Prognostic Factors for Early Recurrence After Resection of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: More than half of pancreatic ductal adenocarcinomas (PDACs) recur within 12 months after curative-intent resection. This systematic review and meta-analysis was conducted to identify all reported prognostic factors for early recurrence in resected PDACs. METHODS: After a systematic literature search, a meta-analysis was conducted using a random effects model. Separate analyses were performed for adjusted vs unadjusted effect estimates as well as reported odds ratios (ORs) and hazard ratios (HRs). Risk of bias was assessed using the Quality in Prognostic Studies tool, and evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation recommendations. RESULTS: After 2903 abstracts were screened, 65 studies were included. Of these, 28 studies (43.1%) defined early recurrence as evidence of recurrence within 6 months, whereas 34 (52.3%) defined it as evidence of recurrence within 12 months after surgery. Other definitions were uncommon. Analysis of unadjusted ORs and HRs revealed 41 and 5 prognostic factors for early recurrence within 6 months, respectively. When exclusively considering adjusted data, we identified 25 and 10 prognostic factors based on OR and HR, respectively. Using a 12-month definition, we identified 38 (OR) and 15 (HR) prognostic factors from unadjusted data and 38 (OR) and 30 (HR) prognostic factors from adjusted data, respectively. On the basis of frequency counts of adjusted data, preoperative carbohydrate antigen 19-9, N status, nondelivery of adjuvant therapy, grading, and tumor size based on imaging were identified as key prognostic factors for early recurrence. CONCLUSIONS: Reported prognostic factors of early recurrence vary considerably. Identified key prognostic factors could aid in the development of a risk stratification framework for early recurrence. However, prospective validation is necessary.

2023 EULAR classification criteria for hand osteoarthritis.

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

American College of Rheumatology/EULAR remission criteria for rheumatoid arthritis: 2022 revision.

OBJECTIVE: In 2011, the American College of Rheumatology (ACR) and EULAR endorsed provisional criteria for remission in rheumatoid arthritis (RA), both Boolean-based and index-based. Based on recent studies indicating that a higher threshold for the patient global assessment (PtGA) may improve agreement between the two sets of criteria, our goals were to externally validate a revision of the Boolean remission criteria using a higher PtGA threshold and to validate the provisionally endorsed index-based criteria. METHODS: We used data from four randomised trials comparing biological disease-modifying antirheumatic drugs to methotrexate or placebo. We tested the higher proposed PtGA threshold of 2 cm (Boolean2.0) (range 0-10 cm) compared with the original threshold of 1 cm (Boolean1.0). We analysed agreement between the Boolean-based and index-based criteria (Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)) for remission and examined how well each remission definition predicted later good physical function (Health Assessment Questionnaire (HAQ) score≤0.5) and radiographic non-progression. RESULTS: Data from 2048 trial participants, 1101 with early RA and 947 with established RA, were included. The proportion of patients with disease in remission at 6 months after treatment initiation increased when using Boolean2.0 compared with Boolean1.0, from 14.8% to 20.6% in early RA and 4.2% to 6.0% in established RA. Agreement between Boolean2.0 and the SDAI or CDAI remission criteria was better than for Boolean1.0, particularly in early disease. Boolean2.0, SDAI, and CDAI remission criteria had similar positive likelihood ratios (LRs) to predict radiographic nonprogression and a HAQ score of ≤0.5 (positive LR 3.8-4.3). The omission of PtGA (BooleanX) worsened the prediction of good functional outcomes. CONCLUSION: Using the Boolean 2.0 criteria classifies, more patients as achieving remission and increases the agreement with index-based remission criteria without jeopardising predictive value for radiographic or functional outcomes. This revised Boolean definition and the previously provisionally endorsed index-based criteria were endorsed by ACR and EULAR.

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.

OBJECTIVES: To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA). METHODS: This systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022. RESULTS: Of 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission. CONCLUSION: The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

Efficacy, duration of use and safety of glucocorticoids: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.

