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OBJECTIVES: This study contributes to the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)s effort to define difficult-to-treat PsA (D2T-PsA), leveraging insights of healthcare professionals who are GRAPPA members. The primary objective is to inform GRAPPAs D2T PsA project, ensuring the consensus definition reflects clinical experience and expertise. METHODS: An online survey was conducted among GRAPPAs healthcare professionals managing PsA patients. The survey covered demographic details, structured questions, and open-ended queries to gather comprehensive insights into the experts viewpoints. RESULTS: About 223 physicians completed the survey, comprising 179 (80.2%) rheumatologists and 40 (17.9%) dermatologists. The majority, 184 (82.5%), favoured establishing distinct definitions for D2T-PsA and complex-to-manage PsA (C2M-PsA). Furthermore, 202 (90.5%) supported a definition that includes objective inflammation signs (clinical, laboratory, imaging, among others). However, opinions varied on the criteria for prior treatment failures, with most (93, 41.7%) favouring a definition that includes at least one conventional synthetic disease-modifying anti-rheumatic drug and two or more biological- or targeted-synthetic-DMARDs with different mechanisms of action. CONCLUSION: The survey reveals a majority opinion among GRAPPA experts favouring the differentiation between D2T-PsA and C2M-PsA, and the inclusion of objective inflammatory markers in these definitions. However, there is less than 50% agreement on the specific treatment failure criteria, particularly regarding the number of therapies needed to classify PsA as D2T. These findings suggest a need for continued discussion to reach a more unified approach in defining D2T-PsA, reflecting the complexity of the condition.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), not only causes significant intestinal inflammation but also leads to extra-intestinal manifestations such as spondyloarthritis (SpA). Although the efficacy of tumor necrosis factor (TNF) inhibitors has been reported for IBD-related SpA, some cases still encounter treatment failure, highlighting the need for novel therapeutic alternatives. Recently, Janus kinase inhibitors have demonstrated their efficacy in IBD and SpA, yet their impact on CD-related SpA remains unexplored. Here we present the first two cases of CD-related peripheral SpA successfully treated with upadacitinib. Additionally, our literature review identified a reported case of CD-related peripheral SpA treated with tofacitinib. All cases achieved clinical remission of both CD and peripheral SpA with Janus kinase inhibitors, and no adverse events or disease relapses were reported during the observation period. Our cases and literature review highlight the promising potential of Janus kinase inhibitors as a novel treatment not only for intestinal inflammation of CD, but also for CD-related peripheral SpA. [ABSTRACT FROM AUTHOR]

Introduction: Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening. Methods: Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10 (PsA only) mg twice daily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction. Results: PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1 tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs. Conclusions: In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history. Trial Registration: ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616. [ABSTRACT FROM AUTHOR]

Clinical research advances medical knowledge and improves healthcare outcomes. However, disparities in research participation hinder progress. The Unmet Research Needs in Spondyloarthritis Conference IV highlighted critical insights and strategies to enhance equity in clinical research. Talks focused on engaging underrepresented communities and addressing disparities in rheumatic diseases, particularly spondyloarthritis (SpA), to ensure research results are generalizable and inclusive. Disparities in SpA management, such as greater back pain severity among Black and Hispanic Americans and sex-based differences in pain management, emphasize the need for equitable research. Dr. Elizabeth Ferucci discussed the racial disparities in rheumatologic care, highlighting the importance of early access to rheumatologists and culturally informed primary care to improve outcomes. Dr. Hani El-Gabalawy's talk on engaging Indigenous communities stressed the importance of community consent and reciprocal benefits. Dr. Sarfaraz Hasni's presentation on mitigating disparities in research participation underscored the need for inclusive practices and strategies to promote diverse representation. Finally, Dr. Edith Williams emphasized institutional approaches to fostering equity, including diverse recruitment practices and institutional review board alignment with diversity priorities. Strategies to enhance equity in clinical research include community engagement, addressing logistical barriers to participation, and ensuring diverse research teams. These approaches can dismantle barriers for underrepresented communities, making research more accessible and reflective of the broader population. The SpA research community must commit to creating structures that foster inclusivity, ensuring medical advancements benefit all populations, especially historically underrepresented groups. The principles and strategies proposed serve as a roadmap for achieving equity in SpA research. [ABSTRACT FROM AUTHOR]

Among patients with axial spondyloarthritis (axSpA), persistent pain remains a critical unmet need. In this review, we discuss the prevalence of chronic pain and fibromyalgia in patients with axSpA and examine the existing knowledge on the pathophysiology of chronic pain in SpA, osteoarthritis, and rheumatoid arthritis. Finally, we discuss the specific unmet needs that must be addressed to improve long-term outcomes in axSpA, specifically those that will improve chronic pain in this patient population. [ABSTRACT FROM AUTHOR]

Is axial spondyloarthritis (axSpA) one disease or does it comprise multiple types? If the latter, how do we define those types--through clinical or imaging features, HLA-B27 status, or by other immunologic features? Data comparing disease outcomes for individuals with nonradiographic vs radiographic axSpA, or for male vs female patients, demonstrate distinctions. So then, how should we define endotypes? Endotypes are known as the subtype of a health condition defined by a functional or pathophysiologic function. Here, we review the endotypes used for defining rheumatoid arthritis, asthma, and psoriatic arthritis. Taking the lessons learned from these diseases, we discuss how they can be applied to defining endotypes in axSpA. A key unmet need for axSpA is access to affected tissues for interrogation of their pathologic mechanisms, from which tissue-specific endotypes can be defined. These tissue-based features should be combined with clinical data and imaging to inform classification criteria in the future. [ABSTRACT FROM AUTHOR]

Objective. Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. Methods. Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability (κ) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement (κ) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models. Results. In exercises I, II, and III, mNY κ were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant κ increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not (κ = 0.00, 95% CI -0.10 to 0.10; P = 0.99). Conclusion. Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of immune-mediated arthritis, which comprises rheumatoid arthritis and spondyloarthritis. This review outlines the key findings and advancements in scRNA-seq studies focused on the pathogenesis of autoimmune arthritis and its clinical application. In rheumatoid arthritis, scRNA-seq has elucidated the heterogeneity among synovial fibroblasts and immune cell subsets in inflammatory sites, offering insights into disease mechanisms and the differences in treatment responses. Various studies have identified distinct synovial fibroblast subpopulations, such as THY1+ inflammatory and THY1- destructive fibroblasts. Furthermore, scRNA-seq has revealed diverse T cell profiles in the synovium, including peripheral helper T cells and clonally expanded CD8+ T cells, shedding light on potential therapeutic targets and predictive markers of treatment response. Similarly, in spondyloarthritis, particularly psoriatic arthritis and ankylosing spondylitis, scRNA-seq studies have identified distinct cellular profiles associated with disease pathology. Challenges such as cost and sample size limitations persist, but collaborative efforts and utilization of public databases hold promise for overcoming these obstacles. Overall, scRNA-seq emerges as a powerful tool for dissecting cellular heterogeneity and driving precision medicine in immune-mediated arthritis. [ABSTRACT FROM AUTHOR]

