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Winter 2025 Press Review – Arthritis Research & Therapy
August 2024 to November 2024
Authors: Halbert Hernández Negrin and Magda Osipyan
Does regression of skin thickening predict improvement of internal organ involvement and survival in patients with diffuse cutaneous systemic sclerosis? A EUSTAR analysis
Wyss et al. (10.1186/s13075-024-03418-2) investigated whether an improvement in skin fibrosis among patients in the EUSTAR cohort with diffuse cutaneous systemic sclerosis (dcSSc) predicts lower progression of lung, renal, cardiac and gastrointestinal manifestations and better survival rate. Out of 1,257 included patients with baseline modified Rodnan skin score (mRSS) ≥7, 883 (70.2%) demonstrated no skin changes during 12±3 months follow-up, skin fibrosis of 282 (22.4%) was regressive, and of 92 (7.3%) was progressive. Regressive skin was associated with significantly reduced probability of lung progression and better survival at follow-up.
Increased serum level of IL-6 predicts poor prognosis in anti-MDA5-positive dermatomyositis with rapidly progressive interstitial lung disease
Niu et al. (10.1186/s13075-024-03415-5) investigated the significance of serum cytokine profiles and peripheral lymphocytes as predictors of the prognosis of anti-MDA5-positive dermatomyositis (DM) with rapidly-progressive interstitial lung disease (RP-ILD). This retrospective study of two cohorts that included 168 patients demonstrated that increased level of serum IL-6 (≥ 13.41pg/mL) , severe lymphopenia and elevated LDH were promising predictors of 6-month all-cause mortality and the occurrence of RP-ILD.
Correlation between circulating cell-free mitochondrial DNA content and severity of knee degeneration in patients with knee osteoarthritis: a cross-sectional study
Wu et al. (10.1186/s13075-024-03438-y) compared the levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) as both an endogenous damage-associated molecular pattern (DAMP) molecule and as a potential biomarker for inflammation. They compared 60 patients with knee osteoarthritis (KOA) with healthy controls (HC) matched for age, sex and body mass index (BMI). The study’s findings showed that plasma ccf-mtDNA was highly expressed in patients with KOA compared with HC. Within the KOA group, levels were significantly associated with the severity of KOA.
Halbert Hernández Negrin
Halbert is an internist, with a Master’s in Autoimmune Diseases from the University of Barcelona. He is currently a rheumatology resident at the Regional University Hospital of Malaga and a PhD student at the University of Malaga. His research interests focus on epidemiological and translational research in systemic autoimmune diseases, specifically in SLE. He is currently collaborating in the European 3TR SLE Study and in the International Multicentre Registry of patients with monogenic and polygenic autoinflammatory diseases (AIDA Project). He is a member of the European Lupus Society and a predoctoral fellow of the American College of Rheumatology (ACR). Halbert is a member of the Newsletter sub-committee.
Magda Osipyan
Magda is a rheumatologist at Vardanants Medical Centre for Innovative Medicine and Yerevan State Medical University, Yerevan, Armenia. Her research interests include SLE, Behcet’s disease and systemic sclerosis. Magda is secretary of the Armenian Rheumatological Association and a member of the EMEUNET Visibility and Global Affairs sub-committee.
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Winter 2025 Press Review – Seminars in Arthritis and Rheumatism
August 2024 to November 2024
Authors: Milena Bond & Ufuk Ilgen
Smoking-related bias of standardized mortality ratios in rheumatoid arthritis: A modeling study
Smoking is related to an increased mortality and known to be more common in rheumatoid arthritis (RA) compared to normal population. Standardized mortality ratios (SMRs) have usually been adjusted for age and sex but not for smoking in mortality studies in RA. In this modelling study based on United States National Health Interview Surveys 1999 – 2004, Ward (10.1016/j.semarthrit.2024.152599) revealed that 10- and 15-year SMRs might be inflated up to 1.23- and 1.17-fold in rheumatoid arthritis (RA) when smoking was not taken into consideration.
The impact of cardiovascular and cerebrovascular disease on the risk of dementia in rheumatoid arthritis: A mediation analysis
Lovering et al. (10.1016/j.semarthrit.2024.152570) found no statistically significant increase in Alzheimer’s disease and related dementias (ADRD) in rheumatoid arthritis (RA) in this retrospective cohort of 877 individuals with RA and 877 controls. Cardiovascular disease (CVD) itself was neither found to increase the risk of ADRD in RA and controls significantly. However, the presence of both RA and CVD acted synergistically on the risk of ADRD (HR=1.75 [95% CI: 1.19-2.58]). In conclusion, there was no mediation but an interaction effect of CVD for ADRD risk in RA.
Clinical and imaging outcomes of different phenotypes of axial spondyloarthritis: 5-year analysis of the DESIR cohort
Sepriano et al. (10.1016/j.semarthrit.2024.152424) compared the long-term outcomes of three phenotypes of axial spondyloarthritis (axSpA), ‘Axial’, ‘Inflammatory back pain (IBP)+Peripheral’ and ‘At risk’, among 576 patients in the DESIR cohort. Over five years, ‘At risk’ patients experienced worse disability (∆BASFI: −0.4 vs. -1.3 to −0.9) and less improvement in quality of life (∆SF36 physical domain: +2 vs. +4 to +6 and mental domain +3 vs. +2 to +7) compared to ‘Axial’ and ‘IBP+Peripheral’ patients, with a significant impact noted in those on bDMARDs. Imaging outcomes were worse in the ‘Axial’ phenotype. These findings suggest that treatment strategies might need to be tailored based on axSpA phenotype.
