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Background: This study aims to determine the rate of inflammatory rheumatic diseases (IRDs) in a cohort of initial referrals and the efficacy of prioritising appointments to the early arthritis clinic (EAC) based on symptom duration. Methods: In the present study, we used algorithm-based telephone triage to assign routine care appointments according to the time between symptom onset and request for an appointment (cut-off criterion: 6 months). This retrospective, monocentric analysis evaluated the effectiveness of our triage in identifying patients with IRDs as a function of the assigned appointment category (elective, EAC, or emergency appointment). Results: A total of 1407 patients were included in the study (34.7% male; 65.3% female). Of the 1407 patients evaluated, 361 (25.7%) presented with IRD. There were significant differences in the frequency of inflammatory diagnoses between appointment categories (p < 0.001): elective 13.8%, EAC 32.9%, and emergency 45.9%. The sample without the emergency category included a total of 1222 patients. The classification into "inflammatory" or "non-inflammatory" in this subsample was as follows: Sensitivity was 37.7%, and specificity was 92.6%. The positive predictive value (PPV) was 59.8%, and the negative predictive value (NPV) was 83.6%. Overall, 80.2% of patients were correctly assigned using the appointment category and C-reactive protein (CRP). Conclusions: The algorithm-based triage system presented here, which focuses on the time between symptom onset and request for an appointment, allows for the prioritisation of appointments in favour of patients with IRDs and thus earlier initiation of therapy.

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Purpose: Early referral of patients with suspicious of rheumatoid arthritis (RA) has an impact on prognosis. Our study aimed to evaluate the clinical characteristics of patients with hands arthralgia who were referred from primary care physicians (PCP) to the rheumatologist.Methods: A descriptive, observational, prospective cohort study was performed. We included patients who visited a PCP for the first time for hands arthralgia. Demographics and the European Alliance of Associations for Rheumatology criteria for arthralgia suspicious for progression to RA plus seven complementary questions, the time to referral, the pressure needed to provoke pain with an automatic squeeze test machine in the metacarpophalangeal joints of both hands, and the diagnoses established at the last review of medical charts from patients on follow-up were documented. The primary outcome was the referral to a rheumatologist. Results: A total of 109 patients were included. The mean age was 49.9 years, 81.6% were women. 30.3% were referred to the rheumatologist. The time to referral was a median of 38 days. The main clinical characteristics associated with referral to the rheumatologist were the “most severe symptoms are present after midnight” (OR=6.29) and the “difficulty with making a fist” (OR=3.67). An isolated “positive squeeze test of metacarpophalangeal joints” was not associated with a referral to the rheumatologist. Conclusions: Among patients with hands arthralgia who attended PCP, those with most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.(AU)

Objetivo: Derivar tempranamente a los pacientes con sospecha de artritis reumatoide (AR) tiene un impacto en su pronóstico. Nuestro estudio tuvo como objetivo evaluar las características clínicas de los pacientes con artralgia de manos que fueron remitidos desde médicos de atención primaria (MAP) al reumatólogo. Métodos: Se realizó un estudio de cohorte descriptivo, observacional, y prospectivo. Incluimos pacientes que acudieron con un MAP por artralgia de manos. Se documentaron criterios demográficos y de la European Alliance of Associations for Rheumatology (EULAR) para artralgia con sospecha de progresión a AR más siete preguntas complementarias, el tiempo de derivación, la presión necesaria para provocar dolor con una máquina automática que comprime las articulaciones metacarpofalángicas, y los diagnósticos establecidos en la última revisión documentados en los expedientes médicos de los pacientes en seguimiento. El resultado principal fue la referencia al reumatólogo. Resultados: Un total de 109 pacientes fueron incluidos. El promedio de edad fue de 49,9 años, 81,6% fueron mujeres, 30,3% fueron referidos al reumatólogo. El tiempo de derivación al reumatólogo tuvo una mediana de 38 días. Las principales características clínicas asociadas con lo anterior fueron: «síntomas más severos presentes después de la medianoche» (OR=6,29) y «dificultad para hacer un puño» (OR=3,67). Una «prueba de compresión positiva de las articulaciones metacarpofalángicas» aislada no se asoció con una derivación al reumatólogo. Conclusión: Entre los pacientes que acudieron con MAP por artralgia de manos, aquellos con síntomas más severos después de la medianoche y que refirieron dificultad para realizar un puño fueron más frecuentemente referidos a una clínica de reumatología. Sin embargo, una prueba de compresión aislada no fue útil para la derivación temprana.(AU)