Background and objectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease involving the spine, peripheral joints, and entheses. Functional impairment of regulatory T cells (Treg) is linked to inflammatory diseases, but limited data is available regarding Treg involvement in axSpA. Treg stability refers to their ability to maintain their functions and characteristics in pro-inflammatory environments. EZH2 and phosphorylated STAT5 (pSTAT5) play a critical role in maintaining Treg stability. We aimed to characterize Treg stability in patients with axSpA. Methods: Peripheral blood mononuclear cells (PBMCs) from axSpA patients, either naïve from targeted therapy or treated by TNF inhibitors (TNFi), and from healthy donors (HD), were freshly isolated. Expression of stability (EZH2, pSTAT5) and suppressive (TNFR2 and CD39) markers by Treg was analyzed by flow cytometry. Results: EZH2 expression by Treg was decreased in axSpA patients as compared to HD (p<0.01). Mechanistic study showed that inhibition of EZH2 attenuated Treg differentiation and suppressive phenotype in vitro. EZH2 was predominantly expressed by highly suppressive TNFR2+ and CD39+ Treg. Additionally, axSpA patients also exhibited a reduced frequency of pSTAT5+ Treg compared to HD (p<0.05), and pSTAT5+ Treg frequency increased at 3 months of TNFi treatment compared to baseline (p<0.05). This last result suggested a restoration of Treg stability upon TNFi treatment. Conclusion: By highlighting a deficient expression of EZH2 and pSTAT5 by Treg, we revealed an impaired Treg stability in axSpA. Deciphering the pathways influenced by these molecules is necessary to assess the potential therapeutic benefits of restoring Treg stability in axSpA. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to establish a correlation between fecal calprotectin levels (FC) and intestinal inflammation in patients with spondyloarthritis without inflammatory bowel disease. Methods: A total of 180 SpA patients were included in the study of them 20.6% required Digital chromoendoscopy (DCE). FC, C-reactive protein (CRP), HLA-B*27 and clinical indices were assessed. Results: Positive fecal calprotectin (PFC) and high fecal calprotectin (HFC) levels were observed in 27.0% and 16.0% of patients, respectively. HFC correlated with a Bath Ankylosing Spondylitis Functional Index (BASFI) score > 4.0 (p = 0.036) and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > 4.0 (p = 0.047). Loss of vascular pattern in the ileum (LVPI) was observed in approximately 70.0% of patients (p = 0.005), which was associated with PFC and abdominal bloating (p = 0.020). LVPI was also linked to microscopic inflammation (p = 0.012) and PFC with abdominal pain (p = 0.007). HFC was significantly associated with alterations in the ileal mucosa (p = 0.009) and LVPI (p = 0.001). Additionally, HFC and diarrhea were associated with LVPI in 27.3% of patients (p = 0.037) and with erosions in the ileum (p = 0.031). Chronic ileal inflammation correlated with HFC (p = 0.015), ASDAS-CRP > 2.1 (p = 0.09), LVPI (p = 0.001), and villous atrophy (p = 0.014). Factorial analysis of mixed data (FAMD) identified significant associations between micro/macroscopic changes in chronic inflammation and HFC (CC = 0.837); increased levels of CRP and microscopic acute inflammation (CC = 0.792); and clinical activity scores of ASDAS-CRP and BASDAI (CC = 0.914). Conlusions: FC levels were significantly elevated in patients with SpA, particularly those with LVPI, suggesting their potential as a valuable biomarker for managing SpA when joint manifestations coincide with ileal villous atrophy. This indicates a shared immune pathway linked to chronic gut damage. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) vaccines aroused concerns about the risk of flares and adverse events in inflammatory arthritis (IA) since the vaccine clinical trials did not specifically investigate this subset of patients. Methods: A systematic literature review and meta-analysis to summarize the data on joint disease flare and adverse events following immunization (AEFI). Two researchers independently evaluated the literature on Pubmed, Scopus, and EMBASE databases from 22nd March 2020 to 30th September 2023. A random-effects model was used to pool odds ratios (OR) (with 95% CI) for the risk of joint disease flares and adverse events. Subgroup analyses were performed to evaluate the risk of disease flare between different IA and adverse events. Heterogeneity was assessed by I2 statistic. Results: A total of 9874 IA patients were included in the study: 6579 (66.6%) patients affected by RA and 3295 (33.4%) spondyloarthritis (SpA). The overall rate of flares was higher in RA vs. SpA (9.1% vs. 5.3%). However, the pooled estimated analysis showed no increased risk of joint disease flare following COVID-19 vaccination in patients affected by RA vs. SpA [OR 0.88, 95% CI: 0.77-1.00]. Furthermore, a subgroup analysis showed an increased risk of joint flares in psoriatic arthritis (PsA) patients vs. RA [OR 0.79, 95% CI: 0.68-0.93, p=0.004]. The pooled estimated analysis revealed no increased risk of AEFI in patients with RA vs. SpA [1.02, 95% CI: 0.63-1.65]. Conclusions: Our meta-analysis summarized the current evidence on joint disease flares and COVID-19 vaccine-associated AEFI in IA patients. Pooled analysis showed an increased risk of disease flares in PsA vs. RA patients. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) describes a group of diseases characterized by chronic inflammation in the spine and peripheral joints. While pathogenesis is still unclear, proinflammatory gut-derived immune cells have been identified in the joints of SpA patients. We previously identified an enriched population of integrin-expressing cells in the joints of SpA patients. Entry of gut-derived cells into joints may be mediated by these integrins. In the current study, we used the SKG murine model of SpA to study the impact of integrin blockade. Mice were injected with antibodies against the integrin α4β7 or the β7 monomer twice a week. Treatment with antibodies against α4β7 reduced disease severity in curdlan-injected SKG mice, with disease scores being comparable between treatment initiation times. Targeting the β7 monomer led to reduced arthritis severity compared to targeting the α4β7 dimer. Treatment with antibodies against α4β7 or β7 decreased expression of these integrins in CD4+ T cells, with the frequency of αE+β7+ T cells in the spleen and lymph nodes correlating with disease severity. In summary, we showed that integrin blockade showed potential for ameliorating disease in a murine model of SpA, lending support for further studies testing integrin blockade in SpA. [ABSTRACT FROM AUTHOR]

Objective To assess the fracture risk of patients with spondyloarthritis (SpA) using the Fracture Risk Assessment Tool (FRAX) and to conduct related risk factor analysis, exploring the applicability of different FRAX models in detecting SpA patients. Methods A total of 130 patients with SpA were enrolled as the patient group, and 130 healthy individuals undergoing health examinations during the same period were selected as the control group. FRAX was used to evaluate the probability of major osteoporotic fractures (MOF) and hip fractures (HF) in the next 10 years for both groups. Additionally, modified FRAX models were employed to assess fracture risk in the patient group, comparing their similarities and differences. Results Regardless of whether bone mineral density (BMD) was included, the risks of MOF and HF in the patient group were higher than those in the control group. When assessed using FRAX without BMD, the MOF risk of SpA patients was significantly higher at 1.57±0.87 than that in the control group at 1.36±0.57 (P<0.001). The HF risk was significantly higher at 0.22±0.43 than that in the control group at 0. 13±0.13 (P=0.019). When assessed using FRAX with BMD, the MOF risk was significantly higher at 2.60±5.10 than that in the control group at 1.37±0.47 (P=0.007). The HF risk was significantly higher at 1. 11±4.83 than that in the control group at 0. 11±0.11 (P=0.019); 2 When assessed SpA patients using the FRAX model without BMD, whether the option of using SpA instead of rheumatoid arthritis (RA) (SpA-FRAX) was selected, the result reached the same intervention threshold. No MOF patients and only 2 HF patients (1.5%) reached the intervention threshold. The detection efficiency improved when assessed using FRAX with BMD, with 2 MOF patients (1.5%) and 9 HF patients (6.2%) reaching the intervention threshold. When using the SpA instead of RA option (SpA-FRAX-BMD), the MOF detection result remained the same with 2 patients (1.5%), but the HF detection result increased to 13 patients (9.2%); ③ The femoral neck BMD in the patient group was significantly lower than that in the control group, and 91% of patients had 25-hydroxyvitamin D3 levels below normal; The result of multiple regression analysis showed that lumbar BMD and blood phosphorus were negatively correlated with FRAX assessment of HF and MOF in SpA patients, while the CT grade of the left sacroiliac joint was positively correlated with them. ẞ collagen degradation products were positively correlated with the risk of MOF. Conclusion The risk of fractures in SpA patients is higher than that in healthy people. When FRAX is used to assess the risk of fractures in SpA patients, the detection efficiency is higher when BMD is included than when it is not. For patients who have already undergone BMD testing, combining the RA option in the corrected FRAX may improve the detection efficiency of FRAX alone. Lumbar BMD, blood phosphorus, left sacroiliac joint lesion grading, and ẞ collagen degradation products are factors that affect the risk of fractures in SpA patients. [ABSTRACT FROM AUTHOR]

