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The strong association of the human leukocyte antigen B∗27 alleles (HLA-B∗27) with spondyloarthritis and related rheumatic conditions has long fascinated researchers, yet the precise mechanisms underlying its pathogenicity remain elusive. Here, we review how interplay between the microbiome, the immune system, and the enigmatic HLA-B∗27 could trigger spondyloarthritis, with a focus on whether HLA-B∗27 presents an arthritogenic peptide. We propose mechanisms by which the unique biochemical characteristics of the HLA-B∗27 protein structure, particularly its peptide binding groove, could dictate its propensity to induce pathological T cell responses. We further provide new insights into how TRBV9+ CD8+ T cells are implicated in the disease process, as well as how the immunometabolism of T cells modulates tissue-specific inflammatory responses in spondyloarthritis. Finally, we present testable models and suggest approaches to this problem in future studies given recent advances in computational biology, chemical biology, structural biology, and small-molecule therapeutics. [Display omitted] In this perspective, Brown et al. synthesize recent studies from different fields to describe how the microbiome, immunity, and metabolism could interact with the risk allele HLA-B∗27 to initiate spondyloarthritis. Special attention is given to unique structural features of HLA-B∗27 and how they interface with the microbial environment. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis manifests as a chronic inflammatory disease primarily affecting the sacroiliac joints and spine. Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (ie, enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (ie, uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common. Timely and accurate diagnosis is challenging and relies on identifying a clinical pattern with a combination of clinical, laboratory (HLA-B27 positivity), and imaging findings (eg, structural damage on pelvic radiographs and bone marrow oedema on MRI of the sacroiliac joints). The Assessment in SpondyloArthritis international Society classification criteria for axial spondyloarthritis are widely used for research and have contributed to a better understanding of the gestalt of axial spondyloarthritis. Persistent disease activity, assessed mainly by the Axial Spondyloarthritis Disease Activity Score, leads to irreversible structural damage and functional impairment. Management involves non-pharmacological (eg, education, smoking cessation, exercise, physiotherapy) and pharmacological therapy. Non-steroidal anti-inflammatory drugs remain first line pharmacotherapy, while tumour necrosis factor, IL-17, and Janus kinase inhibitors are considered second-line therapies. Future advances are expected to increase disease awareness, facilitate early and accurate diagnosis, optimise disease management, and enhance overall quality of life in patients with axial spondyloarthritis. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA) is common but remains poorly understood. In this review article, we aimed to provide guidance regarding the diagnosis and management of this condition. For diagnosis of IBD-associated peripheral SpA (IBD-pSpA), we recommend collaboration with rheumatology for incorporation of clinical symptoms, physical examination findings, joint imaging if applicable, and available diagnostic criteria. For the management of IBD-pSpA, we first recommend assessment and treatment of underlying luminal IBD disease activity. We provide guidance regarding positioning of advanced therapies for IBD in patients with IBD-pSpA based on the limited available literature. For diagnosis of IBD-associated axial SpA, we recommend rheumatology referral to make the diagnosis based on incorporation of symptoms, laboratory data, imaging findings (sacroiliitis), and available diagnostic criteria. For the management of axial SpA, we recommend comanagement with rheumatology and use of either antitumor necrosis factor agents or Janus kinase inhibitors, when applicable. [ABSTRACT FROM AUTHOR]

Objective: Axial spondyloarthritis (axSpA) is an inflammatory disease in which overactive interleukin (IL)‐17A–producing cells are implicated in a central role. Therapeutically, biologics that target IL‐17A, such as secukinumab, have demonstrated improved clinical outcomes. Despite this translational success, there is a gap in understanding why some patients with axSpA do not respond to IL‐17A–blocking therapy. Our study aims to discriminate immune profiles between secukinumab responders (SEC‐R) and nonresponders (SEC‐NR). Methods: Peripheral blood mononuclear cells were collected from 30 patients with axSpA before and 24 weeks after secukinumab treatment. Frequency of CD4+ subsets were compared between SEC‐R and SEC‐NR using flow cytometry. Mature CD45RO+CD45RA‐CD4+ T cells were fluorescent‐activated cell sorting sorted, and RNA was measured using NanoString analysis. Results: SEC‐NR had an increased frequency of IL‐17A–producing RORγt+CD4+ T cells compared to healthy controls before secukinumab treatment (P < 0.01). SEC‐NR had a significant increase of CXCR3+ CD4+ T cells before secukinumab treatment compared to SEC‐R (P < 0.01). Differentially expressed gene analysis revealed up‐regulation of type 1 interferon (IFN)‐regulated genes in SEC‐NR patients compared to SEC‐R patients after receiving the biologic. SEC‐R patients had an up‐regulated cytotoxic CD4+ T cell gene signature before receiving secukinumab treatment compared to SEC‐NR patients. Conclusion: The increased frequency of IL‐17A–producing cells in SEC‐NR patients suggests a larger inflammatory burden than SEC‐R patients. With treatment, SEC‐NR patients have a more pronounced type 1 IFN signature than SEC‐R patients, suggesting a mechanism contributing to this larger inflammatory burden. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease. [ABSTRACT FROM AUTHOR]

