Psoriatic Arthritis Pathobiology and Its Relationship With Clinical Disease Activity

Completed

• Conditions: Arthritis, Psoriatic

• Registration Number: NCT06676176
• Lead Sponsor: Barts & The London NHS Trust

Brief Summary

The study aims to examine the relationship between synovial histopathology and change in clinical disease activity over time in a population of patients with psoriatic arthritis who have failed to respond to first-line treatment. It is a prospective, open-labelled study

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2017-07-20
• Primary Completion: 2020-06-24
• Study Completion: 2020-06-24
• Status Verified: 2024-11
• Study First Submitted QC: 2024-11-04
• Last Update Submitted: 2024-11-04
• Study First Posted: 2024-11-06
• Last Update Posted: 2024-11-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Men and women between 18 and 75 years of age inclusive;
2. Patients with Psoriatic Arthritis as defined by the CASPAR criteria;
3. Patients who have persistent active disease (defined as having 3 or more swollen and 3 or more tender joints) despite an adequate trial of 2 or more standard non-biologic disease-modifying drugs, administered either individually or in combination;
4. Subjects who are naïve to biologic therapy or who have experienced but failed one previous class of biologic agent;
5. The patient must be able to comply with the study visit schedule, treatment plans, lab tests and other study procedures;
6. The patient must be capable of giving informed consent.

Exclusion Criteria

1. Women who are pregnant or breastfeeding;
2. Men and women of childbearing potential who decline to employ adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study;
3. As per care within a standard NHS setting, active infections of a serious nature such as HIV, HBV, pneumonia, or pyelonephritis are to be excluded. A history of previous serious infection is to be assessed individually for risk of re-activation, and a decision to treat (and with which agent) would be made according to the treating physician's discretion, as would normally occur within standard care. Less serious infections (such as upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator;
4. Active TB, or evidence of latent TB without adequate therapy for TB, initiated prior to first dose of biologic. Also excluded are patients with evidence of an old or latent TB infection without documented adequate therapy. Patients with previous or current close contact with an individual with active TB, or history of active TB, and patients who have completed treatment for active TB should have had a thorough evaluation for TB prior to study enrolment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies;
5. History of septic arthritis within a native joint within the last 12 months;
6. Presence of a transplanted organ (with the exception of a corneal transplant occurring more than 3 months prior to screening);
7. Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated, with no evidence of recurrence);
8. History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly;
9. Known recent substance abuse (drug or alcohol);
10. History of or current primary inflammatory joint disease or primary rheumatological autoimmune disease other than PsA;
11. Poor tolerability of venepuncture required for blood sampling during the study period;
12. Patients unable to tolerate synovial biopsy or in whom this is contraindicated (e.g. on anti-coagulants may not be suitable). However, assessment of suitability for the biopsy procedure will be a local decision.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
DAS	4 months	The primary outcome measure is the Disease Activity Score (DAS), a composite score calculated using the Ritchie articular index (range 0-78), swollen joint count (range 0-44), patient--scored global health assessment on a visual analogue scale (range 0-100) and lab--measured erythrocyte sedimentation rate (ESR). This is used to assess the relationship between the level of interleukin(IL)-23 within the psoriatic arthritis synovium and clinical disease activity over time.

Secondary Outcome Measures

Name	Time	Method
Relationship between IL-23 levels within the PsA synovium/ skin and clinical disease activity	4 months
Relationship between clinical disease activity and synovial, skin and/or blood levels of key immune signalling molecules involved in psoriatic disease	4 months	Such as but not limited to cluster of differentiation (CD)3, CD68, FVIII, TNFα, IL-1, IFN-γ, IL-6, IL-17A, IL-17R, IL-20, IL-22, IL-23/12p40, IL-23R, ICAM-1, VCAM-1, TGF-β, VEGF, PDGF, RANK-L, OPG, DKK-1, PNAd, CXCL13, CCL 21, MRP8 (S100A8), MRP14 (S100A9), Complement C3, TGFβ etc.
Relationship, if any, between clinical disease characteristics and genotype	4 months
Relationship between activated inflammatory cells in psoriatic skin and those in the psoriatic synovium	4 months
Relationship between clinical disease activity and synovitis, assessed using grey scale with power doppler US imaging	4 months
Relationship between clinical enthesitis scores (eg. LEI) and US scores of enthesitis	4 months

Trial Locations

Locations (1)

Barts Health NHS Trust; 🇬🇧 London, United Kingdom