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Objectives To investigate, in anti-CCP antibody–positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk), the additional value of US for the prediction of inflammatory arthritis. Furthermore, to define a concise US protocol for feasible risk prediction. Methods Demographic and clinical data were collected in 417 CCP+ at-risk (Leeds CCP cohort) with a baseline US scan assessing synovitis and bone erosions in 36 joints, and a follow-up duration ≥24 months. Multivariable binary regression models for inflammatory arthritis development at 24 months evaluated routine clinical variables associated with inflammatory arthritis alone ('clinical' model) and combined with a 36-joint US scanning protocol ('clinical-US extended' model). A 'clinical-US short' model was also developed. Results At 24 months, 92/417 (22.1%) CCP+ at-risk developed inflammatory arthritis (median time 7 months, interquartile range 3–12). The 'clinical-US extended' model performed better than the 'clinical' model [area under the curve (AUC) 0.788 vs AUC 0.731, respectively, P  < 0.001] with an odds ratio for inflammatory arthritis development of 3.18 (95% CI 1.80–5.63) for US synovitis and 2.54 (95% CI 1.21–5.37) for bone erosions. The 'clinical-US short' model, which retained the wrists, knees and MTP5 joints, performed better (AUC 0.782) than the 'clinical' model (P  < 0.001) and similarly (difference in Akaike information criteria <2) to the 'clinical-US extended' model. Conclusions US provides valuable information for predicting progression to inflammatory arthritis in CCP+ individuals both alone and in addition to clinical variables. US synovitis was associated with a 3-fold increase risk of inflammatory arthritis development. A concise US protocol of six joints provides clinically feasible risk prediction in CCP+ at-risk. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether anti-CCP2-positive at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis (CCP2+ at-risk) develop US subclinical synovitis before inflammatory arthritis and if US subclinical synovitis can be predicted. Methods First, US scans of CCP2+ at-risk individuals who developed inflammatory arthritis ('progressors') were reviewed for subclinical synovitis prior to inflammatory arthritis development. Patients in whom the pre-progression US scan was negative but the scan was conducted >6 months before progression were excluded. Subsequently, regression analyses were performed to identify predictors of US synovitis in CCP2+ at-risk individuals without baseline US abnormalities who had one or more longitudinal US scan and a complete dataset. Results US subclinical synovitis was detected in one or more scan in 75 of 97 progressors (77.3%) {median time to inflammatory arthritis development from first evidence of US synovitis 26.5 weeks [interquartile range (IQR) 7–60]}, in whom one or more scan was available, excluding those with a negative scan >6 months from inflammatory arthritis development (n  = 38). In 220 CCP2+ at-risk individuals with normal baseline US scans, who had one or more longitudinal US scan and a complete dataset, US synovitis was detected in 69/220 (31.4%) [median time to first developing US synovitis 56.4 weeks (IQR 33.0–112.0)]. In the multivariable analysis, only anti-CCP3 antibodies were predictive for the development of US synovitis [odds ratio 4.75 (95% CI 1.97, 11.46); P  < 0.01]. Conclusions In anti-CCP2+ at-risk individuals, a stage of subclinical synovitis usually precedes the development of inflammatory arthritis. Anti-CCP2+/CCP3+ individuals without clinical or US subclinical synovitis may represent the optimal window of opportunity for intervention to prevent joint disease. [ABSTRACT FROM AUTHOR]

Objectives To evaluate real-world efficacy of approved JAK inhibitors (JAKi) tofacitinib and baricitinib in a large, single-centre cohort of RA patients across the treatment pathway, including those refractory to multiple biologic drugs. Methods All RA patients, treated with tofacitinib (from time of compassionate access scheme) or baricitinib since approval in 2017 had DAS28-CRP scores and components recorded at baseline, 3 and 6 months (with retrospective data for compassionate access scheme). Efficacy was evaluated in the total cohort, each treatment group, and subgroups of number of prior biologic classes failed. Results One hundred and fifteen patients were treated with a JAKi (tofacitinib 54, baricitinib 69, 8 both); 76.4% female; mean (s. d.) age 57.3 (14.3) years. On average patients had received three previous bDMARDs; 11 (9.6%) were bDMARD naïve. Combined group baseline DAS28-CRP (s. d.) 5.62(1.14) improved by 1.49(1.44) and 1.67(1.61) at 3 and 6 