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ID PMID Title PublicationDate abstract
23467636 Inequities in access to biologic and synthetic DMARDs across 46 European countries. 2014 Jan OBJECTIVES: We investigated access to biologic and synthetic disease modifying drugs (bDMARDs and sDMARDs) in patients with rheumatoid arthritis (RA) across Europe. METHODS: A cross-sectional study at national level was performed in 49 European countries. A questionnaire was sent to one expert, addressing the number of approved and reimbursed bDMARDs and sDMARDs, prices and co-payments, as well as acceptability of bDMARDs (barriers). Data on socio-economic welfare (gross domestic product per capita (GDP), health expenditure, income) were retrieved from web-based sources. Data on health status of RA patients were retrieved from an observational study. Dimensions of access (availability, affordability and acceptability) were correlated with the country's welfare and RA health status. RESULTS: In total, 46 countries (94%) participated. Six countries did not reimburse any of the five sDMARDs surveyed, and in ten countries no bDMARDs were reimbursed. While the price of annual treatment with an average sDMARD was never higher than GPD, the price of one year treatment with a bDMARD exceeded GPD in 26 countries. Perceived barriers for access to bDMARDs were mainly found among financial and administrative restrictions. All dimensions of access were positively correlated with the country's economic welfare (coefficients 0.69 to 0.86 for overall access scores). CONCLUSIONS: Patients with RA in lower income European countries have less access to bDMARDs and sDMARDs, with particularly striking unaffordability of bDMARDs in some of these countries. When accepting that sDMARDs and bDMARDs are equally needed across countries to treat RA, our data point to inequities in access to pharmacological treatment for RA in Europe.
25405203 Breast cancer risk in rheumatoid arthritis: an update meta-analysis. 2014 BACKGROUND: The incidence of breast cancer in RA patients remains controversial. Thus we performed a meta-analysis to investigate the impact of RA on breast cancer. METHODS: Published literature was available from PubMed, Embase, and Cochrane Library. Pooled standardized incidence rate (SIR) was computed by random-effect model analysis. RESULTS: We identified 16 separate studies in the present study, in which the number of patients ranged from 458 to 84,475. We did not find the increased cancer risk in RA patients (SIR=0.86, 95% CI=0.72-1.02). However, subgroup analysis showed that breast cancer risk in RA patients was positively different in Caucasians (SIR=0.82, 95% CI=0.73-0.93) and non-Caucasians (SIR=1.21, 95% CI=1.19-1.23), respectively. In subgroup analysis by style, a reduced incidence was found in hospital-based case subjects (SIR=0.82, 95% CI=0.69-0.97). Similarly, subgroup analysis for adjusted factors indicated that in A3 (age and sex) and A4 (age, sex, and race/ethnicity) the risk was decreased (SIR=0.87, 95% CI=0.76-0.99; SIR=0.63, 95% CI=0.59-0.67). CONCLUSIONS: The meta-analysis revealed no increased breast cancer risk in RA patients. However, in the subgroup analysis, the risk of breast cancer is increased in non-Caucasians patients with RA while it decreased in Caucasian population, hospital-based case subjects, and A3 group. Such relationship may provide preference for risk of breast cancer in different population.
24874445 Arrhythmic risk in rheumatoid arthritis: the driving role of systemic inflammation. 2014 Sep When compared to the general population, patients with rheumatoid arthritis (RA) have an overall standard mortality ratio of approximately two, with more than 50% of premature deaths attributable to cardiovascular disease (CVD). Moreover, RA patients were twice as likely to experience sudden cardiac death (SCD) compared with non-RA subjects, as a putative consequence of an increased incidence of malignant arrhythmias. Accordingly, mounting data indicate that in patients affected with RA the risk of developing rhythm disturbances, particularly tachyarrhythmias, is high. Although a number of papers reviewing the problem of cardiovascular involvement in RA are currently available, the main focus is on the mechanisms of accelerated atherosclerosis and related ischemic consequences in the clinical setting. On the contrary, only little consideration has been specifically given to the arrhythmic risk so far. In the light of this concern, in the present paper we reviewed the topic with the aim to put together the apparently fragmentary existing information, with particular attention to the putative role of chronic systemic inflammation characterizing the disease. In fact, although the underlying mechanisms accounting the arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by inflammatory activation, able to promote arrhythmias either indirectly, by accelerating the development of structural CVD, and directly by affecting cardiac electrophysiology. In this view, lowering inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk and prevent life-threatening complications in these patients.