Objective: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. Methods: Twenty rheumatology centers participated in this cross‐sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). Results: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. Conclusion: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the following: (1) the frequency of axial spondyloarthritis (axSpA) according to extra‐articular presentation and HLA‐B27 status, (2) clinical and imaging features that distinguish axSpA from non‐axSpA, and (3) the impact of magnetic resonance imaging (MRI) on diagnosis and classification of axSpA. Methods: The Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) study enrolled patients in two multicenter cohorts. Consecutive patients with undiagnosed chronic back pain attending dermatology, ophthalmology, and gastroenterology clinics with psoriasis (PsO), acute anterior uveitis (AAU), or inflammatory bowel disease (IBD) were referred to a local rheumatologist with special expertise in axSpA for a structured diagnostic evaluation. The primary outcome was the proportion of patients diagnosed with axSpA by the final global evaluation. Results: Frequency of axSpA was 46.7%, 61.6%, and 46.8% in patients in SASPIC‐1 (n = 212) and 23.5%, 57.9%, and 23.3% in patients in SASPIC‐2 (n = 151) with PsO, AAU, or IBD, respectively. Among those who were B27 positive, axSpA was diagnosed in 70%, 74.5%, and 66.7% of patients in SASPIC‐1 and in 71.4%, 87.8%, and 55.6% of patients in SASPIC‐2 with PsO, AAU, or IBD, respectively. All musculoskeletal clinical features were nondiscriminatory. MRI was indicative of axSpA in 60% to 80% of patients and MRI in all patients (SASPIC‐2) versus on‐demand (SASPIC‐1) led to 25% fewer diagnoses of axSpA in patients who were HLA‐B27 negative with PsO or IBD. Performance of the Assessment of SpondyloArthritis International Society classification criteria was greater with routine MRI (SASPIC‐2), though sensitivity was lower than previously reported. Conclusion: Optimal management of patients presenting with PsO, AAU, IBD, and undiagnosed chronic back pain should include referral to a rheumatologist. Conducting MRI in all patients enhances diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Survival analyses can provide valuable insights into effectiveness and safety as perceived by prescribers. Here, we aimed to evaluate adalimumab (ADA) survival and the interruption risk factors in a multicentre cohort of patients with hidradenitis suppurativa (HS). Moreover, we performed a subanalysis considering the periods before and after the onset of the COVID‐19 pandemic. Methods: We conducted a retrospective study including 539 adult patients with HS who received ADA from 1 May 2015 to 31 December 2022. Overall drug survival was analysed using Kaplan–Meier survival curves and compared between the subgroups via stratified log‐rank test. Possible predictors for overall drug survival and reasons for discontinuation were assessed using univariate and multivariate Cox regression. Results: Overall, 50.1% were females with a mean age of 43.5 ± 1 years and a mean BMI of 29.5 ± 6.7. At the start of ADA, 95.29% were biologic‐naïve and 24.63% had undergone surgical treatment. During follow‐up, 9.46% of patients required dose escalation, while 39.92% interrupted ADA. Concomitant therapy was used in 64.89% of cases. A subanalyses comparing pre‐ and post‐pandemic periods revealed a tendency to initiate ADA treatment at a younger age, among patient with higher BMI and at a lower HS stage after COVID‐19 pandemic. Interestingly, ADA demonstrated extended survival compared to previous studies, with a median overall drug survival of 56.2 months (95% CI 51.2 to 80.3). The primary causes for discontinuation were inefficacy (51.69%), followed by adverse effects (21.35%). Female sex, longer delay in HS diagnosis, higher baseline IHS4 score and concomitant spondyloarthritis were associated with poorer ADA survival or increased risk of discontinuation. Conclusions: ADA demonstrated prolonged survival (median 56.2 months). While addition of antibiotics did not have a positive effect on survival rate, basal IHS4 proved useful in predicting ADA survival. [ABSTRACT FROM AUTHOR]

