American College Of Rheumatology Research Articles

Advances in the pharmacological management of systemic lupus erythematosus.

Despite setbacks in clinical trials for systemic lupus erythematosus (SLE), three drugs have been approved for SLE and lupus nephritis (LN) treatment in the past decade. Several ongoing clinical trials, some viewed optimistically by the scientific community, underscore the evolving landscape. Emerging clinical data have established specific therapeutic targets in routine clinical practice for treating SLE, aiming to improve long-term outcomes. Research related to treatment of SLE and LN is discussed, focusing on randomized clinical trials during the last 5 years and recommendations for the management of SLE published by the European Alliance of Associations for Rheumatology (EULAR), American College of Rheumatology (ACR), Asia Pacific League of Associations for Rheumatology (APLAR), and Pan-American League of Associations of Rheumatology (PANLAR). The landscape of SLE and LN treatments is evolving, as new drugs and combination treatment approaches redefine the traditional concepts of induction and maintenance treatment phases. As the therapeutic armamentarium in SLE continues to expand, the research focus is shifting from the imperative for new therapies to advancing our understanding of optimal treatment selection for individual patients, steering toward precision medicine strategies.

Clinical and laboratory profiles of systemic lupus erythematosus patients in a new rheumatology clinic in southwestern Nigeria

IntroductionThe aims were to study the sociodemographic characteristics of patients presenting to the clinic and to study the clinical and serological pattern of systemic lupus erythematosus (SLE) in a new rheumatology clinic of a predominantly Yoruba population.Material and methodsThis was a retrospective, cross-sectional study conducted over 7 years (January 2017 – December 2023). Patients who satisfied the 1997 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were enrolled using their medical records. Patients with overlap syndromes and other inflammatory or noninflammatory rheumatic diseases were excluded from the study. Their sociodemographic, clinical, laboratory, and treatment data were retrieved from their medical records and analysed using IBM SPSS version 23.0 software.ResultsA total of 65 patients were diagnosed with SLE with a frequency of 15.8%. The mean age ±SD of the patients at presentation was 33.85 years ±11.01 and the female to male ratio was 9.8 : 1. The median (IQR) duration of symptoms at presentation was 7.0 months (3–24). The common clinical presentations included synovitis (86.2%), acute cutaneous rash (53.8%), oral ulcers (52.3%), nonscarring alopecia (50.8%), and serositis (47.7%). Proteinuria was seen in 37.7% of the patients and the predominant renal histopathological feature was Class IV. Antinuclear antibody was 100% positive with 50.94% of the patients having a titre of 1 : 5,120 and above. Anti- double-stranded deoxyribonucleic acid and anti-Smith antibodies each had 50% prevalence. Dyslipidaemia was found in 76.7% of the patients.ConclusionsThe study’s findings are largely consistent with similar studies done in Africa. Further prospective multi-centred studies are needed to further determine the epidemiological characteristics of the disease in Nigeria with a multi-ethnic population.

Diagnostic Accuracy of Raman Spectroscopy Integrated With Polarized Light Microscopy for Calcium Pyrophosphate-Associated Arthritis.

We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)-associated arthritis (CPPD). This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD. The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3-94.2), specificity 99.1% (95% CI 97.5-99.8), positive likelihood ratio 100.33 (95% CI 32.3-311.3), negative likelihood ratio 0.14 (95% CI 0.07-0.28), positive predictive value 93.5% (95% CI 82.2-97.8), negative predictive value 98.0% (95% CI 82.2-97.8), and accuracy 97.5% (95% CI 95.5-98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects. iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD.

Overlap syndrome of systemic sclerosis with antineutrophil cytoplasmic antibody-associated vasculitis according to 2022 ACR/EULAR criteria.