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PURPOSE: Early referral of patients with suspicious of rheumatoid arthritis (RA) has an impact on prognosis. Our study aimed to evaluate the clinical characteristics of patients with hands arthralgia who were referred from primary care physicians (PCP) to the rheumatologist. METHODS: A descriptive, observational, prospective cohort study was performed. We included patients who visited a PCP for the first time for hands arthralgia. Demographics and the European Alliance of Associations for Rheumatology criteria for arthralgia suspicious for progression to RA plus seven complementary questions, the time to referral, the pressure needed to provoke pain with an automatic squeeze test machine in the metacarpophalangeal joints of both hands, and the diagnoses established at the last review of medical charts from patients on follow-up were documented. The primary outcome was the referral to a rheumatologist. RESULTS: A total of 109 patients were included. The mean age was 49.9 years, 81.6% were women. 30.3% were referred to the rheumatologist. The time to referral was a median of 38 days. The main clinical characteristics associated with referral to the rheumatologist were the "most severe symptoms are present after midnight" (OR=6.29) and the "difficulty with making a fist" (OR=3.67). An isolated "positive squeeze test of metacarpophalangeal joints" was not associated with a referral to the rheumatologist. CONCLUSIONS: Among patients with hands arthralgia who attended PCP, those with most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.

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AIMS: To develop an understanding of what comprises nurse-led care in early rheumatoid arthritis from the perspective of rheumatology nurse specialists in England. DESIGN: Qualitative study. METHODS: Semi-structured telephone interviews with rheumatology nurse specialists in England were conducted in Summer 2020. Interviews were audio-recorded, transcribed verbatim and analysed using reflexive thematic analysis. Reporting follows the appropriate elements of consolidated criteria for reporting qualitative research. RESULTS: Sixteen nurses were recruited and interviews lasted 30-60 min. Four themes with 14 subthemes were identified. A SPECIALIST SERVICE DELIVERED BY EXPERIENCED RHEUMATOLOGY NURSES: Specialist care is provided by experienced nurse specialists with a high degree of autonomy in the rheumatology multidisciplinary team context. ADDRESSING PATIENTS' COMPLEX CARE NEEDS: Care is evidence-based and aims to start treatment, keep in treatment, educate and support. Access to psychology expertise is needed. CARE WITH COMPASSION USING PERSON-CENTRED, HOLISTIC AND EMPATHETIC APPROACHES: Nurses create patient relationships and a positive therapeutic environment. Nurse-led telephone advice lines are essential for treatment adjustment, patient support and empowerment. CONTINUED EVALUATION AND DEVELOPMENT OF THE SERVICE: Consultations are reviewed, and patients are asked for feedback. The COVID-19 pandemic caused disruption, but changes streamlined procedures and improved documentation and communication. CONCLUSION: Nurse-led care in early rheumatoid arthritis is a specialist service delivered with compassion, addressing complex care needs and using person-centred approaches. This study identifies key aspects of care in early disease from the nurse perspective.

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OBJECTIVES: The severity of fatigue in rheumatoid arthritis (RA) has hardly improved in recent decades, leaving a large unmet need. Fortunately, not all RA-patients suffer from persistent fatigue, but the subgroup of patients who suffer the most is insufficiently recognizable at diagnosis. As disease activity is partly coupled to fatigue, Disease-Activity-Score (DAS)-components may associate with the course of fatigue. We aimed to identify the RA-patients who remain fatigued by studying DAS-components at diagnosis in relation to the course of fatigue over a 5-year follow-up period in two independent early RA-cohorts. METHODS: 1560 consecutive RA-patients included in the Leiden Early Arthritis Cohort and 415 RA-patients included in the tREACH-Cohort were studied. Swollen joint count, tender joint count, ESR and Patient Global Assessment (Visual Analogue Scale(VAS),0-100 mm) were studied in relation to fatigue(VAS, 0-100mm) during 5-years using linear mixed models. RESULTS: Higher TJC and PGA at diagnosis were associated with a more severe course of fatigue. The SJC, in contrast, showed an inverse association; patients with mono- or oligo-arthritis at diagnosis remained more fatigued. The combination of aforementioned characteristics revealed that patients presenting with a mono- or oligo-arthritis and PGA ≥ 50 remained the most fatigued over time(+20mm vs polyarthritis with PGA < 50), whilst the DAS-course over time was not different. This subgroup comprised 14% of the early RA-population. Data from the tREACH-cohort showed similar findings. CONCLUSION: RA-patients who remain the most fatigued are characterized by mono- or oligo-arthritis and high PGA(VAS ≥ 50) at diagnosis. This understanding may enable early-intervention with non-pharmacological approaches in dedicated patient groups.

