Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)

UK GCA Consortium: Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)

A multi-centre observational study recruiting prospective and retrospective cohorts of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). The primary aim is to find genetic determinants of GCA and PMR susceptibility, in order to yield novel insights into disease pathogenesis. A subset of the retrospective cohort is also enrolled in a post-marketing surveillance registry of patients eligible for, or receiving tocilizumab, to treat their relapsing or refractory GCA.

Study Overview

• Status: Recruiting
• Conditions: Giant Cell Arteritis; Polymyalgia Rheumatica

Detailed Description

Giant cell arteritis (GCA), also known as temporal arteritis, is the most common form of primary systemic vasculitis, with up to 75,000 cases a year identified in the EU and US. It occurs almost exclusively in people over the age of 50 years and is considered to be a medical emergency. If not treated with high-dose glucocorticoids immediately, the thickening of the inflamed blood vessel wall can cause irreversible visual loss or stroke. GCA can lead to significant morbidity across a variety of systems, due to both the disease, and complications of treatment. Diagnosis may be confirmed with a temporal artery biopsy, imaging (e.g. USS/CT/MRA/PET-CR) or based on clinical signs (e.g. erythrocyte sedimentation rate) and symptoms (e.g. a new headache, jaw claudication, visual disturbances, temporal artery abnormality such as tenderness or decreased pulsation) .

Polymyalgia rheumatica (PMR) is characterised by inflammatory limb-girdle pain with early morning stiffness, and a systemic inflammatory response demonstrated by elevated inflammatory markers.

The UK GCA Consortium is a multi-centre observational study, the main arms of which recruit prospective (participants with suspected GCA) and retrospective cohorts (participants with confirmed GCA diagnosis). Analysis of data collected on these cohorts will help achieve the primary aim of finding genetic determinants of GCA and PMR susceptibility, in order to yield novel insights into disease pathogenesis. Secondary aims, and their associated analyses, are as follows:

• Phenotype: characterising GCA and PMR subtypes, based on clinical features; imaging; cells; subcellular fractions and molecules in the circulation and/or arterial tissue; genetic/epigenetic/transcriptomic/proteomic or metabolomics factors, including next generation sequencing (whole exome sequencing) of selected cases.
• Life impact: determining what aspects of the disease and treatments affect patients' quality of life, as assessed by patient-reported outcomes.
• Long-term outcomes: characterising prognosis of GCA and PMR - both effects of the disease and its treatment - by longitudinal follow-up through electronic linkage to health records.
• Exploratory analyses: exploring the potential role of environmental factors and co-morbidities on phenotype and outcomes.
• Diagnosis, prognosis: improving diagnosis of GCA and PMR, and identifying factors that predict diagnosis, such as diagnostic clinical features, and prognostic and diagnostic biomarkers.
• Disease activity: monitoring participants who commence a synthetic or biological disease-modifying anti-rheumatic drug (s/bDMARD). Finding a biomarker for GCA and PMR disease activity, which might be clinically useful in helping to optimise steroid and s/bDMARD treatments for individual patients.

• Study Type: Observational
• Enrollment (Estimated): 4500

Contacts and Locations

• Study Contact: Name: Louise Sorensen; Phone Number: 0113 343 7764; Email: MRCTarget@leeds.ac.uk