This study applied the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients with systemic sclerosis (SSc) and investigated the frequency of overlap syndrome of SSc and AAV (SSc-AAV-OS). Among the 232 patients diagnosed with SSc, 105 with signs suggestive of small- or medium-vessel vasculitis, which were defined as the present of interstitial lung disease (ILD), peripheral neuropathy, or suspected renal vasculitis, were included in this study and analyzed. Among the 105 SSc patients, the detection rate of ANCA was 19.0%. When the 2022 ACR/EULAR criteria were applied, the frequency of SSc-AAV-OS was 20.0%, which was much higher than 1.7% reported with previous criteria for AAV. ANCA positivity contributed to the reclassification of SSc-AAV-OS more than ANCA negativity in SSc patients with signs suggestive of small- or medium-vessel vasculitis. The frequency of SSc-AAV-OS in SSc patients with signs suggestive of small- or medium-vessel vasculitis at diagnosis was 20.0%. Therefore, we suggest that physicians should perform ANCA tests in SSc patients exhibiting signs suggestive of small- or medium-vessel vasculitis and apply the new criteria for AAV.

Dilemmas in the Diagnosis and Management of Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is characterised by thrombosis (which may be venous, arterial, or microvascular) and/or pregnancy morbidity, in association with persistently positive antiphospholipid antibodies (aPLs). Although thrombosis and pregnancy morbidity are the main clinical criteria for a diagnosis of APS in the revised Sapporo (Sydney) criteria, recently published American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for APS have significantly refined the diagnostic algorithm to include a scoring system clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular thrombosis, obstetric, cardiac valve, and hematologic). Diagnosis of APS is complicated by the fact that significant heterogeneity exists in patients’ clinical presentation, underlying vascular risk factors and methods of detecting aPL. Despite the autoimmune nature of APS, anticoagulation remains the main strategy for secondary prevention of thrombosis. However, optimal antithrombotic treatment in APS patients with arterial thrombosis remains controversial due to a paucity of data from randomised controlled studies. In this paper, we present two cases and highlight the diagnostic and therapeutic challenges they pose and how we approach them in the light of current evidence.

2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities.BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

Review of 2022 Аmerican college of rheumatology (АСR) guideline for the prevention and treatment of glucocorticoid-induced osteoporosis: what’s new?

Glucocorticoids (GC) have been used in medicine since the middle of the twentieth century, including for the treatment of various systemic rheumatic diseases. However, long-term use of GC may be accompanied by the development of serious complications, one of which is secondary osteoporosis, leading to low-energy fractures, which affects the quality of life of patients and may lead to an increased risk of death. This article presents an overview with a discussion of the new edition of the guideline of the American College of Rheumatology (ACR) 2022 for the prevention and treatment of glucocorticoid-induced osteoporosis in adult patients.

P123 Safety and efficacy of filgotinib, an update from the DARWIN 3 phase 2 long-term extension with a maximum of 8.2 years of exposure

