Mechanism of Action of Ustekinumab in Psoriatic Arthritis

Rationale: The overall aim of the study is to determine which downstream cellular and molecular pathways involved in psoriatic arthritis (PsA) pathogenesis are modulated by Interleukine 23/Interleukine12 P40 subunit (IL23/12 P40) blockade. As we have ample evidence that relevant disease-specific pathways are found in the primary target tissues, in particular in synovial tissue obtained from peripheral joints, but not in peripheral blood, we will strongly focus on this compartment by obtaining paired biopsies before and after treatment. Objectives: The primary objective is to assess the effect of IL23/12 P40 blockade on cellular en molecular pathways involved in PsA disease in the synovium, in the synovial fluid and peripheral blood. The secondary objective is to compare which cellular/molecular disease pathways are affected by IL23/12 P40 blockade and not by tumour necrosis factor (TNF) blockade and thereby identify molecular biomarkers which may help to determine which patients may benefit from this treatment in comparison with anti-TNF treatment. Study design: Single centre, 24-week open-label study in subjects with clinically active peripheral psoriatic arthritis receiving treatment with ustekinumab. Synovial biopsies will be obtained from patients before and after 12 and 24 weeks of treatment with ustekinumab. Study population: Patients with a diagnosis of psoriatic arthritis according to the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria with at least one swollen knee or ankle joint who are planning to receive treatment with ustekinumab at the outpatient clinic. In total 16 patients will be included. Intervention: Blood withdrawal and mini-arthroscopies at different timepoints. Main study parameters/endpoints: Primary study parameters/outcome of the study: • Changes in the synovial cellular infiltrate and molecular pathways influenced between baseline and week 12/ week24 Secondary study parameters/outcome of the study: • Comparison of the synovial molecular changes induced by anti-p40 with the changes induced by anti-TNF (analysed in historical samples in a similar patient population and study setting)