School of Infection & Immunity

Study Summary (including aims, timelines and funder):

Psoriatic arthritis (PsA) is an inflammatory arthritis which affects up to 30% of patients with psoriasis. The relationship between the joint disease (inflammatory arthritis) and skin disease (psoriasis) is not completely understood but the immune system is involved in both aspects of the disease. Currently, there is no way of determining which treatment will be most beneficial in individual patients and treatment decisions in clinic remain based largely on "trial-and error" with no good biomarkers to support these decisions.  

With the BASSPA study, we want to better understand inflammation in arthritis and psoriasis. To do this, westudy the immune cells and proteins/biomarkers in blood and urine samples, together with detailed clinical assessments. In addition, we perform biopsies of the skin and joint in a sub-group of people with PsA, so that we can study these cells and proteins in the skin and joints too. 

A better understanding of inflammation in arthritis and psoriasis and how people respond to treatments can help researchers predict how people will respond to different treatments. 

 Primary research objective

• To find disease specific biomarkers and cell types in blood, skin and the lining of joints in patients with PsA.

Secondary research objectives

• To correlate these biomarkers and cell populations with clinical activity.
• To assess the effect of PsA treatments on blood, skin and synovial biomarkers and cell populations.

This prospective, observational study will recruit 30 patients with PsA (and 5 controls with rheumatoid arthritis, RA) who are due to start a disease modifying drug (DMARD) or biologic as part of their standard clinical care. It will measure immune cells and proteins/biomarkers before and during treatment. Participants are followed up for 1 year. 

The first participant was recruited in March 2018 and it is expected that recruitment will conclude at the end of June 2019. 

The study is funded by Boehringer Ingelheim.

Who can participate? (Inclusion/exclusion criteria)

Patients with PsA (30) and RA (5) who have active disease and are due to start or change a disease modifying drug (DMARD) or biologic as part of their standard clinical care.

 What does the study involve?

The study involves 5 visits in a 12-month period. 

At all visits, a clinical assessment is performed, questionnaires completed, and blood tests taken. Urine samples are collected at 3 visits. 

At the first visit, participants also have an ultrasound performed and X-rays of hands and feet. 

A sub-group of 10 patients with PsA will undergo skin and joint biopsies at the first visit. Skin +/- joint biopsies are repeated after 3 months. 

Are there any benefits or risks associated with taking part in this study?

This is an observational study with no direct benefit for the participants. 

As with any invasive procedures, there are risks associated with skin and synovial biopsies. These are discussed in detail with participants who consider participation in the sub-study.  

Study Summary (including aims, timelines and funder):

Rheumatoid arthritis is a relapsing and remitting autoimmune disease. The challenge that we will address is why immune-mediated inflammatory diseases (IMIDs) remit and relapse. Whilst a considerable amount is understood about factors which may contribute to development of RA and about disease mechanisms, nothing is known of the factors that trigger disease relapses (flares), converting the disease from an inactive to an active state. The underpinning mechanism(s) of flare have been difficult to study because they occur unpredictably. By studying patients who flare, we will attempt to capture signals that may determine which patients are most likely to flare, as well as understanding the biology behind the phenomenon of flare itself. This may eventually lead to future work on treatable targets in disease management.   Funder: Medical Research Council

What does the study involve?

In this study, we will recruit patients in remission from RA on traditional disease modifying therapies (DMARDs), namely methotrexate, sulfasalazine, and/or hydroxychloroquine. These patients will then discontinue their DMARDs and be closely followed-up by the research team. Previous research suggests 50% will experience flare, while the remainder will remain in remission. They will have regular assessment of their disease activity (physical examination and questionnaires), along with clinical and research blood samples taken. Urine samples will be taken at each visit. If a patient in the study experiences a flare, they will have an ultrasound-guided synovial biopsy taken under local anaesthetic. Samples of blood, urine and synovium (joint lining) will be analysed for gene expression, synovial cell subtypes, molecular pathways, immune cell profiles, and antibody status. 

After 6 months, if a patient does not experience a flare, they will be referred back to their usual rheumatologist and may be able to remain off of DMARDs. If a patient experiences flare at any time, they will receive steroid treatment and be referred back to their usual rheumatologist to restart their DMARDs. 

Are there any benefits or risks associated with taking part in this study?