Abstract Background/Aims DARWIN 3 (NCT02065700) is a long-term extension (LTE) study assessing the safety and efficacy of filgotinib (FIL) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). In the DARWIN 1 (NCT01888874) and DARWIN 2 (NCT01894516) parent studies, patients received FIL in combination with MTX or FIL monotherapy, respectively. To provide an update on the safety and efficacy of FIL 200 mg (FIL200) in patients with RA, with or without MTX, with a maximum of 8.2 years of exposure. Methods Patients completing the DARWIN 1 and DARWIN 2 phase 2 studies could enter DARWIN 3, receiving FIL200[PE1] +/-MTX. The proportion of patients experiencing treatment-emergent adverse events (TEAEs) were reported, comprising data from both the parent and LTE studies. Efficacy was assessed from LTE baseline using the American College of Rheumatology (ACR) 20/50/70 criteria and DAS28-CRP, up to 264 weeks. Low disease activity and remission were defined as DAS28-CRP ≤3.2 and <2.6, respectively. Results In total, 739 patients were enrolled in DARWIN 3. In the FIL + MTX vs FIL monotherapy groups, TEAEs were reported for 90.9% and 92.1% of patients, respectively (Table). The most common TEAE was infection. In both treatment groups, eight patients had a TEAE leading to death (1.6% and 3.3%, respectively). Exposure-adjusted incidence rates, censored at time of first event for major adverse cardiovascular event, venous thromboembolism, herpes zoster, infections, serious infections, non-melanoma skin cancer (NMSC), malignancies excluding NMSC, gastrointestinal perforations and TEAEs leading to death, will be reported. Through five years, ACR20/50/70 responses were maintained in 86.3%/66.7%/50.7% of the FIL + MTX group and 90.8%/74.8%/51.4% of the FIL monotherapy group, respectively (observed data). DAS28-CRP low disease activity and remission rates (non-responder imputation) at DARWIN 3 baseline were 46.1%/40.1% (FIL + MTX) and 29.6%/24.8% (FIL monotherapy). At Week 264, the proportion of patients achieving low disease activity and remission were 34.0%/34.3% (FIL + MTX) and 27.0%/24.8% (FIL monotherapy). Conclusion With a maximum of 8.2 years of exposure in patients with RA, the FIL safety profile is similar between the background MTX and monotherapy treatment arms. Both arms show sustained efficacy over time. Disclosure P. Emery: Consultancies; Consultant of: AbbVie, AstraZeneca, BMS, Boehringer-Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, Roche, and Samsung. Member of speakers’ bureau; y Speakers bureau: AbbVie, AstraZeneca, BMS, Boehringer-Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, and Samsung. Grants/research support; Grant/research support from: AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, and Samsung. R. Westhovens: Consultancies; Celltrion, Galapagos, and Gilead,. Member of speakers’ bureau; Celltrion, Galapagos, and Gilead. R.H.E. Alten: Consultancies; AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, SanofiGenzyme, UCB, and VIATRIS. L. Dagna: Consultancies; AbbVie, Amgen, AstraZeneca, Biogen, Boehringer-Ingelheim, BMS, Celltrion, Eli Lilly & Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme,. Grants/research support; AbbVie, BMS, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merck Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI,. A. Kavanaugh: Consultancies; Amgen, AbbVie, BMS, Pfizer, UCB, Janssen, Novartis, and Pfizer. K.L. Winthrop: Consultancies; AbbVie, AstraZeneca, BMS, Eli Lilly & Company, Galapagos, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. Grants/research support; BMS and Pfizer. J. Barry: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. R. Besuyen: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. C. Corallo: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. C. Watson: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. N. Martin: Consultancies; Galapagos. M. Genovese: Corporate appointments; Gilead Sciences. Shareholder/stock ownership; Gilead Sciences. A.J. Spindler: None. M. Stanislavchuk: Grants/research support; Amgen, AstraZeneca, Celgene, Eli Lilly, Galapagos, Gilead, Human Genome, Janssen, MSD, Nichi-Iko, Pfizer, and Roche. M. Greenwald: Grants/research support; AbbVie, Aclaris, Galapagos, Janssen, Lilly, and Nimbus.

P135 Association of Serum Anti-Muscarinic 3 Antibodies with Gastrointestinal Disease in Systemic Sclerosis

