The European Alliance of Associations for Rheumatology has released a number of new updates across various disease areas
New pointers on difficult-to-manage and treatment-refractory PsA
EULAR – The European Alliance of Associations for Rheumatology – recently released new evidence-based points to consider and consensus definitions for people with psoriatic arthritis (PsA) who have disease that is difficult to manage (D2M) or does not respond to treatment.
PsA is a progressive inflammatory disease, with both a skin and joint component. Many people with PsA also have cardiometabolic comorbidities and PsA is also linked to other conditions such as gout, osteoarthritis, and fibromyalgia, which can complicate management. Today, there are many good treatment options for PsA – and EULAR management recommendations about which to use and when.
Yet despite this, many people with PsA do not get a satisfactory response to disease-modifying antirheumatic drugs (DMARDs). In other diseases, definitions of D2M and treatment-refractory populations have been published, but there is a gap in PsA. EULAR set out to address this by developing new points-to-consider and consensus definitions. These have been developed by a multidisciplinary taskforce from 15 countries. The group included health professionals across rheumatology and dermatology, as well as patient research partners. The work was completed in line with EULAR standardised operating procedures.
The manuscript – developed by EULAR and published in the October 2025 issue of the Annals of the Rheumatic Diseases – includes four overarching principles and six points to consider.
The principles emphasise that a proportion of people with PsA have an unsatisfactory treatment response despite receiving the current standard of care – this has a significant impact, including on wellbeing and societal functioning. Unsatisfactory treatment response may be multifactorial and establishing the reasons for ongoing signs and symptoms is essential to guide and optimise further management.
The points to consider outline the main factors underpinning the definitions for D2M and treatment-refractory PsA formulated by the taskforce. These include failure to achieve or maintain low disease activity, presence of extra-musculoskeletal manifestations or other comorbidities, plus evidence of inflammatory activity.
Importantly, the work also includes two new consensus definitions. D2M PsA is a wide concept that includes persistent signs and symptoms of disease that are driven by inflammation, comorbidities, and psychosocial or other factors. As such, D2M is an umbrella term. Within this, treatment-refractory disease is defined by persistent disease activity and objective evidence of active inflammation. People with both D2M and treatment-refractory disease will have failed to achieve or maintain a response to at least two biologic or targeted synthetic DMARDs with at least two different mechanisms of action – and will have signs and/or symptoms that are perceived as problematic by the patient and/or the rheumatologist, alongside evidence of persistent disease.
Of note, the paper stresses that the term “difficult” is applied to the disease and not to the individual.
“These definitions aim to provide a framework for research in this area,” explained Prof Helena Marzo-Ortega – lead author on the paper and Honorary Professor of Clinical Translational Rheumatology, University of Leeds, UK.
“Whereas D2M is an umbrella concept encompassing many factors contributing to ongoing symptoms, which may benefit from non-pharmacological interventions, the key to understand treatment non-response is to identify the biology behind it – essentially whether is there inflammation present or not. Dissecting these phenotypes will allow for research to be focused on improved, personalised treatment options as well as prevention.”
This new work should help both healthcare professionals and patients to explore the factors behind non-response in people with persistent symptoms and objective signs of inflammation despite trying a number of different treatments.
EULAR hopes the new definitions will provide a framework to facilitate research in this area, helping to further characterise these populations and test new treatments – ultimately improving care for people living with PsA.
Reference
Marzo-Ortega H, et al. EULAR points to consider and consensus definitions for difficult-to-manage and treatment-refractory psoriatic arthritis. Ann Rheum Dis. 2025 Oct 29:S0003-4967(25)04433-4
New recommendations for lupus nephritis
EULAR has published new recommendations for the management of systemic lupus erythematosus (SLE) with kidney involvement.
The kidneys are affected in up to 60 per cent of people with SLE, ie, lupus nephritis. This is linked to the development of chronic kidney disease (CKD) and potentially kidney failure. The knock-on effect is increased cardiovascular risk and higher mortality.
The general EULAR recommendations for SLE – last updated in 2023 – include some information about kidney disease, but there was a need for additional, more specific interdisciplinary guidance. The specific EULAR recommendations for people with SLE and kidney involvement were first published in 2012 and updated in 2019.
New treatments have been developed since then, and new evidence has accumulated. To address this, EULAR decided that it was time to review and update these recommendations. Researchers, healthcare professionals, and patients worked together to develop new advice.
Of note, the new, updated recommendations include a significantly smaller number of recommendations – down to 13 from 41 in the 2019 version. Some previous recommendations have been removed, some merged, and some are entirely new.
The new work, published in the October 2025 issue of the Annals of the Rheumatic Diseases, includes four overarching principles and 13 individual recommendations.
The overarching principles emphasise that people with SLE should be monitored regularly for signs and symptoms of kidney involvement – with expert input and timely biopsies to ensure the best outcomes. Once kidney involvement has been diagnosed, management should align with the general recommendations for SLE, including use of hydroxychloroquine in all patients.