Objective The Berlin algorithm was developed to help diagnose axial SpA (axSpA), but new studies suggest some features typical of SpA are less specific than previously assumed. Furthermore, evidence is lacking for other SpA subtypes (e.g. peripheral SpA). We aimed to review the evidence on the performance of SpA features for diagnosing each SpA subtype. Methods We conducted a systematic literature review of studies reporting the diagnostic performance of one or more SpA features in patients with suspected SpA. The external reference was the rheumatologist's diagnosis of SpA. Meta-analysis was performed, separately for each SpA subtype, to estimate pooled sensitivity, specificity and positive and negative likelihood ratios (LR+ and LR−, respectively). Meta-regression assessed the effect of covariates (e.g. feature's prevalence) on each feature's performance. Results Of 13 844 articles screened, 46 were included. Sacroiliitis on MRI, damage on pelvic radiographs and elevated CRP had the best balance between LR+ and LR− (LR+ 3.9–17.0, LR− 0.5–0.7) for diagnosing axSpA. HLA-B27 had an LR+ lower than anticipated (LR+ 3.1). Inflammatory back pain (IBP) had a low LR+ (LR+ ≈1), but substantially decreased the likelihood of axSpA when absent (LR− 0.3). Conversely, peripheral features and extramusculoskeletal manifestations showed a high LR+ (LR+ 1.6–5.0), but were as common in axSpA as non-axSpA (LR− ≈1). The specificity of most features was reduced in settings when these were highly prevalent. Limited data precluded a detailed analysis on diagnosing other SpA subtypes. Conclusion Imaging features and CRP have good diagnostic value for axSpA. However, the specificity of other features, especially HLA-B27 and IBP, is lower than previously known. [ABSTRACT FROM AUTHOR]

Objectives The aim of our study was to identify the potential distinct phenotypes within a broad SpA population. Methods We conducted a cross-sectional study using the REGISPONSER registry, which has data from 31 specialist centres in Spain, including patients with SpA who have fulfilled the ESSG criteria. A latent class analysis (LCA) was performed to identify the latent classes underlying SpA according to a set of predefined clinical and radiographic features, independently of expert opinion. Results In a population of 2319 SpA patients, a five-classes LCA model yielded the best fit. Classes named 'Axial with spine involvement' and 'Axial with isolated SI joint involvement' showed a primarily axial SpA phenotype defined by inflammatory back pain and high HLA-B27 prevalence. Patients in class 'Axial + peripheral' showed a similar distribution of manifest variables to previous classes but also had a higher likelihood of peripheral involvement (peripheral arthritis/dactylitis) and enthesitis, therefore representing a mixed (axial and peripheral) subtype. Classes 'Peripheral + psoriasis' and 'Axial + peripheral + psoriasis' were indicative of peripheral SpA (and/or PsA) with high likelihood of psoriasis, peripheral involvement, dactylitis, nail disease, and low HLA-B27 prevalence, while class 'Axial + peripheral + psoriasis' also exhibited increased probability of axial involvement both clinically and radiologically. Conclusion The identification of five latent classes in the REGISPONSER registry with significant overlap between axial and peripheral phenotypes is concordant with a unifying concept of SpA. Psoriasis and related features (nail disease and dactylitis) influenced the phenotype of both axial and peripheral manifestations. [ABSTRACT FROM AUTHOR]

Objective: To assess the unmet needs of South Africans with axial spondyloarthritis (axSpA) focusing on the patient journey, functional disability, and health-related quality of life. Methods: One hundred forty-six South African axSpA patients completed the International Map of Axial Spondyloarthritis (IMAS) online survey. Patient journey, functional disability, activities of daily living, and psychological stress were analyzed in relation to socio-demographic characteristics, disease activity, diagnostic delay, extra-musculoskeletal manifestations, and drug therapy. Results: Majority were female (82.2%) and Caucasian (89.7%) and the mean age of participants, age at onset of initial symptoms, and diagnostic delay were 44.7, 26.7, and 10.8 years, respectively. Participants reported a mean of 3.4 visits to healthcare professionals prior to a definitive diagnosis of axSpA, mostly made by rheumatologists (77.9%). Active disease (BASDAI ≥ 4) was reported by 87%, 69.9% suffered from psychological distress (general health questionnaire-12 score ≥ 3), and more than two-thirds suffered functional limitations in daily, personal, and social activities. Multivariable logistic analysis showed that active disease was more common in females [OR (95% CI) = 4.3 (1.2–15.2)] and was associated with greater functional limitation [OR (95% CI) = 1.1 (1.0–1.2)]. Conclusion: Of all the regions assessed in the IMAS (n = 5557 participants, 27 countries), South Africans reported the longest delay in diagnosis. The South African patient journey depicts a process burdened with diagnostic challenges and delays, coupled with patients experiencing significant personal and social limitations. These results emphasize the urgent need to establish local diagnostic and treatment guidelines for axSpA in South Africa, to reduce diagnostic delay, and to control disease activity associated with functional limitation in axSpA. Key Points • Axial spondyloarthritis (axSpA) in South Africans is associated with significant limitations in physical, mental, and social functioning. • First study to describe the unmet needs of South African patients with axSpA. [ABSTRACT FROM AUTHOR]

Secukinumab is a monoclonal antibody directed against interleukin-17 approved for the treatment of psoriasis and spondyloarthritis. The favorable oncological profile of secukinumab in patients with a history of malignancy has been shown in patients with psoriasis. However, systematic data to this regard have not been published yet for patients with spondyloarthritis. The objective of the present study was to evaluate the oncological safety of secukinumab in patients affected by this group of diseases. We performed a retrospective study in which we identified from our cohort patients with spondyloarthritis treated with secukinumab and with a history of malignancy. These patients' baseline demographic, treatment, rheumatological, and oncological data were collected. The neoplastic outcome (i.e., cancer recurrence or progression) after secukinumab start was then analyzed. Our study included 22 patients with spondyloarthritis. The most frequently reported oncological diagnosis was breast cancer (9 [41%] patients). Secukinumab was started after a median of 24 months following cancer diagnosis. At this time point, all but three patients were in oncological remission. No case of cancer relapse or progression was recorded over a median follow-up of 30 months. In the largest cohort reported to date to this regard, secukinumab was not associated with oncological recurrence or progression in patients with spondyloarthritis with a history of malignancy. Secukinumab may, therefore, represent a safe option in this clinical scenario. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the detection of erosion, sclerosis and ankylosis using 1 mm 3D T1-weighted spoiled gradient echo (T1w-GRE) MRI and 1 mm MRI-based synthetic CT (sCT), compared with conventional 4 mm T1w-TSE. Materials and methods: Prospective, cross-sectional study. Semi-coronal 4 mm T1w-TSE and axial T1w-GRE with 1.6 mm slice thickness and 0.8 mm spacing between overlapping slices were performed. The T1w-GRE images were processed into sCT images using a commercial deep learning algorithm, BoneMRI. Both were reconstructed into 1 mm semi-coronal images. T1w-TSE, T1w-GRE and sCT images were assessed independently by 3 expert and 4 non-expert readers for erosion, sclerosis and ankylosis. Cohen's kappa for inter-reader agreement, exact McNemar test for lesion frequencies and Wilcoxon signed-rank test for confidence in lesion detection were used. Results: Nineteen patients with axial spondyloarthritis were evaluated. T1w-GRE increased inter-reader agreement for detecting erosion (kappa 0.42 vs 0.21 in non-experts), increased detection of erosion (57 vs 43 of 152 joint quadrants) and sclerosis (26 vs 17 of 152 joint quadrants) among experts, and increased reader confidence for scoring erosion and sclerosis. sCT increased inter-reader agreement for detecting sclerosis (kappa 0.69 vs 0.37 in experts) and ankylosis (0.71 vs 0.52 in non-experts), increased detection of sclerosis (34 vs 17 of 152 joint quadrants) and ankylosis (20 vs 13 of 76 joint halves) among experts, and increased reader confidence for scoring erosion, sclerosis and ankylosis. Conclusion: T1w-GRE and sCT increase sensitivity and reader confidence for the detection of erosion, sclerosis and ankylosis, compared with T1w-TSE. Clinical relevance statement: These methods improve the detection of sacroiliac joint structural lesions and might be a useful addition to SIJ MRI protocols both in routine clinical care and as structural outcome measures in clinical trials. [ABSTRACT FROM AUTHOR]