The main perceived ethical issue will be withdrawal of DMARD therapy from patients in clinical remission, although this might in fact be considered potentially beneficial for participants. DMARDs are not without adverse (side) effects, ranging from common symptoms such as nausea to less common but more serious side-effects such as bone marrow suppression, infection, and liver or lung injury. The risk of some of these problems is dependent on cumulative lifetime dosage. With this in mind, regular blood test monitoring is standard care while patients are taking these medications. These add a further inconvenience to patients, as well as additional costs to healthcare providers. Our qualitative data (submitted for publication) and feedback from patients’ engagement groups show that many patients view DMARDs as a significant burden on quality of life, and would value the opportunity of DMARD discontinuation. Minimisation of DMARDs in the setting of RA remission is supported by current RA management guidelines issued by the National Institute of Health and Care Excellence, as well as the European League Against Rheumatism 

Synovial biopsy represents a further potential ethical issue. Minimally invasive ultrasound-guided synovial biopsy has been practiced since 2007. This procedure was specifically developed to minimise discomfort and inconvenience for patients with newly developed arthritis and has been shown to be safe and well tolerated by patients, as well as generating high quality samples, including from patients in clinical remission. The three main units using this technique internationally (including Birmingham) have completed more than 1000 biopsies with no major adverse events. Audit of biopsies in Birmingham has demonstrated that >90% of patients experience nothing more than mild to moderate discomfort during the procedure, with >80% of patients likely to consent to a second biopsy. Biopsy of patients in remission is optional in BIO-FLARE, and would only be considered where a sufficient synovial biopsy target is identified by ultrasound. 

Offsetting these above potential issues is the fact that up to 50% of patients are likely to remain off of DMARDs for prolonged periods of time, potentially for several years. Furthermore, participants will be contributing to an important piece of research that addresses a clinically important question. 

Study contacts for further information

Dr Seán Kerrigan, Glasgow Clinical Research Facility 0141 211 6800 or email: arthritisresearch@glasgow.ac.uk

Study Summary (including aims, timelines and funder):

Psoriatic arthritis (PsA) is an inflammatory arthritis which affects both joint (inflammatory arthritis) and skin (psoriasis). In recent decades, the introduction of extraordinarily effective treatments have transformed patient outcomes. However, a considerable number of patients continue to experience persistent chronic pain, despite apparent disease remission. This may be explained by the existence of alternative sources of pain. We believe that pain is not only caused by joint inflammation, but also the nervous system (brain and nerves).,We call this the  centralised component of pain.

Several studies have explored the central component of pain in different rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and fibromyalgia. Currently, there are no investigations exploring this type of pain in PsA. Even though there are treatments available to manage centralised pain, there are not the clinical tools or biomarkers to help distinguish the different sources of pain.  These are vital to improve the management and ultimately the quality of life of patients.

The CENTAUR study aims to characterise centralised pain in PsA patients. To do this, we are going to use comprehensive measurement including objective pain sensory tests and Magnetic Resonance Imaging (MRI) brain scans alongside  questionnaires and diseases activity measurements.

The primary research objective is to investigate the neurobiology of PsA patients, especially in patients with high centralised pain.

The secondary research objective is to develop a simple questionnaire which may be used routinely in clinic to characterise the type of pain reported by the patients and finally to inform precise treatment decisions.

This observational study will recruit 50 patients with PsA who are due to start a new disease modifying drug (DMARD) as part of standard clinical care. Clinical data, objective and subjective pain assessments will be collected at baseline and selected measures will be repeated at 3 and 6 months.

The recruitment is expected to start in April 2019 and it will conclude at the end of July 2021. 

The study is funded by Versus Arthritis (previously named Arthritis Research UK).

Who can participate? (Inclusion/exclusion criteria)

Patients with a diagnosis of PsA who have evidence of active disease active disease and are due to start a new disease modifying drug (DMARD) as part of their standard clinical care. 

Patients with any contraindication to MRI or with peripheral neuropathy can be not be enrolled in the study.

What does the study involve? 

Eligible patients who agree to participate will attend the clinical research facility at baseline, 3 and 6 months. 

At the baseline visit, the patient will undertake a clinical assessment, blood samples, questionnaire, quantitative sensory testing (QST), and a MRI brain scan. The clinical assessment and blood samples will reflect standard care. The questionnaire will assess symptoms and risk factors of pain. The QST is a well standardised set of tests suitable to measure sensitivity of pressure and visual stimuli. The MRI scan will be recording structural and functional information of the participant brain with particular focus on that areas known to be involved in pain. 

At the 3 and 6 months visits, only the clinical assessments, blood sampling and questionnaire assessments will be performed.

Are there any benefits or risks associated with taking part in this study?

A benefit from taking part in this study may not be directly achieved. However, the future results will help patients with PsA and rheumatic diseases in general. Moreover, joining a clinical trial may reveal a new medical condition that will be properly follow up and treated.

MRI is a very well-known imaging test which is overall safe. It does not involve the use of any radiation. Patients with contraindications to the MRI scan, such as metal implants or claustrophobia, will be appropriately excluded. QST is a set of different procedures commonly employed in research which have been planned following safety standards. However, a temporary discomfort may arise in the areas tested.  

Study contacts for further information 

Dr Flavia Sunzini (Clinical Research Fellow):  Flavia.Sunzini@glasgow.ac.uk

Dr Neil Basu (Chief Investigator): Neil.Basu@glasgow.ac.uk