The 2020 Annual Meeting of the European League Against Rheumatism (EULAR) Congress was held virtually – for the first time in the society’s 73 year history – as a result of the COVID-19 pandemic. Its aim, as in previous years, remained to provide a forum of the highest standard for scientific (both clinical and basic), educational and social exchange between healthcare professionals (HCPs) involved in rheumatology.
EULAR President Prof Iain McInnes
The EULAR e-congress got underway with the traditional opening plenary session, chaired by EULAR President Iain McInnes, which was broadcast live. Prof McInnes promised delegates an exciting and exceptional experience, centred on a high-calibre scientific programme.
This year’s keynote speech on the topic of ‘Innovation for patients with disabilities’ was delivered by Claudio Leverenz. Dr Leverenz explained that, while current technology is focused on mechanical devices built around the patient, the future will see a move to more novel approaches such as exoskeletons and other robotically-controlled systems.
Cutting-edge advances such as Smart Glass have the power to connect all of these devices together into a single unified platform. The ultimate vision is that through these devices and their exponential potential to connect with the whole environment, patients with disabilities will attain true independence, Dr Leverenz concluded.
The opening plenary session continued with Prof John Issacs, EULAR Scientific Committee Chair, who outlined his top daily highlights from the scientific programme - singling out both the People with Arthritis and Rheumatism (PARE) COVID-19 session and the EULAR Recommendations 2020. Prof McInnes concluded the opening session by summarising new EULAR educational programmes and looking with excitement towards future research initiatives.
“The coronavirus pandemic has changed the world in which we live and forced us to move into the virtual universe. All of us as professionals have been affected but especially for our patients with rheumatic and musculoskeletal diseases (RMDs) it has been a time of inordinate anxiety and stress. Therefore, it’s wonderful for us to come together and celebrate rheumatology and all of the achievements in our discipline.”
Prof Iain McInnes, EULAR President
Table of Contents
People with Arthritis and Rheumatism (PARE) and COVID-19
Prognosis, Predictors and Outcomes in Rheumatoid Arthritis
Biological DMARDs in Rheumatoid Arthritis
Dendritic Cells as Therapeutics in Patients with Rheumatoid Arthritis
Arterial and Venous Risks and Management of Inflammatory Rheumatic Diseases
People with Arthritis and Rheumatism (PARE) and COVID-19
John Issacs, Newcastle, UK, began this live session with an update on the current COVID-19 situation. Dr Issacs explained that COVID-19 is ‘much more than just a lung disease’, causing a broad range of symptoms and affecting multiple organ systems. Disease severity is predominantly determined by age and comorbidities. A number of potential treatments are under active investigation for COVID-19, many of which the RMD community are already familiar with. Discussing the now retracted Lancet paper (Mehra M, et al. Lancet 2020) which retrospectively analysed nearly 100,000 patients with COVID-19, Dr Issacs noted ‘surprise’ at the apparent link between hydroxychloroquine (HCQ) and cardiac issues and highlighted inaccuracies and consistencies in the data which require further investigation. Currently, non-pharmacological interventions such as social distancing and contact tracing remain our most effective tools against infection in patients with RMDs, he concluded.
“At the moment we don’t yet know if HCQ is good, bad or indifferent in treating COVID-19.”
John Issacs, Newcastle, UK
Petro Machado, London, UK, examined the existing COVID-19 data on risk factors, which suggests the risk for hospitalisation among patients with RMDs is broadly similar to the general population. Older age, comorbidities and moderate-to-high glucocorticoid (GC) use were associated with a higher risk of hospitalisation, while tumour necrosis factor inhibitor (TNFi) treatment decreased the odds. No impact on hospitalisation risk was detected with biological therapies, non-steroidal anti-inflammatory drugs or HCQ. Moving forward, larger sample sizes will allow the impact of specific RMDs, drugs and comorbidities on COVID-19 infection severity to be studied in greater depth.
Treatments under evaluation for COVID-19
Treatment options under evaluation for COVID-19 infection in patients with RMDs
Petro Machado, London, UK, examined the existing COVID-19 data on risk factors, which suggests the risk for hospitalisation among patients with RMDs is broadly similar to the general population. Older age, comorbidities and moderate-to-high use were associated with a higher risk of hospitalisation, while treatment decreased the odds. No impact on hospitalisation risk was detected with biological therapies, non-steroidal anti-inflammatory drugs or HCQ. Moving forward, larger sample sizes will allow the impact of specific RMDs, drugs and comorbidities on COVID-19 severity to be studied in greater depth.