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Background: Pentraxin 3 (PTX3) is suggested to be both a marker of inflammation and cardiovascular (CV) risk. Aim: The aim of this study was to identify and compare the role of PTX3 in assessment of disease activity and CV risk, in patients with chronic inflammatory diseases, rheumatoid arthritis (RA), and spondyloarthritis (SpA). Methods: The study group consisted of 235 patients (109 RA, and 126 SpA). The following parameters were assessed: disease activity, traditional CV risk factors, carotid intima media thickness (cIMT), PTX3 plasma concentration. Results: The median (IQR) PTX3 concentration was higher in RA than SpA patients [3.44 (2.56– 4.79) vs 2.51 (1.72– 3.62) ng/mL, p< 0.001]. The mean (SD) cIMT value was higher in RA than SpA patients [0.85 (± 0.21) vs 0.75 (± 0.27) mm, p=0.02]. Atherosclerotic plaques were observed in similar number of patients with RA (31, 28.4%) and SpA (34, 27%) (NS). The PTX3 level was significantly higher in RA patients with moderate/high vs low disease activity, and in patients with presence vs no atherosclerotic plagues. In patients with RA correlations were found between PTX3 and disease activity parameters: C-reactive protein, erythrocyte sedimentation rate, tender joint count, disease activity score in 28 joints, white blood cell count (WBC). In multiple linear regression analysis, significantly positive association was confirmed for PTX3 and WBC. No significant relationships were found in patients with SpA. Conclusion: The results of this study point to the dual role of PTX3 in patients with RA, as a biomarker of disease activity, and as a marker of CV complications risk. [ABSTRACT FROM AUTHOR]

Introduction: There are several treatment controversies that have emerged in spondyloarthritis and psoriatic arthritis. These are related to the nature of the conditions as well as to the use of medications. Areas covered: This review, which included a search of PubMed database as well as the references within the articles provides an overview of the nature of spondyloarthritis, controversy over the inclusion of psoriatic arthritis (PsA) as a peripheral spondyloarthritis, and a summary of current treatments for both PsA and axial spondyloarthritis (axSpA), with special emphasis on targeted therapy. The review highlights the differences in response to certain medications, particularly biologic therapy and summarizes the randomized controlled trials in psoriatic arthritis and axial spondyloarthritis providing data about the responses in table format. Expert opinion: There is a need for better outcome measures in axSpA. Currently, the measures are subjective. Imaging may be more appropriate but there is a need for research into the reliability and responsiveness of imaging techniques. In PsA, there may also be better response measures and research into the reliability and responsiveness of available measures is underway. There is also a need for novel therapies as well as biomarkers for response in both diseases. [ABSTRACT FROM AUTHOR]

Objective SpA and PsA represent two frequent inflammatory rheumatic disorders characterized by an increased burden on quality of life due to the association of several comorbidities, especially cardiovascular disease (CVD). The estimated prevalence of CVD ranges from 12 to 19% and differs between the two diseases, however, the incidence of CVD is not completely known. We aimed to systematically review the literature and perform a meta-analysis of controlled observational studies to assess the incidence rate of CVD over time in SpA and PsA. Methods We performed a systematic literature review (SLR) of longitudinal studies with a study period of at least 5 years, including SpA/PsA patients and general population. The main outcome was the occurrence of CVD, including ischaemic heart disease, stroke and death from CV causes. We then performed a random-effects model for meta-analysis. Results The SLR included 34 articles, mainly focused on the association between SpA/PsA and CVD. Twenty-four articles were then selected for the meta-analysis. The overall incidence of CVD was increased in PsA [hazard ratio (HR) 1.28 (95% CI 1.15, 1.43)] and in SpA [HR 1.45 (95% CI 1.22, 1.72)] compared with the general population, with consistency across the different types of CVDs. Interestingly the incidence tended to decrease over time in PsA but not in SpA. Conclusion The SLR and meta-analysis confirmed the increased incidence of CVD in both SpA and PsA patients compared with the general population, although the increase seems to be less prominent in PsA than in SpA. Future studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Vitamin D plays important role in inflammatory rheumatic diseases, which in turn rose an interest for investigating association of its deficiency with disease activity. In this research we aimed to evaluate this matter in the context of spondyloarthritis (SpA), together with treatment modalities and bone density in people diagnosed with axial or peripheral SpA in real-life setting. In our study we enrolled 99 patients with diagnosis of SpA treated at the tertiary level rheumatology department. Serum 25(OH)D levels, treatment modality (NSAIR or DMARDs), disease activity, tobacco smoking habits, mineral density of bone, supplementation and seasonal variations were assessed. We used standardized questionnaires such as ASDAS-CRP, BASFI and joint count, among many others, to evaluate some of the mentioned parameters. Sixty-five percent of patients had vitamin D deficiency. We found marginaly higher activity of disease in subjects with low vitamin D. In cases of peripheral SpA, there was a significant association of higher number of swollen joints and lower vitamin D levels. Additionally, the significant correlation was seen between normal serum vitamin D and supplementation. In our real-life study of patients with SpA we found a significant percentage of vitamin D deficit, with a tendency of slightly higher disease activity in those patients.In order to clarify the impact of the vitamin on disease activity in SpA and the supplementation recommendations for patients with these conditions, the conduction of further studies is required. [ABSTRACT FROM AUTHOR]

The goal of achieving clinical remission in patients with spondyloarthritis does not necessarily include the resolution of entheseal inflammation from a histological perspective. However, enthesis not clinically inflamed, under mechanical stress, may behave differently from healthy subjects considering the physiopathology of SpA. Our goal was to determine whether ultrasound changes in entheses differ between SpA patients in clinical remission and healthy subjects. SpA patients in clinical remission and matched healthy controls were recruited. At baseline, the following variables were measured on the dominant side by ultrasound: thickness of the distal patellar enthesis (hDP), the deep infrapatellar bursa (hDIB), the Achilles enthesis (hA), the preachilleal bursa (hPAB), effusion in the preachileal bursa (hePAB), and the presence of power Doppler signal in both enthesis. All measurements except hDP and hA were collected again after exercise (post-stress ultrasound). 30 patients and 30 controls were enrolled. In all subjects, hDIB, hPAB, and the preachileal bursa occupancy index increased significantly after the exercise. The increase was significantly greater in patients for all variables. At baseline, in patients, hyperemia was detected in one patellar tendon (3.3%) and in two Achilles tendons (6.7%). After exercise, the number of tendons with hyperemia increased to 11/30 (36.7%) and 12/30 (40%), respectively. Among controls, there was no detectable basal hyperemia, but after exercise, it was detected in 1/30 patellar tendons (3.3%) and 2/30 Achilles tendons (6.7%). Exercise triggers a greater effusive and hyperemic synovial response in patients in remission than in healthy controls. These findings suggest that the definition of remission should also include an assessment of the synovial response to mechanical stress. • Patients developed greater bursal distension after exercise than controls. • Some patients, considered to be in clinical remission, developed enthesal hyperemia after physical activity. • The current definition of remission should be reconsidered and include the concept of normalization of the biomechanical stress response. [ABSTRACT FROM AUTHOR]

To ascertain the frequency of enteropathic arthritis among patients diagnosed with inflammatory bowel disease (IBD) and to investigate the relation between spondyloarthritis (SpA) and patients treated for IBD. This study examined 124 adult patients with IBD. The evaluation encompassed both axial and peripheral SpA. Information pertaining to the patients' age, gender, age at the time of IBD and SpA diagnosis, symptoms of inflammatory low back pain (iLBP), dactylitis, peripheral arthritis, history of uveitis, pelvic X-ray, sacroiliac joint magnetic resonance imaging (MRI), ankylosing spondylitis disease actviity score (ASDAS) and Bath ankylosing spondylitis disease actvity index (BASDAI) were compiled. The IBD patients were 82 having ulcerative colitis (UC) and 42 Crohns disease (CD). 58 (46.8 %) were female and 66 (53.2 %) males. 36 (29 %) were diagnosed with SpA, 18 males and 18 females. The age of the patients was 49 ± 11.2 years (18–74 years). The duration of IBD was 5.96 ± 5.54 years (1–29 years). Sacroiliitis was assessed in 60 (48.3 %) patients using MRI. None of the patients had psoriasis or uveitis. Dactylitis was present in 1.6 % and enthesitis in 8 % of patients with IBD. In UC group, 18 (21.9 %) were diagnosed with SpA and in CD group, 18 (42.8 %) had SpA. No significant relationship was found between the diagnosis of UC/CD and the general SpA group. A considerable number of individuals with IBD also experience SpA. Any delay in diagnosing enteropathic arthritis could lead to functional limitations. Therefore, timely diagnosis is crucial to facilitate optimal treatment. [ABSTRACT FROM AUTHOR]