Abstract Background/Aims Gastrointestinal (GI) complications of systemic sclerosis (SSc) are frequent and debilitating with symptoms ranging from reflux to faecal soilage. The pathogenesis of GI disease in SSc is poorly understood. Circulating antibodies against Muscarinic type 3 Receptors (anti-M3R) have been implicated in GI smooth muscle dysfunction and neural activation impairment. We examine whether anti-M3R antibodies associate with objective measures of gastrointestinal symptoms. Methods Sera were collected from SSc patients fulfilling the American College of Rheumatology (ACR) classification criteria for SSc. Healthy control (HC) sera were obtained from age-matched volunteers. SSc patients completed the UCLA GIT 2.0 (UCLA GIT) questionnaire. Serum anti-M3R antibodies were measured using specific enzyme-linked immunosorbent assay (ELISA)(CellTrend GmbH, Germany). SSc sera had elevated anti-M3R antibodies if the concentration exceeded two standard deviations above the mean of HC sera. Statistical comparisons were made using Fisher’s exact test and two sample t-test. Results Sera from 40 SSc patients and five HC were assayed for anti-M3R antibodies. Anti-M3R antibody was higher in SSc patients in comparison to HC (1547 vs 1183U/ml, p = 0.33). Anti-M3R antibody levels were significantly elevated in nine (23%) SSc patients. Cohort characteristics were compared based on anti-M3R antibody levels for SSc patients (Table 1). Group demographics were similar in gender, age and disease duration. There was a trend for higher anti-M3R antibodies in limited compared with diffuse cutaneous SSc subset (66.7 vs 32.2, p = 0.12). Although there was no significant association between Anti-M3R antibody level and GIT score (r = 0.014 p = 0.51), SSc patients with elevated anti-M3R antibody did report numerically more severe reflux symptoms (1.24 vs 0.8, p = 0.23) and fewer lower GI domains of severe soilage (0.56 vs 0.87, p = 0.37) and constipation (0.28 vs 0.52, p = 0.2). Conclusion These results show that there is a subset of SSc patients with elevated anti-M3R antibodies which could be pathogenic by perturbing cholinergic neurotransmission in the GI tract. The trend observed of elevated anti-M3R antibodies with more severe GI symptoms warrants further exploration in a larger cohort of SSc. If confirmed, our findings provide mechanistic rationale for reported benefit from intravenous immunoglobulin on symptom severity in SSc GI disease. Disclosure E. Roblin: None. C. Beesley: None. R. Maclean: None. F. Ahmed: None. C. Murray: None. V.H. Ong: None. C. Denton: Consultancies; C.P.D. has received consulting fees from Arxx Therapeutics, Roche, Janssen, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Boehringer Ingelheim, CSL Behring and Acceleron. Honoraria; C.P.D. has received honoraria from Janssen, Boehringer Ingelheim, and Corbus. Grants/research support; C.P.D. has received research grants to the institution from Servier, Horizon, Arxx Therapeutics and GlaxoSmithKline.

E064 Identifying patients with pulmonary disease in a mixed connective tissue disease cohort

Abstract Background/Aims Respiratory involvement specifically interstitial lung disease (ILD) is a recognised complication of mixed connective tissue disease (MCTD), with a reported prevalence ranging from 40-78%. Surveillance for ILD in other connective tissue diseases such as systemic sclerosis is established clinical practice. Using guidelines recently published by the American College of Rheumatology (2023) we undertook a service evaluation to evaluate current practice for patients in our centre. Methods Electronic case notes were searched using key terms ‘mixed connective tissue disease’, ‘MCTD’ and ‘anti-RNP positive’ to identify patients seen between January 2021-2023. Patients identified were then compared against three MCTD classification criteria (Sharp et al, Alarcon-Sergovia et al and Kasukawa et al). To ensure a robust diagnosis, only those meeting the classification threshold on two or more criterion were included. Results 56 patients were identified however only 44 met two classification criteria and were subsequently included. Mean age was 47.3 years with 40/44 (91%) female. 28/44 (64%) had previous CT chest imaging. In the remaining 16/44 (46%), none had reported symptoms suggestive of ILD in preceding two years. 34/44 (77%) patients had previous pulmonary function testing. In those without, 1/10 had recently reported dyspnoea. 9/44 (20%) had identified MCTD-ILD of which 7/9 (30%) were on immunosuppression, 3/9 for predominant lung disease. Of those with ILD, 7/9 (78%) had had PFTs in the last year. No patients with ILD had undergone assessment for ambulatory desaturation. 7/9 (78%) patients with ILD had received specialist respiratory input, 1 had been seen in a general respiratory clinic, and in 1 case it was unknown. All patients with identified ILD who met established criteria for treatment were receiving immunosuppression. No patient met criteria for progressive fibrotic ILD. No specific disease characteristics (utilising clinical criterion from classification criteria) were demonstrated to have association with ILD (statistical analysis performed using the chi-squared test). No association was demonstrated in patients displaying anti- Ro52 and Ro60 positivity and ILD. Conclusion This evaluation has highlighted that patients with identified MCTD-ILD are being treated and monitored well. However further surveillance for pulmonary involvement both at baseline and then subsequent interval pulmonary function testing needs to improve. This may account for the lower prevalence of ILD in our MCTD cohort in comparison to the literature. Surveillance of pulmonary involvement should take place regardless of clinical disease manifestations displayed. We need to establish feasibility for ambulatory desaturation testing in those with ILD within our outpatient setting. With increasing immunomodulatory treatment available identifying patients with MCTD-ILD is imperative. Disclosure R. Benson: None. K. Mashida: None. M. Ahmad: None. L.G. Spencer: None. Z. McLaren: None. T. Barnes: None.