The psychological impact of COVID-19 was investigated by Rinie Geenen, Utrecht, The Netherlands, in an online survey comparing worry and stress levels during peak COVID-19 infection in 177 Dutch patients with inflammatory arthritis (IA) versus a similar number of well-matched healthy controls. Overall, 53% of patients with IA reported feeling “worried” or “very worried” about COVID-19 infection compared with 27% of healthy controls. However, the level of perceived stress due to the pandemic (although increased versus normal) was found to be comparable in both groups. Similarly, the mental well-being of patients with IA did not appear to be adversely affected. Dr Geenen suggested four key tips that may help patients with IA deal with the negative psychological consequences of the COVID-19 pandemic:
- Change habits e.g. wear gloves during shopping
- Prevent excess worry and anxiety by seeking social support and accessing only trustworthy, fact-based media
- Adopt a healthy lifestyle
- Invest in mental resilience
Patients with RMDs have a lot of questions about COVID-19, with particular concerns centred on the risks associated with immunosuppressant therapy and accessing medical support during the pandemic. Souzi Makri, Limassol, Cyprus, reviewed the important issue of where to find reliable information on COVID-19 and highlighted a number of key sources for use by both physicians and patients.
Reliable resources for patients and HCPs regarding COVID-19
Elsa Mateus, Lisbon, Portugal, shared some best practice examples of how 14 PARE Organisations from across Europe have been dealing with the COVID-19 pandemic. The most common medium for communicating with members was websites with a dedicated COVID-19 area or an FAQs page, while live broadcasts using social media channels and Zoom were key tools for providing support. Advocacy remained an important priority, alongside collaboration with other stakeholders. Dr Mateus noted that fundraising has been significantly impacted by the COVID-19 pandemic.
EULAR Recommendations 2020
The EULAR Recommendations session was one of the highlights of this year’s congress.
Points to consider when incorporating the perspective of young patients with IA into patient-reported outcome measures (PROMs) were reviewed by Paul Studenic, Vienna, Austria. PROMs were determined to be of key value in assessing the impact of IA on daily life, with online and e-solutions preferred in order to facilitate self-management.
Karolina Benesova, Heidelberg, Germany, outlined recommendations on rheumatic immune-related adverse events (AEs) due to cancer immunotherapy - a newly recognised disease entity within the rheumatology sphere. The EULAR Task Force developed a total of four overarching principles and 10 recommendations which have now been published in Annals of the Rheumatic Diseases (Kostine M, et al. Ann Rheum Dis. 2020). The major challenge remains to relieve patient symptoms without altering the oncological outcome and a focus on shared decision-making is paramount, Dr Benesova stressed.
Recommendations on the interpretation of anti-nuclear antibody tests were presented by Pier Luigi Meroni, Milan, Italy. There are clinically relevant differences in performance between the immunofluorescence assay and scintillation proximity assay, he explained, although neither is superior to the other. Optimal test strategy is dependent on the disease of interest and pre-test probability.
Suzanne Verstappen, Manchester, UK, reviewed lifestyle behaviour recommendations to prevent progression of RMDs. Exercise is considered safe in patients with RMDs and both aerobic and strengthening exercises are recommended. Although a healthy, balanced diet is integral to lifestyle improvements, specific food types are unlikely to confer meaningful benefits. Patients with RMDs should aim for a healthy weight and be encouraged to stop smoking, particularly in rheumatoid arthritis (RA) where smoking can affect disease-modifying antirheumatic drug (DMARD) response.
Evidence-based recommendations on the intra-articular treatment of arthropathies were presented by Jacqueline Uson Jaegar, Madrid, Spain. A total of five overarching principles and 12 recommendations were developed as part of this EULAR project, with the aim of facilitating uniformity and quality of care.