Proper assessment of patients with psoriatic arthritis (PsA) requires assessment of all disease domains, including axial disease. Magnetic resonance imaging (MRI) is the method of choice for evaluating axial involvement in PsA. When assessing patients with PsA for spinal involvement, it is important to assess both vertebral body lesions and posterolateral lesions, such as inflammation in facet joints and costovertebral joints, and enthesitis at spinous and transverse processes. The Canada-Denmark (CanDen) assessment system for spine MRIs is the preferred method for detailed evaluation of inflammation and structural damage at various anatomical locations in the spine, and it is reproducible and sensitive to change. The Assessment of Spondyloarthritis international Society (ASAS) has recently published MRI definitions of inflammatory and structural lesions in the spine, incorporating the CanDen definitions of spinal lesions on MRI. Applying the ASAS definitions and the CanDen assessment system in clinical practice and trials is recommended. Ongoing research/studies, not least the Axial Involvement in Psoriatic Arthritis (AXIS) study, may provide a data-driven definition of axial involvement in PsA. Ongoing research is expected to further improve and validate assessment tools for axial PsA and to provide a much-needed data-driven consensus-based definition of axial involvement in PsA. [ABSTRACT FROM AUTHOR]

Objective. Patients may use emergency departments (EDs) to meet their health needs when ambulatory care systems are not sufficient. We aim to describe contributing factors to the decision made by persons with inflammatory arthritis (IA) to present to the ED, as well as their experiences of ED care and postdischarge follow-up. Methods. An embedded mixed-methods approach was taken to contextualize quantitative data with associated free-text responses from an online survey distributed to residents of Alberta with a known IA condition and an ED visit. Results. Eighty-two persons (63% aged 16-55 years, 48% female, 50% urban residents) with rheumatoid arthritis (48%), psoriatic arthritis (12%), spondyloarthritis (6%), or gout (34%) completed the survey. Presenting concerns were arthritis flare (37%), chest pain (15%), injury (12%), and infection (11%). Of all visits, 29% proceeded directly to the ED, 35% attempted accessing ambulatory care first, and 32% arrived for a return visit. In presentations for arthritis flare, patients were aware of the rheumatology service being contacted by the ED provider for advice in just 9% of events. Challenges in healthcare system coordination and system pressures resulted in patients requiring ED attendance to assess their concern. The quality of communication and relationality developed between patients with IA and healthcare providers informed experiences of ED care. Conclusion. Modifying rheumatology ambulatory care models could better meet patient needs and ultimately reduce avoidable ED use by patients with IA. [ABSTRACT FROM AUTHOR]

Objective. Opioid use among individuals with spondyloarthritis is common; however, data on whether these individuals have higher utilization of the healthcare system are lacking. We examined the association between opioid use and healthcare utilization and costs among patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Methods. We included adults with PsA or AS enrolled in the FORWARD registry, with ≥ 1 completed disease activity or disability questionnaire between 2010 and 2019. The exposure was patient-reported opioid use, and the outcomes were annualized healthcare utilization and prescription costs. We used negative binomial regression to assess the association between opioid use and the utilization outcomes, and generalized linear models with γ-distribution and log link function for the association between opioid use and costs. Models were adjusted for age, sex, and hospitalization. AS and PsA were studied separately. Results. Among 828 patients with PsA, 21.4% used opioids; for those with AS, 27.2% of 334 patients reported opioid use. Opioid users had higher healthcare utilization and costs, including increased medical visits, diagnostic tests, direct medical costs, and pharmacy expenses. Opioid users had 32-33% more medical visits annually vs nonusers. Patients using opioids spent more on medical visits annually compared to nonusers (US $3464 vs $2706 for PsA; US $4500 vs $3660 for AS). Conclusion. Compared to patients not using opioids, patients with PsA and AS who used opioids had higher healthcare utilization and higher health-related costs. New care pathways are needed to improve care and reduce costs. [ABSTRACT FROM AUTHOR]

Objective: Diagnosis of spondylodiscitis is usually possible radiographically with magnetic resonance imaging (MRI). However, the first imaging method evaluated in daily practice is conventional radiography. The aim of the study was to determine the sensitivity and specificity of detecting infectious or rheumatological spondylodiscitis in the lumbar region with conventional radiography by rheumatologists. Methods: Among 102 patients with spondylodiscitis on lumbosacral (LS) MRI, 23 patients who also underwent simultaneous conventional LS radiography were included. TThe control group consisted of 52 outpatients with no evidence of spondylodiscitis on LS MRI. Eleven rheumatologists blindly evaluated conventional LS radiographs. Sensitivity, specificity, positive, and negative predictive values of LS conventional radiography were calculated. Results: While the cause was infection in 8/23 (34.7%) of spondylodiscitis patients, it was spondyloarthritis in 15/23 (65.2%). According to LS MRI findings, 23 patients had spondylodiscitis in a total of 31 vertebral units. When we evaluated the detection of spondylodiscitis according to the vertebral unit level, it was mostly at one level [14 (60.8%)], primarily at the L4-5 vertebral unit [13 (56.5%)]. The sensitivity of detecting LS spondylodiscitis on conventional radiography was found to be 52% (30-65), and the specificity was 86% (59-94). While the median (minimum-maximum) sensitivity was 75.0 (50.0-87.5) in patients with infectious spondylodiscitis, it was 46.6 (13.3-76.9) in patients with spondylodiscitis due to spondyloarthritis. Conclusion: Clinicians can miss spondylodiscitis. Although it is evaluated with conventional radiography in the first stage in the presence of appropriate clinical findings, the clinician should be careful and consider more advanced approaches.

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of immune-mediated arthritis, which comprises rheumatoid arthritis and spondyloarthritis. This review outlines the key findings and advancements in scRNA-seq studies focused on the pathogenesis of autoimmune arthritis and its clinical application. In rheumatoid arthritis, scRNA-seq has elucidated the heterogeneity among synovial fibroblasts and immune cell subsets in inflammatory sites, offering insights into disease mechanisms and the differences in treatment responses. Various studies have identified distinct synovial fibroblast subpopulations, such as THY1+ inflammatory and THY1- destructive fibroblasts. Furthermore, scRNA-seq has revealed diverse T cell profiles in the synovium, including peripheral helper T cells and clonally expanded CD8+ T cells, shedding light on potential therapeutic targets and predictive markers of treatment response. Similarly, in spondyloarthritis, particularly psoriatic arthritis and ankylosing spondylitis, scRNA-seq studies have identified distinct cellular profiles associated with disease pathology. Challenges such as cost and sample size limitations persist, but collaborative efforts and utilization of public databases hold promise for overcoming these obstacles. Overall, scRNA-seq emerges as a powerful tool for dissecting cellular heterogeneity and driving precision medicine in immune-mediated arthritis.

Aim: Spondyloarthritis (SpA) is a group of chronic, inflammatory diseases characterized by involvement of the axial and peripheral joints, as well as extra-articular manifestations. It is important to assess disease activity (DA) for treatment and follow-up. Although there are commonly used scoring systems, they may lack sensitivity and specificity in determining DA. One potential biomarker for DA is calprotectin, a calcium-binding protein released from monocytes and macrophages during inflammation. Faecal calprotectin (fCal) is frequently used in the diagnosis and follow-up of inflammatory bowel diseases. Significant intestinal inflammation has also been shown in active SpA. The aim of this study was to test the utility of fCal as a marker of DA. Materials and Methods: The study included patients with ankylosing spondylitis and psoriatic arthritis, admitted to our hospital between October 2019 and February 2020. Patients with gastrointestinal symptoms were excluded. Demographic data, DA scores, and laboratory test results were obtained from patient records. The correlation between fCal levels and DA parameters was analysed. Results: fCal levels were correlated with the erythrocyte sedimentation rate (ESR) but not with C-reactive protein levels. Among the DA scores, only the AS Disease Activity Score (ASDAS)-ESR was found to be correlated. Non-steroid users and cigarette smokers exhibited lower levels of fCal. Conclusion: fCal levels were found to be associated with ESR but not with C-reactive protein levels. fCal is only correlated with ASDAS-ESR, and lower fCal levels were observed in those using non-steroidal drugs and smokers.