Disease-modifying antirheumatic drugs and risk of incident interstitial lung disease among patients with rheumatoid arthritis: A systematic review and meta-analysis
In this systematic literature review encompassing 486,465 rheumatoid arthritis (RA) patients and 3,928 incident interstitial lung disease (ILD) cases, Zhang et al.(10.1016/j.semarthrit.2024.152561) found no significant difference in the odds of ILD development for any conventional, biologic, or targeted synthetic DMARD in 24 randomized controlled trials. In observational studies, the use of methotrexate suggested even a protective role against incident ILD compared to non-use (pooled OR: 0.49 [95% CI: 0.32-0.76]). In a single observational study, tofacitinib users had lower ILD compared to TNF-inhibitor users (OR: 0.36 [95% CI: 0.15-0.87]). Due to several potential biases, further well-designed prospective studies are warranted for definitive conclusions.
Neuropathic pain in spondyloarthritis: Decoding its prevalence, risk factors, and impact on disease activity
In this cross-sectional study of 177 participants with spondyloarthritis, Lopalco et al. (10.1016/j.semarthrit.2024.152557) assessed neuropathic pain with two specialized questionnaires, PainDETECT and Neuropathic Pain Symptom Inventory. 22.2% of the study population had neuropathic pain, which was found to be associated with a high disease activity, female gender, and obesity. This study highlights the importance of integrating neuropathic pain evaluation into the clinical assessment of spondyloarthritis to tailor treatment approaches effectively and improve patient outcomes.
Metabolic syndrome, radiographic osteoarthritis progression and chronic pain of the knee among men and women from the general population: The Rotterdam study
Szilagyi et al. (10.1016/j.semarthrit.2024.152544) evaluated the relationship between osteoarthritis and metabolic syndrome (and its components) in a large cohort of 6,138 individulas over a median period of 5.7 years. They revealed that the presence of metabolic syndrome is associated with radiographic progression of knee osteoarthritis (OR: 1.35 [95% CI: 1.05-1.73] and 1.26 [95% CI: 1.06-1.5] in males and females, respectively). This effect was found to be primarily mediated by an increased body mass index (BMI). However, metabolic syndrome and high triglycerides were still associated with incident chronic knee pain in males after BMI adjustment.
Milena Bond, MD, PhDc
Country: Italy, AustriaMilena Bond is a consultant in rheumatology at the Hospital of Bruneck (Italy) and a PhD candidate at Paracelsus Medical University of Salzburg (Austria). Her research interests focus on systemic vasculitis, and she is part of several international task forces in the field. Milena is a member of the EMEUNET Visibility & Global Affairs Sub-Committee.
E-mail: milena.bond@sabes.it
Ufuk Ilgen, MD
Country: Turkey, GermanyUfuk is a rheumatologist from Turkey. Currently, he is doing his MSc in Translational Medical Research Programme at Heidelberg University, Germany. His main clinical and research interests are the immunopathological background of autoimmune diseases, the concept of autoimmunity and autoantibodies, and RNA biology in endothelial cells. He is a member of the Turkish Society for Rheumatology and European Lupus Society. He is a member of the EMEUNET Country Liaisons Sub-Committee.
E-mail: ufukilgen@gmail.com
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Winter 2025 Press Review – Miscellaneous
August 2024 to November 2024
Author: Aleksandra Opinc-Rosiak and Deniz Bayraktar (Denislav Orlinov)
In severe osteoarthritis, total hip replacement is more effective and comparably safe than resistance training
Frydenal et al. (10.1056/NEJMoa2400141) performed a multicenter, randomized controlled trial on the group of 109 patients with severe hip osteoarthritis to compare the effectiveness of total hip replacement with resistance training. Researchers demonstrated significantly greater improvements in the pain and physical functioning measured by the Oxford Hip Score in patients who underwent total hip replacement. The average increase of the Oxford Hip Score after 6 months was 15.9 points in patients with replaced hip as compared to a 4.5-point increase in the resistance training group. The incidence of serious adverse events was similar between the two groups.
Molecular mimicry may be the key to pathogenesis of MIS-C
Bodansky et al. (10.1038/s41586-024-07722-4) shed light on the pathogenesis of multisystem inflammatory syndrome in children. Reserachers found that autoantibodies in MIS-C patients target a specific epitope within the host protein SNX8, that has a very similar sequence with a nucleocapsid protein of the SARS-CoV-2. This molecular mimicry leads to cross-reactive immune responses, including T cells that recognize both the viral and host epitopes, contributing to the hyperinflammatory state observed in MIS-C.
Neuropsychiatric involvement in SLE is associated with internal organ damage
Nikolopoulous (10.1007/s00296-024-05667-5) performed a post-hoc analysis of five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) to compare internal organ damage reflected by Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (SDI) in patients with neuropsychiatric lupus (NPSLE) and non-NPSLE lupus patients. Researchers found that patients with neuropsychiatric involvement more often had cardiovascular complications, cutaneous lesions, muscle weakness/atrophy and alopecia, proving that the spectrum of possible complications in NPSLE extends far beyond nervous system.