This systematic literature review (SLR) regarding the efficacy, duration of use and safety of glucocorticoids (GCs), was performed to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). Studies on GC efficacy were identified from a separate search on the efficacy of disease-modifying antirheumatic drugs (DMARDs). A combined search was performed for the duration of use and safety of GCs in RA patients. Dose-defined and time-defined GC treatment of any dose and duration (excluding intra-articular GCs) prescribed in combination with other DMARDs were considered. Results are presented descriptively. Two included studies confirmed the efficacy of GC bridging as initial therapy, with equal efficacy after 2 years of initial doses of 30 mg/day compared with 60 mg/day prednisone. Based on a recently performed SLR, in clinical trials most patients starting initial GC bridging are able to stop GCs within 12 (22% patients continued on GCs) to 24 months (10% patients continued on GCs). The safety search included 12 RCTs and 21 observational studies. Well-known safety risks of GC use were confirmed, including an increased risk of osteoporotic fractures, serious infections, diabetes and mortality. Data on cardiovascular outcomes were Inconsistent. Overall, safety risks increased with increasing dose and/or duration, but evidence on which dose is safe was conflicting. In conclusion, this SLR has confirmed the efficacy of GCs in the treatment of RA. In clinical trials, most patients have shown to be able to stop GCs within 12-24 months. Well-known safety risks of GC use have been confirmed, but with heterogeneity between studies.

2021 EULAR points to consider to support people with rheumatic and musculoskeletal diseases to participate in healthy and sustainable paid work.

AIM: As part of its strategic objectives for 2023, EULAR aims to improve the work participation of people with rheumatic and musculoskeletal diseases (RMDs). One strategic initiative focused on the development of overarching points to consider (PtC) to support people with RMDs in healthy and sustainable paid work participation. METHODS: EULAR's standardised operating procedures were followed. A steering group identified six research areas on paid work participation. Three systematic literature reviews, several non-systematic reviews and two surveys were conducted. A multidisciplinary taskforce of 25 experts from 10 European countries and Canada formulated overarching principles and PtC after discussion of the results of literature reviews and surveys. Consensus was obtained through voting, with levels of agreement obtained anonymously. RESULTS: Three overarching principles and 11 PtC were formulated. The PtC recognise various stakeholders are important to improving work participation. Five PtC emphasise shared responsibilities (eg, obligation to provide active support) (PtC 1, 2, 3, 5, 6). One encourages people with RMDs to discuss work limitations when necessary at each phase of their working life (PtC 4) and two focus on the role of interventions by healthcare providers or employers (PtC 7, 8). Employers are encouraged to create inclusive and flexible workplaces (PtC 10) and policymakers to make necessary changes in social and labour policies (PtC 9, 11). A research agenda highlights the necessity for stronger evidence aimed at personalising work-related support to the diverse needs of people with RMDs. CONCLUSION: Implementation of these EULAR PtC will improve healthy and sustainable work participation of people with RMDs.

EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). METHODS: A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A-D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. RESULTS: Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. CONCLUSIONS: The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes.

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis.

BACKGROUND: The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. OBJECTIVE: To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. METHODS: A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. RESULTS: Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. CONCLUSION: These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.

Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update.

BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update.

OBJECTIVES: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. METHODS: An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item. RESULTS: The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations. CONCLUSIONS: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.

EULAR points to consider when analysing and reporting comparative effectiveness research using observational data in rheumatology.

BACKGROUND: Comparing treatment effectiveness over time in observational settings is hampered by several major threats, among them confounding and attrition bias. OBJECTIVES: To develop European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) when analysing and reporting comparative effectiveness research using observational data in rheumatology. METHODS: The PtC were developed using a three-step process according to the EULAR Standard Operating Procedures. Based on a systematic review of methods currently used in comparative effectiveness studies, the PtC were formulated through two in-person meetings of a multidisciplinary task force and a two-round online Delphi, using expert opinion and a simulation study. Finally, feedback from a larger audience was used to refine the PtC. Mean levels of agreement among the task force were calculated. RESULTS: Three overarching principles and 10 PtC were formulated, addressing, in particular, potential biases relating to attrition or confounding by indication. Building on Strengthening the Reporting of Observational Studies in Epidemiology guidelines, these PtC insist on the definition of the baseline for analysis and treatment effectiveness. They also focus on the reasons for stopping treatment as an important consideration when assessing effectiveness. Finally, the PtC recommend providing key information on missingness patterns. CONCLUSION: To improve the reliability of an increasing number of real-world comparative effectiveness studies in rheumatology, special attention is required to reduce potential biases. Adherence to clear recommendations for the analysis and reporting of observational comparative effectiveness studies will improve the trustworthiness of their results.