Abstract Background This study aimed to investigate the accuracy of identifying enthesitis along with other inflammatory lesions and structural lesions on the MRI of the sacroiliac joints (SIJ) by readers of varying experience and how training sessions and workshops could help improve the accuracy. Methods A total of 224 patients with clinical diagnosis of axial spondyloarthritis who underwent SIJ MRI examinations were retrospectively included in this study. Three readers with 5 years, 3 years and 1 year of experience in musculoskeletal imaging were invited to review the SIJ MRI images independently, while the imaging reports of a senior radiologist (> 10 years’ experience) were used as reference. After the first round of image review, a training session and a workshop on the imaging of SIJ in spondyloarthritis were held and the three readers were asked to review the images in the second round. We calculated the accuracy of identifying inflammatory and structural lesions of the three readers as well as the intra-reader agreement. Results Enthesitis could be observed in 52.23% of the axial spondyloarthritis patients, while 81.58% of the patients with enthesitis were accompanied with bone marrow edema. All the three readers showed better accuracy at identifying structural lesions than inflammatory lesions. In the first round of image review, the three readers only correctly identified 15.07%, 2.94% and 0.74% of the enthesitis sites. After the training session and workshop, the accuracy rose to 61.03%, 39.34% and 20.22%. The intra-reader agreement of enthesitis calculated as Cohen’s kappa was 0.23, 0.034 and 0.014, respectively. Conclusion Readers with less experience in musculoskeletal imaging showed lower accuracy of identifying inflammatory lesions, notably enthesitis. Training sessions and workshops could help improve the diagnostic accuracy of the junior readers.

Introduction: Ankylosing Spondylitis (AS) is an inflammatory disorder of unknown cause that primarily affects the axial skeleton, peripheral joints, and extra-articular structures. Typically, the condition starts in the second or third decade. Lower back pain lasting longer than three months, morning stiffness lasting more than 30 minutes, relieved by daily activities, are signs of disease onset. Aim: To establish a correlation between disease severity score Ankylosing Spondylitis Disease Activity Score (ASDAS) and Magnetic Resonance Imaging (MRI) scoring in patients with AS. Materials and Methods: This cross-sectional study was conducted on 66 patients attending the Medicine Emergency/Outpatient Department (OPD)/ward of ESIPGIMSR and ESI Hospital, Basaidarapur, New Delhi, India, who were diagonsed with AS based on the modified New York Criteria. Clinical assessments included ASDAS based on Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP), while MRI disease activity scores were determined using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scoring. The sample size was calculated with a coefficient limit of 10% and a confidence level of 95%. Data analysis was performed using Statistical Packages for Social Sciences (SPSS) version 21.0, a widely used statistical computing and graphics tool. Pearson’s correlation coefficients were computed to explore relationships between variables, including age, disease duration, ASDAS-ESR, and MRI changes. Results: In present study, a total of 66 patients were included, out of which 51 (77.3%) were males and 15 (22.7%) were females. The age group of patients included in present study was 33 years to 44 years with a mean of 37.96 years. In present study, the disease duration ranged from a minimum of two years to a maximum of 10 years with a mean of 5.4 years. The mean ASDAS CRP was 3.687 (minimum-2.80, maximum-4.60), and the disease activity as assessed by MRI score (SPARCC) had a minimum value of 8.85 and a maximum value of 26.2 with a mean of 16.359. In present study, the X-ray grading of sacroiliitis revealed that 19.7% of the subjects were classified as Grade-2, 60.6% as Grade-3, and 19.7% as Grade-4. Conclusion: The clinical disease activity index may not always reflect active inflammation, which is detectable by MRI. Incorporating MRI into diagnostic and treatment strategies for AS is crucial for the accurate assessment of disease severity and better patient outcomes.

Abstract Ankylosing spondylitis (AS), an inflammatory condition affecting axial and peripheral joints, exhibits varying prevalence worldwide. This study sought to ascertain AS incidence and prevalence in Thailand from 2017 to 2020. Utilizing national databases, individuals aged 18 and above with primary AS diagnoses (ICD-10 code M45) were identified. AS prevalence and incidence were calculated with 95% confidence intervals. The total number of AS patients was 13,292 patients in 2017. The prevalence of AS was 20.4 per 100,000 populations (95% CI 20.0–20.7) in 2017. The number of new AS cases, identified during 2018–2020, was 6784, 6805, and 6791 patients, respectively. The incidences of AS in 2018, 2019, and 2020 were comparable with the incidence of 10.4 (95% CI 10.1–10.6) per 100,000-person-years. The peak age at diagnosis was 50–59 years of age between 2018 and 2020. The number of female patients was 57.8%, 57.0%, and 57.6%, in 2018, 2019, and 2020, respectively. In conclusion, AS was relatively rare among Thais and comparable between males and females. The prevalence and incidence of AS in Thailand were identified by the Thailand Database Ministry of Public Health. The epidemiological profile of AS in Thailand might help to plan better care, workforce needs, and public health budgets.

Abstract Background Association of HLA-B27 with spondyloarthritis (SpA) has been known for 50 years, but still remains unexplained. We recently showed that HLA-B27 expressed in wing imaginal disc from HLA-B27/human-β2 microglobulin (hβ2m) transgenic Drosophila deregulated bone morphogenetic protein (BMP) pathway by interacting physically with type I BMP receptor (BMPR1) Saxophone (Sax), leading to crossveinless phenotype. Methods Genetic interaction was studied between activin/transforming growth factor β (TGFβ) pathway and HLA-B27/hβ2m in transgenic Drosophila wings. The HLA-B27-bound peptidome was characterized in wing imaginal discs. In mesenteric lymph node (mLN) T cells from HLA-B27/hβ2m rat (B27 rat), physical interaction between HLA-B27 and activin receptor-like kinase-2 (ALK2), ALK3 and ALK5 BMPR1s, phosphorylation of small mothers against decapentaplegic (SMADs) and proteins of the non-canonical BMP/TGFβ pathways induced by its ligands, and the transcript level of target genes of the TGFβ pathway, were evaluated. Results In HLA-B27/hβ2m transgenic Drosophila, inappropriate signalling through the activin/TGFβ pathway, involving Baboon (Babo), the type I activin/TGFβ receptor, contributed to the crossveinless phenotype, in addition to deregulated BMP pathway. We identified peptides bound to HLA-B27 with the canonical binding motif in HLA-B27/hβ2m transgenic Drosophila wing imaginal disc. We demonstrated specific physical interaction, between HLA-B27/hβ2m and mammalian orthologs of Sax and Babo, i.e. ALK2 and ALK5 (i.e. TGFβ receptor I), in the mLN cells from B27 rat. The magnitude of phosphorylation of SMAD2/3 in response to TGFβ1 was increased in T cells from B27 rats, showing evidence for deregulated TGFβ pathway. Accordingly, expression of several target genes of the pathway was increased in T cells from B27 rats, in basal conditions and/or after TGFβ exposure, including Foxp3, Rorc, Runx1 and Maf. Interestingly, Tgfb1 expression was reduced in naive T cells from B27 rats, even premorbid, an observation consistent with a pro-inflammatory pattern. Conclusions This study shows that HLA-B27 alters the TGFβ pathways in Drosophila and B27 rat. Given the importance of this pathway in CD4 + T cells differentiation and regulation, its disturbance could contribute to the abnormal expansion of pro-inflammatory T helper 17 cells and altered regulatory T cell phenotype observed in B27 rats.

Introduction Recently, diet has received considerable attention as an important factor in inflammatory arthritis. The objective of this study was to evaluate disease activity and fatigue in patients with rheumatoid arthritis and spondyloarthritis (including psoriatic arthritis) depending on their dietary preferences. Material and methods We retrospectively evaluated data of 774 patients collected by the Mida Rheuma App from January 2022 to December 2022. We assessed demographic parameters, major dietary patterns, and food groups (dairy products, fruits, vegetables, processed meat, meat, oily fish, white fish, and sugar) by each patient’s consumption intensity. Disease activity was measured by Routine Assessment of Patient Index Data 3 (RAPID3), Patient’s Global Assessment of Disease Activity (PtGADA), and Patient’s Global Assessment of Pain Intensity (PPAIN). Fatigue was assessed by the Brief Fatigue Inventory (BFI). Depending on the food group, patients were divided into a high-consumption group (HCG; consuming the product 0–2 times per day/per week) and a lowconsumption group (LCG; consuming the product 3 and more times per day/per week). Patients on a specific diet which they followed before inclusion in the analysis were compared with the “eat all group” (EAG). Results The Mediterranean diet group had significantly lower (p < 0.05) RAPID3, PtGADA, and PPAIN (by 9.22%, 8.98%, and 14.3%, respectively), compared with the EAG. In the processed meat HCG, RAPID3, PtGADA, PPAIN, and BFI were significantly higher (14.5%, 18.3%, 16.1%, and 11.8%, p < 0.05) vs. the LCG. The PtGADA, PPAIN, and RAPID3 were significantly lower (p < 0.05) in the oily fish HCG vs. the LCG (18.9%, 18.1%, and 10.6%). Conclusions Our study results suggest that Mediterranean diet and oily fish have a potentially positive impact on patient-reported disease activity and fatigue in patients with inflammatory arthritis. In contrast, processed meat consumption has a negative effect.