25163663 Role of osteopontin in rheumatoid arthritis. 2015 Apr Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. RA is a multifactorial disease with genetic, environmental, and stochastic components related to its susceptibility. It has been demonstrated that the expression of osteopontin (OPN) is upregulated in the RA patients. Numerous studies have indicated that the full-length OPN or even OPN fragments, such as thrombin-cleaved OPN and its receptors, play the key roles in RA pathogenesis. Therapeutic application of siRNA to target OPN or neutralizing antibodies related to OPN epitopes in RA animal models are in progress, and some results are encouraging. However, there is a long way to go along with the clinical trials. This review focuses on the recent development in research associated with the OPN role in the pathogenesis of RA and provides insights concerning the OPN targeting as therapeutic approaches for patients with RA.
24444595 Cervical spine involvement early in the course of rheumatoid arthritis. 2014 Jun OBJECTIVES: Cervical spine involvement in rheumatoid arthritis (RA) is considered a feature of long-standing disease. We describe two patients who presented with cervical symptoms as early features of RA. METHODS: We report two RA cases with cervical spine involvement as early features and use MEDLINE to review the literature concerning the frequency and disease duration of this manifestation and its imaging with plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI). RESULTS: An 80-year-old man with cervical myelopathy from a C1-C2 rheumatoid pannus underwent decompression surgery before development of peripheral synovitis from RA. A 63-year-old woman presented with neck pain and polyarthritis at RA diagnosis, with imaging that confirmed a C1-C2 rheumatoid pannus. Onset of cervical spine involvement in RA is generally after 10 years of disease duration, ranging from 3 months to 45 years after peripheral synovitis among patients with seropositive erosive RA. Occurring in 9-88% of RA patients, cervical spine involvement may result in cervical instability due to either mechanical compression or vascular impairment of the spinal cord. Bone erosions and atlanto-axial subluxation on standard radiographs are two major signs of cervical spine involvement in RA. MRI identifies earlier signs of RA and has a higher sensitivity in detecting bone erosions compared to conventional radiography. CONCLUSIONS: Cervical spine involvement in RA is not an uncommon condition but is rare at early disease onset. Symptoms of cervical pain and myelopathy should prompt a thorough neurological examination accompanied by imaging.
22956596 The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthrit 2013 Jul PURPOSE: To determine the sensitivity to change of the US7 score among RA patients under various therapies and to analyze the effect of each therapeutic option over 1 year. To estimate predictors for development of destructive bone changes. METHODS: Musculoskeletal ultrasound (US7 score), DAS28, CRP and ESR were performed in 432 RA patients at baseline and after 3, 6 and 12 months. The cohort was divided into four sub-groups: first-line DMARDs (Group 1; 27.3%), therapy switch: DMARDs to second DMARDs (Group 2; 25.0%), first-line biologic after DMARDs therapy (Group 3; 35.4%) and therapy change from biologic to second biologic (Group 4; 12.3%). RESULTS: The US7 synovitis and tenosynovitis sum scores in grey-scale (GSUS) and power Doppler ultrasound (PDUS) as well as ESR, CRP decreased significantly (p<0.05) after 12 months in group 1 to 3. Group 1+2 also illustrated a significant change of DAS28 after 1 year (p<0.001). Only in Group 4, the US7 erosion sum score decreased significantly from 4.3 to 3.6 (p=0.008) after 1 year. Predictors capable of forecasting US erosions after one year were: higher score of US7 synovitis (p<0.001), of US7 erosions in GSUS (p<0.001), as well as of DAS28 (p<0.001) at baseline. CONCLUSIONS: The comparable developments of the US7 score with clinical and laboratory data illustrates its potential to reflect therapeutic response. Therefore, the novel US7 score is sensitive to change. Patients who switched from one biologic to another exhibited a significant decline in erosions after 12 months, while the erosions scores in the other groups were stable.