2022 EULAR points to consider for remote care in rheumatic and musculoskeletal diseases.

BACKGROUND: Remote care and telehealth have the potential to expand healthcare access, and the COVID-19 pandemic has called for alternative solutions to conventional face-to-face follow-up and monitoring. However, guidance is needed on the integration of telehealth into clinical care of people with rheumatic and musculoskeletal diseases (RMD). OBJECTIVE: To develop EULAR points to consider (PtC) for the development, prioritisation and implementation of telehealth for people with RMD. METHODS: A multidisciplinary EULAR task force (TF) of 30 members from 14 European countries was established, and the EULAR standardised operating procedures for development of PtC were followed. A systematic literature review was conducted to support the TF in formulating the PtC. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtC were formulated. The use of telehealth should be tailored to patient's needs and preferences. The healthcare team should have adequate equipment and training and have telecommunication skills. Telehealth can be used in screening for RMD as preassessment in the referral process, for disease monitoring and regulation of medication dosages and in some non-pharmacological interventions. People with RMD should be offered training in using telehealth, and barriers should be resolved whenever possible.The level of agreement to each statement ranged from 8.5 to 9.8/10. CONCLUSION: The PtC have identified areas where telehealth could improve quality of care and increase healthcare access. Knowing about drivers and barriers of telehealth is a prerequisite to successfully establish remote care approaches in rheumatologic clinical practice.

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19.

OBJECTIVES: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. METHODS: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. RESULTS: We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.

Influence of COVID-19 pandemic on decisions for the management of people with inflammatory rheumatic and musculoskeletal diseases: a survey among EULAR countries.

OBJECTIVES: To investigate how the first wave of COVID-19 pandemic influenced decisions of rheumatologists and health professionals in rheumatology regarding the management of patients with inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: An English-language questionnaire was developed by a EULAR working group and distributed via national rheumatology societies of EULAR countries, EMEUNET and individual working group members. Responses were collected using an online survey tool. Descriptive statistics were calculated. RESULTS: We analysed 1286 responses from 35/45 EULAR countries. Due to containment measures, 82% of respondents indicated cancellation/postponement of face-to-face visits of new patients (84% of them offering remote consultation) and 91% of follow-up visits (96% with remote consultation). The majority of respondents (58%) perceived that the interval between symptom onset and first rheumatological consultations was longer during containment restrictions than before. Treatment decisions were frequently postponed (34%), and the majority (74%) of respondents stated that it was less likely to start a biological disease modifying anti-rheumatic drug (DMARD)/targeted synthetic DMARD during the pandemic, mainly because of patients' fear, limited availability of screening procedures and decreased availability of rheumatological services. Use of (hydroxy)chloroquine (HCQ) and tocilizumab (TCZ) for the COVID-19 indication was reported by 47% and 42% of respondents, respectively, leading to a shortage of these drugs for RMDs indications according to 49% and 14% of respondents, respectively. CONCLUSION: Measures related to containment of COVID-19 pandemic led to a perceived delay between symptom onset and a first rheumatological visit, postponement of treatment decisions, and shortage of HCQ and TCZ, thereby negatively impacting early treatment and treat-to-target strategies.

2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.

BACKGROUND: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard. OBJECTIVES: To develop recommendations for the implementation of self-management strategies in IA. METHODS: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations. RESULTS: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients. CONCLUSION: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.

2019 EULAR points to consider for non-physician health professionals to prevent and manage fragility fractures in adults 50 years or older.

OBJECTIVE: To establish European League Against Rheumatism (EULAR) points to consider for non-physician health professionals to prevent and manage fragility fractures in adults 50 years or older. METHODS: Points to consider were developed in accordance with EULAR standard operating procedures for EULAR-endorsed recommendations, led by an international multidisciplinary task force, including patient research partners and different health professionals from 10 European countries. Level of evidence and strength of recommendation were determined for each point to consider, and the mean level of agreement among the task force members was calculated. RESULTS: Two overarching principles and seven points to consider were formulated based on scientific evidence and the expert opinion of the task force. The two overarching principles focus on shared decisions between patients and non-physician health professionals and involvement of different non-physician health professionals in prevention and management of fragility fractures. Four points to consider relate to prevention: identification of patients at risk of fracture, fall risk evaluation, multicomponent interventions to prevent primary fracture and discouragement of smoking and overuse of alcohol. The remaining three focus on management of fragility fractures: exercise and nutritional interventions, the organisation and coordination of multidisciplinary services for post-fracture models of care and adherence to anti-osteoporosis medicines. The mean level of agreement among the task force for the overarching principles and the points to consider ranged between 8.4 and 9.6. CONCLUSION: These first EULAR points to consider for non-physician health professionals to prevent and manage fragility fractures in adults 50 years or older serve to guide healthcare practice and education.

2020 EULAR points to consider for the prevention, screening, assessment and management of non-adherence to treatment in people with rheumatic and musculoskeletal diseases for use in clinical practice.