Kidney involvement has a risk for CKD and is best managed by an interdisciplinary care team including rheumatology and nephrology – and with shared decisions between the patient and their physician.
Finally, management aims not only to prevent CKD progression, but also flares of nephritis, address comorbidities, and improve health-related quality-of-life. They stress that both immunosuppressive therapy and non-immune therapy are essential to ensure a favourable long-term prognosis.
The 13 new statements focus on the role of kidney biopsy, the recommendation for combination immunosuppressive treatment for most patients – including steroids, synthetic immunosuppressives, and biologics, as well as the importance of kidney protective drugs to reduce the risk for CKD. They also lay out specific guidance for patients with renal response versus those with persistently active or relapsing disease and for women who may be seeking pregnancy.
“The updated EULAR recommendations highlight the two pillars of management for SLE patients with kidney involvement: Combined immunosuppressive treatment to control the inflammatory process, and kidney protective measures – both lifestyle and pharmaceutical – to delay the occurrence or progression of CKD,” said Prof Antonis Fanouriakis, corresponding author on the paper and Assistant Professor for Rheumatology, Attikon University Hospital and the National Kapodistrian University of Athens, Greece.
“With the cooperation of rheumatologists and nephrologists, and active patient participation in decision-making, it is hoped that prognosis of kidney involvement for patients with SLE will further improve in the near future.”
EULAR hopes the updated and streamlined recommendations will give physicians more evidence on which to base their therapeutic decisions for this challenging manifestation of lupus.
Reference
Fanouriakis A, et al. EULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update. Ann Rheum Dis. 2025 Oct 16:S0003-4967(25)04412-7
New disease activity score for antiphospholipid syndrome
EULAR has developed a new disease activity score that quantifies the level of disease activity in people with antiphospholipid syndrome (APS). It awaits prospective validation, but could be useful to help measure activity as opposed to severity – tracking symptoms over time, both in clinical trials and in everyday practice.
APS is characterised by the presence of antiphospholipid antibodies and a broad spectrum of clinical features, causing obstetric as well as thrombotic, microvascular, and non-thrombotic (TMN) symptoms. These can range in severity and people may have involvement at only one or multiple sites.
Increasing evidence suggests that APS might be driven by an interplay between both thrombotic and inflammatory mechanisms. In 2023, EULAR worked with the American College of Rheumatology to develop classification criteria for APS, which focused on five key domains. But in addition to these, a disease activity score that assesses different clinical manifestations would be useful to help evaluate people’s response to treatment in clinical trials, as well as for monitoring disease in observational studies and clinical practice.
Of note, the concept of disease activity is separate from severity, and refers to new-onset events such as a new venous thromboembolism, or the improvement of thrombocytopaenia after treatment.
To address this, EULAR set out to develop and validate a new disease activity score, which they have called EAPSDAS. The project initially generated 170 items. Of these, 24 items are included in the new EAPSDAS TMN scale, and six items in the obstetric scale. Separate stand-alone scores have been defined for these two domains because combining them would bias the results against anyone who is not pregnant. Additionally, the tool has been designed as a scale rather than an index, since some APS manifestations are episodic, whereas others are more continuous.
To use the EAPSDAS, the observation time for the TMN scale is divided into monthly intervals, with the highest-rated score achieved for each patient in any monthly interval over the entire observation time is defined as the maximum score. The average of each monthly score over the observation time is defined as the average TMN score. The maximum score gives an indication of the highest or peak level of activity, while the average score provides an indication of the persistence. For the obstetric scale there is no average since only a single event may occur. “Given that new treatment targets and potential novel agents are emerging in APS, the development of EAPSDAS will help enable well-designed clinical trials for new treatments in people living with APS”, said Prof Maria Tektonidou, lead author on the paper and Head of the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Greece. “Using EAPSDAS as a primary outcome in future clinical trials for new treatments of the thrombotic, obstetric, microvascular nephropathy), and non-thrombotic (such as thrombocytopaenia or cardiac valve disease) APS manifestations will help evaluate disease activity status and response to therapy.”
Reference
Tektonidou MG, et al. Development and validation of a EULAR disease activity score in antiphospholipid syndrome. Ann Rheum Dis. 2025 Nov 19:S0003-4967(25)04437-1
New points to consider in adult-onset Still’s disease
EULAR has identified an unmet clinical need around the assessment of disease activity in people with adult-onset Still’s disease (AOSD). Its newly-published ‘points to consider’ document aims to address this gap, and provide the basis for developing a reliable and simple tool for clinical practice.
AOSD is a rare inflammatory disorder. Thanks to a new initiative, AOSD is now considered to be the adult counterpart of systemic juvenile idiopathic arthritis (SJIA), but in both cases the cause is unknown. People with AOSD typically have fever, arthritis, a skin rash, and systemic involvement across multiple organs. But there can be differing clinical patterns – both in individual people’s presentation and across flare and remission.