25542810 Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) +49 A>G gene polymorphism in Egyptian 2015 Mar 1 BACKGROUND: The gene encoding cytotoxic T lymphocyte associated antigen-4 (CTLA-4) has been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The aim of this work is to assess the association of this polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. SUBJECTS AND METHODS: This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy controls from the same locality. For all subjects, DNA was genotyped for CTLA-4 +49 A>G (rs231775) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The frequency of the CTLA-4 G allele was significantly higher among cases compared to controls (37.1% vs. 23.4%, OR=1.93; 95% CI=1.29-2.89, p=0.002). Also, the frequency of CTLA-4 +49 G allele carriage (AG+GG genotypes) was significantly higher among cases with RA compared to controls (61.6% vs. 41.8%, OR=2.23, 95% CI=1.32-3.77, p=0.003). Logistic regression analysis showed that cases positive to the G allele (GA+GG genotypes) had less frequency of rheumatoid deformities and also a lower DAS28-CRP score, yet with a higher visual analogue scale (VAS) i.e. more functional disability than other cases. CONCLUSIONS: CTLA-4 +49 G allele carriage was associated with increased susceptibility and functional disability of RA in Egyptian patients.
24666980 Successful arthrodesis of the first metatarsophalangeal joint in patients with inflammator 2014 May Arthrodesis of the first metatarsophalangeal (MTP) joint has been a reliable treatment option for end-stage osteoarthritis (OA) and rheumatoid arthritis (RA). The disease process is very different between these 2 types of degeneration. It is unknown whether first MTP fusions performed for each disease process will heal the same or differently. The purpose of the present study was to compare the fusion rate and interval to fusion between patients with first MTP OA and those with RA. The present study was an institutional review board-approved retrospective radiographic and medical record review funded by a not-for-profit educational research grant. The demographic and clinical variables were collected and compared between the 2 groups. A total of 155 first MTP fusion procedures for OA and RA were analyzed. Of these, 116 (74.83%) had been performed for pain from OA and 39 (25.16%) for RA. The RA group had a statistically significantly shorter interval to fusion than did those with OA (93 and 113 days, respectively; p = .025). The overall incidence of fusion for those with RA was 94% and for those with OA was 89%; however, this difference was neither clinically nor statistically significantly different (p = .36). The incidence of first MTP arthrodesis was high for both patients with OA and those with RA, and those with RA appeared to achieve fusion more rapidly.
24485351 Applying biologic therapies to the management of patients with rheumatoid arthritis. 2014 Feb The challenge of providing uniformly effective rheumatoid arthritis care has thus far defied a simple solution. Variations in care range from the appropriate adjustment or switching of therapy subsequent to increased disease activity to the selection of therapeutic agent chosen following failure. This program is designed to improve the understanding of advances in immunopathologic discoveries that provide valuable aid in individualized treatment plans and the appropriate patient selection of available DMARDS and biologic therapeutics. Also, expert rheumatologists will discuss the latest data of head-to-head trials and recommendations for clinical effectiveness. This CME program will bring rheumatologists and other health care professionals up to date in managing their patients with rheumatoid arthritis.
23002057 Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. 2013 Dec Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially affecting the joints and leading, if untreated, to progressive joint damage and disability. Cytokines, a group of small inducible proteins, which act as intercellular messengers, are key regulators of the inflammation that characterizes RA. They can be classified into pro-inflammatory and anti-inflammatory groups. Numerous cytokines have been implicated in the regulation of RA with complex up and down regulatory interactions. This paper considers a two-variable model for the interactions between pro-inflammatory and anti-inflammatory cytokines, and demonstrates that mathematical modelling may be used to investigate the involvement of cytokines in the disease process. The model displays a range of possible behaviours, such as bistability and oscillations, which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility and remitting-relapsing disease. We also show that the dose regimen as well as the dose level are important factors in RA treatments.
