Combination of Biologic and Anti-obesity Therapies in Psoriatic Arthritis

Summary

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.

Timeline

Start

2026-03-09

Primary completion

2028-02

Completion

2030-05

Publications

• Background Green A, Shaddick G, Charlton R, Snowball J, Nightingale A, Smith C, Tillett W, McHugh N; PROMPT study group. Modifiable risk factors and the development of psoriatic arthritis in people with psoriasis. Br J Dermatol. 2020 Mar;182(3):714-720. doi: 10.1111/bjd.18227. Epub 2019 Sep 2.
• Background Love TJ, Zhu Y, Zhang Y, Wall-Burns L, Ogdie A, Gelfand JM, Choi HK. Obesity and the risk of psoriatic arthritis: a population-based study. Ann Rheum Dis. 2012 Aug;71(8):1273-7. doi: 10.1136/annrheumdis-2012-201299. Epub 2012 May 14.
• Background Li W, Han J, Qureshi AA. Obesity and risk of incident psoriatic arthritis in US women. Ann Rheum Dis. 2012 Aug;71(8):1267-72. doi: 10.1136/annrheumdis-2011-201273. Epub 2012 May 5.
• Background Setty AR, Curhan G, Choi HK. Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses' Health Study II. Arch Intern Med. 2007 Aug 13-27;167(15):1670-5. doi: 10.1001/archinte.167.15.1670.
• Background Ferguson LD, Linge J, Dahlqvist Leinhard O, Woodward R, Hall Barrientos P, Roditi G, Radjenovic A, McInnes IB, Siebert S, Sattar N. Psoriatic arthritis is associated with adverse body composition predictive of greater coronary heart disease and type 2 diabetes propensity - a cross-sectional study. Rheumatology (Oxford). 2021 Apr 6;60(4):1858-1862. doi: 10.1093/rheumatology/keaa604.
• Background Li B, Huang H, Zhao J, Deng X, Zhang Z. Discrepancy in Metabolic Syndrome between Psoriatic Arthritis and Rheumatoid Arthritis: a Direct Comparison of Two Cohorts in One Center. Rheumatol Ther. 2023 Feb;10(1):135-148. doi: 10.1007/s40744-022-00502-4. Epub 2022 Oct 20.
• Background Loganathan A, Kamalaraj N, El-Haddad C, Pile K. Systematic review and meta-analysis on prevalence of metabolic syndrome in psoriatic arthritis, rheumatoid arthritis and psoriasis. Int J Rheum Dis. 2021 Sep;24(9):1112-1120. doi: 10.1111/1756-185X.14147. Epub 2021 Jun 2.
• Background Ferguson LD, Siebert S, McInnes IB, Sattar N. Cardiometabolic comorbidities in RA and PsA: lessons learned and future directions. Nat Rev Rheumatol. 2019 Aug;15(8):461-474. doi: 10.1038/s41584-019-0256-0. Epub 2019 Jul 10.
• Background Vallejo-Yague E, Burkard T, Moller B, Finckh A, Burden AM. Comparison of Psoriatic Arthritis and Rheumatoid Arthritis Patients across Body Mass Index Categories in Switzerland. J Clin Med. 2021 Jul 20;10(14):3194. doi: 10.3390/jcm10143194.
• Background Ishchenko A, Pazmino S, Neerinckx B, Lories R, de Vlam K. Comorbidities in Early Psoriatic Arthritis: Data From the Metabolic Disturbances in Psoriatic Arthritis Cohort Study. Arthritis Care Res (Hoboken). 2024 Feb;76(2):231-240. doi: 10.1002/acr.25230. Epub 2024 Jan 15.
• Background Gupta S, Syrimi Z, Hughes DM, Zhao SS. Comorbidities in psoriatic arthritis: a systematic review and meta-analysis. Rheumatol Int. 2021 Feb;41(2):275-284. doi: 10.1007/s00296-020-04775-2. Epub 2021 Jan 9.
• Background Gok K, Nas K, Tekeoglu I, Sunar I, Keskin Y, Kilic E, Sargin B, Acer Kasman S, Alkan H, Sahin N, Cengiz G, Cuzdan N, Albayrak Gezer I, Keskin D, Mulkoglu C, Resorlu H, Bal A, Duruoz MT, Kucukakkas O, Yurdakul OV, Alkan Melikoglu M, Aydin Y, Ayhan FF, Bodur H, Calis M, Capkin E, Devrimsel G, Ecesoy H, Hizmetli S, Kamanli A, Kutluk O, Sen N, Sendur OF, Tolu S, Toprak M, Tuncer T. Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi-center study. Rheumatol Int. 2022 Apr;42(4):659-668. doi: 10.1007/s00296-021-04971-8. Epub 2021 Aug 28.
• Background Sattar N, Sattar LJ, McInnes IB, Siebert S, Ferguson LD. Obesity substantially impacts rheumatic and musculoskeletal diseases: time to act. Ann Rheum Dis. 2025 Jun;84(6):894-898. doi: 10.1016/j.ard.2025.02.013. Epub 2025 Mar 16.
• Background Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005 Mar;64 Suppl 2(Suppl 2):ii14-7. doi: 10.1136/ard.2004.032482.

Drugs

Indications