EULAR recommendations for the management of systemic lupus erythematosus: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

Perceptions and experiences of individuals at-risk of rheumatoid arthritis (RA) knowing about their risk of developing RA and being offered preventive treatment: systematic review and thematic synthesis of qualitative studies.

OBJECTIVES: There is increasing interest in identifying individuals at-risk of rheumatoid arthritis (RA) and initiating early treatment to prevent or delay the onset of arthritis. We aimed to describe the perceptions and experiences of at-risk individuals and to inform the conduct of clinical trials and studies, and clinical practice. METHODS: A systematic review and thematic synthesis of qualitative studies was conducted. Two review authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist and assessed confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative Research approach. RESULTS: Seven studies involving 115 individuals at-risk of developing RA were included. Three major themes (seven subthemes) were identified: understanding the risk of developing RA (knowledge of RA and identification of potential risk factors); preventive interventions to reduce the risk of developing RA (understanding the value and role of preventive interventions, and engagement with preventive interventions); and perceptions of predictive testing for RA (benefits of predictive testing, decision to undertake predictive testing and concerns about predictive testing). Moderate confidence in most review findings was evident. CONCLUSION: While there are clear benefits in informing individuals at-risk of RA about their risk following predictive testing and offering preventive treatment, there are potential barriers to engagement, intensified by the burden of uncertainty. Identification of the optimum approaches for presenting risk information, including the risks and benefits of engaging with preventive interventions, is urgently needed to support individuals at-risk of RA in their decision making. PROSPERO REGISTRATION NUMBER: CRD42021236034.

2019 update of the EULAR recommendations for the management of systemic lupus erythematosus.

Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative.

In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in patients with chronic inflammatory rheumatic diseases. We also aimed to develop a pragmatic reporting form to foster the implementation of the points to consider. In accordance with the EULAR Standardised Operating Procedures, the process comprised (1) a systematic literature review of existing recommendations on reporting, screening for or preventing six selected comorbidities: ischaemic cardiovascular diseases, malignancies, infections, gastrointestinal diseases, osteoporosis and depression and (2) a consensus process involving 21 experts (ie, rheumatologists, patients, health professionals). Recommendations on how to treat the comorbidities were not included in the document as they vary across countries. The literature review retrieved 42 articles, most of which were recommendations for reporting or screening for comorbidities in the general population. The consensus process led to three overarching principles and 15 points to consider, related to the six comorbidities, with three sections: (1) reporting (ie, occurrence of the comorbidity and current treatments); (2) screening for disease (eg, mammography) or for risk factors (eg, smoking) and (3) prevention (eg, vaccination). A reporting form (93 questions) corresponding to a practical application of the points to consider was developed. Using an evidence-based approach followed by expert consensus, this EULAR initiative aims to improve the reporting and prevention of comorbidities in chronic inflammatory rheumatic diseases. Next steps include dissemination and implementation.

Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force.

BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. OBJECTIVE: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. METHODS: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. RESULTS: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). CONCLUSIONS: The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

2014 Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations.

In this article, the European League Against Rheumatism (EULAR) standardised operating procedures for the elaboration, evaluation, dissemination and implementation of recommendations endorsed by the EULAR standing committees published in 2004 have been updated. The various steps from the application to implementation have been described in detail.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update.

In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.

Synthesis of guidance available for assessing methodological quality and grading of evidence from qualitative research to inform clinical recommendations: a systematic literature review.

OBJECTIVE: To understand (1) what guidance exists to assess the methodological quality of qualitative research; (2) what methods exist to grade levels of evidence from qualitative research to inform recommendations within European Alliance of Associations for Rheumatology (EULAR). METHODS: A systematic literature review was performed in multiple databases including PubMed/Medline, EMBASE, Web of Science, COCHRANE and PsycINFO, from inception to 23 October 2020. Eligible studies included primary articles and guideline documents available in English, describing the: (1) development; (2) application of validated tools (eg, checklists); (3) guidance on assessing methodological quality of qualitative research and (4) guidance on grading levels of qualitative evidence. A narrative synthesis was conducted to identify key similarities between included studies. RESULTS: Of 9073 records retrieved, 51 went through to full-manuscript review, with 15 selected for inclusion. Six articles described methodological tools to assess the quality of qualitative research. The tools evaluated research design, recruitment, ethical rigour, data collection and analysis. Seven articles described one approach, focusing on four key components to determine how much confidence to place in findings from systematic reviews of qualitative research. Two articles focused on grading levels of clinical recommendations based on qualitative evidence; one described a qualitative evidence hierarchy, and another a research pyramid. CONCLUSION: There is a lack of consensus on the use of tools, checklists and approaches suitable for appraising the methodological quality of qualitative research and the grading of qualitative evidence to inform clinical practice. This work is expected to facilitate the inclusion of qualitative evidence in the process of developing recommendations at EULAR level.