23734961 Evaluation of corneal parameters with scheimpflug imaging in patients with rheumatoid arth 2013 Oct PURPOSE: To evaluate corneal parameters of rheumatoid arthritis (RA) patients by Pentacam-HR. METHODS: Seventy RA patients and 100 control subjects were enrolled. All participants underwent Pentacam (Pentacam-HR, Oculus, Germany) evaluation. Both RA and control groups were divided into two subgroups as dry eye (DE) (Schirmer test with topical anesthesia (STA) ≤ 5 mm) and without DE (STA > 5 mm). RESULTS: Pachymetric measurements and the mean corneal volume were significantly lower in RA group (p < 0.001). Disease duration was negatively correlated with pachymetric measurements in RA group. Pachymetric measurements and corneal volume of RA patients with DE were significantly lower than all the other subgroups. Control subgroups with or without DE were similar in pachymetric measurements and corneal volume. CONCLUSIONS: The results suggest that RA patients have thinner corneas compared to control subjects that may be affected by disease duration. Furthermore, coexistence of DE and RA seems to aggravate the thinning of cornea as well.
22772459 Usefulness of ultrasonography-proven tenosynovitis to monitor disease activity of a patien 2013 May We introduced abatacept (ABT) in a very early rheumatoid arthritis (RA) patient with active tenosynovitis of hands defined by musculoskeletal ultrasonography (MSKUS). MSKUS-proven tenosynovitis remarkably improved at 2 months in spite of clinical exacerbation, followed by clinical remission at 5 months. MSKUS abnormalities also disappeared. Although ABT was discontinued due to an adverse event after the sixth infusion, she remained in clinical remission as well as imaging remission by MSKUS at 13 months.
24050751 Diagnostic accuracy of combined tests of anti cyclic citrullinated peptide antibody and rh 2014 Jan OBJECTIVES: To evaluate the diagnostic properties of combined tests of anti cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF) in the diagnosis of rheumatoid arthritis (RA). METHODS: We performed an extensive research between January 2000 and January 2013 of the published literature. A random-effects model was used to summarise data from 24 studies that conformed to our inclusion criteria. Heterogeneity among studies was evaluated by threshold effect analysis and meta-regression. RESULTS: The summary estimates for anti-CCP antibody and RF positivity (both serum markers had to be positive) in the diagnosis of RA were: sensitivity 57% (95% confidence interval (CI), 55% to 59%), specificity 96% (CI, 96% to 97%), positive likelihood ratio (LR) 13.84 (CI, 10.56 to 18.12), negative LR 0.46 (CI, 0.40 to 0.52), diagnostic odds ratio (DOR) 33.02 (CI, 23.89 to 45.64). The pooled data for anti-CCP antibody or RF positivity (one serum marker had to be positive) were: sensitivity 78% (CI, 76% to 80%), specificity 82% (CI, 81% to 84%), positive LR 4.24 (CI, 3.61 to 4.97), negative LR 0.27 (CI, 0.22 to 0.34), DOR 16.95 (CI, 12.96 to 22.18). CONCLUSIONS: Both anti-CCP antibody and RF positivity are useful for ruling in the diagnosis of RA, and positivity combined improves the probability of true positivity in the diagnosis. Anti-CCP antibody or RF positivity shows low specificity and positive LR, and should be integrated with other examinations to make a final diagnosis.
24041708 Ultrasonography in the diagnosis and management of patients with inflammatory arthritides. 2014 Feb In primary care and internal medicine settings clinicians are often reluctant to take advantage of the resources that ultrasonography (US) offers as a diagnostic tool in the initial management of patients with inflammatory arthritis, despite the recognised importance of an accurate and timely diagnosis of rheumatoid arthritis (RA) and of early referral to ensure optimal patient management. Both grey-scale (GS) and power Doppler (PD) imaging have been extensively used in early detection of synovitis and bone erosions in patients with inflammatory arthritides. We reviewed the main data on the clinical use of US in the initial management of patients with inflammatory arthritis, focusing on RA diagnosis in patients with undifferentiated arthritis, prediction of disease severity, differential diagnoses and assessment of synovitis in children with juvenile idiopathic arthritis (JIA). The role of US in assessing treatment response and monitoring disease activity in clinical remission was also briefly evaluated. The reliability of US as a diagnostic tool in rheumatological diseases has greatly advanced in the last years and the use of this imaging technique, in association with conventional assessments such as physical examination and serological tests, should be considered more often also in primary care settings.