Study Locations

• United Kingdom
  • Abergavenny, United Kingdom
    • Recruiting
    • Nevill Hall Hospital, Aneurin Bevan University Health Board
    • Contact: Eleri Thomas
  • Aylesbury, United Kingdom
    • Recruiting
    • Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
    • Contact: Malgorzata Magiliano
  • Bangor, United Kingdom, LL57 2PW
    • Recruiting
    • Betsi Cadwaladr University Health Board
    • Contact: Subhra Raghuvanshi
    • Contact: Yasmeen Ahmad
    • Contact: Alessandro Ciapetti
  • Barnsley, United Kingdom
    • Completed
    • Barnsley Hospital, Barnsley Hospital NHS Foundation Trust
  • Basildon, United Kingdom
    • Recruiting
    • Basildon University Hospital, Basildon and Thurrock University Hospitals NHS Foundation Trust
    • Contact: Anupama Nandagudi
  • Basingstoke, United Kingdom
    • Recruiting
    • Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust
    • Contact: Emma Williams
  • Bath, United Kingdom
    • Recruiting
    • Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust
    • Contact: Sarah Skeoch
  • Birmingham, United Kingdom
    • Recruiting
    • Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust
    • Contact: Asad Khan
  • Birmingham, United Kingdom
    • Recruiting
    • Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
    • Contact: Susie Mollan
  • Bristol, United Kingdom
    • Recruiting
    • Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust
    • Contact: Jo Robson
  • Burton Upon Trent, United Kingdom
    • Recruiting
    • Queen's Hospital, University Hospitals of Derby and Burton NHS Foundation Trust
    • Contact: Ramasharan Laxminarayan
  • Bury Saint Edmunds, United Kingdom
    • Recruiting
    • West Suffolk Hospital, West Suffolk NHS Foundation Trust
    • Contact: Shweta Bhagat
  • Cambridge, United Kingdom
    • Recruiting
    • Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
    • Contact: Ei Phyu Htut
  • Chelsea, United Kingdom
    • Recruiting
    • Chelsea and Westminster Hospital, Chelsea and Westminster Hospital NHS Foundation Trust
    • Contact: Amjad Jilani
  • Chelsea, United Kingdom
    • Recruiting
    • West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust
    • Contact: Diana Davis
  • Chertsey, United Kingdom
    • Recruiting
    • Ashford and St Peter's Hospitals, Ashford & St Peter's Hospitals NHS Foundation Trust
    • Contact: Rod Hughes
  • Chester, United Kingdom
    • Recruiting
    • Countess of Chester Hospital, Countess of Chester NHS Foundation Trust
    • Contact: Deepti Kapur
  • Christchurch, United Kingdom
    • Recruiting
    • Christchurch Hospital, University Hospitals Dorset NHS Foundation Trust
    • Contact: Jonathan Marks
  • Croydon, United Kingdom
    • Recruiting
    • Croydon University Hospital, Croydon Health Service NHS Trust
    • Contact: Sarah Levy
  • Darlington, United Kingdom
    • Recruiting
    • Darlington Memorial Hospital, County Durham and Darlington NHS Foundation Trust
    • Contact: Nathan Rushby
  • Derby, United Kingdom
    • Recruiting
    • Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust
    • Contact: Azza Hussein
  • Doncaster, United Kingdom
    • Recruiting
    • Doncaster Royal Infirmary, Doncaster and Bassetlaw Hospitals NHS Foundation Trust
    • Contact: Chee-Seng Yee
  • Dundee, United Kingdom
    • Completed
    • Ninewells Hospital and Medical School, NHS Tayside
  • Exeter, United Kingdom
    • Recruiting
    • Royal Devon and Exeter Hospital, Royal Devon and Exeter NHS Foundation Trust
    • Contact: Mahdi Abusalameh
  • Frimley, United Kingdom
    • Completed
    • Frimley Park Hospital, Frimley Park Hospital NHS Foundation Trust
  • Gateshead, United Kingdom
    • Recruiting
    • Gateshead Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust
    • Contact: Vadivelu Saravanan
  • Glasgow, United Kingdom
    • Completed
    • Inverclyde Royal Hospital, NHS Greater Glasgow and Clyde
  • Glasgow, United Kingdom
    • Completed
    • Royal Alexandra Hospital, NHS Greater Glasgow and Clyde
  • Glasgow, United Kingdom
    • Completed
    • Vale of Leven Hospital, NHS Greater Glasgow and Clyde
  • Great Yarmouth, United Kingdom
    • Completed
    • James Paget Hospital, James Paget University Hospitals NHS Foundation Trust
  • Guildford, United Kingdom
    • Completed
    • Royal Surrey County Hospital, Royal Surrey County Hospital NHS Foundation Trust
  • Harrogate, United Kingdom
    • Recruiting
    • Harrogate and District Hospital, Harrogate and District NHS Foundation Trust
    • Contact: Andrew Gough
  • Hull, United Kingdom
    • Recruiting
    • Hull Royal Infirmary, Hull and East Yorkshire NHS Trust
    • Contact: Yusuf Patel
  • Ipswich, United Kingdom
    • Completed
    • Ipswich Hospital, East Suffolk and North Essex Nhs Foundation Trust
  • Keighley, United Kingdom
    • Recruiting
    • Airedale General Hospital, Airedale NHS Foundation Trust
    • Contact: Shabina Sultan
  • Kendal, United Kingdom
    • Recruiting
    • Westmorland General Hospital, University Hospitals of Morecambe Bay NHS Foundation Trust
    • Contact: Marwan Bukhari
  • Kings Lynn, United Kingdom
    • Completed
    • The Queen Elizabeth Hospital, The Queen Elizabeth Hospital Kings Lynn NHS Foundation Trust
  • Lancaster, United Kingdom
    • Recruiting
    • Royal Lancaster Infirmary, University Hospitals of Morecambe NHS Foundation Trust
    • Contact: Marwan Bukhari
  • Leeds, United Kingdom
    • Recruiting
    • Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Foundation Trust
