Combination of Biologic and Anti-obesity Therapies in Psoriatic Arthritis
COMBAT-PsA
1 other identifier
interventional
45
1 country
4
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Mar 2026
Longer than P75 for not_applicable
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 11, 2026
CompletedFirst Posted
Study publicly available on registry
March 2, 2026
CompletedStudy Start
First participant enrolled
March 9, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2030
May 4, 2026
April 1, 2026
1.9 years
February 11, 2026
April 28, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Correlation of molecular changes in biopsies (skin, synovial and adipose) with weight loss
Percentage change in weight (in kg) from baseline will be correlated with changes in molecular markers in tissues (synovium, skin and adipose). This is an experimental medicine (and not efficacy) study that will utilise a range of advanced spatial and other tissue omics to measure molecular markers in these tissues at baseline and 12 weeks. It is not possible or appropriate to specify a single biomarker or measure for this.
12 weeks
Secondary Outcomes (2)
Correlation of changes in molecular signatures in the peripheral blood with weight loss.
12 weeks
Comparison of molecular changes in biopsies (skin, synovial and adipose) and in the peripheral blood with weight loss versus those with immunomodulation by IL-17A inhibition.
12 weeks
Other Outcomes (2)
Correlation of changes in molecular signatures in the peripheral blood with weight loss.
Weeks 4, 24, 36 and 52.
Correlation of changes in weight with PsA disease activity measures.
Weeks 4, 12, 24, 36 and 52.
Study Arms (3)
Tirzepatide group
ACTIVE COMPARATORIxekizumab group
ACTIVE COMPARATORCombined tirzepatide and ixekizumab
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Prior/Concomitant Therapy:
- Previous treatment with tirzepatide or any GLP-1 receptor agonist.
- Previous treatment with Ixekizumab.
- Previous treatment with BOTH secukinumab AND Bimekizumab. \[note: Previous treatment with one of EITHER secukinumab OR Bimekizumab for PsA/psoriasis is allowed PROVIDED: i) Last dose was \>6months before baseline AND ii) Therapy was not stopped due to an IL-17-related side effect OR due to complete primary lack of response.
- Previous treatment with rituximab.
- Failed \>3 classes of advanced therapies (regardless of given for PsA or psoriasis), including but not limited to:
- TNF inhibitors (adalimumab, etanercept, certolizumab, golimumab, and infliximab)
- IL-12/23 inhibitors (ustekinumab)
- IL-23 inhibitors (guselkumab and risankizumab)
- IL-17 Inhibitors (secukinumab or bimekizumab)
- Selective co-stimulation modulators (abatacept)
- Janus Kinase or tyrosine kinase 2 inhibitors (tofacitinib, upadacitinib and deucravacitinib) Note: Prior exposure to phosphodiesterase-4 inhibitors, such as apremilast and conventional synthetic DMARDs, such as methotrexate, are not considered as advanced therapies.
- If currently receiving conventional DMARDs, or apremilast, must have been treated for at least 12 weeks prior to first biopsy visit and on a stable dose for at least 8 weeks prior to first biopsy visit.
- Use or oral, intra-articular, IM or IV corticosteroids 4 weeks prior to first biopsy visit or anticipated/planned prior to the week 12 biopsy visit.
- Topical steroids within 2 weeks of first biopsy visit (participants on topical corticosteroids at baseline willing to leave these off 2 weeks prior to biopsy will be eligible).
- +60 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NHS Greater Glasgow and Clydelead
- University of Glasgowcollaborator
- Eli Lilly and Companycollaborator
Study Sites (4)
University Hospitals Birmingham NHS Foundation Trust
Birmingham, England, B12 2GW, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, England, CV2 2DX, United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, England, NE7 7DN, United Kingdom
NHS Greater Glasgow and Clyde
Glasgow, Scotland, G12 0XH, United Kingdom
Related Publications (14)
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.
PMID: 31209855BACKGROUNDLove 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.
PMID: 22586165BACKGROUNDLi 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.
PMID: 22562978BACKGROUNDSetty 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.
PMID: 17698691BACKGROUNDFerguson 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.
PMID: 33147607BACKGROUNDLi 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.
PMID: 36264448BACKGROUNDLoganathan 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.
PMID: 34076348BACKGROUNDFerguson 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.
PMID: 31292564BACKGROUNDVallejo-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.
PMID: 34300360BACKGROUNDIshchenko 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.
PMID: 37667975BACKGROUNDGupta 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.
PMID: 33423070BACKGROUNDGok 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.
PMID: 34453579BACKGROUNDSattar 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.
PMID: 40090785BACKGROUNDGladman 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.
PMID: 15708927BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carl Goodyear, PhD,
University of Glasgow
- PRINCIPAL INVESTIGATOR
Naveed Sattar, MBChB, PhD,
University of Glasgow
- PRINCIPAL INVESTIGATOR
Lyn Ferguson, MBChB, PhD,
University of Glasgow
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- No masking is involved
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2026
First Posted
March 2, 2026
Study Start
March 9, 2026
Primary Completion (Estimated)
February 1, 2028
Study Completion (Estimated)
May 1, 2030
Last Updated
May 4, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- ICF, CSR
- Time Frame
- The IPD and supporting information will be available for 10 years after the study report is completed, which is expected in June 2028.
- Access Criteria
- After study closure, baseline (pre-treatment) samples in the Immune Mediated Inflammatory Diseases Research Tissue Bank may be accessed and used for future studies by researchers in the University of Glasgow, Eli Lilly or third-party academic institutions. Access to surplus follow-up (post-treatment) samples held in the IMID RTB is restricted to researchers in the University of Glasgow or Eli Lilly for internal research purposes only. All requests for access must be submitted through the established application process of the Research Tissue Bank, which ensures appropriate governance and ethical oversight of the use of research samples, including that use is in line with the existing study contracts
After the study ends, anonymous information and samples may also be shared with other trusted researchers, such as universities, the NHS, or healthcare research groups in the UK or other countries. Any request to use this resource will be carefully checked by a special review group, including experienced researchers, doctors, and patient representatives, to make sure it is appropriate and used only for bona fide research.