Annalies Boonen, Maastricht, Netherlands, summarised points to consider when designing, analysing and reporting studies with work participation as an outcome domain. This guidance is now available for researchers when conducting and reporting studies involving work or with work as part of an outcome. It is hoped this guidance will contribute to high-quality studies which improve healthy and sustainable work participation among patients with IA, Dr Boonen concluded.
Rheumatoid Arthritis Management
A new EULAR overarching principle in RA management
Josef Smolen, Vienna, Austria, reviewed the 2019 updated EULAR recommendations for management of RA, recently published in the June issue of Annals of the Rheumatic Diseases. Key changes include the addition of a new overarching principle and slight revisions to some recommendations. Dr Smolen explained that the caveat ‘current practice would be to start a biological DMARD (bDMARD)’ has been removed from recommendation 8 as there is now sufficient data to show Janus kinase (JAK) inhibitors are equivalent to biologics. The management algorithm has also been reshaped but remains essentially unchanged.
“A decade after their initial development, the EULAR RA management recommendations have achieved a steady state in terms of treatment target, strategy and therapeutic approaches based on overwhelming evidence and expert opinion.”
Josef Smolen, Vienna, Austria
Psoriatic Arthritis Management
Laure Gossec, Paris, France, presented the 2019 update of EULAR recommendations for the management of psoriatic arthritis (PsA) with pharmacological therapies, which includes one new overarching principle and two new recommendations. According to the new overarching principle ‘in managing patients with PsA, consideration should be given to each musculoskeletal manifestation and treatment decisions made accordingly.’ Key changes to the recommendations include delineation of mono versus oligo-arthritis and the therapeutic positioning of all three bDMARD categories on the same level after conventional synthetic DMARD (csDMARD) failure, albeit with preference for interleukin (IL)-17 or IL-12/23 inhibitors when there is relevant skin involvement. JAK inhibitors are now recommended for patients with inadequate response to at least one csDMARD or bDMARD, or where bDMARDs are not appropriate. Cautious tapering of DMARDs can also be considered in patients with sustained remission. Dr Gossec explained that the treatment landscape in PsA is now rich in new therapies and updated guidelines aim to integrate all available drugs into a graduated management approach.
EULAR Projects: Non-Adherence
One of the final sessions of this year’s congress was devoted to the EULAR Project on non-adherence, an important issue given that an estimated 30–80% of patients with RMD are non-adherent to their current treatment regimen. Valentin Ritschl, Vienna, Austria, outlined key recommendations/points to consider from the EULAR Task Force on the detection, assessment and management of non-adherence in patients with RMDs.
John Weinman, London, UK, explained that medication non-adherence remains a major issue in RA but one which clinicians can play a key role in identifying and improving. Patient beliefs remain the most important underlying driver of motivation to take treatment. Both tools and training are needed to improve the open discussion of adherence issues and their effective management.
Marieke Voshnaar, Enschede, The Netherlands, described medication adherence in RA as an interplay of barriers and facilitators. Reduction in symptoms, maintenance of independence and shared-decision making have been identified as the most important factors driving patients’ adherence. This knowledge can help facilitate fruitful communication between HCPs and patients on the issue of adherence and guide the development of effective interventions, tailored to individual needs.
“Communication skills were considered to be crucial to adherence - for example, being able to communicate in a timely manner with a rheumatologist about side-effects which prevented patients from using their prescribed medication.”
Marieke Voshnaar, Enschede, The Netherlands
Ivo Vlaev, Oxford, UK, presented research showing the difficulties rheumatologists face in engaging women of reproductive age in shared decision-making around pregnancy, treatment and adherence. The perceived knowledge and skills gap for UK physicians is higher than that of their German and US counterparts - and educational interventions are needed to plug this.
Prognosis, Predictors and Outcomes in Rheumatoid Arthritis
Jeffery Sparks, Boston, USA, disclosed results from a retrospective cohort study examining pneumonia risk in RA using machine learning approaches. Patients with seropositive RA were found to have a 2-fold increased risk for pneumonia which was not explained by confounders such as smoking status, comorbidities or erythrocyte sedimentation rate level.
Laurance Duquenne, Leeds, UK, presented findings from a study including 107 patients, showing that patient-reported outcomes – including general health, global pain and health assessment questionnaire scores – deteriorate in the 12 weeks before progression to clinical disease in individuals at-risk of IA. ‘At-risk’ in this study was defined as clinically suspect arthralgia or anti-citrullinated protein antibody positivity.
