Immune Metabolic Associations in Psoriatic Arthritis (IMAPA)

Immune Metabolic Associations in Psoriatic Arthritis Study

To use apremilast in clinical practice as a molecular probe to evaluate the effects of PDE4 inhibition on the cardiometabolic status and immune profile in patients with PsA and psoriasis.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Psoriatic Arthritis
• Intervention / Treatment: Drug: Apremilast 30mg

Detailed Description

Psoriatic arthritis (PsA) and psoriasis are characterised by immune, metabolic, and vascular dysfunction. There is an increase in Major Adverse Cardiovascular Events in people with PsA and psoriasis not explained by conventional cardiovascular risk factors. Furthermore, obesity in psoriasis is associated with increased risk of developing PsA3. Dietary interventions leading to weight loss >5% are associated with a higher rate of achievement of minimal disease activity in overweight/obese patients with PsA treated with TNF inhibitors. Phosphodiesterase 4 (PDE4) inhibition with apremilast is licensed for the treatment of PsA and psoriasis and has been noted to be associated with weight loss. There is also data from animal models to suggest a role for PDE4 in glucose metabolism. However, the exact mechanisms underlying this are unclear and warrant investigation in humans. PDE4 may help explain the link between the immune and cardiometabolic dysfunction that characterises PsA and psoriasis, with pathogenic and therapeutic implications.

This study aims to use apremilast as a clinical molecular probe to evaluate the effects of PDE4 inhibition on metabolic, vascular, and immune status in patients with PsA and psoriasis. The hypothesis is that PDE4 inhibition mediates profound and synergistic effects on immune and metabolic pathways in these conditions to improve metabolic status and normalise dysregulated immunity.

Measurement of metabolic, immunological and vascular outcomes in 60 patients (40 with PsA and 20 with psoriasis) receiving apremilast as part of their standard clinical care will be taken. A subgroup of 20 participants with PsA will also undergo more in-depth investigations including MRI of abdominal fat, subcutaneous fat biopsy, measurement of vascular endothelial function using EndoPAT and more detailed deep-immunophenotyping. Patients will be recruited from rheumatology and dermatology clinics in NHS Greater Glasgow and Clyde (primary site) and two other recruiting sites in Scotland via the Scottish Collaborative Arthritis Research network (SCAR).

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• United Kingdom
  • Scotland
    • Glasgow, Scotland, United Kingdom, G31 2ER
      • Glasgow Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with PsA and psoriasis.

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Have either a diagnosis of PsA (n=40) fulfilling the CASPAR criteria or Chronic plaque psoriasis (confirmed by dermatologist) (n=20)
3. Eligible for apremilast therapy in line with the licence and SMC approval
4. Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

1. History of or current autoimmune rheumatic disease other than PsA or psoriasis
2. Severe renal disease (eGFR ≤30ml/min)
3. Liver disease with ALT/AST >4 times ULN
4. Haemoglobin ≤9 g/dl
5. Inflammatory bowel disease or coeliac disease
6. Patients with any cancer currently receiving chemo- or radiotherapy
7. Severe depression and/or history of suicidal ideation or attempts.
8. Currently receiving other leflunomide or biologics
9. Current oral steroids or IM steroids within 6 weeks of baseline.
10. Clinically meanigful weight loss of >3kg, current or planned use of weight loss medication e.g. orlistat, or severe calorie restriction within the first 3 months of the study
11. Current insulin therapy for diabetes
12. Current use of GLP-1 agonists or dipeptidyl peptidase-4 (DPP-IV) inhibitors
13. Statin therapy started/stopped or dose altered within 3 months of baseline visit
14. Thyroxine started or dose altered within 6 weeks of baseline
15. Acitretin within 8 weeks of baseline
16. Pregnancy or breast feeding
17. Women planning to become pregnant during the study period
18. Women of reproductive age or male partners of women of reproductive age unwilling to use effective contraception while taking apremilast & for at least 28 days after last dose of apremilast
19. Known HIV, hepatitis B and C infection
20. Patient unable to participate in long term data collection

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cardiometabolic profile	To characterise dynamic changes in cardiometabolic profile with formal assessment at 3 months.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipids	Change in lipid profile	6 months
NMR metabolomic profile	Change in NMR metabolomic profile	6 months
Blood pressure	Change in blood pressure	6 months
endothelial function	change in endothelial function	3 months
MRI imaging	change in visceral, subcutaneous, liver, and pancreatic fat as assessed by MRI imaging	3 months
GLP-1 levels	Change in fasting & post-prandial GLP-1 levels	6 months
adipose tissue	Change in adipose tissue composition	3 months
immune profile	Change circulating cytokines	6 months

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Investigators: Principal Investigator: Stefan Siebert, MBChB PhD, Glasgow University and NHS GGC

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Actual): October 12, 2019
• Study Completion (Actual): October 25, 2019

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 16, 2018

Study Record Updates

• Last Update Posted (Actual): November 25, 2019
• Last Update Submitted That Met QC Criteria: November 22, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: apremilast; PDE4 inhibition; cardiometabolic; immune profile
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Arthritis; Psoriasis; Arthritis, Psoriatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: GN16RH008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No