Objectives: The aim of this cross-sectional study was to investigate if serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and CC chemokine ligand 17 (CCL17) correlate with disease activity in axial spondyloarthritis (axSpA) and peripheral spondyloarthritis (pSpA) patients. Patients and methods: The cross-sectional study was conducted with 80 individuals (48 females, 32 males; mean age: 47.7±11.5 years) between March 2021 and September 2021. Of the participants, 20 were axSpA, 20 were pSpA, and 20 were active rheumatoid arthritis patients, and the remaining 20 were healthy controls. Age, sex, body mass index, disease duration, comorbid diseases, smoking status, medical treatments, C-reactive protein (CRP) level and human leukocyte antigen B27 (HLA-B27) positivity were recorded. Serum GM-CSF and CCL17 levels were analyzed by ELISA. Ankylosing Spondylitis Disease Activity Score with CRP (ASDAS-CRP) was used to evaluate the disease activity of patients with spondyloarthritis. Functional status of spondyloarthritis patients was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI). Results: While the serum GM-CSF levels were similar in the axSpA and pSpA groups, they were significantly higher than the healthy control group (p=0.021 and p=0.009, respectively). There was a significant correlation between GM-CSF levels and ASDAS-CRP (r=0.545, p=0.013) and BASFI (r=0.546, p=0.013) in the axSpA group. In active axSpA patients, the cut-off value for GM-CSF was 15.89 pg/mL (sensitivity 50%, specificity 100%). No differences were detected in serum CCL17 levels among the groups. Conclusion: The results suggest that serum GM-CSF levels may be used as a new marker for the evaluation of disease activity in axSpA, and GM-CSF might be a therapeutic target. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to investigate and compare clinical features, disease activity, and the overall disease burden among psoriatic arthritis (PsA) patients across seven distinct geographic regions in Türkiye. Patients and methods: A multicenter cross-sectional study involving 1,134 PsA patients from 25 referral centers across seven regions was conducted. Demographic and clinical characteristics, comorbidities, joint involvement, extra-articular manifestations, and disease activity measures were evaluated across regions. Results: A total of 1134 PsA patients from seven different geographic regions in Türkiye participated in this study. The highest number of participants was from the Marmara region (n=409), with subsequent representation from Central Anatolia (n=370), Aegean (n=139), Mediterranean (n=60), Black Sea (n=60), Eastern Anatolia (n=60), and Southeastern Anatolia (n=36) regions. There were significant variations in demographic profile, including age, body mass index, age of disease onset, educational status, comorbidities, and family history of both psoriasis and PsA. Clinical features, such as enthesitis, dactylitis, uveitis, and joint involvement, demonstrated significant variation across regions. Additionally, disease activity measures, including pain, patient and physician global assessments, acute phase reactants, disease activity indices, quality of life, and functional status, displayed considerable regional differences. Conclusion: This nationwide study revealed substantial regional diversity in demographic data, clinical characteristics, disease activity, and quality of life among PsA patients in Türkiye. These findings stress the need to customize treatment approaches to address regional needs and to conduct further research to uncover reasons for disparities. It is crucial to enhance region-specific approaches to improve patient care and outcomes for PsA. [ABSTRACT FROM AUTHOR]

Background and Aims Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We aimed to compare the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched, population-based, reference individuals. Methods We identified 147 080 FDRs and 25 945 spouses of patients with incident IBD [ N  = 39 203] during 2006–2016, and 1 453 429 FDRs and 258 098 spouses of matched reference individuals [ N  = 390 490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987–2017. Cox regression was used to estimate hazard ratios [HRs] of SpA. Results During follow-up, 2430 FDRs of IBD patients [6.5/10 000 person-years] and 17 761 FDRs of reference individuals [4.8/10 000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95% CI:1.29, 1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR = 1.44; 95% CI:1.34,1.5 6] and of IBD patients aged <18 years at diagnosis [HR = 1.46; 95% CI: 1.27, 1.68]. IBD patients' spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs 3.5/10 000 person-years; HR = 1.22; 95% CI:1.09, 1.37]. No subgroup-specific risk pattern was identified among spouses. Conclusions The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Uveitis may occur in the course of systemic inflammatory rheumatic diseases (IRD), or it may be the first clinical manifestation of these diseases. The aim of this study was to determine the incidence of IRD in patients whose initial clinical manifestation was non-infectious uveitis. METHODS: The study included adult patients diagnosed as having noninfectious uveitis in the department of ophthalmology and referred to rheumatology for further investigation of potential rheumatic diseases as underlying etiology of uveitis. The patients' demographic and clinical features, laboratory, and imaging findings were examined. RESULTS: One hundred six patients who were diagnosed as having uveitis (42.4% anterior, 2.8% intermediate, 19.8% posterior, and 34.9% panuveitis) were included. Just over half (52.8%) of the patients were male and the mean age was 40.1±14.8 years. The mean age at the uveitis attack was 38.7±15 years. One-third (33%) of the patients were diagnosed as having rheumatologic disease (spondyloarthritis (SpA) n=10, Behcet disease (BD) n=17, vasculitides n=2, sarcoidosis n=2, undifferentiated connective tissue diseases n=3, rheumatoid arthritis n=1). SpA was diagnosed in 20% of patients presenting with anterior uveitis. BD was detected in 27% of patients referred with panuveitis and in 33.3% of patients whose first clinical finding was posterior segment involvement. Bilateral uveitis was detected in two-thirds of patients with posterior uveitis and tended to recur more frequently (p=0.014). CONCLUSION: Rheumatic diseases have been identified in approximately one-third of patients presenting with different types of uveitis. Investigations addressing systemic rheumatic diseases are of paramount importance in patients with uveitis because they may change diagnosis and treatment processes. [ABSTRACT FROM AUTHOR]

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Purposeof Review: Male fertility is an emergent issue that should be considered in clinical practice, when dealing with chronic inflammatory diseases in young men. As it is known, the chronic inflammation is the main pathophysiologic mechanism in some rheumatological conditions such as spondyloarthritis (SpA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Therefore, it is paramount to be aware if these diseases could impair male fertility, both due to the inflammation or to the treatments needed: we reviewed the literature on the most relevant and recent evidence on male fertility in patients affected by SpA, AS and PsA. Recent Findings: Rheumatological inflammatory diseases (included SpA, AS and PsA) could impair the family planning in man life, especially when diagnosed at young age. Moreover, focusing on sperm quality, it seems that a link between sperm quality impairment and a higher disease activity exist. Focusing on therapies, Tumor Necrosis Factor inhibitors showed a safety profile on human male fertility in clinical studies. Recently, a prospective study and two double-blind placebo-controlled trials assessed the impact of methotrexate and Filgotinib on semen parameters, respectively, showing a safety profile of these drugs on human semen quality. However, there are no clinical data on the impact of Interleukin (IL)17 inhibitors(i), IL12-23i and IL23i. Summary: Concerning male fertility in SpA, AS and PsA, an unmet clinical need is still present and new studies are needed to understand the association between these diseases and male fertility, and the implication of the therapies used for these diseases. This narrative review provides an overview of the available data on male fertility in patients affected by SpA, AS and PsA. [ABSTRACT FROM AUTHOR]

Copyright of Namık Kemal Tıp Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives We aimed to study trabecular bone score (TBS) association with disease parameters and vertebral fractures (VFs) in patients with axial spondyloarthritis. Methods Patients diagnosed with axial spondyloarthritis were included in this cross-sectional study. Dual-energy X-ray absorptiometry was used to measure BMD in the lumbar spine and TBS. Low TBS was defined as ≤1.31. The association between TBS and disease parameters including Ankylosing Spondylitis Disease Activity Score (ASDAS), BASDAI, BASFI and BASMI was studied using logistic regressions. Results Our study included 56 patients, with a mean age of 38.9 ± 13.5 years and a mean disease duration of 12.7 ± 7.7 years. Patients with low TBS were significantly older and had higher waist circumference and body mass index. These patients also showed greater clinical activity, as evidenced by higher ASDAS-CRP, BASFI and BASMI scores (P  < 0.05). In multivariate logistic regression, low TBS was associated with all disease parameters, except for BASMI: BASDAI (OR [95% CI] = 3.68 [1.48–9.19], P  = 0.005), ASDAS-CRP (OR [95% CI] = 2.92 [1.20–7.10], P  = 0.018), BASFI (OR [95% CI] = 1.04 [1.01–1.08], P  = 0.018), BASMI (OR [95% CI] = 1.36 [0.99–1.87], P  = 0.062). However, no association was observed between TBS and VFs. Conclusion TBS was associated with active spondyloarthritis, suggesting increased bone fragility in these patients. However, TBS failed to demonstrate an association with VFs. [ABSTRACT FROM AUTHOR]