“It is likely that individuals at risk of IA evolve through a transition period where a state of imminent progression could be defined.”
Laurance Duquenne, Leeds, UK
Whole-blood RNA expression of inflammatory and immune genes has value in the prediction of IA according to an exploratory study carried out by Ellis Neimantsverdriet, Leiden, The Netherlands. Lowered expression of six genes was associated with an increased risk of IA development in patients with arthralgia.
Six top hit genes linked to IA
Six genes associated with an increased risk of IA in patients with arthralgia have been identified
Based on a study of 212 patients, the Symptoms in Persons At Risk of RA questionnaire can be used to accurately predict RA, reported Laurette van Boheemen, Amsterdam, The Netherlands. Pain that moves from side-to-side provided added predictive value, with an area under the curve of 0.70 at 1 year follow-up for the extended model versus 0.67 for the Amsterdam prediction model.
Eric Mattheson, Rochester, USA, presented data over the whole of the INBUILD trial, showing that nintedanib had a clinically meaningful effect on the progression of interstitial lung disease (ILD) in patients with autoimmune-related ILDs.
Effect of nintedanib versus placebo on the progression of interstitial lung disease (ILD) in patients with autoimmune-related ILDs
Bernard Combe, Montpellier, France, discussed a 10-year analysis of 813 patients with early RA from the Etude et Suivi des POlyarthrites Indifferenciees Recentes (ESPOIR) cohort. Results support a dose and time-dependent impact of very low-dose GC treatment (median 1.9 mg/day), with a long-term high risk of severe outcomes. Safety risks linked to low-dose GC treatment rose with time, becoming significant at 10 years. This indicates that low-dose GC treatment is associated with delayed harmfulness which manifests with increasing cumulative dose.
Laura Martinez-Prat, Barcelona, Spain, presented results from screening panel experiments which have identified anti-protein-arginine deiminase (PAD)1 and PAD6 as novel autoantigens in RA. This research also found that the anti-PAD4 immune response in RA employs three isotypes (IgG, IgA and IgM), of which anti-PAD4 IgA was significantly associated with joint erosion. Dr Martinez-Prat suggested a panel for detection of antibodies to the five key PAD enzymes may aid in diagnosis, prognosis and patient stratification in RA.
Cythnia Yang, Rotterdam, The Netherlands, showcased results from a multinational, real-world cohort analysis of over 164,000 adult patients with RA which was used to successfully develop and validate prediction models for adverse health outcomes in those patients initiating first-line methotrexate (MTX) monotherapy. The models developed were able to identify patients at risk of serious infection, myocardial infarction and stroke, and may help pave the way towards more personalised care.
Felice Rivellese, London, UK, presented findings from a study comparing clinical, histological and molecular features of synovial biopsies from joints of different size in an early RA cohort. Synovial biopsy of large joints at disease presentation identified patients with different histopathological features, genetic markers and clinical outcomes. The involvement of different joint compartments in early RA may therefore contribute to disease heterogeneity and carries potential physiopathological and clinical implications, Dr Rivellese concluded.
Key risks with low-dose GC treatment
Key risks identified with low-dose GC treatment in patients with early RA
Synovial biopsy of large joints
Synovial biopsy of large joints in early RA
Post-hoc analysis of the PreCePRA trial suggests that improved patient global disease activity assessment could be the main driver of improved Disease Activity Score-28 (DAS-28) low disease activity results with certolizumab in patients with a higher CNS pain response. Patient global assessment visual analogue scale improvement was largest in the certolizumab group versus placebo with high pre-treatment CNS pain response, explained Jurgen Reich, Erlangen, Germany.
Cornelia Allaart, Leiden, The Netherlands, reviewed the 17-year follow-up data from the BeSt cohort. Excess mortality was still evident in patients with RA from the BeSt cohort when compared with the healthy, general Dutch population after 17 years of treatment. However, no significant differences in survival outcomes were found between the four therapeutic strategies evaluated.