Objective. To assess the effect of bimekizumab on pain, morning stiffness, and fatigue in patients with nonradiographic and radiographic axial spondyloarthritis (axSpA) in the phase III BE MOBILE studies (ClinicalTrials.gov: NCT03928704 and NCT03928743). Methods. Patients were randomized to bimekizumab 160 mg or placebo every 4 weeks; and all patients received bimekizumab from week 16. Patients reported spinal pain, peripheral pain, morning stiffness, and fatigue to week 52. Total and nocturnal spinal pain were each assessed on a 0-10 numerical rating scale (NRS). Individual Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) items (0-10--point NRS) assessed peripheral arthritis pain (question [Q] 3), enthesitis pain/discomfort (Q4), morning stiffness (mean of Q5 and Q6), and fatigue (Q1). Functional Assessment of Chronic Illness Therapy Fatigue subscale score (FACIT-Fatigue) is also reported. Results. At week 16, bimekizumab-treated patients reported lower mean nocturnal spinal pain, total spinal pain, and BASDAI scores (nominal except for nocturnal spinal pain; all P ≤ 0.001), as well as higher FACIT-Fatigue scores (nominal P < 0.05) vs placebo, indicating improved symptom levels. Improvements continued to week 52 in continuous bimekizumab-treated patients and in placebo-bimekizumab switchers. A higher proportion of bimekizumab- vs placebo-randomized patients achieved increasingly stringent thresholds for low spinal and peripheral pain at week 16; this was sustained or improved at week 52. Results were similar for morning stiffness and fatigue. At week 52, over half of patients were considered FACIT-Fatigue responders (≥ 8-point increase in score). Conclusion. Bimekizumab treatment led to rapid improvements in levels of pain and morning stiffness. Substantial improvements were seen in all domains across the full disease spectrum of axSpA and continued to week 52. [ABSTRACT FROM AUTHOR]

Objective. To provide a set of living treatment recommendations that will give contemporary guidance on the management of patients with axial spondyloarthritis (axSpA) in Canada. Methods. The Spondyloarthritis Research Consortium of Canada (SPARCC), in conjunction with the Canadian Rheumatology Association, organized a treatment recommendations panel composed of rheumatologists, researchers, allied health professionals, and a patient advocate. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach was used, in which existing guidelines were adopted or adapted to a Canadian context. Recommendations were also placed in a health equity framework. Results. Fifty-six recommendations were made for patients with active axSpA, stable axSpA, active or stable axSpA, for comorbidities, and for assessment, screening, and imaging. Recommendations were also made for principles of management, disease monitoring, and ethical considerations. Conclusion. These living treatment recommendations will provide up-to-date guidance for the management of axSpA for Canadian practice. As part of the living model, they will be updated regularly as changes occur in the treatment landscape. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of Crohn’s disease (CD) and axial spondyloarthritis (axSpA) is challenging, with CD refractory to anti-TNF antibodies. Here, we present for the first time a case treated with dual-targeted therapy (DTT) using the anti-IL-23 monoclonal risankizumab and the anti-TNF antibody certolizumab pegol. Case Presentation: Our patient initially presented with axSpA at the age of 27. Nine years later, CD was diagnosed by the age of 36. One year after the diagnosis of CD, a spontaneous ileal perforation occurred as part of a disease course refractory to multiple anti-TNF antibodies and intolerance to immunomodulators. However, the axSpA showed a response to the anti-TNF certolizumab pegol. After stopping certolizumab pegol, we enrolled the patient into the M15-991 induction trial (MOTIVATE) and the maintenance trial (FORTIFY) testing the anti-IL-23 antibody risankizumab versus placebo in CD with failure to prior biological therapy. As a result, risankizumab induced a CD response but failed to control the axSpA. Considering the CD refractory and the axSpA responding to anti-TNFs, we initiated a DTT with risankizumab and certolizumab pegol. Risankizumab and certolizumab pegol together improved both CD and axSpA. As adverse events, there were only two episodes of spontaneously resolving common colds during the 19-month reviewed period. Conclusion: DTT using risankizumab and certolizumab pegol is effective in CD and axSpA without serious adverse events in our patient. Combining biologicals that target specific pathways in immune-mediated diseases promises excellent potential in CD associated with extraintestinal manifestations. [ABSTRACT FROM AUTHOR]