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OBJECTIVES: Undifferentiated peripheral inflammatory arthritis (UPIA) may have 3 different courses, including evolution to differentiated arthritis, remaining undifferentiated, and self-limited course. The purpose of this study was to provide a real-world evidence for predictors of outcomes in UPIA in a longitudinal cohort of patients. METHODS: Patients enrolled in the CTDRC-UA cohort were screened for eligibility. Inclusion criteria were: (i) having synovitis in ≥ 1 joint, (ii) not meeting the criteria of any other rheumatic disease, (iii) having at least 2 visits per year, iv) included in the cohort during the period of 2004 to 2021, and (v) having active disease at cohort entry. Two hundred and three patients who met the inclusion criteria were followed up until January 2023. RESULTS: Medication-free remissions occurred in 42 (20.7%) cases. In 24 (11.8%) cases, the disease met the criteria of other rheumatic diseases, of which rheumatoid arthritis (RA) was the most common. In addition, joint damage occurred in 33 (16.3%) cases. Predictors of medication-free remissions were absence of comorbidity, starting a sustained remission at ≤ 6 months, and having no flare. Factors associated with disease evolution to RA were anti-citrullinated peptide antibody (ACPA) positivity, non-adherence to therapy, not going into sustained remission and having flare. Delay in treatment for > 3 months and being ACPA positive were the predictors of joint damage. CONCLUSION: Although the majority of UIPA cases treated with step-up combination therapy with DMARDs do not progress to RA, most require continued treatment and a few achieve medication-free remissions. Key Points • Undifferentiated peripheral inflammatory arthritis (UPIA) can progress to rheumatoid arthritis in 11% of cases; and lack of sustained remission, being anti-citrullinated peptide antibody positive, non-adherence to therapy, and having flare are its predictors. • Medication-free remissions occur in 21% of patients with UPIA; and absence of comorbidity, starting a sustained remission at ≤ 6 months, and having no flare are its predictors. • Initiating treatment in the window of opportunity may lead to a better joint outcome.

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INTRODUCTION: This study sought to analyze the benefit of an early induction therapy with a biological disease-modifying anti-rheumatic drugs (bDMARD) during the first year of treatment with a 5-year follow-up in early rheumatoid arthritis (ERA). METHODS: We included ERA patients from the UCLouvain Brussels cohort who met the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria and were naïve to DMARDs. ERA patients were divided into two groups according to whether they received an induction bDMARD therapy or a standard therapy with methotrexate (MTX). Clinical response after the induction treatment at 6 and 12 months followed by a MTX maintenance therapy at 36 and 60 months was evaluated. RESULTS: Data from 470 ERA patients were collected, 189 received a bDMARD and 281 initiated MTX alone. In the bDMARD group, disease activity and HAQ were higher at baseline. A total of 391 patients were followed up to 5 years. We then divided each group into two subgroups according to the last treatment they received at 5 years: bDMARD > MTX (n = 95), bDMARD > bDMARD (n = 59); MTX > MTX (n = 134), MTX > bDMARD (n = 103). During the induction, we observed a clinical response with a large number of patients achieving DAS28-CRP remission. According to a treat-to-target (T2T) approach, remission rate was stable on MTX monotherapy or rescued by the addition or prolongation of a bDMARD. Interestingly, bDMARD followed by a MTX maintenance therapy experienced a stable and sustained DAS28-CRP remission rate in 53% of the ERA patients at year 5. CONCLUSIONS: Long-term remission is an achievable goal in ERA. Our results suggest that a bDMARD induction therapy followed by MTX maintenance therapy could be an interesting option.