months, respectively, comparable in individual JAKi groups; with 24% in at least low disease activity at 3 months. The biggest improvement was observed in the biologic-naïve group (mean DAS28-CRP improved from 5.16–2.14 after 6 months); while those with prior exposure to minimum three bDMARD classes had DAS28-CRP improvement of >1.2. Five out of 8 patients treated with both JAKi sequentially responded. Twelve patients previously unresponsive to IL-6 blockade responded to JAKi. No unexpected safety events were recorded. Two cases of venous thromboembolism were observed. Conclusion JAK inhibition is effective in a real-world population of RA patients, including in a subset of patients refractory to multiple previous bDMARDs. [ABSTRACT FROM AUTHOR]

Objectives To investigate the prevalence, distribution and predictive value for the development of inflammatory arthritis (IA) of conventional radiography (CR) bone erosions (BE) in anti-CCP positive (CCP+) at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis. Methods Baseline CR of the hands and feet of 418 CCP+ at-risk individuals were analysed. The presence of US-BE was explored in the anatomical areas in which CR-BE were reported. Hands and feet CR at the time of progression were analysed in a subset of individuals who developed IA (73/123, 59.3%). Logistic regression analyses were performed to calculate the predictive value of baseline CR-BE for the development of IA in 394 CCP+ individuals with ≥1 follow-up visit. Results BE were detected in 17/418 (4.1%) CCP+ at-risk individuals (median Simple Erosions Narrowing Score-BE = 2.0, IQR: 1.0–2.0; median Sharp van der Heijde score-BE = 4.0, IQR: 3.0–8.5), most frequently in the foot joints (11/17, 64.7% individuals). A total of 123/394 (31.2%) CCP+ at-risk individuals developed IA; 7/17 (41.2%) with, and 116/377 (30.8%) without BE on CR (P  = 0.37). US-BE were found in 4/7 (57.1%) individuals with CR-BE who developed IA, but only in 1/10 (10.0%) who did not. At the time of progression, new BE were detected in 4/73 (5.5%) CCP+ individuals on repeated CR. In the regression analyses, baseline CR-BE were not predictive for the development of IA. Conclusions In CCP+ at-risk individuals with MSK symptoms, CR-detected BE are uncommon and do not predict the development of IA. [ABSTRACT FROM AUTHOR]

Objectives: Around 1% of the population test positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies. This biomarker predicts the progression to rheumatoid arthritis (RA) but over a variable time frame. To increase its clinical relevance, this study sought to determine (1) if the proportion of anti-CCP-positive individuals could be enriched by case selection of people attending primary care with new non-specific musculoskeletal (MSK) symptoms but without clinical synovitis (CS) and (2) whether these individuals progress rapidly to inflammatory arthritis (IA), in particular RA.Methods: In this prospective cohort study, individuals aged ≥18 years with new non-specific MSK symptoms, without CS, were recruited from primary care in the UK. Anti-CCP-positive individuals were invited for follow-up in the rheumatology department, Leeds. Those who tested negative were sent questionnaires 12 months later.Results: 2028 individuals were recruited. Of these, 2.8% (57/2028) were anti-CCP positive, of whom 47% (27/57) developed IA - 24 RA, 1 undifferentiated IA (UIA), 2 polymyositis; 92.6% (25/27) within 12 months, median 1.8 months (IQR 1.0-4.3, range 0.3-16.1). Of the anti-CCP-negative individuals, 1.3% (20/1559) developed IA (1 UIA, 13 RA, 6 psoriatic arthritis); 75% (15/20) within 12 months. The relative risk for developing RA within 12 months in the anti-CCP-positive group was 66.8 (95% CI 32.2 to 138.4, p<0.001); for IA, it was 45.5 (95% CI 25.4 to 81.6, p<0.001).Conclusions: Selecting individuals with new non-specific MSK symptoms without CS enriched the prevalence of anti-CCP positivity to 2.8%. Those who tested positive had a high risk of rapidly developing RA. The cost-effectiveness of this approach will need to be determined.Trial Registration Number: NCT02012764. [ABSTRACT FROM AUTHOR]