24754646 Use of a validated algorithm to estimate the annual cost of effective biologic treatment f 2014 Aug OBJECTIVES: To estimate biologic cost per effectively treated patient with rheumatoid arthritis (RA) using a claims-based algorithm for effectiveness. METHODS: Patients with RA aged 18-63 years in the IMS PharMetrics Plus database were categorized as effectively treated if they met all six criteria: (1) a medication possession ratio ≥80% (subcutaneous) or at least as many infusions as specified in US labeling (intravenous); (2) no biologic dose increase; (3) no biologic switch; (4) no new non-biologic disease-modifying anti-rheumatic drug; (5) no new or increased oral glucocorticoid; and (6) ≤1 glucocorticoid injection. Biologic cost per effectively treated patient was defined as total cost of the index biologic (drug plus intravenous administration) divided by the number of patients categorized by the algorithm as effectively treated. Similar methods were used for the index biologic in the second year and for a second biologic after a switch. RESULTS: Rates that the index biologic was categorized as effective in the first year were 31.0% etanercept (2243/7247), 28.6% adalimumab (1426/4991), 28.6% abatacept (332/1160), 27.2% golimumab (71/261), and 20.2% infliximab (474/2352). Mean biologic cost per effectively treated patient, per the algorithm, was $50,141 etanercept, $53,386 golimumab, $56,942 adalimumab, $73,516 abatacept, and $114,089 infliximab. Biologic cost per effectively treated patient, using this algorithm, was lower for patients who continued the index biologic in the second year and higher after switching. CONCLUSIONS: When a claims-based algorithm was applied to a large commercial claims database, etanercept was categorized as the most effective and had the lowest estimated 1-year biologic cost per effectively treated patient. This proxy for effectiveness from claims databases was validated against a clinical effectiveness scale, but analyses of the second year or the year after a biologic switch were not included in the validation. Costs of other medications were not included in cost calculations.
23819345 [Diagnosis and problems in therapy of interstitial lung disease associated with rheumatoid 2013 Rheumatoid arthritis (RA) is an inflammatory rheumatic disease of unknown etiology, which is characterized by symmetric, chronic, and erosive arthritis (synovitis) of the peripheral joints and systemic inflammatory involvement of the viscera. Lung pathology, including interstitial lung disease (ILD), is one of the common extra-articular manifestations in RA. ILD is considered to be present in almost 25% of the RA patients. To study a prognosis in RA patients with ILD was the objective of some investigations in the past decade, the majority of which concluded that the mean survival after the diagnosis was about 3 years. These indicators may reflect the predominance of usual interstitial pneumonia (UIP) in patients in specific trials as this type of lung disease is associated with a poorer prognosis. In addition, there are discrepant results on survival differences between RA patients with ILD and those with idiopathic ILD. However, the data were limited by a small number of cases in both medical centers and daily clinical practice. ILD is the only extra-articular manifestation of RA, the rate of which is increasing. ILD is considered to be a cause of death in nearly 6% of all the patients with RA. The pattern of ILD may be determined by high-resolution computed tomography and may be a major prognostic marker; the development of UIP is worst. The material is dedicated to the successes recently achieved in the diagnosis and therapy of RA-associated ILD. The state-of-the-art of investigations in this area is discussed.
24889289 The development and initial validation of a questionnaire to measure help-seeking behaviou 2015 Dec BACKGROUND: Early treatment for rheumatoid arthritis (RA) is vital. However, people often delay in seeking help at symptom onset. An assessment of the reasons behind patient delay is necessary to develop interventions to promote rapid consultation. OBJECTIVE: Using a mixed methods design, we aimed to develop and test a questionnaire to assess the barriers to help seeking at RA onset. DESIGN: Questionnaire items were extracted from previous qualitative studies. Fifteen people with a lived experience of arthritis participated in focus groups to enhance the questionnaire's face validity. The questionnaire was also reviewed by groups of multidisciplinary health-care professionals. A test-retest survey of 41 patients with newly presenting RA or unclassified arthritis assessed the questionnaire items' intraclass correlations. RESULTS: During focus groups, participants rephrased questions, added questions and deleted items not relevant to the questionnaire's aims. Participants organized items into themes: early symptom experience, initial reactions to symptoms, self-management behaviours, causal beliefs, involvement of significant others, pre-diagnosis knowledge about RA, direct barriers to seeking help and relationship with GP. The test-retest survey identified seven items (out of 79) with low intraclass correlations which were removed from the final questionnaire. CONCLUSION: The involvement of people with a lived experience of arthritis and multidisciplinary health-care professionals in the preliminary validation of the DELAY (delays in evaluating arthritis early) questionnaire has enriched its development. Preliminary assessment established its reliability. The DELAY questionnaire provides a tool for researchers to evaluate individual, cultural and health service barriers to help-seeking behaviour at RA onset.