E067 Bimekizumab maintained efficacy responses through 52 weeks in biologic disease-modifying antirheumatic drugnaïve patients with psoriatic arthritis who were responders at week 16: results from BE OPTIMAL, a phase 3, activereference study

E067 Bimekizumab maintained efficacy responses through 52 weeks in biologic disease-modifying antirheumatic drugnaïve patients with psoriatic arthritis who were responders at week 16: results from BE OPTIMAL, a phase 3, activereference study

E062 Nailfold capillaroscopy: its application in routine clinical practice

Abstract Background/Aims Nailfold capillaroscopy (NFC) is a non-invasive tool to evaluate the structural microvascular abnormalities found in systemic sclerosis (SSc). NFC allows for the visualization of the capillary bed at the nailfold, providing valuable insights into the structure and function of these capillaries. NFC helps differentiate primary from secondary Raynaud’s phenomenon (RP). Abnormal NFC is included in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria and due to its predictive value of developing SSc is included in the Very Early Diagnosis of SSc (VEDOSS) criteria. Dudley Group NHS FT runs a consultant-led service supported by a specialty trainee where clinical review is carried out alongside NFC using video capillaroscopy. Patients can be referred to this clinic from rheumatology or respiratory colleagues. Methods We audited all patients who had attended a monthly NFC clinic between September 2021 and October 2023. We reviewed clinical letters and electronic patient record system and collected details of: demographics; immunology; clinical characteristics; reason for attending the clinic; NFC findings; and diagnosis. NFC findings were classified as normal or abnormal (to include scleroderma pattern and non-specific changes). Data was analysed using excel for individual variables and their comparison with nailfold capillaroscopy results. Results We identified 80 patients, of which 63 (79%) were females and median age was 54.5 years. ANA was positive in 64 (80%) patients, SSc and myositis immunology blots were positive in 41 (51%) and 4 (5%) respectively. Clinical characteristics included RP in 71 (89%) and interstitial lung disease (ILD) in 17 (21%). The reasons for attending the NFC clinic were categorised as: to exclude secondary causes of RP (52; 65%); to aid diagnosis of suspected SSc (23; 29%); surveillance of known SSc (5; 6%). NFC was normal in 42 patients. In the 38 patients where NFC was abnormal the clinical diagnosis was categorised as: primary RP (8; 10%); SSc spectrum of disease (17; 21%); and another CTD (20; 25%). Of patients with SSc spectrum of disease: 24% (4/17) had a diagnosis of VEDoSS; 47% (8/17) Limited Cutaneous SSc; and 29% (5/17) Diffuse SSc. The presence of RP and ANA was not significantly different in patients with abnormal NFC. There was a non-significant association between the presence of ILD and abnormal NFC. 9/17 (52%) patients with ILD had an abnormal NFC compared to 18/63 (29%) patients without ILD (p = 0.059). Conclusion NFC is a simple procedure in conjunction with a clinical review to enhance the early diagnosis of SSc and exclusion of secondary Raynaud’s. It supports education and training as a tool for learning as being part of the curriculum. Disclosure S.A. Tabassum: None. K.M.J. Douglas: None. E. Udeshika: None.

