To compare the effectiveness of MTX monotherapy with MTX and LEF combination therapy in cDMARD-naïve psoriatic arthritis patients.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is the difference in efficacy between monotherapy MTX and
combination therapy MTX plus LEF on Psoriatic Arthritis Disease Activity Score
(PASDAS) at 16 weeks.
Key secondary parameters are: change in skin score, enthesitis score,
dactylitis score and swollen/tender joint count. Furthermore, the difference in
immunoprofile, treatment failure, and the percentage of (S)AE*s between the two
groups will be assessed.
Secondary outcome
Key secondary parameters are: change in skin score, enthesitis score,
dactylitis score and swollen/tender joint count. Furthermore, the difference in
immunoprofile, treatment failure, and the percentage of (S)AE*s between the two
groups will be assessed.
Background summary
Psoriatic arthritis (PsA) is a heterogeneous disease which involves at least
five domains: peripheral joint disease, enthesitis, dactylitis, axial
involvement, and skin and nail psoriasis. Once diagnosed PsA is notoriously
difficult to treat. Monotherapy with first-line disease-modifying antirheumatic
drugs (conventional (c)DMARDs: e.g. methotrexate, leflunomide) appears to lack
efficacy in a substantial portion of patients. The effectiveness of cDMARDs on
multiple domains in PsA is either inconsistent or not known. Furthermore, the
effectiveness of combination cDMARD therapy in PsA has not been researched in
representative studies. A combination of Methotrexate (MTX) and Leflunomide
(LEF) has been proven effective in patients with rheumatoid arthritis.
Therefore, we hypothesize that MTX and LEF combination therapy is superior to
MTX monotherapy in patients with psoriatic arthritis.
Study objective
To compare the effectiveness of MTX monotherapy with MTX and LEF combination
therapy in cDMARD-naïve psoriatic arthritis patients.
Study design
Monocentre, pragmatic, double-blind, placebo-controlled, randomized clinical
trial in cDMARD-naïve psoriatic arthritis patients. Patients will be randomised
1:1 to receive either MTX monotherapy (arm 1) or MTX and LEF combination
therapy (arm 2). Treatment response will be assessed at 16 weeks and in case
of treatment failure, further treatment decisions are based on shared decision
making between patient and treating physician and according to local treatment
protocol (usual care).
Intervention
One group receives methotrexate 25 mg (oral or subcutaneous) once weekly plus
2 placebo tablets daily. The other group receives methotrexate 25 mg (oral or
subcutaneous) once weekly plus 2 leflunomide 10 mg tablets daily.
Study burden and risks
-Venapuncture (4x), low risk. This will be done according to our local toxicity
protocol and is part of usual care when patients start with cDMARD therapy.
Only if patients participate in the additional blood sampling for the
explorative immunoprofiling objective, an extra venapuncture at baseline will
be performed (if it is not possible to combine this with regular blood
drawing).
-Clinical examinations and questionnaires (two assessment points), low burden.
The intervention will be embedded in daily clinical care. The study visits will
be planned in combination with the regular clinical visit. Filling out of
questionnaires will take 15-30 minutes.
-Therapeutic intervention with either monotherapy MTX (first line treatment in
usual care ) or combination therapy MTX and LEF( used as second line treatment
regimen in usual care) in PsA patients in the St Maartenskliniek, low risk .
The cDMARDs that will be administered in this trial are common and registered
treatments for patients with PsA.
Hengstdal 3
Ubbergen 6574 NA
NL
Hengstdal 3
Ubbergen 6574 NA
NL
Listed location countries
Age
Inclusion criteria
-Adult male or female;-Age *18 years;-Clinical diagnoses of PsA;-Evidence of active disease defined as *2 swollen joints, dactylitis counts as 1 swollen joint.;-Subjects that have used cDMARDs and/or bDMARDs before, must have discontinued this treatment for at least 6 months prior to baseline visit. ;-Subjects who are already taking NSAIDs/COX-2 inhibitors may participate in the study but the dose has to be stable for at least one week prior to first dose of study drug;-Oral or injected corticosteroids (intramuscular, intravenous and intra-articular) have to be discontinued 8 weeks prior to first dose of study drug
Exclusion criteria
-Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 2 years after the last dose of study drug or up to 11 days after treatment when washout procedure is executed.;-Male subject who is considering fathering a child or donating sperm during the study or for approximately 2 years after the last dose of study drug or up to 11 days after treatment when washout procedure is executed.;-History of an inadequate response to MTX or LEF (prescribed by a rheumatologist for joint disease). ;-Current severe infection including, but not limited to:;oActive human immunodeficiency virus (HIV);oActive TB;-History of an allergic reaction or significant sensitivity to constituents of the study drugs (MTX/LEF);-Current or history of liver insufficiency;-History of clinically significant (per Investigator's judgment) drug or alcohol abuse within the last 6 months prior to baseline visit. ;-Current or recent history of a severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular or neurologic disease. ;-History of any fibromyalgia or diagnosis of inflammatory rheumatic disease other than PsA. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly.;-Abnormal laboratory values within 1 month prior to baseline visit: ;oSerum alanine transaminase (ALT) > 1.5 × ULN;;oEstimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m2;;oTotal white blood cell count (WBC) < 3,000/*L;;oPlatelet count < 100,000/*L;;oHemoglobin < 10 g/dL (6.3 mmol/L).;-Current persistent hypertension requiring start or change of treatment regimen;-Malignancy in the past 5 years except for non-melanoma skin cancer
Design
Recruitment
Medical products/devices used
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 | EUCTR2018-002362-39-NL |
| CCMO | NL66544.091.18 |