Dietary fatty acids and rheumatoid arthritis risk
Kang et al. (10.55563/clinexprheumatol/91tmfb) investigated the data of 50,352 participants from the National Health and Nutrition Examination Survey conducted by the Centers for Disease Control and Prevention in the United States (1999-2020) and determined that higher ingestion of both n-3 and n-6 fatty acids are linked with a reduced risk of RA, with the associations being more prominent among females. A dose-response analysis identified a non-linear and U-shaped correlation between the intake of n-3 fatty acids and the risk of RA. A linear negative connection was observed between the intake of n-6 fatty acids and the risk of RA.
Impact of occupation type on disease burden in psoriatic arthritis patients
Colla et al. (10.1007/s10067-024-07077-1) assessed disease activity, work disability, and drug response/retention rates in 564 Swiss patients with Psoriatic Arthritis (PsA) among two different occupation’s types: blue-collar workers (manual labor) versus white-collar workers (more sedentary occupations). The authors suggested that physically demanding occupations correlate with increased rates of work disability among PsA patients, particularly men. However, treatment response seems to be unaffected by the occupation type.
Aleksandra Opinc-Rosiak
Aleksandra is a trainee in rheumatology and a research and teaching assistant at the Department of Rheumatology, Medical University of Lodz. Her main clinical and research interests include idiopathic inflammatory myopathies, CTD-ILD and autoantibodies. She is a member of Polish Rheumatology Society, iMyoS, EEACI. Aleksandra is a member of EMEUNET Newsletter Subcommittee and a current Country Liaison for Poland.
Deniz Bayraktar (Denislav Orlinov)
Denis is a physiotherapist by background and an Associate Professor at Izmir Katip Celebi University in Türkiye. His major interest is the effects of different exercise approaches in childhood and adulthood rheumatic diseases. He is the president of the Turkish of HPR Association and the HPR representative of Auto-Inflammatory Working Party in PReS. He is also an affiliate scientist at Arthritis Research Canada. Denis is a member of the EMEUNET Social Media Sub-Committee. -
Tell me something interesting
EULAR SHORT-TERM SCIENTIFIC GRANT – AN EXCITING OPPORTUNITY
THE BEGINNING
In 2021, I received the EULAR Scientific training grant for young fellows. I had the pleasure to visit one of the Centers of Excellence in rheumatology. My preferred center of excellence was the Department of Rheumatology at King’s College Hospital, London and the Weston Education Center. It was with great excitement that as part of my visit, I was given the opportunity to engage with a clinical project focusing on the “Prevalence of Interstitial Lung Disease at the Time of Diagnosis of Rheumatic Inflammatory Diseases” under the supervision of Dr. Elena Nikiphorou and Professor James Galloway, passionate professionals at the very core. Dr. Nikiphorou and I crossed paths through EMEUNET. As an active participant in the organization for years, Dr. Nikiphorou has held the position of Chair of EMEUNET. Her enthusiasm is contagious and inspiring; we have built a beautiful friendship that grew into a fruitful collaboration.
Dr Elena Nikiphorou (on the left) and Professor James Galloway (on the right) INTERESTING FACTS ABOUT KING’S COLLEGE LONDON
- King’s was established in 1829 under the patronage of King George IV and the Duke of Wellington.
- King’s alumni include 14 Nobel laureates.
- In December 2024, King’s College London was ranked in the top 1% of universities worldwide for sustainability.
For more interesting facts about King’s College London history click here.
THE EXPERIENCE
With great anticipation, I arrived on my first day of the program at Weston Education Center. This is one of the UK’s largest and most successful centres for research and education. Having the opportunity to blend in with the team was a true honour. I particularly enjoyed different clinics held once every two weeks, which, aside from early inflammatory arthritis clinics, included a sarcoidosis clinic held in conjunction with pulmonologists and dermatologists. As a leading centre in sarcoidosis, the discussion and examination of patients with different disease manifestations were extremely interesting. I also attended psoriatic arthritis clinics, antenatal clinics, and clinics on tuberculosis and rheumatic diseases.
Another interesting experience was the regular multidisciplinary team meetings discussing difficult-to-treat cases in rheumatology and biologics, and the lung transplant multidisciplinary meetings.
Every week, a team member delivered interesting lectures focused on their research and the results obtained.
Denmark Hill Campus where Weston Education Center is located and the very cosy rest area inside the Weston Education Center 
The Weston Education Centre THE RECREATIONAL ACTIVITIES – a King’s Experience
As you can imagine, London is a great place to visit anytime, not only for research but also for sightseeing – fromiconic landmarks like Buckingham Palace and Tower Bridge to world-renowned galleries and museums, top chefs’ gourmet experiences, and multi-award winning musicals (as the Lion King musical), however, this is another story.
Lyceum Theatre which presents the musical “The Lion King” CONCLUSION
It is all about teamwork! Vivid memories and good friendships are what will last. Thank you, King’s College London, for the hospitality during my whole stay!
I am most grateful to Professor James Galloway and Dr. Elena Nikiphorou!
At dusk on my way home I have captured one of the emblematic arcs of King’s College (a favourite photo)
MESSAGE TO YOUNG RHEUMATOLOGY FELLOWS
I would highly recommend the EULAR scientific exchange program to young fellows in rheumatology.
The exchange experience is a great opportunity to interact and collaborate with colleagues, exchange experiences, and gain knowledge from some of the best professionals in the field of rheumatology. Nothing in life is random, and there is always a good reason behind the people who cross our paths.