Tumor necrosis factor alpha induced protein 3, interleukin 10, tumor necrosis factor alpha, and interleukin 17F genes polymorphisms in Algerian patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation. Its pathogenesis involves immunological, genetic, and environmental factors. We investigate the association between Tumor Necrosis Factor α Protein 3 (TNFAIP3), Interleukin 10 (IL10), Tumor Necrosis Factor α (TNF α), and Interleukin 17F (IL17F) polymorphisms with susceptibility to RA. 191 patients with RA diagnosed according to the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification and 190 healthy subjects were recruited. Rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and C-reactive protein (CRP) were measured. Genotyping of the polymorphisms was performed by real-time PCR. Analysis of the allelic frequencies of TNFAIP3 showed a positive association OR (95% CI) = 1.46 (1.01-2.09); p = 0.04, but failed to meet the criteria of significance after Bonferroni Correction. The genotypic and allelic distribution of the IL10, IL17F, and TNFα showed no significant difference when comparing the RA group with controls. Furthermore, the genotype codominant model shows a moderate positive association in the presence of ACPA (OR (95% CI) = 2.82 (1.22-6.24); p = 0.01. None of the polymorphisms studied was associated with RF and CRP production. Our results show that there is a tendency for the AG genotype of IL10-1082 to be associated with the production of ACPA in patients with RA. None of the variants studied were associated with RA susceptibility in Algerians.

Classification of rheumatoid arthritis: is it time to revise the criteria?

Classification criteria have been developed for rheumatoid arthritis (RA) and other rheumatic diseases in order to gather a homogeneous patient population for clinical studies and facilitate the timely implementation of therapeutic measures. Although classification criteria are not intended to be used for diagnosis, they are frequently used to support the diagnostic process in clinical practice, including clinical decision-making. The 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for RA are capable of identifying the majority of symptomatic patients with RA already in the earliest stages of the disease who are not yet showing radiographic changes. These patients will also profit from the early implementation of therapy with disease-modifying antirheumatic drugs (DMARDs). However, the risk of misclassification is higher as compared with the former 1987 ACR criteria, which were considerably less sensitive to the recognition of patients with early RA. Of note, the presence of rheumatoid factors (RFs) and anticitrullinated protein antibodies (ACPAs) has been attributed equal weight in the 2010 ACR/EULAR criteria and may contribute up to 50% of the score needed for being classified as RA. However, while ACPAs have been proven to be the most specific serological markers of RA, the specificity of RF is moderate, especially at lower titres. This may lead to the misclassification of RF-positive patients and, consequently, the unjustified implementation of DMARD therapy. Therefore, issues arise on how comprehensive the criteria should be and whether they should be updated and adapted to findings from the past two decades that might increase both their specificity and sensitivity.

Efficacy and Safety of Secukinumab in US Patients with Psoriatic Arthritis: A Subgroup Analysis of the Phase 3 FUTURE Studies.

The aim of this work is to evaluate secukinumab vs. placebo in a challenging-to-treat and smaller US patient subpopulation of the international FUTURE 2-5 studies in patients with psoriatic arthritis (PsA). Data were pooled from US patients enrolled in the phase 3 FUTURE 2-5 studies (NCT01752634, NCT01989468, NCT02294227, and NCT02404350). Patients received secukinumab 300 or 150 mg with subcutaneous loading dose, secukinumab 150 mg without subcutaneous loading dose, or placebo. Categorical efficacy and health-related quality-of-life (QoL) outcomes and safety were evaluated at week 16. Subgroup analyses were performed based on tumor necrosis factor inhibitor (TNFi) status and body mass index (BMI). For hypothesis generation, odds ratios (ORs) for American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment were estimated using logistic regression without adjustment for multiple comparisons. Of 2148 international patients originally randomized, 279 US patients were included in this pooled analysis. Mean BMI was > 30 kg/m2 and 55.2% had prior TNFi treatment. ORs for ACR20/50/70 significantly favored patients receiving secukinumab 300 mg and 150 mg with loading dose vs. placebo (P < 0.05), but not those receiving secukinumab 150 mg without loading dose vs. placebo. For PASI75, ORs favored all secukinumab groups over placebo (P < 0.05); for PASI90 and PASI100, only the secukinumab 300-mg group was significantly favored over placebo (P < 0.05). In this challenging sub-population of US patients with PsA, secukinumab provided rapid improvements in disease activity and QoL. Patients with PsA and active psoriasis might benefit more from secukinumab 300mg than 150mg.

