Calprotectin (S100A8/A9) and S100A12 in inflammatory arthritis : clinical and epidemiological studies of rheumatoid and psoriatic arthritis

Rheumatoid- and psoriatic arthritis (RA and PsA) are the two most prevalent inflammatory joint diseases in Caucasian. Different biomarkers in peripheral blood may contribute in the diagnostic and prognostic process, as well as in assessing the disease activity of the individual patient. The concentration of the leukocyte protein complex calprotectin (S100A8/A9) is increased in inflamed joints and in peripheral blood of patients with various inflammatory diseases. S100A12 is another S100 protein that more recently has been described as a proinflammatory protein in arthritis. Disease manifestations and prognosis in RA and PsA have both articular and non-articular aspects, and these should be adressed during treatment of the patients. The risk of cardiovascular disease is increased in RA, and to a lesser extent in PsA. Supplementation with fish oil has modest beneficial effects in RA both for arthritis and collateral health. The overall aim of the study was to investigate calprotectin and S100A12 as biomarkers of disease activity or distinct clinical features in patients with either RA or PsA. In addition, we wanted to estimate the prevalence of PsA in our population and to explore effects of short-term oral supplementation with seal oil. We found a prevalence of PsA in the county of Hordaland equivalent to 1.95 per 1000. If given a prevalence of psoriasis at 1.4%, this corresponds to a PsA prevalence among psoriatics of 14%. The levels of calprotectin were elevated in stool samples from patients with PsA, suggesting asymptomatic psoriatic enteropathy. In a clinical trial with seal oil to patients with PsA we found improvement in subjective measures and a significant shift in the fatty acid composition in peripheral blood, toward a putative antiinflammatory profile. We found that both calprotectin and S100A12 levels in serum correlate with disease activity parameters in RA. High levels of S100A12 were detected in patients with RA, as well as new conformational states of this protein. The S100 proteins did not perform better than CRP as inflammatory

A randomized double blind comparison of short-term duodenally administrated whale and seal blubber oils in patients with inflammatory bowel disease and joint pain

Compared with soy oil, 10 days treatment with seal oil (SO), 10 mL×3 daily, self-administrated through a nasoduodenal feeding tube, relieves joint pain in patients with inflammatory bowel disease (IBD). This randomized, controlled, double blind pilot trial compares SO and whale oil (WO) administered similarly by duodenal tube, for 10 days in 18 patients with IBD-related joint pain (n=9 per group). Other long chain n-3 polyunsaturated fatty acids were prohibited 7-days prior to and during study. Significant changes from baseline to study end were observed in both groups: reduced plasma arachidonic acid to eicosapentaenoic acid ratio and prostaglandin E2 (PGE2) levels (tendency in WO group), decreased IBD-related joint pain and IBD-disease activity, and improved quality of life. These changes were not significantly different between SO and WO groups. Inhibition of cyclooxygenase is consistent with amelioration of IBD-related joint pain, but, as active control was used, effects need confirmation

Value of MRI and ultrasound for prediction of therapeutic response and erosive progression in patients with early rheumatoid arthritis managed by an aggressive treat-to-target strategy

Objectives To investigate if inflammation detected by MRI or ultrasound at rheumatoid arthritis (RA) onset is predictive of erosive progression or poor response to methotrexate monotherapy, and to investigate if subclinical inflammation in remission is predictive of future treatment escalation or erosive progression.Methods In a 2-year study, 218 patients with disease-modifying antirheumatic drug-naïve early RA were treated by a tight-control treat-to-target strategy corresponding to current recommendations. MRI and ultrasound were performed at regular intervals. Baseline imaging-based inflammation measures were analysed as predictors for early methotrexate failure and erosive progression using univariate and multivariate regression adjusted for clinical, laboratory and radiographic measures. In patients in remission after 1 year, imaging measures were analysed as predictors of treatment escalation and erosive progression during the second year. The added value of imaging in prediction models was assessed using receiver operating characteristic analyses.Results Baseline MRI inflammation was associated with MRI erosive progression and ultrasound with radiographic erosive progression. No imaging inflammation measure was associated with early methotrexate failure. Imaging inflammation was present in a majority of patients in clinical remission. Tenosynovitis was associated with treatment escalation, and synovitis and tenosynovitis with MRI/radiographic erosive progression during the second year. Imaging information did not improve prediction models for any of the outcomes.Conclusions Imaging-detected inflammation, both at diagnosis and in remission, is associated with elements of future disease development. However, the lack of a significant effect on prediction models indicates limited value of systematic MRI and ultrasound in management of early RA

Development of a feasible and responsive ultrasound inflammation score for rheumatoid arthritis through a data-driven approach

Objective: To develop and validate a responsive and feasible ultrasound inflammation score for rheumatoid arthritis (RA). Methods: We used data from cohorts of early RA (development) and established RA starting/switching biologic therapy (validation). 4 tendons and 36 joints were examined by a grey scale (GSUS) and power Doppler semiquantitative ultrasound (PDUS) scoring system (full score). Ultrasound score components were selected based on factor analyses of 3-month change in the development cohort. Responsiveness was assessed by standardised response means (SRMs). We assessed the proportion of information retained from the full score by linear regression. Results: 118 patients with early and 212 patients with established RA were included. The final ultrasound score included 8 joints (metacarpophalangeal 1–2–3, proximal interphalangeal 2–3, radiocarpal, metatarsophalangeal 2–3) and 1 tendon (extensor carpi ulnaris) examined bilaterally. The 6-month SRMs for the final score were −1.24 (95% CI −1.47 to −1.02) for GSUS, and −1.09 (−1.25 to −0.92) for PDUS in early RA, with 87% of total information retained for GSUS and 90% for PDUS. The new score performed somewhat better than formerly proposed scores in the validation cohort. Conclusions: The Ultrasound in Rheumatoid Arthritis 9 joint/tendon score (USRA9) inflammation score showed good responsiveness, retained most of the information from the original full score and overall performed better than previous scores in a validation cohort

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

Objective: To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design: Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting: Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants: 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions: 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures: The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and nonprogression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results: 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions: The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology