Background Early diagnosis and early treatment with DMARDs lead to better outcomes in rheumatoid arthritis (RA) (1,2). The 2010 ACR/EULAR criteria for RA were developed for early classification (3) and have good sensitivity, lower specificity and overall moderate accuracy. Their usefulness to lead treatment selection has not been investigated yet. Objectives To compare clinical remission (CR) rates in patients with early polyarthritis in which the decision to start methotrexate (MTX) was based on the 1987 ACR vs 2010 ACR/EULAR criteria, over the first 12 months follow up. Methods This is an observational non concurrent cohort study. Patients classified as RA or undifferentiated arthritis (UA) attending for the first time our early arthritis clinic (2005-2013) were eligible for inclusion. At baseline, before October 2010, patients classified as RA according to the 1987 criteria were treated with MTX (from 10 mg/wk up to 20 mg/wk), while patients with UA received hydroxychloroquine (HCQ) (1987 cohort). After October 2010, patients fulfilling the 2010 criteria received MTX (from 15 mg/wk up to 25mg/wk), while UA received HCQ (2010 cohort). Low-dose prednisone could be given according to clinician's decision. Patients were seen every 2 months in the first six months and every 3 afterwards; treatment was increased in order to achieve low disease activity (DAS28<3.2). CR (DAS28<2.6) was evaluated at every visit. Analyses were performed with a Cox proportional hazard regression analysis, and results presented as hazard ratios (HR) and 95% confidence intervals (CI). Results Out of 676 patients, 467 were included in the 1987 cohort and 209 in the 2010 cohort. There were no significant differences between the two cohorts in terms of age, gender, VAS pain, RF and ACPA positivity. Patients in the 2010 cohort had significantly fewer median (IQR) tender (4 (2-8) vs 5 (2-10), p=0.018) and swollen joints (4 (2-7) vs 6 (3-10), p<0.0001) over 28 joints, ESR (19 (10-34) vs 22 (13-39), p=0.007) and CRP (0.4 (0.3-1.2) vs 0.7 (0.31-2.09), p=0.001), mean (SD) DAS28 (4.44 (1.14) vs 4.74 (1.25), p=0.005) and median (IQR) HAQ (0.75 (0.375-1.25) vs 1 (0.5-1.625), p=0.0001). Comparing the two cohorts, the 2010 cohort was more likely to achieve CR even when the analysis was limited to patients who strictly followed the protocol or actually received MTX, both in crude and adjusted analyses (Tab1). Table 1 Crude HR (95% CI) Adjusted HR (95% CI)* ACR/EULAR 2010 vs ACR 1987 All subjects (N=676) 1.83 (1.50, 2.22) 1.73 (1.34, 2.22) Per protocol (N=413) 1.79 (1.39, 2.29) 1.49 (1.11, 2.02) MTX users (N=265) 1.96 (1.46, 2.64) 2.18 (1.14, 4.17) *Adjusted for age, gender, baseline DAS28, symptom duration, MTX dose, glucocorticoid use. Conclusions Patients with early arthritis in which the decision to start MTX is driven by the 2010 criteria achieve more often CR compared to those treated according to the 1987 criteria. Beside the limited diagnostic accuracy of the 2010 criteria, these results support their usefulness as trea...
BackgroundThe increased availability of modern imaging in clinical practice has led to its more extensive use. In the field of osteoarthritis (OA), recommendations on the use of imaging in clinical trials have been developed, but there has been less focus on routine clinical management.ObjectivesTo develop evidence-based recommendations for the use of imaging in the clinical management of OA.MethodsA task force convened by the European League Against Rheumatism including rheumatologists, radiologists, generalists, methodologists and patients from 9 countries developed recommendations based on both evidence obtained through systematic literature review (SLR) and expert opinion. The task force initially identified the areas of application of imaging in OA and developed research questions to drive the SLR. Imaging modalities included were conventional radiography, ultrasound, magnetic resonance imaging, computed tomography, radioisotope scan. Anatomical areas of interest were knee, hip, hand and foot. Based on the priorities identified by the task force, the role of imaging in making a diagnosis of OA and identifying OA features (including soft tissue, bone and cartilage involvement), in detecting alternative diagnoses, the impact of imaging on disease management, in defining prognosis (natural history of the disease and response to treatment), in the follow up of the disease and to guide treatment were addressed. Research evidence was searched systematically for each question and separately for each anatomic area using PubMed and Embase.ResultsThe systematic review retrieved 6858 references, after the assessment of 1317 full papers, 380 studies were included. The results of the systematic review were presented to the task force, and consensus recommendations derived. These cover areas such as (exact wording not included for brevity reasons): the lack of need for imaging in diagnosis of patients who present with usual OA symptoms; role of imaging in differential diagnosis; consideration of the challenges in using imaging for routine monitoring of OA where there is no change in clinical status; what should be the feasible first choice modality and what issues were relevant to how images were acquired; how anatomical site of OA may influence use and type of imaging; and the role of imaging and intra-articular injection. Significant gaps in the literature underpinned the recommendations for future research that were also developed.ConclusionsBased on the results of a SLR and expert opinion, recommendations on the use of imaging in the clinical management of OA were developed.Disclosure of InterestNone declared
Background:Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with inflammatory arthritis. The growing attention to the CV risk characterizing patients with autoimmune inflammatory disease led EULAR to provide recommendations on CV risk management (1). To date, there are no data on the adherence to EULAR recommendation among Italian rheumatologists.Objectives:Our objective was to measure the level of awareness and the attitude to manage CV risk.Methods:Italian rheumatologists were invited to anonymously answer a web-based questionnaire designed by the steering committee of the Cardiovascualr and Obesity in Rheumatic Diseases (CORDIS) study group of the Italian Society of Rheumatology. The first part of the questionnaire concerned demographic information; the subsequent questions concerned the attitude to assess CV risk and the limitations for not assessing, the specific CV risks considered in the clinical practice and their management. Data are presented using standard summary statistics and were expressed as mean+/-standard deviation or median (interquartile range) according to variables’ distribution.Results:One thousand-three hundred rheumatologists (of whom 500 are under 40 and 100 over 70 years of age) have been invited by email to complete the survey. The questionnaire has been filled by 102 rheumatologists (7.85%) (53 females and 49 males) with a median age of 38 years (32-48) and a median of 4 (0-15) years of specialization. Most of the physician who answered the questionnaire works in University Hospitals (67/102; 65.7%), 22 out of 102 (21.6%) in non-academic Hospitals, and the remaining 12,7% in territorial outpatient clinics.When asked if they usually evaluate CV risk in patients with autoimmune rheumatic diseases, 67/102 (67.2%) answered positively, 18 no (17.6%) and 7 did not answer the question; 82% of those who routinely assess the CV do it by themselves. The barriers limiting the assessment of CV risk included: i) lack of time (79%); ii) complex management (12%); inadequate training (9%).As for the CV risk factors, lipid profile, hypertension and diabetes are assessed by most of the rheumatologists (90%, 89% and 88%, respectively), family history by 78% and body mass index by 75.3% and waist circumference only by 25% of those who completed the survey.Finally, only 18.6% stated that they manage by themselves CV risk in patients with autoimmune rheumatic diseases while 50% refer patients to other specialists and 23.4% to general practitioner.Conclusion:Despite the growing awareness on the CV risk characterizing patients with autoimmune rheumatic disease, about one third of young Italian rheumatologists does not strictly adhere to the EULAR recommendations on CV management, mostly due to insufficient time during the routine care visits.References:[1] Agca R et al. Ann Rheum Dis 2017; 76: 17-28.Disclosure of Interests:Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Fabiola Atzeni: None declared, Gianluca Erre: None declared, Andreina Manfredi: None declared, Elena Bartoloni Bocci: None declared, Matteo Piga: None declared, Garifallia Sakellariou Speakers bureau: Abbvie, Novartis, MSD, Ombretta Viapiana: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB
BackgroundSerum Calprotectin has been tested as a marker of disease activity in psoriatic (PsA) and rheumatoid (RA) arthritis. In RA and in PsA on TNF inhibitors in remission calprotectin correlates with power-Doppler (PD) positive ultrasonographic (US) synovitis, while there is no data on untreated patients with new-onset PsA.ObjectivesTo investigate the correlation and association between calprotectin and US synovitis in patients with new-onset PsA and in a control group of RA.MethodsConsecutive patients with PsA and a group of age and gender-matched patients with RA, referred to an early arthritis clinic (2005–2014) were included. Demographic and clinical features, including a 44 joint count for tenderness and swelling (TJC, SJC) and C-reactive protein (CRP) were recorded. US of wrists (radiocarpal, intracarpal and ulnocarpal) and MCP joints with grey scale (GS) and PD synovitis scored 0–3 at each site, with a total score from the sum of each site, was available at the same time, as well as serum samples to measure calprotectin concentration. Serum levels of calprotectin were compared by Mann Whitney test in PsA and RA. The correlation between calprotectin, TJC, SJC, CRP and US PD and GS was evaluated by Spearman’s correlation coefficient, while the association of calprotectin concentrations and PD synovitis by regression analysis. Secondary analyses separating poliarticular and oligoarticular (SJC ≤4) PsA and using different definitions of synovitis (GS >1, PD >1) were performed.Results156 patients (78 PsA and 78 RA) were included (RA: male 28.2%, mean (sd) age 51.9 (13.3); PsA male 32%; mean age 51.7 (13.5)). Patients with RA had significantly higher CRP (median, IQR) (0.6, 0.3–2.1 vs 0.36, 0.3–1, p 0.04), SJC (7, 5–12 vs 6, 3–9, p 0.008), GS (6, 4–11 vs 5, 2–7, p 0.01) and PD (2, 0–9 vs 1, 0–3, p 0.003) scores. Calprotectin (ng/ml, median, IQR) did not significantly differ in PsA (3123, 2063–4669) and RA (2556, 1615–4441), also when separating poliarticular and oligoarticular PsA. In patients with PsA, calprotectin significantly correlated with GS score (rho 0.340, p 0.007), PD score (rho 0.290,p 0.02) and with the presence of PD (categorical variable) (rho 0.263, p 0.04), while in RA there were no statistically significant correlations. When separating poliarticular and oligoarticular PsA, a significant correlation between calprotectin and GS score (rho 0.369, p 0.01) and PD score (rho 0.363, p 0.02) was confirmed in poliarticular but not oligoarticular disease. In both RA and PsA SJC and TJC did not significantly correlate with calprotectin. Calprotectin showed a statistically significant correlation with CRP in both PsA (rho 0.273, p 0.01) and RA (rho 0.27, p 0.01), showing concurrent validity. In regression analysis, calprotectin levels did not associate with the presence of PD in PsA also when using a more stringent cut-off. Similar results were achieved in RA.ConclusionsIn untreated patients with early onset PsA, but not in RA, calprotectin correlates with US PD-positive synovitis, especially in poliar...
Background:According to guidelines, the use of steroid and/or hyaluronate (HA) intra-articular injections for knee osteoarthritis (KOA) is controversial. Heterogeneity of studies and difference in HAs characteristics does not allow to draw safe conclusions. One of the major concerns is the accuracy of the procedure as up to 1/3 of injections could miss joint space when performed blindly (1), negatively affecting the efficacy of HA that needs to be placed correctly in the joint spaceObjectives:The aim of our study was to evaluate the longterm efficacy of a novel association of a Cross-Linked Sodium Hyaluronate Combined With Triamcinolone Hexacetonide (SHCTH) in patients with KOA in a real life setting.Methods:We retrospectively evaluated the clinical and ultrasonographic (US) data of patients (pts) affected by symptomatic KOA with intra-articular injections of SHCTH (1 injection every 6 months). Pts with concomitant inflammatory arthropaties were excluded. US guidance was carried out with the “in plane” technique choosing either the lateral suprapatellar or midpatellar approach. All pts were evaluated for pain with a VAS 0-10 for pain at baseline and after 2 weeks, 1, 3, 6, 9 and 12 months, with the WOMAC questionnaire and with US, scoring joint effusion, synovial hypertrophy (SH) and power Doppler (PD) synovial signal. Due to the retrospective design, the WOMAC data were available as VAS or Likert scales; to allow comparability these values were standardized. Clinical and US variables at different time points were compared using the Wilcoxon rank sing test, the McNemar test or the paired samples t-test, depending on the variable.Results:49 knees (43 pts, median age 70.6 years, 24 women) were included in the study. Kellgren Lawrence grade was 1 for 5 knees, 2 for 10, 3 for 17 and 4 for 9. SHCTH was delivered correctly in the joint space in all patients as assessed by US check during the injection and no side effects occurred. Of the 49 knees, 28 had an available 6 months follow-up, while 21 completed the 12 months follow-up, with an attrition mostly related to the COVID 19 pandemic. A rapid and sustained statistically significant decrease of both VAS pain and the WOMAC subscales was observed. The reduction of pain was already significant at 2 weeks, probably thanks to the corticosteroid component. At US evaluation, effusion significantly decreased at all time points. Although SH scores also significantly decreased, the effect on the proportion of affected joints was not as relevant. The reduction of PD was significant until month 9. Detailed results are presented in Table 1.Conclusion:Our data show that US guided SHCTH injections provide a rapid and sustained clinical response in patients with symptomatic OA. Besides the effect on pain, the US data confirm the effect of the drug on the inflammation. US guidance guaranteed the correct placement of the product in all patients and eliminated the bias of wrong placement that may occur with blind injections, thus allowing to draw safe conclusions on the efficacy of SHCTH for the treatment of KOA.References:[1]Jones A, Regan M, Ledingham J, et al. Importance of placement of intra-articular steroid injections. BMJ 1993;307:1329–30.Table 1.Table 1. Clinical and US measures. p values refer to the comparison with baseline. WOMAC subscales were compared by paired samples t test. *hypothesis test not applicablebaseline2 weeks1 month3 months6 months9 months12 monthsVAS (median,IQR)6 (5-8)3 (1-4.25) p<0.00012 (0.5-3-5) p<0.00011.5 (0-3) p<0.00011.5 (0-4) p<0.00011 (0-2.75) p<0.00011 (0-3.25) p<0.0001WOMAC pain--p 0.028p 0.0004p 0.0036p 0.0096p 0.0064WOMAC stiffness--p 0.048p 0.040p 0.0388p<0.0001p 0.0083WOMAC function--p 0.043p 0.0005p 0.0014p 0.01p 0.007Effusion 0-3 (median,IQR)2 (1-2)-1 (0-1) p<0.00011 (0-1) p<0.00011 (0-1) p 0.00010 (0-1) p<0.00011 (0-1) p<0.0001Synovial Hypertrophy 0-3 (median,IQR)1 (1-2)-1 (1-1) p 0.0021 (1-1) p 0.00011 (1-1) p 0.00011 (0-1) p 0.00011 (0.5-1) p 0.0001PD 0-3 (median,IQR)0 (0-0)-0 (0-0) p 0.030 (0-0) p 0.030 (0-0) P 0.061 (0-1) p 0.010 (0-0) p 0.31Disclosure of Interests:None declared.
Background The introduction of DAS-driven intensive treatment strategies in early rheumatoid arthritis (RA) has allowed the achievement of drug-induced clinical remission in a significant percentage of cases. Previous studies have also suggested the possibility, in selected patients, of remission maintenance for prolonged periods following treatment suspension. Despite these observations, three critical issues remain unsolved: 1) whether achievement of stable clinical remission and suppression of inflammation can coincide with reversal of the pathogenetic process, 2) the possibility to define parameters able to predict in which patients treatment can be suspended, 3) the primary dynamics as well as the anatomic and biologic substrate of relapse. Objectives To investigate, through a pilot assessment, the clinical outcome and ultrasonographic-synovitis dynamics of RA patients in DMARDs-induced SDAI remission, during a 12 months drug-free follow-up. Methods From December 2011, all RA patients followed at the Pavia's Early Arthritis Clinic achieving stable clinical remission and candidate to treatment suspension are referred to a dedicated Remission Clinic (RemC). Inclusion criteria for RemC referral: 1) introduction of DMARDs treatment within 12 months from symptoms' onset, 2) at least 24 months DMARDs treatment with a DAS28-driven intensive protocol, 3) stable DAS28 clinical remission (DAS28<2.6) for at least 6 months in the absence of corticosteroids. All patients allowed to drug-free follow-up at RemC are monitored at three months' intervals (for the first 12 months) through complete clinical, ultrasonographic (hands-feet-axillary lymph nodes) and immunologic screenings. Hands-feet radiographs are performed at baseline and every 12 months. Treatment with DMARDs is re-introduced in case of moderate disease activity (MDA, DAS28>3.2) or radiographic progression. Results 32 consecutive RA patients (females n=22, ACPA positive n=10) in DAS28 and SDAI remission (SDAI<3.3) at the baseline visit have been followed-up for 12 months after treatment withdrawal and monitored every 3 months. Treatment re-introduction due to MDA was required in 9/32 patients (28%) during follow-up. In 7/32 (22%) it was observed unstable remission with transient states of low disease activity, while in 16/32 patients (50%) stable DAS28 remission was maintained in all visits (T0-T12). Ultrasonographic stratification at baseline showed the absence of power Doppler signal in hands-wrists in 23/32 of patients (SDAI<3.3-PD=0). Despite the absence of clinical and sub-clinical signs of synovitis at recruitment, 5/23 (22%) patients relapsed, while in 11/18 (61%) a transient or persistent reappearance of defined PD signal (PD>1) was detected during follow-up despite the lack of requirement of DMARDs re-introduction according to study criteria. Conclusions Suspension of DMARDs with short term maintenance of good clinical status is an achievable goal after treat-to-target and tight control strategies in early RA. However, despite the presence of ...
BackgroundEarly diagnosis and prognostic stratification are central issues in the management of early arthritis and rheumatoid arthritis (RA), with several baseline features affecting relevant outcomes 1,2.ObjectivesTo evaluate the influence of referral criteria and pattern of joint involvement on the achievement of DAS28 remission at 12 months in patients with early arthritis.MethodsConsecutive patients attending an early arthritis clinic between 2005 and 2013 were enrolled. Referral criteria included joint stiffness>30 minutes, joint swelling and positive squeezing test (ST) at metacarpophalangeal or metatarsophalangeal joints. Baseline demographic features, disease activity, symptom duration and pattern of symptom onset (inflammatory pain, joint stiffness, monoarthritis, oligoarthiritis or polyarthritis) were recorded. Patients classified as RA were treated with methotrexate, while patients with undifferentiated arthritis with hydroxichloroquine. Low-dose oral prednisone could be given. Patients were subsequently treated according to a DAS28 driven step-up protocol in order to achieve low disease activity3, they were seen every 2 months in the first six months and every 3 afterwards, DAS28 was recorded at each evaluation. The outcome of interest was clinical remission (DAS28<2.6) occurring within the first 12 months of follow-up. Analyses on remission were done using a Cox proportional hazard regression analysis, results presented as crude hazard ratios (HR) and 95% confidence intervals (CI) and adjusted for age, gender, symptom duration at presentation, rheumatoid factor and/or ACPA positivity, baseline DAS28, use of steroids and MTX dose.ResultsA total of 772 patients were included. Mean age (SD) was 57.78 (14.94) years, 73.06% were female, 36.9% had positive rheumatoid factor, 68.6% fulfilled the 2010 criteria for RA, mean DAS28 was 4.60 (1.23) median (IQR) symptom duration was 15.1 (8.8-28.8) weeks (IQR). 72.7% were referred for positive ST, 66.7% for joint effusion, 56.5% for stiffness. 56.7% of patients presented with polyarthritis, 17.3% with inflammatory pain, 15.3% with oligoarthritis, 4.8% monoarthritis, 3.8% stiffness, 1.8% other presentation. The influence of referral criteria and clinical onset on remission achievement at 12 months is collected in Table 1.ConclusionsPatients referred for ST positivity are less likely to achieve remission at 12 months than patients referred for swelling or stiffness. Similarly patients with oligoarticular or polyarticular onset achieve remission less frequently.ReferencesSymmons DP et al, J Rheumatol. 1998;25(6):1072-7.Machold KP et al, Rheumatology 2007;46:342–349.Sakellariou G. et al, Ann Rheum Dis 2013;72:245-9.Disclosure of InterestNone declared
Background and objectives Early diagnosis and treat-to-target strategies in rheumatoid arthritis (RA) have allowed the achievement of remission in a significant percentage of cases. Despite the possibility of remission maintenance even after treatment suspension, three critical issues remain unsolved: 1) to what extent suppression of inflammation can coincide with reversal of the pathogenic process, 2) the parameters able to predict in which patients treatments can be suspended, 3) the dynamics of relapse. In this study we investigated the outcome and predictors of relapse in a cohort of RA patients during drug-free follow-up after remission achievement with conventional DMARDs. Materials and methods 62 RA patients achieving stable remission and candidate to DMARD suspension were recruited from our early arthritis clinic (EAC) according to the following criteria: 1) introduction of MTX within 12 months from symptoms’ onset, 2) at least 24 months of MTX treatment with a DAS28-driven protocol, 3) DAS28 < 2.6 for ≥6 months in the absence of corticosteroids. Following treatment suspension, patients were monitored at three months’ intervals through clinical-ultrasonographic (hands-feet)-radiographic and immunologic screenings (serological analyses and multicolour FACS profiles). The primary outcome was the maintenance of DAS28 < 3.2 in all visits (EAC target). Results Baseline stratification showed SDAI remission in 77.4% of the patients, SDAI remission with hands power Doppler (PD) = 0 in 50%, while the absence of detectable clinical-subclinical synovitis (SJC44 = 0, PD hands-feet = 0) in 35.5%. At 12 months from recruitment, clinical relapse was observed in 42.5% of the patients with maintenance of clinical, functional and radiographic stability in 40.7%. As inferred by cumulative survival analyses through 24 months, in patients achieving SDAI remission, high titers of ACPA (with a strengthening effect of ACPA-RF double positivity) were the strongest predictor of relapse, independent of remission duration, further baseline remission depth and ultrasonographic status (HR [95% CI] = 4.19 [1.23–14.28], p = 0.02). In ACPA(high) patients, despite the achievement of stringent clinical-ultrasonographic remission at the time of drug withdrawal, isotype switched IgG ACPA serum levels were on average unchanged compared to paired values at disease diagnosis, with recognition of active spontaneous secretion by isolated PBMC ex-vivo and a specific association with systemic increased rates of proliferation within switched memory B cells (Ki67+IgD-CD27+) (p < 0.05). Conclusions DMARD suspension/drug-holiday are possible options in a proportion of RA patients achieving stable remission. Ongoing immune activation (ACPA production with a possible cooperative function of RF) is the strongest predictor of disease reactivation in patients achieving DMARDs-induced clinical-ultrasonographic control of the inflammatory process.
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