American College of Rheumatology (ACR) and Food and Drug Administration (FDA) Summit: Summary of the Meeting May 17-18, 2022.

On May 17-18, 2022, the ACR and the FDA co-sponsored a public meeting to address topics of mutual interest and importance in assessing long-term safety and clinical efficacy, as well as novel approaches to clinical trials in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). During the two-day consensus-building summit, rheumatologists, other health care professionals, and FDA staff provided a broad perspective on current clinical development challenges and potential approaches to address them. Key takeaways are summarized in this document, including issues related to innovative clinical trial designs, use of novel outcome measures such as magnetic resonance imaging (MRI) and patient-reported outcomes (PROs), and use of innovative approaches to collecting data including registries and digital health technology (DHT).

Knowledge of and stated adherence to the 2020 ACR Guideline for Gout Management: Results of a survey of US rheumatologists.

This report evaluates rheumatologists' stated adherence to and agreement with the 2020 American College of Rheumatology (ACR) Guideline for the Management of Gout. A 57-item questionnaire was administered to US rheumatologists. Stated adherence scores were based on several guideline recommendations reported to be followed by rheumatologists in practice, whereas stated agreement scores were based on whether respondents always followed the recommendations. All 201 rheumatologists completed the questionnaire. The mean overall stated adherence score was 11.5 (maximum: 15), whereas the mean overall stated agreement score was 7.7 (maximum: 14). Less experienced rheumatologists (≤8 years; n=49) were likely to claim adherence to more individual ACR recommendations than those with more experience (>8 years; n=152; mean stated adherence score: 12.3 vs 11.3; P ≤ 0.05). Rheumatologists who claimed to see ≤75 patients with gout in 6 months (n=66) had a mean stated adherence score of 12.1 versus 11.2 for those who claimed to have seen >75 patients (P ≤ 0.05). Approximately 78% of rheumatologists claimed to follow the guideline for initiating urate-lowering therapy (ULT), and 89% were likely to prescribe allopurinol as a first-line ULT. Claimed adherence to recommendations for dosing was lower (febuxostat, 43%; allopurinol, 39%). Rheumatologists from academic settings were more likely to prescribe an interleukin-1 inhibitor for gout flares. The self-reported practice of the surveyed US rheumatologists was generally concordant with the 2020 ACR Guideline for the Management of Gout. However, there were gaps in guideline knowledge and stated adherence among rheumatologists, mainly concerning the dosing of treatment regimens.