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OBJECTIVES: The value of US-defined tenosynovitis in predicting the persistence of inflammatory arthritis is not well described. In particular, the predictive utility of US-defined tenosynovitis of larger tendons is yet to be reported. We assessed the value of US-defined tenosynovitis alongside US-defined synovitis and clinical and serological variables in predicting persistent arthritis in an inception cohort of DMARD-naïve patients with early arthritis. METHODS: One hundred and fifty DMARD-naïve patients with clinically apparent synovitis of one or more joints and a symptom duration of ≤3 months underwent baseline clinical, laboratory and US (of 19 bilateral joints and 16 bilateral tendon compartments) assessments. Outcomes were classified as persistent or resolving arthritis after 18 months' follow-up. The predictive value of US-defined tenosynovitis for persistent arthritis was compared with those of US-defined synovitis, and clinical and serological variables. RESULTS: At 18 months, 99 patients (66%) had developed persistent arthritis and 51 patients (34%) had resolving disease. Multivariate logistic regression analysis showed that US-detected digit flexor tenosynovitis [odds ratio (OR): 6.6, 95% CI: 2.0 , 22.1, P = 0.002] provided independent predictive data for persistence over and above the presence of US-detected joint synovitis and RF antibodies. In the RF/ACPA-negative subcohort, US-defined digit flexor tenosynovitis remained a significant predictive variable (OR: 4.7, 95% CI: 1.4, 15.8, P = 0.012), even after adjusting for US-defined joint synovitis. CONCLUSION: US-defined tenosynovitis provided independent predictive data for the development of persistent arthritis. The predictive role of US-defined digit flexor tenosynovitis should be further assessed; investigators should consider including this tendon site as a candidate variable when designing imaging-based predictive algorithms for persistent inflammatory arthritis development.

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OBJECTIVE: MRI of small joints plays an important role in the early detection and early treatment of rheumatoid arthritis. Despite its sensitivity to demonstrate inflammation, clinical use is hampered by accessibility, long scan time, intravenous contrast, and consequent high costs. To improve the feasibility of MRI implementation in clinical practice, we introduce a modified Dixon sequence, which does not require contrast and reduces total acquisition time to 6 min. Because the reliability in relation to conventional MRI sequences is unknown, we determined this. METHODS: In 29 consecutive early arthritis patients, coronal and axial T2-weighted modified Dixon acquisitions on 3.0 T MRI scanner were acquired from metacarpophalangeal 2-5 to the wrist, followed by the standard contrast-enhanced protocol on 1.5 T extremity MRI. Two readers scored osteitis, synovitis and tenosynovitis (summed as total MRI-inflammation), and erosions (all summed as total Rheumatoid Arthritis MRI Score (RAMRIS)). Intraclass correlation coefficients (ICCs) between readers, and comparing the two sequences, were studied. Spearman correlations were determined. RESULTS: Performance between readers was good/excellent. Comparing modified Dixon and conventional sequences revealed good/excellent reliability: ICC for total MRI-inflammation score was 0.84 (95% CI:0.70-0.92), for erosions 0.90 (95% CI:0.79-0.96), and for the total RAMRIS score 0.88 (95% CI:0.77-0.94). The scores of total MRI-inflammation, total erosions, and total RAMRIS were highly correlated (ρ = 0.80, ρ = 0.81, ρ = 0.82, respectively). CONCLUSION: The modified Dixon protocol is reliable compared to the conventional MRI protocol, suggesting it is accurate to detect MRI inflammation. The good correlation may be the first step towards a patient-friendly, short and affordable MRI protocol, which can facilitate the implementation of MRI for early detection of inflammation in rheumatology practice.