Background: The phosphodiesterase 4 (PDE4) inhibitor apremilast downregulates the production of IL-23 and other pro-inflammatory cytokines involved in the pathogenesis of psoriatic arthritis (PsA). Aim: To investigate the effects of apremilast on the production of cytokines by peripheral blood monocyte-derived macrophages, innate-like lymphocyte cells (ILCs), mucosal-associated invariant T (MAIT) cells, γδ T cells, natural killer (NK) cells, and NKT-like cells from patients with PsA manifesting different clinical responses to the treatment. Methods: Peripheral blood samples were obtained from patients with PsA at baseline and after 1 and 4 months of apremilast therapy (n = 23) and 20 controls with osteoarthritis. Cytokine expression in peripheral blood monocyte-derived macrophages and ILCs/MAIT/γδT/NK/NKT-like cells was tested by RT-PCR and FACS analyses, respectively; cytokine levels in culture supernatants and sera were analyzed by ELISA. Results: PsA monocyte-derived macrophages exhibited higher expressions of IL-23, IL-1β, and TNF-α, compared with OA controls, more profoundly in patients responding to apremilast. There were 17/23 (74%) PsA patients who were classified as responders to apremilast at 4 months, and a baseline serum IL-23 >1.4 pg/mL was associated with the responder status (AUCROC 0.79; sensitivity 100%, specificity 68%). Of note, apremilast led to a significantly reduced expression of IL-23 in peripheral blood monocyte-derived macrophages; IL-17 in ILC1 and in T cells of responder patients; IFN-γ in γδ T lymphocytes. Conclusion: An enhanced myeloid inflammatory signature characterizes PsA monocyte-derived macrophages, and serum IL-23 levels represent candidate biomarkers for PsA response to apremilast. [ABSTRACT FROM AUTHOR]

Background: Gabapentinoids are increasingly prescribed in inflammatory arthritis (IA), despite no trial evidence for efficacy at managing pain in this population. Observational studies in non-IA populations suggest gabapentinoids are associated with fractures but are limited by methodological heterogeneity/potential residual confounding. Patients with IA generally have an increased risk of fracture so may be particularly vulnerable. We examined the relationship between fractures and gabapentinoids in patients with IA who had all been prescribed a gabapentinoid at some point (to minimise confounding by indication). Methods: Our matched case–control study used linked national data from English primary care (Clinical Practice Research Datalink Aurum) and Hospital Episode Statistics. A cohort was constructed of adults with IA, contributing data 01/01/2004–31/03/2021, and ever prescribed oral gabapentinoids. Cases with an incident fracture post-cohort inclusion were ascertained and 1:5 risk set-matched (on age/gender/gabapentinoid type) with controls. Gabapentinoid prescription exposure was categorised as follows: (a) current (overlapping with fracture date); (b) recent (ending 1–60 days pre-fracture); and (c) remote (ending > 60 days pre-fracture). Conditional logistic regression models determined ORs with 95% CIs for fractures with current or recent vs. remote gabapentinoid use, adjusting for confounders. Results: A total of 2485 cases (mean age 63.0 years; 79.4% female) and 12,244 controls (mean age 62.7 years; 79.6% female) were included. Of cases: 1512 received gabapentin, 910 pregabalin, and 63 both drugs; 65.6% were remote, 5.5% recent, and 28.9% current users. In adjusted models, current gabapentinoid use had an increased risk of fracture (OR vs. remote: 1.36 [95% CI 1.22, 1.51]). Similar associations were seen with gabapentin (OR 1.38 [1.19, 1.60]) and pregabalin (OR 1.40 [1.18, 1.66]). Similar or higher levels of association were seen for all gabapentin/pregabalin doses except moderate/very high dose gabapentin. Associations were strongest in those starting gabapentinoids more recently. Conclusions: Our study suggests a modest association between current gabapentinoid use and fractures in patients with IA, after accounting for measured and time-invariant unmeasured confounding. Whilst other unmeasured confounding remains possible, given the absence of evidence for gabapentinoid efficacy in patients with IA who are particularly vulnerable to fractures, this highlights a need for efforts to deliver safer gabapentinoid prescribing in this population. [ABSTRACT FROM AUTHOR]