Validity and diagnostic overlap of functional somatic syndrome diagnoses

ObjectiveWe present the first study that investigates the validity and the diagnostic overlap of the three main functional somatic syndrome (FSS) diagnoses, i.e. chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), irrespective of help-seeking behaviour or diagnostic habits, and irrespective of differences in diagnostic thresholds for chronicity or symptom interference. MethodsThis cross-sectional analysis was performed in 89,781 participants of the general-population cohort Lifelines. Diagnostic criteria for CFS (Centers for Disease Control and Prevention), FM (American College of Rheumatology) and IBS (Rome IV) were assessed by questionnaire. Additional items were added to enable studying the effects of differences in thresholds for minimum symptom chronicity (varying from three for FM to six months for CFS and IBS), and symptom interference (required for CFS but not for FM and IBS). ResultsThe diagnostic criteria were met by 3.1% for CFS, 6.6% for FM, and 5.5% for IBS participants. The number of participants that met criteria for all three diagnoses was 45 times higher than what would have been expected based on chance. After alignment of the chronicity and symptom interference criteria to circumvent differences in diagnostic thresholds, the overlap between diagnoses increased to 152 times. Furthermore, there was a similar pattern of symptom occurrence, particularly for those fulfilling diagnostic criteria for CFS and FM. ConclusionThe diagnostic overlap of different FSS was much higher than would be expected by chance, and substantially increased when FSS were more chronic and serious in nature.

The Role of Etanercept in Controlling Clinical and Radiological Progression in Rheumatoid Arthritis: A Systematic Review.

Etanercept (ETN) is a disease-modifyinganti-rheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA) that works as a tumor necrosis factor inhibitor (TNF inhibitor) by blocking the effects of naturally occurring TNF. This review will evaluate the effect of ETN as a monotherapy or combination therapy with methotrexate (MTX) in the treatment of RA. This systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. A systematic search was done on PubMed and Google Scholar from 1999 to 2023. Predefined eligibility criteria were set for selected studies, which include: free full-text articles published; randomized control trials (RCTs); systematic reviews and meta-analyses; and observational studies in a patient with RA treated with ETN as initial therapy or as an add-on to conventional disease-modified therapy. Hence, the data had been extracted, and a quality assessment of each study was done by two individual authors. When comparing patients who received 15-25 mg of MTX with those who also received 25 mg of ETN in combination, 71% achieved American College of Rheumatology 20 (ACR20) by 24 weeks, compared to 27% in the MTX and placebo groups (p<0.001), and 39% achieved American College of Rheumatology 50 (ACR50), compared to 3% in the placebo + MTX group (p<0.001). Low disease activity (DAS 28)was more common in patients who had both MTX and ETN (64.5% with DAS <2.4 and 56.3% with DAS 28 <3.2) compared to patients who received only one medication (44.4% with DAS <2.4 and 33.2% with DAS 28 <3.2 for ETN and 38.6% with DAS <2.4 and 28.5% with DAS 28 <3.2 for MTX, with P<0.01). ETN demonstrated smaller changes from baseline in the modified Sharp score (TSS) and erosion scores (ES) at 12 months and two years, as well as a decreased change in the ES score at one year (with a trend of P value = 0.06 for the TSS score), in comparison to those receiving DMARD. Reactions at the injection site (42% vs. 7%, P<0.001) were the only events that occurred significantly more frequently in the ETN plus-MTX group. Combining ETN and MTX appears to help control RA symptoms by decreasing the American College of Rheumatology (ACR) response and DAS score, as well as halting the disease's progression on X-rays. The most common adverse effects were reactions to ETN administered alone at the injection site, likely because of patient awareness of the treatment received. There was also concern about tuberculosis and malignancy, but no recent data is available. Therefore, a larger clinical trial with longer follow-up is required to ascertain long-term safety and benefits.

Imaging Innovations in the Screening, Diagnosis, and Monitoring of Systemic Autoimmune Disease-Related Interstitial Lung Disease

Interstitial lung disease (ILD) is a common and serious complication of systemic autoimmune rheumatic diseases (SARD). The prevalence and prognosis of ILD vary depending on the type and severity of the underlying SARD. Recently, two drugs have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ILD in SARD, and the American College of Rheumatology (ACR) has issued guidelines for the screening and monitoring of these patients. Therefore, it is essential to detect and manage ILD in SARDs as early as possible. High-resolution CT of the chest is the current gold standard test for diagnosis of ILD, yet, it is not uniformly performed as an initial diagnostic test. This review discusses the latest advances in imaging techniques for the diagnosis, assessment, and follow-up of SARD-ILDs.