Mrinalini Dey, Liverpool, UK, outlined findings from the METEOR (Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology) database assessing the effect of increased body mass index (BMI) on TNFi response in patients with established RA. Obesity was shown to be associated with reduced treatment response to monoclonal antibody TNFi but no association between increased BMI and etanercept response was seen. Using BMI to direct biologic drug choice could prove a simple and cost-effective approach to personalised medicine, Dr Dey concluded.
The four BeSt treatment approaches
Therapeutic strategies evaluated in patients with RA in the BeSt cohort
An estimated proportion of adults with RA who are overweight or obese
Visiting a rheumatologist within 6 weeks of symptom onset had clear benefits for achieving sustained DMARD-free remission, but not for radiographic progression, said Ellis Neimantsverdriet, Leiden, The Netherlands. This conclusion was based on an analysis of two observational European cohorts which investigated evidence for the first EULAR recommendations on early RA. These recommendations state that:
- Patients presenting with arthritis (any joint swelling associated with pain or stiffness) should be referred to, and seen by, a rheumatologist within 6 weeks after onset of symptoms
- Patients at risk of persistent arthritis should be started on DMARDs as early as possible (ideally within 3 months) even if they do not fulfil classification criteria for an inflammatory rheumatologic disease
Biological DMARDs in Rheumatoid Arthritis
Findings from the Phase IV, randomised, open-label ARCTIC REWIND trial which compared stable versus tapered and withdrawn treatment with TNFi in RA remission were showcased by Siri Lillegraven, Oslo, Norway. Flare rate remained low in patients with long-standing RA remission treated with stable TNFi doses but increased steeply (by over 50%) when tapering to withdrawal. Reinstated treatment produced a good response.
“This study indicates that in patients with RA in sustained remission on TNFis, continued treatment should be the preferred choice.”
Siri Lillegraven, Oslo, Norway
Martin Schaefer, Berlin, Germany, analysed the impact of biological DMARDs with different modes of action on fatigue in over 5500 patients from the German Biologics Register, RABBIT (Rheumatoide Arthritis: Boebachtung der Biologika Therapie). Treatment with IL-6 inhibitors significantly increased the chance of attaining low fatigue levels within 6 months. Former smokers, female patients and those with sleep disorders were less likely to reach low fatigue levels.
ACR20 response (%) in patients with moderate-to-severely acute RA in the CREDO1 study
Results from the Phase III, randomised, double-blind, placebo-controlled CREDO1 study of olokizumab in moderate-to-severely active RA were presented by Rumen Stoilov, Sofia, Bulgaria. Treatment with olokizumab over a 24-week period was superior to placebo across the primary endpoint (ACR20 response) and secondary endpoints, with onset of efficacy 4–8 weeks after treatment initiation. Although the incidence of treatment-emergent serious AEs was numerically 4–8 weeks after treatment initiation. Although the incidence of treatment-emergent serious AEs was numerically higher in the olokizumab arms versus placebo, no unexpected safety signals occurred. There were also no discernable efficacy or safety differences between the two different olokizumab dose regimens (every 2 weeks [Q2W] or every 4 weeks [4QW]), noted Dr Stoilov.
Tocilizumab is associated with an increased risk of diverticulitis and gastrointestinal perforation (GIP) according to results of a prospective, propensity-matched cohort study using data collected from three observational French registries: REGATE (REGistry RoAcTEmra), AIR-PR (French AutoImmunity and Rituximab/Rheumatoid Arthritis registry) and ORA (Orencia [abatacept] and RA registry). The increased risk of GIP might be explained by an increased risk of diverticulitis with misleading clinical presentation, said study author Claire Rempenault, Montpellier, France.
Data from the Korean College of Rheumatology Biologics Registry (KOBIO) have shown that machine learning artificial intelligence models are able to predict patient remission with an accuracy of 57.2–73.7%, reported Dr Bon San Koo, Soeul, Korea. The important clinical features that affected remission rates differed between biologics.
Kosuke Ebina, Osaka, Japan, disclosed data from the ANSWER cohort study evaluating the drug retention of seven biologics and tofacitinib in biologic-naïve and -switched patients. ‘Remarkable’ differences in drug retention rates were observed. These results may provide a useful insight into overall treatment effectiveness and tolerability and help to promote precision medicine with bDMARDs in real-world settings, Dr Ebina suggested.