23487337 Rheumatoid arthritis. 2013 Feb Since the advent of disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis, there has been an increasing emphasis on the early diagnosis and monitoring of this condition. This has led to the greater involvement of advanced imaging techniques such as ultrasound and MRI. Ultrasound appearances of common findings in rheumatoid arthritis are discussed in this review. Comparison of ultrasound in terms of sensitivity and specificity with other imaging modalities and with clinical examination is also made. Quantification is also discussed as a tool to allow assessment of response to drug therapy, an area that is likely to progress further as techniques become increasingly reproducible. Finally, as ultrasound techniques continue to develop, its involvement in the management of patients with rheumatoid arthritis is increasing. New techniques such as fusion imaging and sonoelastography, while at present still largely research-based entities, may offer increasingly improved diagnostic benefits in the field of inflammatory arthropathy.
23981749 Patterns of angiotensin converting enzyme insertion/deletion gene polymorphism among an Eg 2013 Jun AIM: This case control study was designed to determine the patterns of angiotensin converting enzyme insertion/deletion (ACE I/D) gene polymorphism in rheumatoid arthritis (RA) patients and healthy controls. METHODS: The study population was divided into two groups: the study group included 66 RA patients diagnosed according to the American College of Rheumatology (ACR) classification criteria for RA, and the control group included 66 healthy adults who were age-and sex-matched to the RA group. All RA patients were assessed by Disease Activity Score (DAS28), ACR Classification of Global Functional Disability Status and Sharp's score as outcome measures. Gene investigations for ACE I/D polymorphism were performed by polymerase chain reaction (PCR) in both groups. RESULTS: The ACE I/D polymorphism was the (D/D) genotype in 60.6% (n = 40) of RA patients, the (I/D) genotype in 31.8% (n = 21) and the (I/I) genotype in 7.6% (n = 5). The frequency of (D) carriage was significantly higher in the RA cases than in the control group (76.5% vs. 53.8%, respectively, P = 0.0002). ACE D allele carriers were at higher risk of RA, 2.8 times higher than (I) carriers and those who had the homozygote (DD) genotype had 5.6 times the possibility of having RA. No correlations were observed between the homozygote (DD) genotype and disease activity or severity in RA patients. CONCLUSIONS: Our study suggests that high frequency of the ACE D allele contributes to the heritability of RA susceptibility compared to other ACE alleles. On the other hand, no association was detected between ACE I/D polymorphism and the severity of RA.
24590079 [Evidence-based recommendations for the management of undifferentiated peripheral inflamma 2014 May INTRODUCTION: Peripheral arthritis is the most common presenting complaint in clinical rheumatology. Unequivocal identification of the underlying entity can be difficult, particularly at an early stage. Such cases are commonly referred to as undifferentiated peripheral inflammatory arthritis (UPIA). Since evidence-based recommendations for the clinical management of UPIA are lacking, this international 3e initiative convened 697 rheumatologists from 17 countries to develop appropriate recommendations. METHODS: Based on a systematic literature research in Medline, EMBASE, Cochrane Library, and the ACR/EULAR abstracts of 2007/2008, 10 multinational recommendations were developed by 3 rounds of a Delphi process. In Germany, a national group of experts worked on 3 additional recommendations using the same method. The recommendations were discussed among the members of the 3e initiative and the degree of consensus was analyzed as well as the potential impact of the recommendations on clinical practice. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed for the development of 10 multinational recommendations concerning differential diagnosis, diagnostic and prognostic value of clinical assessments, laboratory tests and imaging techniques, and monitoring of UPIA. In addition, 3 national recommendations on the diagnostic and prognostic value of a response to anti-inflammatory therapy on the analysis of synovial fluid and on enthesitis were developed by the German experts based on 35 out of 5542 references. CONCLUSIONS: The article translates the 2011 published original paper of the international 3e initiative (Machado et al., Ann Rheum Dis 70:15-24, 2011) and reports the methods and results of the national vote and the additional 3 national recommendations.