The environment was highly academic and professional yet warm, humble and friendly. The team encourages and welcomes young people like me from abroad, sharing knowledge and experience.
The experience gained, albeit for a short period of time, remains invaluable and inspiring.
Rositsa Dacheva on behalf of the Newsletter Sub-committe
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ACR Convergence 2024 Highlights- Rheumatoid Arthritis: Clinical (therapeutic)
Efficacy, Safety, Pharmacokinetics of Anti-CD40 Antibody Abiprubart in Patients with Rheumatoid Arthritis: A Phase 2, Randomized, Placebo-Controlled 12-week-treatment Proof-of-Concept Study
Abstract format and assignment number: Oral presentation 1678
Presenting author: E. Jenkins (United States)
Date: Sunday, 17th November 2024
Abiprubart, an anti-CD40 monoclonal antibody, was evaluated in a phase 2 trial for RA patients refractory to b/tsDMARDs. The 5 mg/kg weekly dose achieved a statistically significant reduction in DAS28-CRP (-2.17 vs. -1.61, p=0.0470) at 12 weeks compared to placebo. A pooled analysis also showed significant efficacy (-2.04 vs. -1.52, p=0.010). Rheumatoid factor levels decreased by >40%, indicating robust target engagement. Safety was favorable, with mild/moderate adverse events. Further studies, including phase 2B in Sjögren’s syndrome, are planned.
Safe Switching from Originator Tocilizumab to MSB11456 Tocilizumab Biosimilar in Subjects with Moderate-to-Severe Rheumatoid Arthritis: Efficacy, Safety and Immunogenicity Data Following Treatment Transition in a Pivotal, Randomized, Double-blind, Phase III Study
Abstract format and assignment number: Oral presentation 1681
Presenting author: A. Illes (Switzerland)
Date: Sunday, 17th November 2024
The Phase III APTURA I study demonstrated that MSB11456, the first tocilizumab biosimilar approved by FDA and EMA, achieved clinical biosimilarity to reference tocilizumab in moderate-to-severe RA patients. Transitioning from reference to MSB11456 at Week 24 showed sustained efficacy, safety, and immunogenicity up to Week 52. Improvements in DAS28-ESR/CRP and other disease activity measures were maintained, with no notable safety differences. This supports MSB11456 as a cost-effective, accessible alternative for RA.
Subcutaneous Abatacept vs Adalimumab Head-to-Head Comparison in Adults with Early, Dual Seropositive Rheumatoid Arthritis, Positive for the Shared Epitope HLA Class II Risk Alleles, and an Inadequate Response to Methotrexate: Results from a Phase 3 Trial
Abstract format and assignment number: Oral presentation 2671
Presenting author: M. Weinblatt (United States)
Date: Tuesday, 19th November 2024
The AMPLIFIED trial assessed abatacept (ABA) versus adalimumab (ADA) in early RA patients with high anti-CCP2 titers and shared epitope (SE) positivity. At 24 weeks, ACR50 rates, DAS28, and PROs were similar between groups. ABA showed greater reductions in autoantibodies, but SE and autoantibody levels did not predict superior treatment response. Both treatments were well-tolerated, with comparable adverse event rates. The trial did not confirm the prior hypothesis that SE and autoantibodies could predict ABA efficacy over ADA.
Prevention of the Development of Rheumatoid Arthritis by a 1-year Course of Methotrexate in ACPA-negative Arthralgia Patients at Increased Risk for Rheumatoid Arthritis: 4 Year Results of the TREAT EARLIER Trial
Abstract format and assignment number: Oral presentation 2672
Presenting author: Q. Dumoulin (Netherlands)
Date: Tuesday, 19th November 2024
The TREAT EARLIER trial investigated the effectiveness of methotrexate in preventing ACPA-negative rheumatoid arthritis (RA) in clinically suspect arthralgia (CSA). After 4 years, methotrexate reduced RA development in ACPA-negative participants with increased risk (8.6% vs 29.0%, HR 0.27), but had no effect in low-risk participants. Additionally, physical function and grip strength improved in the increased-risk group. These findings suggest methotrexate could prevent ACPA-negative RA in CSA patients with increased risk.
Timeframe for Initiating Methotrexate and Vaccine Response Against Pneumococcus in Rheumatoid Arthritis: The VACIMRA Study
Abstract format and assignment number: Oral presentation 2676
Presenting author: J. Morel (France)
Date: Tuesday, 19th November 2024
Rheumatoid arthritis (RA) patients vaccinated with PCV13 one month prior to methotrexate (MTX) initiation showed significantly higher immunological response rates at one month (88% vs. 75% by ELISA, p < 0.01) compared to simultaneous vaccination with MTX. These higher responses persisted at one year, with similar RA control and no differences in glucocorticoid or targeted DMARD use between groups. The findings emphasize the importance of completing pneumococcal vaccination before starting MTX therapy in RA patients.
Roba Ghossan
Roba is a rheumatologist at the Department of Rheumatology of Cochin Hospital APHP in Paris, France. Her main clinical and research interests include Inflammatory Rheumatic Diseases, MSK Ultrasound and Epidemiology.
Roba is a member of the French Society of Rheumatology and the society’s young rheumatologists section (REF). She is a member of the EMEUNET Social Media Sub-Committee.
