Determinants of outcome in early arthritis

Ultrasound is useful in providing information on subclinical joint and tendon inflammation that is not clinically evident. Current ultrasound technology has very high sensitivity in detecting subtle ultrasound pathology even in healthy joints. In order to use ultrasound effectively it is therefore important to understand the extent of ultrasound findings in healthy individuals, particularly in age ranges where rheumatological disease presents. I have developed a large collaborative network of units experienced in musculoskeletal ultrasound in order to investigate the extent of these ultrasound changes (i.e. synovial hypertrophy, Power Doppler, effusion, osteophytes and erosion) in a large cohort of healthy individuals. Healthy individuals exhibit ultrasound changes in the small joints of the hands, wrists and feet. There is an age-dependent effect of these changes. Synovial effusion is common across all age groups. Ultrasound has also been established as a predictive tool to identify early arthritis patients who will progress to persistent clinical synovitis. The predictive potential of joint synovitis as measured by ultrasound is well documented. The predictive potential of tendon inflammation measured by ultrasound is not clear. I have investigated the utility of tendon ultrasound variables in the prediction of rheumatoid and persistent arthritis development. Finger flexor tendon showed very promising capacity to predict both rheumatoid arthritis (RA) and persistent arthritis in patients who present within 12 weeks of symptom onset. This is even after taking into account conventional predictors such as RA-related autoantibodies and ultrasound joint synovitis. Finger flexor tendons should thus be considered as a candidate variable when designing prediction algorithms for early arthritis patients. The ability to predict those who will develop rheumatoid arthritis could allow clinicians to better identify those who require immunosuppressant therapy within the therapeutic window of opportunity. However, the duration of this therapeutic window of opportunity has never been prospectively investigated, particularly in the context of how mode of onset may affect treatment response. Mode of onset refers to how rapid the joint symptoms develop at initial presentation. In this thesis, I classified mode of onset as abrupt, acute or palindromic. I have studied the relationship between treatment response and symptom duration prior to starting DMARDs treatment, taking into account the mode of onset. It appears the mode of onset has a measurable impact on treatment response in RA patients. This novel finding should be further assessed in a larger cohort

The OMERACT emerging leaders program: The good, the bad, and the future

The Journal of Rheumatology Copyright © 2019. All rights reserved. Objective. To describe the experience of the first OMERACT Emerging Leaders Program (ELP). Methods. A Delphi process identified positive aspects, areas for improvement, and future directions. Core items were defined as essential if they received ≥ 70% ratings. Results. Participants valued relatable/accessible mentors (100%), including an OMERACT Executive mentor (100%), and a support network of peers (90%). Key items for future development were funding support (100%) and developing knowledge about OMERACT processes (90%) and politics (80%). Conclusion. The ELP has the potential to provide targeted training for early career researchers to develop relevant skills for future leadership roles within OMERACT

Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis

OBJECTIVE: To investigate serum antibody reactivity against a panel of post-translationally modified vimentin peptides (PTMPs) in patients with early inflammatory arthritis. METHODS: A panel of PTMPs was developed. Microtitre plates were coated with peptides derived from vimentin that were identical in length and composition except at one amino acid that was changed to introduce one of three post-translational modifications (PTMs)—either a citrullinated, carbamylated or acetylated residue. Sera of 268 treatment-naive patients with early inflammatory arthritis and symptoms ≤3 months' duration were tested. Patients were assigned to one of three outcome categories at 18-month follow-up (rheumatoid arthritis (RA), persistent non-RA arthritis and resolving arthritis). RESULTS: Antibodies against citrullinated, carbamylated and acetylated vimentin peptides were detected in the sera of patients with early inflammatory arthritis. The proportion of patients seropositive for all antibody types was significantly higher in the RA group than in the other groups. Anti cyclic citrullinated peptide (CCP)-positive patients with RA had higher numbers of peptides recognised and higher levels of antibodies against those peptides, representing a distinct profile compared with the other groups. CONCLUSIONS: We show for the first time that antibodies against acetylated vimentin are present in the sera of patients with early RA and confirm and extend previous observations regarding anticitrullinated and anticarbamylated antibodies

The role of ultrasound-defined tenosynovitis and synovitis in the prediction of rheumatoid arthritis development

Objectives Tenosynovitis (TS) is common in early arthritis. However, the value of US-defined TS in predicting RA development is unclear. We assessed the predictive utility of US-defined TS alongside US-defined synovitis and clinical and serological variables in a prospective cohort of early arthritis patients. Methods One hundred and seven patients with clinically apparent synovitis of one or more joint and symptom duration ⩽3 months underwent baseline clinical, laboratory and US assessment of 19 bilateral joint sites and 16 bilateral tendon compartments. Diagnostic outcome was determined after 18 months, applying the 2010 ACR/EULAR classification criteria for RA. The predictive values of US-defined TS for persistent RA were compared with those of US-defined synovitis, clinical and serological variables. Results A total of 4066 US joint sites and 3424 US tendon compartments were included in the analysis. Forty-six patients developed persistent RA, 17 patients developed non-RA persistent disease and 44 patients had resolving disease at follow-up. US-defined TS in at least one tendon compartment at baseline was common in all groups (RA 85%, non-RA persistent disease 71% and resolving 70%). On multi-variate analysis, US-defined digit flexor TS provided independent predictive data over and above the presence of ACPA and US-defined joint synovitis. Conclusion US-defined digit flexor TS provided independent predictive data for persistent RA development in patients with early arthritis. The predictive utility of this tendon site should be further assessed in a larger cohort; investigators designing imaging-based predictive algorithms for RA development should include this tendon component as a candidate variable