    • Contact: Sarah Mackie
  • Leicester, United Kingdom
    • Recruiting
    • Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust
    • Contact: Kehinde O Sunmboye
  • Liverpool, United Kingdom
    • Recruiting
    • Aintree University Hospital, Aintree University Hospitals NHS Trust
    • Contact: Robert Moots
  • Llantrisant, United Kingdom
    • Recruiting
    • Royal Glamorgan Hospital, Cwm Taf University Health Board
    • Contact: Ceril Rhys Dillon
  • London, United Kingdom
    • Recruiting
    • Hammersmith Hospital, Imperial College Healthcare NHS Trust
    • Contact: James Peters
  • London, United Kingdom
    • Recruiting
    • King's College Hospital, King's College Hospital NHS Foundation Trust, London
    • Contact: Eoin O'Sullivan
  • London, United Kingdom
    • Recruiting
    • Royal Free Hospital, Royal Free NHS Foundation Trust
    • Contact: Animesh Singh
  • London, United Kingdom
    • Recruiting
    • St George's Hospital, St George's University Hospitals NHS Foundation Trust
    • Contact: Nidhi Sofat
  • London, United Kingdom
    • Recruiting
    • University College London Hospital, University College London NHS Foundation Trust
    • Contact: Vanessa Morris
  • Manchester, United Kingdom
    • Recruiting
    • Manchester Royal Infirmary, Manchester University NHS Foundation Trust
    • Contact: Ben Parker
  • Newcastle, United Kingdom
    • Recruiting
    • Freeman Hospital, The Newcastle-upon-Tyne Hospitals NHS Foundation Trust
    • Contact: John Isaacs
  • North Shields, United Kingdom
    • Recruiting
    • North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust
    • Contact: Ischmael Atchia
  • Northampton, United Kingdom
    • Recruiting
    • Northampton General Hospital, Northampton General Hospital NHS Trust
    • Contact: Pradip Nandi
  • Norwich, United Kingdom
    • Completed
    • Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom
    • Recruiting
    • Queens Medical Centre, Nottingham University Hospitals NHS Trust
    • Contact: Peter Lanyon
  • Oxford, United Kingdom
    • Not yet recruiting
    • Oxford Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust
    • Contact: Raashid Luqmani
  • Peterborough, United Kingdom
    • Recruiting
    • Peterborough City Hospital, North West Anglia NHS Foundation Trust
    • Contact: Poonam Sharma
  • Plymouth, United Kingdom
    • Recruiting
    • Derriford Hospital, University Hospital Plymouth NHS Trust
    • Contact: Jon King
  • Poole, United Kingdom
    • Recruiting
    • Poole Hospital, University Hospitals Dorset NHS Foundation Trust
    • Contact: Muhammad Khursid
  • Preston, United Kingdom
    • Recruiting
    • Minerva Health Centre, Lancashire and South Cumbria NHS Foundation Trust
    • Contact: Sarah Horton
  • Preston, United Kingdom
    • Recruiting
    • Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust
    • Contact: Hedley Emsley
    • Contact: Anna Bhargava
  • Salford, United Kingdom
    • Recruiting
    • Salford Royal Hospital, Salford Royal NHS Foundation Trust
    • Contact: Sanjeet Kamath
  • Scarborough, United Kingdom
    • Recruiting
    • Scarborough General Hospital, York and Scarborough Teaching Hospitals NHS Foundation Trust
    • Contact: Zaid Al-Saffar
  • Southend-on-Sea, United Kingdom
    • Recruiting
    • Southend University Hospital, Southend University Hospital NHS Foundation Trust
    • Contact: Bridgett Masunda
  • Stevenage, United Kingdom
    • Recruiting
    • Lister Hospital, East and North Hertfordshire NHS Trust
    • Contact: Thiraupathy Marianayagam
  • Stoke-on-Trent, United Kingdom
    • Recruiting
    • Haywood Hospital, Midlands Partnership NHS Foundation Trust
    • Contact: Ajit Menon
  • Swindon, United Kingdom
    • Recruiting
    • Great Western Hospital, The Great Western Hospitals NHS Foundation Trust
    • Contact: David Collins
  • Torquay, United Kingdom
    • Completed
    • Torbay Hospital, Torbay and South Devon NHS Foundation Trust
  • Truro, United Kingdom
    • Recruiting
    • Royal Cornwall Hospital, Royal Cornwall Hospitals NHS Trust
    • Contact: David Hutchinson
  • Wakefield, United Kingdom
    • Recruiting
    • Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust
    • Contact: Chamila Hettiarachchi
  • Warrington, United Kingdom
    • Recruiting
    • Warrington Hospital, Warrington and Halton Hospitals NHS Foundation Trust
    • Contact: Hala Sadik
  • Warwick, United Kingdom
    • Completed
    • Warwick Hospital, South Warwickshire NHS Foundation Trust
  • Winchester, United Kingdom
    • Recruiting
    • Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust
    • Contact: Emma Williams
  • Wirral, United Kingdom
    • Recruiting
    • Arrowe Park Hospital, Wirral University Hospital NHS Foundation Trust
    • Contact: Emmanuel George
  • Wishaw, United Kingdom
    • Recruiting
    • University Hospital Wishaw, NHS Lanarkshire
    • Contact: James Dale
  • York, United Kingdom
    • Completed
    • York Hospital, York and Scarborough Teaching Hospitals NHS Foundation Trust
  • Kent
    • Canterbury, Kent, United Kingdom, CT 1 3NG
      • Recruiting
      • Queen Elizabeth the Queen Mother Hospital
      • Contact: Denise De Lord
  • Merseyside
    • Prescot, Merseyside, United Kingdom, L35 5DR
      • Recruiting
      • Whiston Hospital
      • Contact: Julie Dawson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients predominantly recruited from secondary but can be identified and/or recruited in primary care.