BACKGROUND: Non-adherence to treatment could preclude reaching an optimal outcome. Thirty to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to the agreed treatment. OBJECTIVES: The objective was to establish points to consider (PtCs) for the prevention, screening, assessment and management of non-adherence to (non-)pharmacological treatments in people with RMDs. METHODS: An EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included healthcare providers (HCPs), comprising rheumatologists, nurses, pharmacists, psychologists, physiotherapists, occupational therapists and patient-representatives from 12 European countries. A review of systematic reviews was conducted in advance to support the TF in formulating the PtCs. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtCs were formulated. The PtCs reflect the phases of action on non-adherence. HCPs should assess and discuss adherence with patients on a regular basis and support patients to treatment adherence. As adherence is an agreed behaviour, the treatment has to be tailored to the patients' needs. The level of agreement ranged from 9.5 to 9.9 out of 10. CONCLUSIONS: These PtCs can help HCPs to support people with RMDs to be more adherent to the agreed treatment plan. The basic scheme being prevent non-adherence by bonding with the patient and building trust, overcoming structural barriers, assessing in a blame-free environment and tailoring the solution to the problem.

EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19.

OBJECTIVES: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. METHODS: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. RESULTS: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. CONCLUSIONS: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.

Testing different thresholds for patient global assessment in defining remission for rheumatoid arthritis: are the current ACR/EULAR Boolean criteria optimal?

OBJECTIVES: This study aimed to evaluate different patient global assessment (PGA) cut-offs required in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission definition for their utility in rheumatoid arthritis (RA). METHODS: We used data from six randomised controlled trials in early and established RA. We increased the threshold for the 0-10 score for PGA gradually from 1 to 3 in steps of 0.5 (Boolean1.5 to Boolean3.0) and omitted PGA completely (BooleanX) at 6 and 12 months. Agreement with the index-based (Simplified Disease Activity Index (SDAI)) remission definition was analysed using kappa, recursive partitioning (classification and regression tree (CART)) and receiver operating characteristics. The impact of achieving each definition on functional and radiographic outcomes after 1 year was explored. RESULTS: Data from 1680 patients with early RA and 920 patients with established RA were included. The proportion of patients achieving Boolean remission increased with higher thresholds for PGA from 12.4% to 19.7% in early and 5.9% to 12.3% in established RA at 6 months. Best agreement with SDAI remission occurred at PGA cut-offs of 1.5 and 2.0, while agreement decreased with higher PGA (CART: optimal agreement at PGA≤1.6 cm; sensitivity of PGA≤1.5 95%). Changing PGA thresholds at 6 months did not affect radiographic progression at 12 months (mean ꙙsmTSS for Boolean, 1.5, 2.0, 2.5, 3.0, BooleanX: 0.35±5.4, 0.38±5.14, 0.41±5.1, 0.37±4.9, 0.34±4.9, 0.27±4.7). However, the proportion attaining HAQ≤0.5 was 90.2%, 87.9%, 85.2%, 81.1%, 80.7% and 73.1% for the respective Boolean definitions. CONCLUSION: Increasing the PGA cut-off to 1.5 cm would provide high consistency between Boolean with the index-based remission; the integer cut-off of 2.0 cm performed similarly.

EULAR points to consider for the use of big data in rheumatic and musculoskeletal diseases.

BACKGROUND: Tremendous opportunities for health research have been unlocked by the recent expansion of big data and artificial intelligence. However, this is an emergent area where recommendations for optimal use and implementation are needed. The objective of these European League Against Rheumatism (EULAR) points to consider is to guide the collection, analysis and use of big data in rheumatic and musculoskeletal disorders (RMDs). METHODS: A multidisciplinary task force of 14 international experts was assembled with expertise from a range of disciplines including computer science and artificial intelligence. Based on a literature review of the current status of big data in RMDs and in other fields of medicine, points to consider were formulated. Levels of evidence and strengths of recommendations were allocated and mean levels of agreement of the task force members were calculated. RESULTS: Three overarching principles and 10 points to consider were formulated. The overarching principles address ethical and general principles for dealing with big data in RMDs. The points to consider cover aspects of data sources and data collection, privacy by design, data platforms, data sharing and data analyses, in particular through artificial intelligence and machine learning. Furthermore, the points to consider state that big data is a moving field in need of adequate reporting of methods and benchmarking, careful data interpretation and implementation in clinical practice. CONCLUSION: These EULAR points to consider discuss essential issues and provide a framework for the use of big data in RMDs.