To study whether polytherapy (methotrexate plus sulfasalazine plus hydroxychloroquine) results in more patients with inactive disease and therefore less patients who need treatment with a TNF inhibitor after 6 months of treatment compared to primary…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the number of patients in both treatment
strategies who have active disease after 6 months of treatment.
Secondary outcome
- To compare side effects and tolerability of treatment in both treatment
arms
- To compare the number of patients that are treated with a TNF inhibitor after
12 months of treatment in both arms
- To compare the number of patients that need to switch to subcutaneous MTX
after 3 months of treatment in both treatment arms
- To compare ACR Pedi scores (30, 50, 70, 90) in both treatment groups at 3,
6, 9, and 12 months and the number of patients with inactive disease at 3, 9
and 12 months of treatment
- To compare functional ability and quality of life in both treatment arms
- To provide cost-effectiveness data concerning the first year of DMARD therapy
in both groups
- To identify possible predictors of response such as serologic markers,
urinary markers, genetic biomarkers and faecal microbiota
Background summary
Initial disease modifying antirheumatic drug (DMARD) therapy with methotrexate
in children with juvenile idiopathic arthritis (JIA) has low efficacy (±20%
inactive disease after 6 months) and is often poorly tolerated. For this
reason, it has been proposed that TNF-inhibitors may be used as a first-line
treatment. The response to TNF inhibitors is often more rapid, but the
treatment has the downside of parenteral use and high costs. In adults with
rheumatoid arthritis, polytherapy with a combination of DMARDs has been proven
to be very effective. We therefore propose that polytherapy with methotrexate
plus sulfasalazine plus hydroxychloroquine could be beneficial for children
with juvenile idiopathic arthritis who require DMARD therapy.
Study objective
To study whether polytherapy (methotrexate plus sulfasalazine plus
hydroxychloroquine) results in more patients with inactive disease and
therefore less patients who need treatment with a TNF inhibitor after 6 months
of treatment compared to primary MTX monotherapy in children with newly
diagnosed JIA.
Study design
A multicentre, single-blinded, randomized treat to target, one-year follow-up
clinical trial
Intervention
Patients are randomly assigned to one of two treatment strategies:
monotherapy with methotrexate (in combination with prednisolone bridging) or
polytherapy with methotrexate plus sulfasalazine plus hydroxychloroquine (in
combination with prednisolone bridging). When ACR Pedi 50 is not met after 3
months of treatment, methotrexate will be given subcutaneously. When at 6
months inactive disease is not reached a TNF-inhibitor will be started.
Study burden and risks
This study focuses on the treatment of JIA and can therefore only be performed
in children (2-16 years old). During the study, blood sampling and visits to
the outpatient clinic are part of regular care. The side effects of polytherapy
are expected to be similar or slightly increased compared to methotrexate
monotherapy. Participation in this study may lead to earlier achievement of
inactive disease and therefore no need to administer methotrexate
subcutaneously or to switch to (subcutaneous) biologic treatment.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
- Patients with persistent or extended oligoarticular JIA,
RF-negative polyarticular JIA, RF-positive polyiarticular JIA, psoriatic JIA,
enthesitis- related JIA or undifferentiated JIA according to ILAR
Classification criteria
- Active synovitis;
- Requiring DMARD therapy according to the treating pediatric rheumatologist.
In case of persistent oligoarticular JIA this means patients with poor clinical
prognostic factors, for example according to Beukelman;
- Age between 2-16 years;
- Treated in one of the Dutch paediatric rheumatology centers;
- A maximum of 18 months of symptoms;
Exclusion criteria
- Systemic onset Juvenile Idiopathic Arthritis - Previous
treatment with DMARDs (including study medication) or biological - Any
concurrent illness that would constitute an increased risk for side effects of
medication, is associated with an increased risk for severe infections or in
the opinion of the treating physician is a contraindication for treatment with
any of the initial therapies or participation in the trial as such. - Current
or prior history of blood dyscrasias. Abnormal safety baseline blood test e.g.
haemoglobin <= 5 mmol/l; haematocrit <= 27%; platelet count <= 125 x 109 /L; white
blood cell count <= 3.5x 109 /L; serum creatinine >= 2 times the laboratory*s
upper limit of normal; aspartate aminotransferase (AST [SGOT]) and alanine
aminotransferase (ALT [SGPT]) >= 2 times the laboratory*s upper limit of normal.
- Pregnancydie in meerd
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 |
|---|---|
| EudraCT | EUCTR2014-003260-20-NL |
| CCMO | NL53170.058.15 |