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Galectin-1 (Gal1) plays a regulatory role in the immune system. We have recently validated that Gal1 serum (sGal1) levels are increased in rheumatoid arthritis (RA) patients compared to healthy donors (HDs); however, there is no information on Gal1 in spondyloarthritis (SpA). Objective: To compare Gal1 levels in patients with SpA versus RA as a diagnostic biomarker. Methods: We studied sGal1 levels in HD (n = 52), SpA (n = 80) and RA patients (n = 64) who were randomly divided into discovery and validation sets. Synovial fluid (SF) from osteoarthritis (OA) (n = 28), peripheral SpA (n = 28) and RA (n = 28) were studied. In SpA patients, we analyzed the association between clinical parameters and sGal1 levels. Results: sGal1 levels were significantly lower in patients with SpA with respect to RA and similar to those of the HD. A cut-off of 20.50 ng/mL (sGal1) allowed one to differentiate RA patients from SpA and HD (Odd Ratio (OR) 8.23 and 12.64, respectively). Gal1 SF levels in SpA were slightly lower than OA patients and significantly lower than RA patients. No correlation was observed between sGal1 levels and clinical parameters in SpA patients. Conclusion: Gal1 could act as a diagnostic biomarker of RA and would allow one to distinguish SpA and RA patients.

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This study aimed to analyze the factors that influence anti-citrullinated protein antibody (ACPA) titers in a seropositive early arthritis (EA) population under non-protocolized treatment with disease-modifying anti-rheumatic drugs (DMARDs). A total of 130 ACPA-positive patients from the PEARL (Princesa Early Arthritis Longitudinal) study were studied along a 5-year follow-up. Sociodemographic, clinical, and therapeutic variables, along with serum samples, were collected at five visits by protocol. Anti-cyclic citrullinated peptide 2 (CCP2) ACPA titers were measured by ELISA. The effect of different variables on anti-CCP2 titers was estimated using longitudinal multivariate analysis models, nested by visit and patient. Data from 471 visits in 130 patients were analyzed. A significant decrease in anti-CCP2 titers was observed at all time-points, compared to baseline, following the decline of disease activity. In the multivariate analysis, active or ever smoking was significantly associated with the highest anti-CCP2 titers while reduction in disease activity was associated with titer decline. After adjusting for these variables, both conventional synthetic (cs) and biologic (b) DMARDs accounted for the decline in anti-CCP2 titers as independent factors. Conclusion: In patients with EA, an early and sustained reduction in ACPA titers can be detected associated with the decline in disease activity, irrespective of the treatment used.

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BACKGROUND: To determine whether gene-gene interaction network analysis of RNA sequencing (RNA-Seq) of synovial biopsies in early rheumatoid arthritis (RA) can inform our understanding of RA pathogenesis and yield improved treatment response prediction models. METHODS: We utilized four well curated pathway repositories obtaining 10,537 experimentally evaluated gene-gene interactions. We extracted specific gene-gene interaction networks in synovial RNA-Seq to characterize histologically defined pathotypes in early RA and leverage these synovial specific gene-gene networks to predict response to methotrexate-based disease-modifying anti-rheumatic drug (DMARD) therapy in the Pathobiology of Early Arthritis Cohort (PEAC). Differential interactions identified within each network were statistically evaluated through robust linear regression models. Ability to predict response to DMARD treatment was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Analysis comparing different histological pathotypes showed a coherent molecular signature matching the histological changes and highlighting novel pathotype-specific gene interactions and mechanisms. Analysis of responders vs non-responders revealed higher expression of apoptosis regulating gene-gene interactions in patients with good response to conventional synthetic DMARD. Detailed analysis of interactions between pairs of network-linked genes identified the SOCS2/STAT2 ratio as predictive of treatment success, improving ROC area under curve (AUC) from 0.62 to 0.78. We identified a key role for angiogenesis, observing significant statistical interactions between NOS3 (eNOS) and both CAMK1 and eNOS activator AKT3 when comparing responders and non-responders. The ratio of CAMKD2/NOS3 enhanced a prediction model of response improving ROC AUC from 0.63 to 0.73. CONCLUSIONS: We demonstrate a novel, powerful method which harnesses gene interaction networks for leveraging biologically relevant gene-gene interactions leading to improved models for predicting treatment response.