E-mail: roba.ghossan@gmail.com
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ACR Convergence 2024 Highlights- Rheumatoid Arthritis: Clinical (non-therapeutic)
Fracture Incidence Rates in Persons with Rheumatoid Arthritis by Disease Activity Level
Abstract format and assignment number: Oral presentation 1748
Presenting author: R. Elam (United States)
Date: Sunday, 17th November 2024
In this study, higher fracture incidence rates (IRs) were found in individuals with rheumatoid arthritis (RA) compared to those without, especially in those with higher disease activity. A retrospective cohort study (2016-2018) using RISE data linked to Medicare claims revealed that RA patients with disease activity above remission had higher rates of hip fractures and major osteoporotic fractures (MOF). This underscores the need for bone health monitoring in RA patients, particularly those with high disease activity.
What Are the Benefits of Treating Rheumatoid Arthritis Patients to Remission After Achieving Low Disease Activity in Clinical Practice?
Abstract format and assignment number: Oral presentation 1743
Presenting author: M. Weinblatt (United States)
Date: Sunday, 17th November 2024
This study from the BRASS registry assessed the incremental benefit of achieving remission in rheumatoid arthritis (RA) patients initially at low disease activity (LDA). Patients with CDAI ≤2.8 (remission) showed better functional outcomes and reduced durable medical equipment (DME) use compared to those with CDAI between 6 and 10. Achieving remission led to significant improvements in MDHAQ function scores and reduced DME use. New treatments targeting remission may reduce RA-related disability and healthcare costs.
Disease-associated Central Nervous System Activation Predicts Good Clinical Response to Tumor Necrosis Factor Inhibition in Rheumatoid Arthritis Patients – “The PreCePRA Study”
Abstract format and assignment number: Oral presentation 0871
Presenting author: J. Rech (Germany)
Date: Saturday, 16th November 2024
This study investigates whether high central nervous system (CNS) activation, measured through functional MRI (fMRI), predicts better clinical responses to TNF inhibitors (TNFi) in rheumatoid arthritis (RA). Patients were stratified based on fMRI voxel size and randomized to receive certolizumab-pegol (CZP) or placebo. Results showed that patients with high CNS activation (HV-CZP) achieved significantly better outcomes, particularly in patient-reported measures, compared to the placebo group, suggesting that CNS activation can predict TNFi response in RA.
The Impact of Body Mass Index on Cardiovascular Risk in Rheumatoid Arthritis Varies Across Anticitrullinated Protein Antibody Status and Biologic Use
Abstract format and assignment number: Oral presentation 0870
Presenting author: G. Karpouzas (United States)
Date: Saturday, 16th November 2024
This study explored how BMI influences cardiovascular risk in rheumatoid arthritis (RA) patients, factoring in ACPA status and bDMARD use. For ACPA-positive patients, higher BMI correlated with increased major adverse cardiovascular events (MACE). In ACPA-negative patients, BMI was inversely linked to MACE risk, but only in bDMARD users. The results highlight complex interactions, showing that BMI’s impact on cardiovascular outcomes varies based on disease markers and treatment.
Disease Activity Is Strongly Associated with RA-related Lung Disease and Interstitial Lung Disease in Early RA: Results from a Multicenter, Prospective Cohort Study
Abstract format and assignment number: Oral presentation 0802
Presenting author: G. McDermott (United States)
Date: Saturday, 16th November 2024
In this prospective multicenter study of early RA, 16% of patients developed RA-related lung diseases (ILD, bronchiectasis, emphysema). Active RA, male sex, and older age were significant predictors of lung disease, with moderate/high disease activity strongly linked to increased odds of ILD. The findings suggest that managing disease activity early in RA may reduce the risk of developing lung diseases, highlighting the importance of early diagnosis and effective treatment to prevent both articular and extra-articular complications.
Roba Ghossan
Roba is a rheumatologist at the Department of Rheumatology of Cochin Hospital APHP in Paris, France. Her main clinical and research interests include Inflammatory Rheumatic Diseases, MSK Ultrasound and Epidemiology.
Roba is a member of the French Society of Rheumatology and the society’s young rheumatologists section (REF). She is a member of the EMEUNET Social Media Sub-Committee.
E-mail: roba.ghossan@gmail.com
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ACR Convergence 2024 Highlights – SLE and APS
A Novel, Potent and Selective TLR7/8 Small Molecule Inhibitor Blocks TLR7/8 Pathway in the Presence of HCQ and Demonstrates Robust Preclinical Efficacy in Lupus Models
Abstract format and assignment number: Poster 0085
Presenting author: C Shang (USA)
Date: Saturday, 16th November 2024
This study investigates a novel, selective TLR 7/8 inhibitor as a potential therapeutic addition to hydroxychloroquine in systemic lupus erythematosus (SLE). While HCQ suppressed TLR9 activation in SLE patient blood samples, TLR7/8 pathways remained active, indicating HCQ’s limited effect on TLR7/8. The TLR7/8 inhibitor effectively blocked TLR7/8-induced cytokine production and immune cell activation in vitro and improved disease markers such as survival, proteinuria and renal histopathology in murine lupus models. These findings support the combined use of TLR7/8 inhibition with HCQ to better target lupus pathogenesis.