Factors affecting drug retention of biologics
Dendritic Cells as Therapeutics in Patients with Rheumatoid Arthritis
As part of this live bench-to-bedside session, Yuliya Kurochkina, Novosibrisk, Russian Federation presented findings from a study investigating the mechanism of action of dexamethasone-modified dendritic cells (dexDCs) in 20 patients with RA. DexDCs were found to exert an immunosuppressive effect on autologous T-cells via the indication of apoptosis, anergia and T-regulatory cell activation, supporting a potential therapeutic application in DC-based vaccines.
Arterial and Venous Risks and Management of Inflammatory Rheumatic Diseases
This Live ‘HOT’ (How To Treat) session provided an update on the management of thrombotic risk across the spectrum of inflammatory rheumatic diseases. Zoltan Szekanecz, Debrecen, Hungary, summarised the key drug-related risks of arterial (ATE) and venous thromboembolism (VTE) based on the latest available data from cross-sectional and retrospective analyses. Two large prospective studies have also shed further light on this important issue. The ENTRACTE study of 3000 patients with RA showed no increased risk of cardiovascular (CV) events with tocilizumab, despite on-therapy elevations in lipid levels. While in the CANTOS study, carried out in the non-rheumatic patients with inflammatory atherosclerosis, the two higher doses of canakinumab reduced the risk of the primary CV endpoint versus placebo.
Therapeutic considerations: Thrombotic risk
Therapeutic considerations for the management of thrombotic risk in inflammatory rheumatic diseases
Implementing High Intensity Exercise in RMDs
This Health Professionals in Rheumatology session outlined the benefits of high intensity exercise in patients with RMDs and discussed how to incorporate it successfully into clinical decision-making.
Benete Pedersen, Copenhagen, Denmark, explored the acute and long-term anti-inflammatory effects of exercise. IL-6 has been identified as the critical link between physical inactivity and accumulation of visceral fat, which is a severe risk factor for diabetes, CV disease and cancer. Research suggests that IL-6 is required for exercise-mediated reduction in adipose tissue and epicardial fat loss following exercise. In a randomised, controlled trial involving 592 individuals, treatment with the IL-6 blocker tocilizumab was seen to ameliorate the positive effect of exercise on visceral fat mass.
The question of how to adapt exercise therapy in patients with RMD with multimorbidity was addressed by Silje Halvorsen Sveaas, Kristiansand, Norway. Dr Sveaas emphasised the importance of ensuring patients are well-informed and adjusting exercise to individual fitness levels. All exercise should incorporate a warm and cool-down session and should progress slowly, with gradual increases in exercise load, duration and frequency. Dr Sveeas also noted that exercise should be adapted to symptoms such as pain and fatigue. Pain during exercise should kept at a level of ≤5 (on a 0–10 scale) and intensity reduced if pain persists for more than 24 hours.
Wilfred Peter, Leiden, Netherlands, discussed issues around the implementation of high intensity exercise in patients with RMD. Dr Peter recommended using the general principles of healthy physical activity and adapting these to individual/disease-specific problems, adopting a systematic approach to any comorbidities. Exercise plans should be centred around FITT PRO (frequency, intensity, time, type of exercise and progression) and other training principles, with routine monitoring and evaluation for effects, safety, adherence and red flags.
Red flags for participation in exercise
Red flags for participation in exercise for patients with RMDs
“The additional effect of high intensity exercise is uncertain. Moderate intensity for healthy people can be vigorous for those with RMDs.”
Wilfred Peter, Leiden, Netherlands
Jade Skeates, Corsham, UK, presented results from a 10-week trial evaluating a progressive resistance training programme (PRTP) in patients with IA. A total of 147 patients completed the study, carrying out seven resistance exercises weekly. Significant and clinically meaningful improvements in all measured outcomes – including strength, activities of daily living performance, well-being, self-efficacy and fatigue – occurred over the 10-week period.
Closing Remarks
Notwithstanding the success of the first-ever EULAR e-congress, President Prof McInnes expressed his hope that the meeting will be back in physical form next year - noting that “face-to-face meetings are and will remain the ideal format to share knowledge and promote optimal solutions for clinical practice, research and patient care”. EULAR 2021 is scheduled to take place in Paris, France between 2nd and 5th June when the baton of Presidency will handed to Annamaria Lagnocco.
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