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Title: Diagnosis and management of early inflammatory arthritis
Author: Nam, Jacqueline Leong
ISNI:       0000 0004 5371 3899
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2015
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Rheumatoid arthritis (RA) represents a disease continuum from the pre-clinical period, through undifferentiated inflammatory arthritis (IA) to early then established RA. Improved patient outcomes in recent years reflect early diagnosis, prompt disease-modifying anti-rheumatic drug (DMARD) therapy, treat-to-target strategies and use of biological therapies (bDMARDs) particularly following failure of conventional synthetic therapies (csDMARDs). Optimal use of bDMARDs in early disease, however, has not been established. Early detection in the pre-clinical stage is potentially achievable with modern diagnostics but understanding of how to use these biomarkers is lacking. A systematic literature review on the use of bDMARDs was performed and confirmed the efficacy of bDMARDs in patients with established RA. Few studies were found addressing their use in early disease. Two randomised controlled trials were performed to explore early bDMARD intervention. The first, in early DMARD-naïve RA, compared methotrexate and infliximab to methotrexate and high-dose intravenous methylprednisolone as induction therapy, followed by a treat-to-target strategy; both arms demonstrated efficacy with no significant between-group differences. In the second, early DMARD naïve IA patients treated with combination etanercept and methotrexate had earlier clinical improvement than methotrexate monotherapy; however both groups achieved good 12 month outcomes. In a longitudinal cohort study conducted in secondary care, 50% of patients with musculoskeletal (MSK) symptoms and anti-cyclic citrullinated peptide (anti-CCP) antibodies progressed to clinical IA. Use of additional biomarkers including rheumatoid factor, shared epitope and ultrasound enabled further risk stratification for progression. In a primary care cohort, the anti-CCP antibody was positive in 2.8% with new nonspecific MSK symptoms with almost half progressing to IA. In summary, in early DMARD naïve IA, use of bDMARD may not be superior to csDMARDs with a treat-to-target approach. In patients with MSK symptoms, anti-CCP testing identifies individuals at risk of developing IA; additional biomarkers improve prediction and are feasible for clinical use.
Supervisor: Conaghan, Philip ; Emery, Paul Sponsor: Merck Sharp & Dohme Limited ; Pfizer ; AbbVie ; National Institute for Health Research (NIHR)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available