Anti-HSP90α as a Protective Natural Antibody Against Secondary Antiphospholipid Syndrome in Systemic Lupus Erythematosus
Abstract format and assignment number: Poster 0098
Presenting author: M Barguil Macedo (USA)
Date: Saturday, 16th November 2024
This study explored the role of anti-HSP90α IgG antibodies in systemic lupus erythematosus and their potential protective effect against secondary antiphospholipid syndrome. Using plasma samples from two cohorts, anti-HSP90α IgG levels were measured in SLE patients and controls. SLE patients with APS showed significantly lower anti-HSP90α IgG levels compared to those without APS. In vitro, anti-HSP90α IgG reduced platelet activation markers (TSP-1, PF-4), suggesting it may inhibit HSP90-induced platelet activation, potentially reducing thrombosis risk in APS. This highlights a novel, protective role of anti-HSP90α IgG in SLE-related APS.
Novel Autoantibodies Identified in the Antiphospholipid Syndrome
Abstract format and assignment number: Poster 0105
Presenting author: S Hu (China)
Date: Saturday, 16th November 2024
This study identifies novel autoantibodies in APS using a proteome microarray. Six candidate autoantibodies (SULT2B1, NPM1, AGO1, SERPINB2, ACVR2B, IRAK4) were validated by ELISA, with anti-SULT2B1 and anti-AGO1 elevated in primary APS and anti-NPM1 associated with secondary APS, SLE, cardiac valve issues and triple antibody positivity. These findings highlight potential new diagnostic markers for APS, pending further validation.
External Validation and Extension of Population-Based Systemic Lupus Erythematosus Risk Prediction Models Using Genetics, and Lifestyle and Environmental Factors
Abstract format and assignment number: Poster 0843
Presenting author: JJE Koopman (USA)
Date: Saturday, 16th November 2024
This study validated systemic lupus erythematosus risk prediction models using genetic, lifestyle and environmental factors in the Mass General Brigham Biobank, involving 535 SLE patients and 2,135 matched controls. Three multivariable models were compared, including genetic risk scores and lifestyle/environmental factors such as smoking, alcohol use, obesity and depression. Model 3, which combined genetics with lifestyle and environmental factors, achieved the highest discrimination (AUC 0.81–0.82) for predicting SLE. These models could potentially support screening in at-risk populations, leveraging accessible genetic and lifestyle data for prevention efforts.
Allogenic CD19 CAR NK Cells Therapy in Refractory Systemic Lupus Erythematosus: An Open-label, Single Arm, Prospective and Interventional Clinical Trial
Abstract format and assignment number: Oral presentation L17
Presenting author: Y Yu (China)
Date: Tuesday, 19th November 2024
This study assessed the safety and efficacy of CD19-targeting CAR-NK cell therapy in 20 patients with severe, refractory systemic lupus erythematosus. After preconditioning with cyclophosphamide and fludarabine, patients received CAR-NK infusions, with median follow-up of 5 months. B-cell recovery occurred within 2-3 months, with mild cytokine release syndrome in 2 patients and no severe adverse events. Among those followed for over 6 months, 50% achieved DORIS-defined remission, and 75% achieved lupus low disease activity state, indicating potential for durable remission in SLE.
Omar Dhrif MD
Omar is an internal medicine specialist from University Tunis El Manar, and an internal medicine fellow at Dijon University Hospital, France. His main clinical and research interests focus on vasculitis, global access to healthcare and educational therapy. Omar is the past-treasurer of the Tunisian Association of Young Internists, co-founder of the Francophonic Young Internists Group, member of the Research Committee of the Tunisian Society of Internal Medicine and American College of Rheumatology Social Media Ambassador. Omar is a member of the EMEUNET Social Media sub-committee.
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ACR Convergence 2024 Highlights – Other Connective Tissues Diseases and Vasculitis
Efficacy and Safety of Upadacitinib in Patients with Giant Cell Arteritis (SELECT-GCA): A Double-Blind, Randomized Controlled Phase 3 Trial
Abstract format and assignment number: Oral presentation 0770
Presenting author: P. Merkel (USA)
Date: Saturday, 16th November 2024
The SELECT-GCA trial is the first randomized controlled trial evaluating the efficacy of upadacitinib (7.5 mg/d or 15 mg/d), versus placebo, in patients with newly diagnosed or relapsing giant cell arteritis. The rate of sustained remission was superior to placebo only in the group receiving 15 mg/d. Another abstract describing the results in subgroup analysis confirmed these results in most subgroups.
A Multicenter, Randomized, Controlled Trial to Evaluate the Effects of Low-dose Glucocorticoids Compared to Stopping Glucocorticoids to Maintain Remission of Granulomatosis with Polyangiitis: The TAPIR Trial
Abstract format and assignment number: Oral presentation 0774
Presenting author: P. Merkel (USA)
Date: Saturday, 16th November 2024
In the TAPIR study, the authors compared two strategies of glucocorticoid treatment in patients with granulomatosis with polyangiitis in remission. Patients who stopped glucocorticoids had more relapses than patients maintaining 5 mg/d of prednisone. But interestingly, there was no difference between the two strategies in patients receiving rituximab.
Plasma Exchange for Severe Alveolar Hemorrhage in ANCA-Associated Vasculitis: Emulation of a Target Trial
Abstract format and assignment number: Oral presentation 0826
Presenting author: AC. Sanna (France)
Date: Saturday, 16th November 2024
The PEXIVAS study did not show any decrease of mortality with the use of plasma exchange in alveolar hemorrhage during ANCA associated vasculitis. In this emulated trial, the authors wanted to evaluate the potential benefits of plasma exchanges in patient with severe diffuse alveolar hemorrhage. But, even in severe patients, plasma exchanges did not improve early mortality.