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Galectin 1 (Gal1) exerts immunomodulatory effects leading to therapeutic effects in autoimmune animal models. Patients with rheumatoid arthritis have been reported to show higher Gal1 serum levels than the healthy population. Our study aimed to find genetic variants on the Gal1 gene (LGALS1) modulating its expression and/or clinical features in patients with early arthritis (EA). LGALS1 was sequenced in 53 EA patients to characterize all genetic variants. Then, we genotyped rs9622682, rs929039, and rs4820293, which covered the main genetic variation in LGALS1, in 532 EA patients. Gal1 and IL-6 serum levels were measured by ELISA and Gal1 also by western blot (WB) in lymphocytes from patients with specific genotypes. Once disease activity improved with treatment, patients with at least one copy of the minor allele in rs9622682 and rs929039 or those with GG genotype in rs4820293 showed significantly higher Gal1 serum levels (p < 0.05). These genotypic combinations were also associated with higher Gal1 expression in lymphocytes by WB and lower IL-6 serum levels in EA patients. In summary, our study suggests that genetic variants studied in LGALS1 can explain heterogeneity in Gal1 serum levels showing that patients with higher Gal1 levels have lower serum IL-6 levels.

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BACKGROUND: While low-dose oral glucocorticoids (GCs) are recommended in the management of early arthritis, their impact on mortality is unclear. The aim of this study is to evaluate the effect of GCs on mortality in patients with early arthritis, by linking clinical and administrative databases. METHODS: The study included patients with new-onset rheumatoid arthritis (RA) or undifferentiated arthritis (2005-2010), who received DMARDs (MTX in RA or UA with poor prognosis, hydroxychloroquine in UA) and were alive at the second year of follow-up. Low-dose GCs could be prescribed. Clinical and administrative data were linked from Administrative Health Databases (AHD) of the corresponding province, which provided us with information on drug delivery, comorbidities, hospitalization, and mortality. The effect of GCs in the first year was defined using a dichotomous variable or a 3-level categorization (not delivered, ≤7.5 mg/day, or >7.5 mg/day of prednisone) on all-cause mortality, assessed with Cox regression, either crude or adjusted for age, gender, Charlson Comorbidity Index (CCI) or single comorbidities, ACPA, HAQ, and MTX in the first year. A secondary analysis of the effect of GCs on related hospitalizations (for cardiovascular events, diabetes, serious infections, osteoporotic fractures) was also carried. RESULTS: Four hundred forty-nine patients were enrolled (mean age 58.59, RA 65.03%) of which 51 (11.36%) died during the study. The median (IQR) follow-up was equal to 103.91 (88.03-126.71) months. Treatments with GCs were formally prescribed to 198 patients (44.10%) at ≤7.5 mg/day, although by the end of the study such treatments were received by 257 patients (57.24%); 88 patients (19.6%) were treated with GCs at >7.5 mg/day. In adjusted analyses, the GC delivery (HR, 95% CI 1.35 (0.74, 2.47)) did not significantly predict mortality - both at a low (HR, 95% CI 1.41 (0.73, 2.71)) and at a high (HR, 95% CI 1.23 (0.52, 2.92)) dosage. When "all-cause hospitalization" was used as an outcome, the analysis did not show a difference between patients receiving GC and patients not receiving GC. CONCLUSION: In patients with early inflammatory arthritis, the initial GC dose was higher than that prescribed by rheumatologists; however, on background treatment with DMARDs, GC treatments did not seem to increase mortality and hospitalizations.

