Methotrexate and leflunomide combination therapy in psoriatic arthritis

-Adult male or female

-Age ≥16 years

-Clinical diagnoses of Psoriatic arthritis

-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

-Intramuscular and intra-articular corticosteroids have to be discontinued 8 weeks prior to first dose of study drug. With the exception of a failed intra-articular corticosteroid injection (defined as remaining swelling and (if previously present) tenderness of the injected joint 2 weeks after the injection). In the case of a failed injection, patients can participate in the study 2 weeks after the intra-articular injection

-Oral corticosteroids have to be discontinued 10 days prior to first dose of study drug

-If fumaric acid is used at baseline, this will be discontinued and switched to study medication (according to usual care)

-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:

o Active human immunodeficiency virus (HIV)

o Active TB

-History of an allergic reaction or significant sensitivity to constituents of the study drugs

-Current or history of hepatic disease, including, but not limited to:

o Non-alcoholic Fatty Liver Disease (NAFLD)

o Non-alcoholic Steatohepatitis (NASH)

o Alcoholic cirrhosis

-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. With the exception of an inflammatory rheumatic disease that has been in complete remission for at least 6 months, according to treating physician’s judgment. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly or if currently no active signs of fibromyalgia are present other than those which can be explained by PsA

-Abnormal laboratory values within 1 month prior to baseline visit:

o Serum alanine transaminase (ALT) > 1.5 × ULN;

o Estimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m2;

o Total white blood cell count (WBC) < 3,000/μL;

o Platelet count < 100,000/μL;

o Hemoglobin < 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