Results of a One Year Randomized Double-Blind Placebo-Controlled Trial with Methotrexate 25mg Per Week for Recently Diagnosed Polymyalgia Rheumatica
Abstract format and assignment number: Oral presentation 1697
Presenting author: T. Bolhuis (The Netherlands)
Date: Sunday, 17th November 2024
Methotrexate is the most commonly used glucocorticoid sparing agent in PMR, despite contradictory studies. In this randomized controlled trial, methotrexate 25 mg/week was not superior to placebo, in association to glucocorticoids, for the remission at 52 weeks. Moreover, no glucocorticoid sparing effect was observed during the first year.
Efficacy and Safety of Nipocalimab, an Anti-FcRn Monoclonal Antibody, in Primary Sjogren’s Disease: Results from a Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study (DAHLIAS)
Abstract format and assignment number: Oral presentation 2527
Presenting author: P. Ruscitti (Italy)
Date: Monday, 18th November 2024
So far, there is no drug approved for Sjögren’s disease. Nipocalimab is a monoclonal targeting the FcRN and accelerating the clearance of antibodies, including autoantibodies. In this phase 2 trials, some clinical outcomes were assessed and the decrease in ESSDAI was significantly higher in patients receiving the nipocalimab. Results of a phase 3 trial are now expected to confirm these interesting data.
Guillermo Carvajal Alegria
Guillermo is an associate professor of rheumatology at the University of Tours and in the rheumatology department of the Tours University Hospital, France. His research interest are polymyalgia rheumatica and giant cell arteritis, ultrasonography and procedures for clinical research and administration of biopharmaceuticals for scientific research. He is part of the board of directors of the French Rheumatology Society and of steering committee of the French College of Teaching Rheumatologists. He is a member of the EMEUNET Visibility & Global Affairs sub-committee. -
ACR Convergence 2024 Highlights – Spondyloarthritis: Clinical (therapeutic)
Nonsteroidal Anti-Inflammatory Drug Use and Incident Hypertension Among Patients with Axial Spondyloarthritis
Abstract format and assignment number: Poster 0540
Presenting author: J. Meade Aguilar (USA)
Date: Saturday, 16th November 2024
In this retrospective study, the authors evaluated the relation between NSAID use and incident hypertension in a longitudinal inception cohort of patients with axial spondyloarthritis (axSpA) using data from a longitudinal French DESIR cohort of early spondyloarthritis with 72-month follow-up. It found no significant association between high-dose NSAID use and the development of hypertension. The anti-inflammatory effects of NSAIDs on disease activity might counterbalance the risk of incident hypertension that is known to occur in the general population.
The Assessment of SpondyloArthritis International Society (ASAS) Definition of Difficult-to-Manage Axial Spondyloarthritis
Abstract format and assignment number: Oral presentation 0819
Presenting author: D. Poddubnyy (Germany)
Date: Saturday, 16th November 2024
ASAS presented its definition of ‘difficult-to-manage axSpA’ (D2M axSpA) at the 2024 ACR Convergence. The definition encapsulates treatment failure, suboptimal disease control, and physician or patient acknowledgment of problematic signs/symptoms in patients diagnosed with axSpA by a rheumatologist. “Treatment-refractory” disease is a part of the D2M group, which can be concluded after excluding other reasons for non-response and requires a history of specific treatment failure and the presence of objective signs of inflammatory activity.
Guselkumab and IL-17 Inhibitors Show Comparable Treatment Persistence and Effectiveness in Psoriatic Arthritis: 6-month Interim Results of the PsABIOnd Observational Cohort Study
Abstract format and assignment number: Oral presentation 1464
Presenting author: L. Gossec (France)
Date: Sunday, 17th November 2024
The authors presented the interim analysis of the first ≥600 participants (pts) enrolled out of 1300 planned pts in PsABIOnd. The aim was to assess treatment persistence and achievement of clinical psoriatic arthritis (PsA) outcomes at 6 months. PsA pts had similar persistence on treatment with guselkumab or IL17i, and comparable rates of effectiveness across various PsA domains at 6 months.
What Is the Impact of Prior TNF Inhibitor Treatment on the Time to Achieve Low Disease Activity and the Durability of Low Disease Activity? Real-world Results Based on 17 858 European Patients with Axial Spondyloarthritis Initiating a TNF Inhibitor or an IL-17A Inhibitor
Abstract format and assignment number: Oral presentation 1756
Presenting author: J. Heberg (Denmark)
Date: Sunday, 17th November 2024
The authors aimed to assess the time to achieve low disease activity (LDA) from the initiation of a TNFi or an IL-17Ai, as well as the duration of achieved LDA, in patients with axSpA and 0, 1 or 2 prior TNFi treatments. The time to achieve LDA increased with the number of prior TNFi in both TNFi and IL-17Ai treatments. While the duration of LDA was shorter for TNFi-experienced than biologic-naïve patients initiating IL-17Ai, prior TNFi did not affect durability in patients initiating TNFi.
