steroids should be reduced first);
3. 6 months of stable low disease activity while using adalimumab or etanercept (operationalised by either a DAS28 < 3.2 or judgment of low disease activity by rheumatologist at at least two subsequent visits);
4. 6 months stable treatment with adalimumab or etanercept (previous dose reduction/interval increase is allowed when more than three months ago) and stable DMARDs and corticosteroids for more than 4 weeks;
5. Previous (unsuccessful) dose de-escalation of current or previous biological is no exclusion criterion;
6. Informed consent;
7. Ability to measure the outcome of the study in this patient (e.g. life expectancy > 1 year, no planned relocation);
8. Ability to read and communicate well in Dutch.
|- Exclusion criteria||Co morbidity that also requires treatment with anti-TNF and thus prevents dose reduction.|
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||12-dec-2011|
|- planned closingdate||1-jan-2014|
|- Target number of participants||180|
|- Interventions||Randomisation into control or intervention group.|
In the control group usual care and tight control (visit every 3 months, extra visit in case of flare, DAS28 measurement on day of outpatient clinic visit, standardised treatment protocol)is provided.
In the intervention group tight control is provided and the treating rheumatologist is advised to try to increase the interval of adalimumab or etanercept.
If a patient uses adalimumab the dosage will be kept the same and the interval will be stepwise increased every three months from 14 to 21 to 28 days, after that the adalimumab will be stopped. If a patient uses etanercept, the dosage will be kept the same and the interval will be stepwise increased very three months from 7 to 10 to 14 days, after that the etanercept will be stopped. When a persistent flare occurs in disease activity, the treatment is intensified and interval is shortened back to the last effective interval.
|- Primary outcome||Cumulative incidence of patients fulfilling prespecified loss of response/flare criteria in the intervention and the usual care group after 9 months and after 18 months of follow up.|
|- Secondary outcome||1. Cost effectiveness (cost minimisation) ratio between intervention group and usual care group for the 9 month induction phase and for the 12 months maintenance phase;|
2. Predictive values/characteristics of a prediction model including (change in) serum drug levels and PET arthritis;
3. Proportion of patients with a change in modified Sharp-van der Heijde Score> MCIC in the intervention and usual care group.
|- Timepoints||Visit at 0,3,6,9,12,15,18 months in both groups
In case of flare of disease activity an extra visit is planned.|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Drs. N. Herwaarden, van|
|- CONTACT for SCIENTIFIC QUERIES||Dr. A.A. Broeder, den|
|- Sponsor/Initiator ||Sint Maartenskliniek Nijmegen|
(Source(s) of Monetary or Material Support)
|Sint Maartenskliniek Nijmegen|
|- Brief summary||Background:|
TNF Blocking agents are effective in the treatent of Rheumatoid Arthritis (RA), with adalimumab and etanercept being the two most frequently used agents in the Netherlands. These drugs are associated with side effects, including a dose dependent increased risk for infection. Also, these agents are much more expensive than traditional anti-rheumatic drugs (DMARDs), thus increasing the costs of treatment. Therefore, it seems rational to give these drugs in the lowest effective dose and stop the treatment when it is no longer necessary.
There are data that suggest that dose reduction and withdrawal of TNF blocking agents is feasible in a subgroup of patients without relevant increase in disease activity. However, a number patients will not be able to reduce doce and will develop a temporary increase in disease activity. Therefore it is usefull to find predictive factors for succesfull dose reduction.
The main objectives are to evaluate effectiveness, cost effectiveness and safety of a dose reduction and withdrawal strategy compared to usual care and to find predictive factors for succesfull down titration/withdrawal.
Pragmatic open randomised controlled cost effectiveness strategy trial, stratified for anti-TNF agent. This study has an induction phase from 0-9 months and a maintenance phase from 6 to 18 months.
Patients with rheumatoid arthritis using adalimumab or etanercept for at least 6 months and stable low disease activity during this time.
Control group: usual care with tight control. A visit is planned every three months, DAS28 measurement is provided on the day of the outpatient clinic visit. There is a standardised protocol wich offers treatment suggestions in case of loss of response and patients are encouraged to contact the outpatient clinic when they experience more complaints.
Background treatment, monitoring of disease, tight control and flare criteria is the same as in the usual care group.
With addition of a dose reduction and withdrawal strategy advice to the treating rheumatologist. If a patient uses adalimumab, the interval will be stepwise increase every three months: 14,21,28 days and stop. For etanercept: 7,10,14 days and stop. In case of a persistant flare, the interval is shortened back to the last effective interval.
The primary outcome of this study will be the cumulative incidence of flare in intervention and usual care group after 8 and 18 months of follow up.
Secondary outcomes of this study include cost effectiviness ratio between intervention and usual care group. Predictive factors for succesfull dose reduction and progression of radiological damage.
|- Main changes (audit trail)||17-Mar-2013: Newly formulated primary outcome - NM|
Primary outcome: Asses whether the difference in cumulative incidence in persistent RA flares (DAS28 increase of more than 1.2 or a DAS28 increase of more than 0.6 with a current DAS28≥3.2) with a duration of >3 months between the intervention group and the usual care group does not exceed the non-inferiority margin of 20% after 18 months follow up.
|- RECORD||21-dec-2011 - 23-mrt-2013|