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BACKGROUND: Arthritis is a common condition, and the prompt and accurate assessment of hand arthritis in primary care is an area of unmet clinical need. We have previously developed and tested a screening tool combining machine-learning algorithms, to help primary care physicians assess patients presenting with arthritis affecting the hands. The aim of this study was to assess the validity of the screening tool among a number of different Rheumatologists. METHODS: Two hundred and forty-eight consecutive new patients presenting to 7 private Rheumatology practices across Australia were enrolled. Using a smartphone application, each patient had photographs taken of their hands, completed a brief 9-part questionnaire, and had a single examination result (wrist irritability) recorded. The Rheumatologist diagnosis was entered following a 45-minute consultation. Multiple machine learning models were applied to both the photographic and survey/examination results, to generate a screening outcome for the primary diagnoses of osteoarthritis, rheumatoid and psoriatic arthritis. RESULTS: The combined algorithms in the application performed well in identifying and discriminating between different forms of hand arthritis. The algorithms were able to predict rheumatoid arthritis with accuracy, precision, recall and specificity of 85.1, 80.0, 88.1 and 82.7% respectively. The corresponding results for psoriatic arthritis were 95.2, 76.9, 90.9 and 95.8%, and for osteoarthritis were 77.4, 78.3, 80.6 and 73.7%. The results were maintained when each contributor was excluded from the analysis. The median time to capture all data across the group was 2 minutes and 59 seconds. CONCLUSIONS: This multicentre study confirms the results of the pilot study, and indicates that the performance of the screening tool is maintained across a group of different Rheumatologists. The smartphone application can provide a screening result from a combination of machine-learning algorithms applied to hand images and patient symptom responses. This could be used to assist primary care physicians in the assessment of patients presenting with hand arthritis, and has the potential to improve the clinical assessment and management of such patients.

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Rheumatoid arthritis (RA) is a highly prevalent autoimmune disease and the most common form of autoimmune inflammatory arthritis. Studies of RA pathogenesis have contributed significantly to understanding the basis for complex immune-mediated disease, identified key steps in the development of autoimmune activation and joint damage in RA, and led to the development of targeted therapies that opened up the era biologic therapy. Current studies are linking differences in gene expression to abnormalities in cellular function that will help optimize therapy for individual patients and advance the goal of personalized medicine. Our evolving understanding and current important issues in RA are highlighted.

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BACKGROUND: Arthritis is a common condition, which frequently involves the hands. Patients with inflammatory arthritis have been shown to experience significant delays in diagnosis. AIM: To develop and test a screening tool combining an image of a patient's hands, a short series of questions and a single examination technique to determine the most likely diagnosis in a patient presenting with hand arthritis. Machine learning techniques were used to develop separate algorithms for each component, which were combined to produce a diagnosis. METHODS: A total of 280 consecutive new patients presenting to a rheumatology practice with hand arthritis were enrolled. Each patient completed a nine-part questionnaire, had photographs taken of each hand and had a single examination result recorded. The rheumatologist diagnosis was recorded following a 45-min consultation. The photograph algorithm was developed from 1000 previous hand images and machine learning techniques were applied to the questionnaire results, training several models against the diagnosis from the rheumatologist. RESULTS: The combined algorithms in the present study were able to predict inflammatory arthritis with an accuracy, precision, recall and specificity of 96.8%, 97.2%, 98.6% and 90.5% respectively. Similar results were found when inflammatory arthritis was subclassified into rheumatoid arthritis and psoriatic arthritis. The corresponding figures for osteoarthritis were 79.6%, 85.9%, 61.9% and 92.6%. CONCLUSION: The present study demonstrates a novel application combining image processing and a patient questionnaire with applied machine-learning methods to facilitate the diagnosis of patients presenting with hand arthritis. Preliminary results are encouraging for the application of such techniques in clinical practice.

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BACKGROUND: There is a paucity of literature that examines how patient-reported outcomes correspond to early radiographic progression of thumb carpometacarpal (CMC) osteoarthritis (OA). This study examines how Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Patient-Rated Hand and Wrist Evaluation (PRWHE) scores change over 36 months in subjects with early CMC OA. METHODS: Ninety-one subjects with symptomatic early thumb CMC OA were enrolled. Differences in AUSCAN and PRWHE scores were measured between subjects at baseline and at 18-month follow-up, and between the subjects at baseline and at 36-month follow-up. Radiographic progression was defined as an increase in modified Eaton Stage. Differences in AUSCAN and PRWHE scores were compared between these 2 groups in order to determine if radiographic progression was associated with a greater change in AUSCAN and PRWHE at 18- and 36-month follow-up. RESULTS: At 18- and 36-month follow-up visits, there were no significant differences in AUSCAN or PRWHE compared to baseline. Multivariable logistic regression analysis did not reveal any significant differences between subjects with radiographic progression to subjects without radiographic progression at 18-month follow-up. At 36-month follow-up, this analysis did demonstrate that subjects with evidence of radiographic progression had a significant increase in the PRWHE pain subscale. CONCLUSION: AUSCAN and PRWHE scores were not found to significantly progress at 18-month and 36-month follow-up. However, when comparing the subset of subjects with and without radiographic OA, subjects with early CMC OA who had 1 stage of radiographic progression were found to have a significantly higher intensity of pain on the PRWHE pain subscale at 36-month follow-up.