Imaging has transformed the understanding of inflammatory and degenerative arthritis in both peripheral and axial disease. In axial inflammation, fat suppression magnetic resonance imaging (MRI) has unravelled the role of sub-fibrocartilaginous osteitis in axial spondyloarthritis and the role of peri-entheseal vertebral body osteitis and subsequent spinal new bone formation. Established or late-stage axial psoriatic arthritis (PsA) cases often exhibit impressive para-marginal or chunky syndesmophytosis on conventional X-ray that pathologically represents entheseal soft tissue ossification. However, the spinal entheseal soft tissue and contiguous ligamentous tissues are poorly visualized on MRI in subjects with early inflammatory back pain including those with axial PsA. In this article, we highlight the need for imaging modalities to discern the crucial soft tissue "ligamentous" component of axial PsA towards diagnosis, prognosis and therapy validation. We issue a clarion call to focus advanced imaging methodology on spinal ligamentous soft tissue that represents the last hidden backwater of PsA immunopathology that needs visualization to fully decipher axial PsA pathogenesis. This in combination with the existing ability to visualize ligamentous bony anchorage site osteitis is needed to define a gold standard test for axial PsA. [ABSTRACT FROM AUTHOR]

Axial involvement in psoriatic arthritis (PsA) has been a major feature of the disease since the original description by Wright and Moll. However, despite over 50 years of study, there is still no accepted definition of axial PsA, nor validated classification criteria. Numerous observational studies have described a phenotype of axial involvement that differs from classical ankylosing spondylitis (AS or axial spondyloarthritis) both clinically and radiographically, and in the frequency of the HLA-B27 antigen. These differences are important clinically, as axial PsA may be less prominent than AS, and in terms of treatment. This short review discusses these issues and offers some clarification for clinicians. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) is a group of chronic inflammatory diseases affecting the spine and peripheral joints, causing pain, stiffness, and reduced mobility. This narrative review examines how lifestyle factors—specifically smoking, alcohol consumption, and unhealthy diet—contribute to the onset and progression of SpA. It highlights their impact on disease activity, comorbidities, radiographic damage, and treatment response. Therefore, healthcare providers are encouraged to support patients in making personalized lifestyle changes. These findings underscore the importance of a comprehensive approach to SpA management, integrating lifestyle modifications with conventional therapies for optimal disease control and improved outcomes. [ABSTRACT FROM AUTHOR]

Background: To assess gender differences in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS) study from around the globe. Method: IMAS is a cross‐sectional online survey (2017–2022) of 5557 unselected axSpA patients from 27 countries. The current analysis assessed differences between males and females for: sociodemographic, health behaviors, disease characteristics, patient‐reported outcomes, mental comorbidities, and treatments. Univariable and multivariable logistic regression analysis was used to evaluate the relationship between gender and disease characteristics, patient‐reported outcomes, comorbidities, and treatments. Results: Data from 5555 patients reporting gender were analyzed: 3492 from Europe, 769 from North America, 600 from Asia, 548 from Latin America, and 146 from Africa. Globally, 55.4% were females, with higher proportions in South Africa (82.2%) and lower in Asia (20.8%). Compared to males, a lower percentage of females smoked and consumed alcohol. The diagnostic delay was significantly longer (+2.4 years) in females, while the frequency of HLA‐B27 positivity of axSpA was lower in females. The use of axSpA pharmacological treatment was more common in females with a higher proportion having ever taken nonsteroidal anti‐inflammatory drugs (NSAIDs), conventional synthetic DMARDs (csDMARDs), and biologic DMARDs (bDMARDS). Conclusions: Identifying the specific disease characteristics associated with gender in patients with axSpA may help to improve the diagnosis and management of the disease, and thereby reduce the disease burden for patients around the world. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis is a common form of chronic inflammatory rheumatic disease in adults, the treatment of which is based on non-pharmacological elements on the one hand, and pharmacological options on the other, such as non-steroidal anti-inflammatory drugs in the first line, followed by biological or targeted synthetic treatments. The therapeutic objective is remission or a low level of disease activity; if this objective is not achieved, the treatment is rotated or changed. Multiple changes is one factor illustrating the inability to achieve disease control and may lead to the notion of a difficult-to-treat disease (D2T). This requires a consensual definition including, beyond the number or therapeutic changes, the assessment of all the dimensions of the disease (objective signs of inflammation, residual pain, degenerative changes, psychosocial context). Recognising D2T patients will enable us to identify a particular population and the factors associated with this condition. When faced with a D2T disease, we need to analyse the causes of treatment failure and take into account the different components of the disease and the patient. In the absence of any prospect of new therapeutic targets in the short term for this disease, patient management may involve intensification of non-pharmacological means and evaluation of new therapeutic strategies such as combinations of targeted treatments. [ABSTRACT FROM AUTHOR]