Introduction: Ankylosing Spondylitis (AS) is an inflammatory disorder of unknown cause that primarily affects the axial skeleton, peripheral joints, and extra-articular structures. Typically, the condition starts in the second or third decade. Lower back pain lasting longer than three months, morning stiffness lasting more than 30 minutes, relieved by daily activities, are signs of disease onset. Aim: To establish a correlation between disease severity score Ankylosing Spondylitis Disease Activity Score (ASDAS) and Magnetic Resonance Imaging (MRI) scoring in patients with AS. Materials and Methods: This cross-sectional study was conducted on 66 patients attending the Medicine Emergency/ Outpatient Department (OPD)/ward of ESIPGIMSR and ESI Hospital, Basaidarapur, New Delhi, India, who were diagonsed with AS based on the modified New York Criteria. Clinical assessments included ASDAS based on Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP), while MRI disease activity scores were determined using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scoring. The sample size was calculated with a coefficient limit of 10% and a confidence level of 95%. Data analysis was performed using Statistical Packages for Social Sciences (SPSS) version 21.0, a widely used statistical computing and graphics tool. Pearson's correlation coefficients were computed to explore relationships between variables, including age, disease duration, ASDAS-ESR, and MRI changes. Results: In present study, a total of 66 patients were included, out of which 51 (77.3%) were males and 15 (22.7%) were females. The age group of patients included in present study was 33 years to 44 years with a mean of 37.96 years. In present study, the disease duration ranged from a minimum of two years to a maximum of 10 years with a mean of 5.4 years. The mean ASDAS CRP was 3.687 (minimum-2.80, maximum-4.60), and the disease activity as assessed by MRI score (SPARCC) had a minimum value of 8.85 and a maximum value of 26.2 with a mean of 16.359. In present study, the X-ray grading of sacroiliitis revealed that 19.7% of the subjects were classified as Grade-2, 60.6% as Grade-3, and 19.7% as Grade-4. Conclusion: The clinical disease activity index may not always reflect active inflammation, which is detectable by MRI. Incorporating MRI into diagnostic and treatment strategies for AS is crucial for the accurate assessment of disease severity and better patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. Methods: Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. Results: The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. Conclusion: This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory condition affecting about one-third of individuals with psoriasis. Defining axial involvement in PsA (axPsA) remains debated. While rheumatologists guide clinical practice, consensus on axPsA is still lacking. This paper explores historical and upcoming definitions from the Axial Involvement in Psoriatic Arthritis (AXIS) study, which aims to establish a validated axPsA definition. Epidemiological data reveal diverse axPsA prevalence rates, emphasizing its complex relationship with peripheral arthritis and enthesitis. Unique genetic, clinical, and radiological features differentiate axPsA from ankylosing spondylitis (AS), necessitating refined classification criteria. The recommendations from the Assessment of Spondylarthritis international Society (ASAS) provide valuable guidance due to the limited direct evidence. Emerging therapies, including interleukin-23 (IL-23) inhibitors or Janus kinase (JAK) inhibitors, are under investigation for axPsA. Currently, secukinumab, an interleukin-17 (IL-17) inhibitor, is an evidence-based option for axPsA management. However, given the variability in individual patient responses and disease manifestations, personalized, evidence-based treatment approaches remain essential for optimizing patient outcomes. In the final section, two real-life cases illustrate the challenges in managing axPsA, emphasizing the importance of tailored therapies. Achieving precision in defining axPsA remains a formidable task, making detailed criteria essential for effective strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS), an inflammatory condition affecting axial and peripheral joints, exhibits varying prevalence worldwide. This study sought to ascertain AS incidence and prevalence in Thailand from 2017 to 2020. Utilizing national databases, individuals aged 18 and above with primary AS diagnoses (ICD-10 code M45) were identified. AS prevalence and incidence were calculated with 95% confidence intervals. The total number of AS patients was 13,292 patients in 2017. The prevalence of AS was 20.4 per 100,000 populations (95% CI 20.0–20.7) in 2017. The number of new AS cases, identified during 2018–2020, was 6784, 6805, and 6791 patients, respectively. The incidences of AS in 2018, 2019, and 2020 were comparable with the incidence of 10.4 (95% CI 10.1–10.6) per 100,000-person-years. The peak age at diagnosis was 50–59 years of age between 2018 and 2020. The number of female patients was 57.8%, 57.0%, and 57.6%, in 2018, 2019, and 2020, respectively. In conclusion, AS was relatively rare among Thais and comparable between males and females. The prevalence and incidence of AS in Thailand were identified by the Thailand Database Ministry of Public Health. The epidemiological profile of AS in Thailand might help to plan better care, workforce needs, and public health budgets. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs and biologic therapy are recognized as standard treatments for ankylosing spondylitis. However, in developing countries like Turkey, the cost of biological treatments can escalate to significant levels. Our study aims to assess the effectiveness of sulfasalazine in axial symptoms, typically considered a secondary treatment in ankylosing spondylitis. We conducted a retrospective analysis of the medical records of patients diagnosed with ankylosing spondylitis. These patients were prescribed sulfasalazine due to the persistence of axial symptoms. After a 3 mo course of sulfasalazine treatment, patients were assessed for changes in sediment and C-reactive protein values, ankylosing spondylitis disease activity score-sedimentation rate and ankylosing spondylitis disease activity score-C-reactive protein values, visual analog scale, bath ankylosing spondylitis disease activity index, and bath ankylosing spondylitis functional index results and morning stiffness durations. In this study, conducted with sulfasalazine treatment, significant improvements were observed across multiple parameters. Morning stiffness duration decreased in 22 patients. Median C-reactive protein levels decreased from 9.99 mg/l (range: 2-53, interquartile range: 12.21) to 6.81 mg/l (range: 1-18, interquartile range: 8.16). Similarly, the median ESR reduced from 20.53 mm/h (range: 4-48, interquartile range: 15.47) to 12.81 mm/h (range: 2-33, interquartile range: 10.57). Ankylosing spondylitis disease activity score-C-reactive protein scores improved from 3.62±0.732 to 2.67±0.93, and ankylosing spondylitis disease activity score-ESR scores improved from 3.54±0.66 to 2.57±0.80. Moreover, patients reported lower visual analogue scale scores, decreasing from 7.39±1.44 to 5.58±1.97. The global disease evaluation by doctors showed a decrease from an average score of 6.33±1.47 (range: 4-10) to 5.11±1.68 (range: 2-8). Ankylosing spondylitis quality of life questionnaire scores improved from 7.92±2.41 to 5.36±2.73. Bath ankylosing spondylitis disease activity index scores decreased from 6.31±1.70 to 4.37±1.76, and bath ankylosing spondylitis functional index scores improved from 3.76±1.98 to 2.79±1.63. These improvements were statistically significant across all measured parameters before and after sulfasalazine treatment (p<0.05). In developing countries like ours, where access to biological drugs which derived from living organisms, can be challenging for economically disadvantaged individuals with limited socioeconomic resources, and where the probability of inducing side effects such as infections, an elevated risk of cancer, and neurological diseases is a concern, sulfasalazine could be considered a more affordable and relatively safer option before resorting to biological treatments for managing ankylosing spondylitis. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) is an autoimmune disease that has several clinical manifestations with certain characteristics. In this report, we present the case of an immobilized 54-year-old female with SpA who complained of a painful swollen left leg. Laboratory workup and imaging study supported the diagnosis of SpA complicated with deep vein thrombosis (DVT). The patient was given glucocorticoid, an anticoagulant, and medical rehabilitation. Symptoms improved following treatment. SpA increases the inflammatory state, leading to the increased risk of DVT. Holistic and comprehensive treatment is required in SpA patients with DVT to prevent further exacerbation or poorer prognosis. [ABSTRACT FROM AUTHOR]