Although there are treatment options for people with AOSD, there is no accepted definition for what constitutes a clinical response to these, making it hard to compare results across different studies, or to set management goals in the clinic. To address this, EULAR put together a taskforce of healthcare professionals and patient research partners. Experts were asked to suggest suitable clinical features for measuring disease activity and the candidates were assessed and voted on over a series of meetings. The aim was to move towards specific criteria for a clear definition of disease activity, which could help to identify patients who require more aggressive treatment.
The manuscript – published in the December 2025 issue of EULAR Rheumatology Open – includes three overarching principles and 11 points to consider.
The principles emphasise the importance of adopting a definition of disease activity that is valid, reliable, and easily transferable in any clinical setting. The development of specific criteria for assessing disease activity should include a precise definition of the clinical features, which could better describe the patient condition.
The points to consider outline the need to include fever as one of the variables of the core set. Other items highlighted are skin rash, arthritis and arthralgia, and systemic involvement. Laboratory findings such as hyperferritinaemia, inflammatory markers, and increased white blood cell count can also be useful – both at onset and for identifying relapse and flare – and transaminases are a useful marker of systemic involvement.
A key need alongside a definition of disease activity is an objective definition of remission. Also, still to be developed is a disease-specific patient-reported outcome that can assess the patient perspective.
“Establishing a reproducible definition of remission could help us move towards a new therapeutic target that we can use both in trials and in the clinic,” said Prof Roberto Giacomelli, corresponding author on the paper and Professor of Rheumatology, Fondazione Policlinico Campus Bio-Medico, Rome, Italy. “This will definitively initiate the era of treat-to-target in AOSD.”
The new points to consider should be read in conjunction with the 2024 recommendations on the diagnosis and management of both children and adults with Still’s disease. Of note, the recommendations include the absence of disease-related signs together with normal inflammatory markers as a definition for clinically inactive disease – and persistence for six months without need for glucocorticoids as a definition for remission.
However, these are based on findings in children more than adults, and so it remains to be seen whether there will be complete overlap across the age span. For instance, some characteristics such as splenomegaly and hepatomegaly are more common in adults than children, and adults also have other comorbidities, and these differences could impact the definitions. However, it is also important to note that – since SJIA and AOSD are now considered a unique disease – a joint effort is needed to achieve uniform management.
Reference
Ruscitti P, et al. The EULAR points to consider regarding the development of criteria for the assessment of the disease activity in adult-onset Still’s disease. EULAR Rheumatology Open. 2025 Dec 11:10.1016/j.ero.2025.11.015
New classification criteria for haemochromatosis arthropathy
EULAR has developed the first classification criteria for haemochromatosis arthropathy (HA) from a unique derivation cohort using rigorous methodology.
HA is a distinctive arthropathy associated with genetic haemochromatosis. This has many consequences, including liver cirrhosis, diabetes, and a distinctive arthropathy. Cases are most often reported in people with high ferritin and the C282Y homozygous mutation in the HFE gene. But at present, there is a knowledge gap around the pathogenesis, and more information is needed about the link between gene mutations, hepcidin deficiency, iron loading, and joint disease. Of note, there are no classification criteria for HA and this has limited research into this arthropathy.
To address these gaps, EULAR put together a taskforce to review the features of HA and create possible classification criteria, before testing these in people with known HA – as well as in a control group of people with other diseases that look very similar, such as generalised osteoarthritis and calcium pyrophosphate deposition disease. The result was a points-based classification model that can be used in people with joint pain, plus the C282Y homozygous HFE mutation, and past evidence of iron loading.
The model uses eight variables that cover age at symptom onset, clinical and radiographic features at the metacarpophalangeal, distal interphalangeal, and ankle joints, and history of surgery at the hip or ankle. Each of these items is easily assessed in routine clinical practice and together they are thought to be the best discriminators versus disease mimics. To achieve the threshold a person must score at least five out of 11, across a minimum of three criteria. This approach, which represents the first classification criteria designed to be used in this group of people, provides 93.3 per cent specificity and 71.4 per cent sensitivity for classifying HA.
“We are delighted to have produced the first classification criteria for this much neglected and poorly understood arthropathy,” said Prof Patrick Kiely, lead author on the paper and Professor of Clinical Practice in Rheumatology, St George’s University Hospital, London, UK.
“Our hope is that this will stimulate renewed academic interest and good quality trials to advance our understanding of this condition – and ultimately to develop new treatments to stop the progression of joint disease in these people.”
The criteria are not diagnostic and should only be used to recruit patients for research studies, noted EULAR.
Reference
Kiely PDW, et al. EULAR 2025 Classification Criteria for Haemochromatosis Arthropathy. Ann Rheum Dis. 2025: Nov 4:S0003-4967(25)04434-6
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