Comparing Methotrexate monotherapy with methotrexate Plus LEflunomide combination ThErapy in Psoriatic Arthritis: A pragmatic randomized placebo-controlled double-blind clinical trial.

INTERVENTION: Trade Name: Leflunomide (Arava) Product Name: Leflunomide Pharmaceutical Form: Capsule Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Trade Name: Methotrexate (pharmachemie) Product Name: Methotrexate Pharmaceutical Form: Injection CONDITION: Adults diagnosed with Psoriatic Arthritis Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: To compare the effectiveness of MTX monotherapy with MTX and LEF combination therapy in cDMARD‐naïve psoriatic arthritis patients. Primary end point(s): PASDAS score at 16 weeks Secondary Objective: 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. Timepoint(s) of evaluation of this end point: Baseline; week 16 SECONDARY OUTCOME: Secondary end point(s): Clinical: ; ‐The difference in proportion of patients in LDA state, PASDAS =3.2, in PsA patients between the two arms at week 16 ; ‐The difference in proportion of patients in LDA state (DAPSA =14) in PsA patients between the two arms at week 16 ; ‐The change of DAPSA score from baseline to 16 weeks ; ‐The difference in proportion of patients fulfilling Minimal Disease Activity (MDA) criteria between the two arms at week 16 ; ‐The disease impact and quality of life of patients with PsA from pre‐ to post treatment: ; •PsA impact of disease (PSAID) at baseline and week 16 ; •Health assessment questionnaire (HAQ) at baseline and week 16 ; •Short Form (12) Health Survey (SF12) at baseline and week 16 ; ‐The change in skin score (PGA, BSA) between baseline and 16 weeks ; ‐The change in swollen joint count between baseline and 16 weeks ; ‐The change in tender joint count between baseline and 16 weeks ; ‐The change in dactylitis score between baseline and 16 weeks ; ‐The change in enthesitis score between baseline and 16 weeks ; ; Laboratory: ; ‐To assess whether baseline ‘ immunoprofiling’ factors of patients are predictive for treatment response on MTX monotherapy or MTX and LEF combination therapy ; ; Safety: ; ‐The safety of MTX and LEF combination therapy, by comparing the percentage of adverse events and serious adverse events between the 2 arms ; Timepoint(s) of evaluation of this end point: baseline ; week 16 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8