Exploring Weight Trends in Psoriatic Arthritis: Unraveling Effects of Drugs
Abstract format and assignment number: Oral presentation 2639
Presenting author: P Mehta (Canada)
Date: Monday, 18th November 2024
The authors aimed to study the change in weight with the use of csDMARDs, biologic (b)DMARDs, Janus kinase inhibitors (JAKi) and apremilast, along with other factors affecting weight across a cohort of patients with PsA. Significant weight loss was observed after initiation of IL17i, IL23i and csDMARDs in PsA, as compared to weight before initiation of these drugs. However, amongst the drugs, the use of TNFi and IL12/23i was associated with weight gain, whereas apremilast was associated with weight loss when compared across the cohort.
Jean-Guillaume Letarouilly MD PhD
Jean-Guillaume is a consultant rheumatologist at Lille University Hospital (France). His research interests include axial spondyloarthritis and psoriatic arthritis, the crosstalk with inflammatory bowel diseases and psoriasis, and difficult-to-treat axial spondyloarthritis and psoriatic arthritis.
He is a member of Young-GRAPPA and of the EMEUNET Visibility and Global Affairs Subcommittee.
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ACR Convergence 2024 Highlights – Spondyloarthritis: Clinical (non-therapeutic)
Global Recruiting Patterns Are Associated with Placebo Response Rates in Clinical Trials of Psoriatic Arthritis
Abstract format and assignment number: Oral presentation 0772
Presenting author: A. Kerschbaumer (Austria)
Date: Saturday, 16th November 2024
This study analyzed placebo arms in psoriatic arthritis clinical trials, revealing that placebo response rates (ACR20) have increased over time, correlating with a shift in recruitment toward less affluent countries. This trend may result from limited access to healthcare in these regions, leading to higher regression to the mean.
The findings highlight the influence of geographic and socioeconomic factors on trial outcomes and call for consideration in trial design and interpretation.
Associations and Impact of Kinesiophobia on Patient Reported Outcomes and Performance-based Mobility Measures in Patients with Axial Spondyloarthritis
Abstract format and assignment number: Poster 0548
Presenting author: D. Kiefer (Germany)
Date: Saturday, 16th November 2024
The study explores the impact of kinesiophobia, assessed by the Tampa scale, on patient-reported outcomes and mobility in axial spondyloarthritis (axSpA). Results show that higher kinesiophobia levels are associated with poorer outcomes, reduced performance in mobility tests, and lower quality of life. The findings suggest that addressing kinesiophobia could improve physical function and patient-reported experiences in axSpA management.
Different Prevalence of Intestinal Inflammation in Radiographic and Non-radiographic Axial Spondyloarthritis. Data from EISER Study
Abstract format and assignment number: Poster 0554
Presenting author: C. Merino (Spain)
Date: Saturday, 16th November 2024
The study found higher intestinal inflammation prevalence in radiographic axSpA (r-axSpA) than in non-radiographic axSpA (nr-axSpA), assessed via ileocolonoscopy performed in 287 patients. Inflammation was more common in patients with higher disease activity (ASDAS >2.1) and in HLA-B27-positive individuals. These findings suggest a stronger gut-joint axis involvement in r-axSpA, supporting stratified patient care and further investigation into shared inflammatory pathways.
Predicting Disease Flares in Axial Spondyloarthritis Using Machine Learning in the METEOR-SpA Registry
Abstract format and assignment number: Poster 0559
Presenting author: D. Benavent (Spain)
Date: Saturday, 16th November 2024
A study using the METEOR-SpA registry applied machine learning to predict disease flares in axial spondyloarthritis (axSpA) patients treated with b/tsDMARDs. Among 1,199 patients, 16.4% experienced flares within six months.
The best-performing model, constructed by reduced logistic regression, identified four predictors of flare within 6 months: lower ASDAS, history of enthesitis, number of previous flares, and longer treatment duration.
Investigating the Association Between Alcohol Consumption and Spinal Radiographic Progression in Axial Spondyloarthritis: A Longitudinal Cohort Analysis over a Period of 6 Years
Abstract format and assignment number: Oral presentation 0822
Presenting author: E. Gendron (Canada)
Date: Saturday, 16th November 2024
This study evaluated whether alcohol consumption influences spinal radiographic progression in axial spondyloarthritis (axSpA) over six years. Using data from 387 patients (769 radiographic intervals), researchers found that alcohol consumption was associated with increased odds of progression, particularly in males and those with radiographic axSpA (r-axSpA). The relationship was not mediated by inflammation (ASDAS), suggesting other mechanisms. Future studies should explore non-inflammatory pathways influencing structural damage.
Individualizing NSAIDs in Axial Spondyloarthritis Through a Series of N-of-1 Clinical Trials with Bayesian Analysis
Abstract format and assignment number: Poster 1476
Presenting author: M. Hwang (USA)
Date: Sunday, 17th November 2024
Using N-of-1 trials analysed with Bayesian statistics, the study evaluated individual patient responses to NSAIDs, aiming to optimise treatment effectiveness and minimise side effects. No particular NSAID was globally chosen over the other NSAIDs but on a patient level, the preferred drug conferred a greater reduction in ASDAS compared to the others. This methodology supports tailored treatments by integrating patient-specific data into clinical decision-making.
Olivier Fakih
Olivier is a rheumatology fellow at the Department of Rheumatology of Besançon University Hospital in France.
His research interests include the epidemiology of inflammatory rheumatic diseases, in particular, mortality and comorbidities in spondyloarthritis. Olivier is a member of the French Society of Rheumatology and the society’s young rheumatologists section (REF).
He is a member of the EMEUNET Education Sub-Committee.