Psoriatic Arthritis Pathobiology and Its Relationship With Clinical Disease Activity (PSABRE)

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

Study Overview

• Status: Completed
• Conditions: Arthritis, Psoriatic

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E1 4DG
    • Barts Health NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a prospective observational study of PsA patients who have persistent disease activity despite an adequate trial of standard non-biologic disease-modifying therapy, and who may proceed to receive their first or second biologic drug as the next treatment strategy.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observational; This study will be an observational study of a cohort of psoriatic arthritis patients who have failed to achieve sufficient response to standard non-biologic therapy. As they start their next treatment, this study aims to investigate the evolution of these patients in terms of the clinical, molecular and cellular profiles within the joint lining, peripheral blood and skin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DAS	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.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	4 months
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

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): June 24, 2020
• Study Completion (Actual): June 24, 2020

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Actual): November 6, 2024
• Last Update Submitted That Met QC Criteria: November 4, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Joint Diseases; Spinal Diseases; Spondylarthropathies; Skin Diseases, Papulosquamous; Skin Diseases; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: 010368 BHT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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