Objectives: To investigate, in anti-CCP antibody-positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk), the additional value of US for the prediction of inflammatory arthritis. Furthermore, to define a concise US protocol for feasible risk prediction., Methods: Demographic and clinical data were collected in 417 CCP+ at-risk (Leeds CCP cohort) with a baseline US scan assessing synovitis and bone erosions in 36 joints, and a follow-up duration ≥24 months. Multivariable binary regression models for inflammatory arthritis development at 24 months evaluated routine clinical variables associated with inflammatory arthritis alone ('clinical' model) and combined with a 36-joint US scanning protocol ('clinical-US extended' model). A 'clinical-US short' model was also developed., Results: At 24 months, 92/417 (22.1%) CCP+ at-risk developed inflammatory arthritis (median time 7 months, interquartile range 3-12). The 'clinical-US extended' model performed better than the 'clinical' model [area under the curve (AUC) 0.788 vs AUC 0.731, respectively, P < 0.001] with an odds ratio for inflammatory arthritis development of 3.18 (95% CI 1.80-5.63) for US synovitis and 2.54 (95% CI 1.21-5.37) for bone erosions. The 'clinical-US short' model, which retained the wrists, knees and MTP5 joints, performed better (AUC 0.782) than the 'clinical' model (P < 0.001) and similarly (difference in Akaike information criteria <2) to the 'clinical-US extended' model., Conclusions: US provides valuable information for predicting progression to inflammatory arthritis in CCP+ individuals both alone and in addition to clinical variables. US synovitis was associated with a 3-fold increase risk of inflammatory arthritis development. A concise US protocol of six joints provides clinically feasible risk prediction in CCP+ at-risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To investigate whether anti-CCP2-positive at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis (CCP2+ at-risk) develop US subclinical synovitis before inflammatory arthritis and if US subclinical synovitis can be predicted., Methods: First, US scans of CCP2+ at-risk individuals who developed inflammatory arthritis ('progressors') were reviewed for subclinical synovitis prior to inflammatory arthritis development. Patients in whom the pre-progression US scan was negative but the scan was conducted >6 months before progression were excluded. Subsequently, regression analyses were performed to identify predictors of US synovitis in CCP2+ at-risk individuals without baseline US abnormalities who had one or more longitudinal US scan and a complete dataset., Results: US subclinical synovitis was detected in one or more scan in 75 of 97 progressors (77.3%) {median time to inflammatory arthritis development from first evidence of US synovitis 26.5 weeks [interquartile range (IQR) 7-60]}, in whom one or more scan was available, excluding those with a negative scan >6 months from inflammatory arthritis development (n = 38). In 220 CCP2+ at-risk individuals with normal baseline US scans, who had one or more longitudinal US scan and a complete dataset, US synovitis was detected in 69/220 (31.4%) [median time to first developing US synovitis 56.4 weeks (IQR 33.0-112.0)]. In the multivariable analysis, only anti-CCP3 antibodies were predictive for the development of US synovitis [odds ratio 4.75 (95% CI 1.97, 11.46); P < 0.01]., Conclusions: In anti-CCP2+ at-risk individuals, a stage of subclinical synovitis usually precedes the development of inflammatory arthritis. Anti-CCP2+/CCP3+ individuals without clinical or US subclinical synovitis may represent the optimal window of opportunity for intervention to prevent joint disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To investigate the prevalence, distribution and predictive value for the development of inflammatory arthritis (IA) of conventional radiography (CR) bone erosions (BE) in anti-CCP positive (CCP+) at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis., Methods: Baseline CR of the hands and feet of 418 CCP+ at-risk individuals were analysed. The presence of US-BE was explored in the anatomical areas in which CR-BE were reported. Hands and feet CR at the time of progression were analysed in a subset of individuals who developed IA (73/123, 59.3%). Logistic regression analyses were performed to calculate the predictive value of baseline CR-BE for the development of IA in 394 CCP+ individuals with ≥1 follow-up visit., Results: BE were detected in 17/418 (4.1%) CCP+ at-risk individuals (median Simple Erosions Narrowing Score-BE = 2.0, IQR: 1.0-2.0; median Sharp van der Heijde score-BE = 4.0, IQR: 3.0-8.5), most frequently in the foot joints (11/17, 64.7% individuals). A total of 123/394 (31.2%) CCP+ at-risk individuals developed IA; 7/17 (41.2%) with, and 116/377 (30.8%) without BE on CR (P = 0.37). US-BE were found in 4/7 (57.1%) individuals with CR-BE who developed IA, but only in 1/10 (10.0%) who did not. At the time of progression, new BE were detected in 4/73 (5.5%) CCP+ individuals on repeated CR. In the regression analyses, baseline CR-BE were not predictive for the development of IA., Conclusions: In CCP+ at-risk individuals with MSK symptoms, CR-detected BE are uncommon and do not predict the development of IA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)