|- candidate number||9111|
|- NTR Number||NTR2754|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||14-feb-2011|
|- Secondary IDs||171102014 ZonMw|
|- Public Title||Afbouw strategieŰn bij door anti-TNF&MTX ge´nduceerde remissie bij Reumato´de Arthritis. Moeten we MTX of anti-TNF als eerste afbouwen?|
|- Scientific Title||TApering strategies in TNFi&MTX induced remission in Rheumatoid Arthritis. Should we taper MTX or TNFi first?|
|- hypothesis||In RA patients that achieved disease remission by treatment with the combination of metothrexate and anti-TNF, there is a difference in (cost-)effectiveness when medication is tapered according to strategy A (metothrexate first) compared to strategy B (anti-TNF first).|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis|
|- Inclusion criteria||1. RA patients;|
2. Aged >17 years;
3. Treated with MTX&adalimumab or etanercept;
4. DAS44 <= 1.6 for two consecutive time points (3 months).
|- Exclusion criteria||1. Not being able to understand, speak and write in Dutch;|
2. Being diagnosed with a psychiatric or personality disorder.
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mrt-2011|
|- planned closingdate||31-aug-2015|
|- Target number of participants||355|
|- Interventions||Randomization into two arms:|
1. Tapering methotrexate first, then etanercept or adalimumab;
2. Tapering etanercept or adalimumab first, then methotrexate.
|- Primary outcome||1. Number of flares in each arm;|
2. Incremental Cost Effectiveness Ratio (ICER) of one strategy over the other.
|- Secondary outcome||1. Radiographic progression after 1 and 2 years;|
2. HAQ, the SF36, sick leave, productivity loss at work and cost-effectiveness modelled over the long term.
|- Timepoints||1. 3-monthly evaluation of disease activity and collection of questionnaires;|
2. 2 years of follow-up.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||MD. MSc. T.M. Kuijper|
|- CONTACT for SCIENTIFIC QUERIES||Prof. J.M.W. Hazes|
|- Sponsor/Initiator ||Erasmus Medical Center, Rotterdam|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||Background:|
Economic evaluation of tapering medication in Rheumatoid Arthritis (RA) is important because of the increasing use of expensive biologicals in the treatment of RA. Previous uncontrolled cohort studies showed that it is possible to taper anti-TNF or MTX while maintaining remission of disease in approximately 40% of the rheumatoid arthritis (RA) patients that use the combination of MTX&anti-TNF. This is not yet common practice which may relate to the fact that it is unclear which step down (tapering) regime would be optimal. There are no head-to-head studies available comparing the tapering of MTX with tapering of anti-TNF in MTX&anti-TNF using patients in clinical remission.
Our main aim is to evaluate the effectiveness and cost-effectiveness of two tapering strategies:(i)MTX tapering and (ii)anti-TNF tapering in RA patients with MTX&anti-TNF(adalimumab/etanercept) induced remission.
A multicenter randomised single-blind controlled trial with a parallel cost-effectiveness study will be set up to compare the outcomes of the 2 tapering strategies over a 2-yr period.
RA patients, aged>17 years, treated with MTX &adalimumab or etanercept, DAS<=1.6 for two consecutive time points (3 months), being able to understand, speak and write in Dutch and having no psychiatric or personality disorders. Patients will be excluded if they need to taper or stop their medication due to other reasons such as the wish to get pregnant or a scheduled surgery.
Two tapering strategies will be evaluated.
Tapering MTX: The baseline dosage will be tapered in two steps over 12 months. In the first 3 months the dosage of MTX will be gradually reduced to half the baseline dosage, followed by a 3 month consolidation period, than in 3 months gradually tapered to a quarter of the baseline dosage with a minimum of 5 mg per week. Again this will be followed by a consolidation period of 3 months. Thereafter the MTX will be stopped. Anti-TNF will be continued for these 15 months.
Tapering anti-TNF: The baseline dosage of anti-TNF will be tapered in two steps over 12 months. In the first step by dividing the baseline dose to halve and this will be continued for 6 months. In the second step the baseline dose will be reduced to a quarter of the baseline dose, again followed by a 6-months consolidation period. Thereafter the anti-TNF treatment is stopped. Baseline MTX dosage will be continued for 15 months.
Tapering will be terminated if the DAS >1.6 at one of the 3-month follow-ups. Depending on the DAS increase patients are either switched to the last effective dosage(DAS>2.4) or continued in current dosage (DAS1.6-2.4) while 1 intra-muscular injection with glucocorticosteroids will be allowed each 3-month period. No further attempts will be taken to taper medication during the first 15 months of the study. From 15 months onwards, rheumatologists are free to prescribe any disease modifying anti rheumatic drug (DMARD) that they think is necessary to continue tight-controlled care aiming for remission.
Primary outcomes of the study:
Primary outcome clinical effectiveness: Disease flare defined as DAS44>2.4 in the first 15 months.
Primary outcome cost-effectiveness: Incremental Cost Effectiveness Ratio (ICER) of tapering MTX versus tapering anti-TNF in terms of cost per QALY gained and in terms of cost per tapered patient.
Secundary outcome of the study:
Secondary outcomes will include radiographic progression at 1 and 2 years, the HAQ, the SF36, sick leave, productivity loss at work and cost-effectiveness modelled over the long term.
|- Main changes (audit trail)|
|- RECORD||14-feb-2011 - 21-feb-2011|