Objective: The goal was to develop and validate classification criteria for axial juvenile spondyloarthritis (SpA; AxJSpA). Methods: This international initiative consisted of four phases: (1) item generation, (2) item reduction, (3) criteria development, and (4) validation of the AxJSpA criteria by an independent team of experts in an internationally representative validation cohort. Results: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free‐listing exercise using input from international physicians, which collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included the following: imaging of active inflammation, imaging of structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% confidence interval [CI] 91.4%–99.7%), sensitivity of 64.3% (95% CI 54.9%–73.1%), and area under the receiver operating characteristic curve of 0.81 (95% CI 0.76%–0.86%). Conclusion: The new AxJSpA classification criteria require an entry criterion and a physician diagnosis of juvenile SpA and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies. [ABSTRACT FROM AUTHOR]

To assess the prevalence of clinically active disease in axial spondyloarthritis (axSpA) and its associated factors in a large global sample of patients from the International Map of Axial Spondyloarthritis (IMAS) study. IMAS is a cross-sectional online survey (2017–2022) of 5557 axSpA patients. Patients were divided between those with active disease (BASDAI ≥4) and without active disease (BASDAI <4). The factors evaluated were sociodemographic, lifestyle, patient-reported outcomes, employment, disease characteristics, extra-musculoskeletal manifestations, and treatment. Logistic regression analysis stratified by gender were used to evaluate the relationship between investigated factors and active disease. In the present study, 5295 patients who had responded to the BASDAI scale were included in the present study: 3231 were from Europe, 770 from North America, 600 from Asia, 548 from Latin America, and 146 from Africa. The mean age was 43.8 ± 12.9 years and 55.4% were females. Patients reported a mean BASDAI of 5.4 (±2.1) with 75% having active disease (BASDAI ≥4). In South Africa, 87.0% of patients reported having active disease, compared to 68.5% in Asia. Multivariable logistic regression showed an association of active disease with higher functional limitation, greater spinal stiffness, difficulty finding a job due to axSpA and worse mental health in both genders. For males, younger age and shorter diagnostic delay, and for females, no physical activity and presence of inflammatory bowel disease were associated with active disease. Three quarters of patients with axSpA reported clinically active disease, with higher proportion of patients with active disease in South Africa and lower proportion in Asia. Our results underline the complexity of the clinical disease activity concept in axSpA and the need for a holistic approach in the patient management, care and treatment. [ABSTRACT FROM AUTHOR]

There are still controversies about the efficacy of cycling to a second tumor necrosis factor inhibitor (TNFi) in patients with inflammatory arthritis. The aim of this study was to evaluate survival, persistence and effectiveness of golimumab (GLM) in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) with previous experience with other TNFi and to compare these results with TNFi naive patients. Observational cohort of consecutive patients with RA, PsA and axSpA who had started treatment with GLM according to medical indication. bDMARD naive and TNFi experienced patients were selected. A total of 147 (62.3%) bDMARD naive and 45 (19.1%) TNFi experienced patients were included. Patients were followed up for a total of 441.5 patients/year, 55 (28.6%) discontinued GLM, 42 (28.6%) and 13 (28.9%) in each group, respectively (p = 0.967). The majority (63.6%) suspended due to inefficacy, followed by lack of access (23.6%) and adverse events (9.1%). Median GLM survival was 74.0 months (95% CI 57.0, 91.0) and 71.0 months (95% CI 37.0, 105.0), in the bDMARD naive and TNFi experienced patients, respectively (p = 0.695). Drug persistence at 6, 12, 24 and 36 months was 92.8%, 88.1%, 76.1%, 65.4% and 93.1%, 77.4%, 74.2%, 68.5%, respectively. In the multivariable analysis, having public health insurance was associated with higher risk of drug discontinuation (HR 2.56, 95% CI 1.28–5.00, p = 0.008). TNFi experienced patients did not show significantly higher risk of GLM suspension (HR 1.35, 95% CI 0.70–2.57, p = 0.370). In this cohort, TNFi experienced patients had comparable survival and persistence of treatment with GLM. Having public health insurance was associated with lower drug retention rates. [ABSTRACT FROM AUTHOR]