Description

Inclusion Criteria:

• Willing to self-identify an ethnic group, such as Caucasian, Asian, Afro-Caribbean.
• Have a firm clinical diagnosis of GCA or PMR, or (for patients identified prospectively) GCA or PMR should be more likely than any alternative explanation for the patient's symptoms.
• Able and willing to give informed consent. Patients will be 50 years of age or over, unless both biopsy-proven and a clinically classical case of GCA.

Exclusion Criteria:

• Patient unwilling or unable to give fully informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Retrospective; A patient who has a diagnosis of GCA or PMR
Prospective; Patient with suspected GCA and PMR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome for genetic susceptibility studies:	Diagnosis of GCA (or PMR), confirmed by a specialist (e.g. rheumatologist, ophthalmologist) with relevant expertise.	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotype	Clinical phenotype or subtype of GCA/PMR based on disease features and imaging undertaken as part of routine clinical practice, and on research tests, such as imaging performed for research purposes, cells, subcellular fractions and molecules in the circulation and/or arterial tissue and genetic/ epigenetic/ transcriptomic/ proteomic or metabolomic factors, including next generation sequencing (whole exome sequencing) of selected cases.	At baseline
Life impact questionnaires	Assessment of the impact the disease and treatment has on the patients' lives as reported by the patient	At baseline
Long term outcomes	Longitudinal follow-up of patients (as far as is possible from medical and electronic records and without requiring additional study visits) to define prognosis/disease outcomes, such as ischaemic manifestations, aneurysm formation, duration of steroid therapy, disease flares, complications related to steroid therapy.	At baseline
Diagnosis of GCA/PMR	Diagnosis in patients presenting with suspected GCA/PMR (prospective study).	Through study completion, an average of 1 year
Exploratory analyses	To investigate role of genetics, environmental factors (e.g. diet and sunlight) and co-morbidities (e.g. periodontal disease) on disease phenotype and outcome as assessed by the patient-administered questionnaires.	At baseline
Disease activity defined as an increase in clinical and patient reported activity of disease	Participants commencing a synthetic or biological disease modifying anti-rheumatic drug with or without additional steroid therapy will have their disease activity assessed.	At baseline
Proteomic and genomic analyses on serum, plasma and urine samples.	A variety of 'omic technologies will be applied to cell populations isolated from the blood and/or routine diagnostic arterial biopsies, including, but not limited to, RNASeq and a variety of proteomic approaches.	At baseline

Collaborators and Investigators

• Sponsor: University of Leeds
• Collaborators: University of Oxford
• Investigators: Principal Investigator: Ann Morgan, University of Leeds

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2005
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Skin Diseases; Skin Diseases, Vascular; Vasculitis; Vasculitis, Central Nervous System; Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
• Other Study ID Numbers: MM05/7037

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No