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OBJECTIVES: International guidelines stress timely DMARD initiation in early arthritis as well as when classification criteria are not yet fulfilled. Consequently, undifferentiated arthritis (UA) patients may be increasingly treated with DMARDs. Since UA is a diagnosis of exclusion, the introduction of the 2010 classification criteria presumably decreased the UA population, as former UA patients became regarded as RA. Consequently, the contemporary definition of UA has changed into: no clinical diagnosis and not fulfilling the 1987 nor 2010 RA-criteria. Importantly, placebo-controlled trials on DMARD efficacy in contemporary UA are absent. We aimed to study whether enhanced treatment strategies across the last 25 years improved outcomes in contemporary UA, whereby inclusion period was used as instrumental variable for DMARD treatment. METHODS: UA was defined, retrospectively, as clinical arthritis (joint swelling at physical examination) neither fulfilling the 1987 nor 2010 RA-criteria or any other clinical diagnosis. In total, 1132 UA patients consecutively included in the Leiden Early Arthritis Clinic between 1993 and 2019 were divided into five inclusion periods: 1993-1997, 1998-2005, 2006-2010, 2011-2014 and 2015-2019. The frequency of DMARD initiation was compared across the inclusion periods, as were the following outcomes: 28-joint DAS with CRP (DAS28-CRP) and the HAQ Disability Index (HAQ-DI) during follow-up, prevalence of DMARD-free-status within 10 years (DFS; spontaneous remission or sustained remission after DMARD stop) and progression to RA (according 1987/2010 criteria). RESULTS: The contemporary UA population is mainly autoantibody negative, with a median swollen joint count of 2, tender joint count of 3 and HAQ score of 0.6. These characteristics were similar across the inclusion periods. DMARD treatment increased from 17% (1993-1997) to 52% (2015-2019) and methotrexate became more common. The DAS28-CRP during follow-up improved from 2011 onwards (-0.18 to -0.25 DAS units; P < 0.05). Disability scores during follow-up did not significantly improve. DFS prevalence also remained similar: 58%, 57% and 61% for 1993-1997, 1998-2005 and 2006-2010, respectively (P = 0.77). Likewise, the percentages of RA development did not decrease (14%, 21%, 26%, 18% and 27%, respectively). CONCLUSION: Although intensified DMARD treatment slightly improved disease activity scores, physical functioning and long-term outcomes did not improve. This suggests overtreatment in the contemporary UA population and underlines the importance of developing stratification methods suitable for this patient-population.

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With the availability of effective treatment with targeted synthetic and biologic disease-modifying anti-rheumatic drugs (ts/bDMARDs) for psoriatic arthritis (PsA), it is crucial to identify predictors of access to this treatment since disease onset. We retrospectively enrolled patients with peripheral PsA, assessed in an early arthritis clinic from 2005 to 2020. The main baseline demographic, clinical and ultrasonographic (assessment of bilateral wrist and metacarpophalangeal joints) features were evaluated through descriptive statistics and tested as predictors by univariate and multivariate Cox models. The outcome of interest was the indication for ts/bDMARDs within 2 years from diagnosis. We included 238 patients with PsA, with a mean (sd) age of 51.04 (13.98) years; 90 (37.8%) were male, and the median (IQR) symptom duration was 6.12 (3.29-12.25) months. In univariate analyses, C-reactive protein (RR, 95% CI 1.204 (1.065,1.362)), Visual Analogue Scale (VAS) pain (1.027 (1.005,1.048)), the number of tender joints on 28 joints (1.087 (1.025, 1.153)), and a synovial power Doppler (PD) score > 1 (3.63 (1.307, 10.08)) emerged as significant predictors. C-reactive protein, VAS pain and PD confirmed their predictive value also in multivariate models. These results provide preliminary evidence on the features that might characterize patients with early peripheral PsA requiring more intensive monitoring and treatment escalation.