Combination of Biologic and Anti-obesity Therapies in Psoriatic Arthritis
This is a trial to find out how weight loss (achieved by the use of tirzepatide) or ixekizumab treatment affects the characteristics of skin, joint and fat tissues in patients with Psoriatic Arthritis, Psoriasis and obesity/overweight BMI \>=27. Participants will be allocated either Tirzepatide, Ixekizumab or both. Samples of joint tissue, fat and skin will be taken at the start of the study and week 12. Blood and urine samples will also be taken. The primary objective will be to assess the changes seen in the joint, fat and skin tissue samples 12 weeks after starting the medications (additional analysis will be done on the optional 36 week samples). Secondary objectives will be * To assess the changes seen in blood 4, 12, 36 and 52 weeks after starting the medication. * To compare the changes seen in tissue and blood between Ixekizumab and Tirzepatide/Weight loss. * To see how the changes seen in the tissue relate to weight loss.
• Age \>= 18 years and \<=75 years
• Have a documented diagnosis of PsA for at least 6 months AND fulfil the CASPAR criteria (Defined as \>=3 points)
• Have active PsA defined as \>=3 swollen and \>=3 tender joints (dactylitis counts as a swollen joint).
• Have a BMI \>= 27 kg/m\^2
• Have at least one affected joint amenable to ultrasound-guided synovial biopsy (and must undergo successful synovial biopsy prior to randomisation)
• Have at least one psoriatic plaque amenable to biopsy (up to a maximum of 5 participants per treatment arm can be recruited without skin biopsy if no suitable lesion
• Capable of giving signed informed consent
• Willing and able to participate in the study and undergo synovial, adipose and skin (if appropriate) biopsies (under local anaesthetic) on at least 2 occasions