Young people's perspectives on patient-reported outcome measures in inflammatory arthritis: results of a multicentre European qualitative study from a EULAR task force.

INTRODUCTION: Although patient-reported outcome measures (PROMs) are increasingly used in clinical practice and research, it is unclear whether these instruments cover the perspective of young people with inflammatory arthritis (IA). The aims of this study were to explore whether PROMs commonly used in IA adequately cover the perspective of young people from different European countries. METHODS: A multinational qualitative study was conducted in Austria, Croatia, Italy and the Netherlands. Young people with either rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Still's disease, psoriatic arthritis (PsA) or spondyloarthritis (SpA), aged 18-35 years, participated in semistructured focus group interviews. Thematic analysis was used and data saturation was defined as no new emergent concepts in at least three subsequent focus groups. RESULTS: Fifty-three patients (21 with RA/JIA/Still's, 17 with PsA, 15 with SpA; 72% women) participated in 12 focus groups. Participants expressed a general positive attitude towards PROMs and emphasised their importance in clinical practice. In addition, 48 lower level concepts were extracted and summarised into 6 higher level concepts describing potential issues for improvement. These included: need for lay-term information regarding the purpose of using PROMs; updates of certain outdated items and using digital technology for data acquisition. Some participants admitted their tendency to rate pain, fatigue or disease activity differently from what they actually felt for various reasons. CONCLUSIONS: Despite their general positive attitude, young people with IA suggested areas for PROM development to ensure that important concepts are included, making PROMs relevant over the entire course of a chronic disease.

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

Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

Nutrition in RMDs: is it really food for thought? Focus on rheumatoid arthritis.

BACKGROUND: The relationship between food and health is known since the antiquity and in the field of rheumatic and musculoskeletal diseases (RMDs), mainly rheumatoid arthritis (RA), a large number of studies has been published over the last 50 years encompassing different aspects of nutrition. This led to postulate a role of nutrients for both primary prevention of RMDs in the general population and secondary prevention of disease flares and complications in patients with an established RMD. MAIN BODY OF ABSTRACT: We aimed to summarise and critically discuss current evidence on the role of different nutrients and dietary regimens in RMDs with a focus on RA. Over the last years, some seminal papers proved that some compounds, such as salt, can directly modulate the immune system and large epidemiological studies have been linking dietary patters with the risk to develop RMDs. However, physicians' knowledge about the role of diet in disease prevention and treatment is often poor and ultimately diet is rarely perceived as a companion of pharmacological treatment. CONCLUSIONS: Based on the currently available evidence, we are not (yet?) in the phase of putting diet on the same level as pharmacological treatment in RMDs and in particular, RA, but future studies will likely shed additional light on this controversial topic and at least might suggest a value as dietary prevention of risk factors.

Patient-physician collaboration in rheumatology: a necessity.

Over the past few decades, there has been significant and impressive progress in the understanding and management of rheumatic diseases. One of the key reasons for succeeding in making this progress has been the increasingly stronger partnership between physicians and patients, setting a milestone in patient care. In this viewpoint, we discuss the recent evolution of the physician-patient relationship over time in Europe, reflecting on the 'journey' from behind the clinic walls through to clinical and research collaborations at national and international level and the birth of healthcare professional and 'rheumatic' patient organisations. The role of expert patients and patient advocates in clinical and scientific committees now represents a core part of the decision-making process. In more recent years and following the recognition that the young patients, physicians and academics have a voice and needs of their own, including the need to be educated and instructed, has encouraged the establishment of youth organisations, enabling change and innovation to take place at a uniquely different level.

Person-focused care for young people with rheumatic and musculoskeletal diseases: young rheumatologists' and EULAR Young PARE perspectives.

In recent years, the evolution of healthcare challenged the management of people with rheumatic and musculoskeletal diseases (RMDs). From disease-centred care to person-focused care, a holistic approach along with patient empowerment about their disease, improved the physician-patient relationship and allowed to achieve better outcomes with lower healthcare costs. Nevertheless, RMDs may occur from childhood to the old age and to date very few studies have addressed the needs and priorities of young people with RMDs. However, the image of RMDs is still associated with the elderly population. In this regard, the group of young people with arthritis and rheumatism in Europe (PARE) was recently developed within European League Against Rheumatism to represent the voice of the young affected and to carry out projects aiming for a better understanding of these specific aspects. This viewpoint discusses the needs and priorities of young people compared with adult people with RMDs, based on the available literature and on the results of the PARE Youth research project, aiming to identify the next steps of actions that need to be taken to improve the current situation.