Seronegative spondyloarthritis (SpA) is an umbrella term that includes ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, and arthritis related to inflammatory bowel disease. Apart from AS, these other conditions predominantly affect the appendicular skeleton. Both the foot and ankle are frequently involved peripheral joints. According to the latest Assessment of Spondyloarthritis International Society criteria, imaging is a key way to diagnose peripheral seronegative SpA. Common imaging features are enthesitis, synovitis, tenosynovitis, erosive and bone-proliferative changes in the affected joints, and effusion. Although magnetic resonance imaging is the gold standard technique, ultrasound (US) is a cost-effective imaging method that can readily detect the features just described. Additionally, it can semi-quantify inflammatory changes, helping in treatment and dose modifications. Imaging-guided procedures, such as biopsies and steroid injections, are routinely performed using US. Furthermore, US can easily be deployed at outpatient rheumatology clinics, making it an ideal point-of-care investigation. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the musculoskeletal system, skin and nails. In addition to peripheral joints, inflammation of the spine and sacroiliac joints may occur. Yet, research into this axial phenotype has lagged behind partly because of the challenge in its clinical identification with a lack of specific clinical, molecular or imaging biomarkers. In the absence of a validated definition of what constitutes axial PsA (axPsA), guidelines for the management of axial involvement in PsA in clinical practice are scarce. On the basis of a literature review and their clinical expertise, a group of rheumatology experts provide their opinion to aid the diagnosis and management of axial PsA in clinical practice. [ABSTRACT FROM AUTHOR]

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The impact of mental health on women with arthritis is significant, highlighting the unique psychological challenges they face in managing chronic inflammatory conditions like rheumatoid arthritis, spondylarthritis, and other immune-mediated arthritis. Depression, anxiety, fatigue, cognitive dysfunction, and sleep disturbances are prevalent yet often underrecognized issues that exacerbate the burden of arthritis. The complex relationship between physical and mental health requires an integrated approach to care, including psychological support, patient education, and the provision of resources to address the unique needs of women with arthritis. Strategies such as integrating mental health services into rheumatologic care, promoting physical activity, and addressing caregiving burdens are crucial to improving mental health outcomes. By breaking the cycle of mental health challenges, healthcare providers can improve both the physical and emotional well-being of women with arthritis, enhancing their quality of life and disease management. This article explores the common mental health disorders in arthritis, the barriers to seeking mental health care, and possible remedial measures to address these challenges effectively. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated muscle ultrasound in spondyloarthritis (SpA) patients receiving biologic disease-modifying antirheumatic drugs (b-DMARDs) early in treatment. Methods: A prospective study was conducted with 110 b-DMARD-naive SpA patients. The baseline and control muscle strength, physical performance tests, ultrasonographic muscle parameters, and disease activity scores of 67 controlled patients were examined. Results: During the follow-up period, there were significant improvements in the thickness of the gastrocnemius medialis (GM) muscle (p<0.001), the length of the GM fascicle (p=0.031), the thickness of the rectus femoris (RF) muscle (p<0.001), the crosssectional area of the RF (RFCSA) muscle (p<0.001), the thickness of the rectus abdominis (RA) muscle (p<0.001), the thickness of the transverse abdominis (TA) muscle (p=0.004), and the thickness of the external oblique (EO) muscle (p=0.042). Besides, ASDAS-CRP scores were related to GM muscle thickness, RFCSA, and TA muscle thickness percent changes in patients whose disease activity regressed from high to moderate (respectively; p=0.030, p=0.040, p=0.002). Conclusion: Muscle ultrasound examination can show muscle mass improvement in SpA patients during treatment. [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]

Spondyloarthritis (SpA) is a prevalent genetic disorder that significantly impairs mobility, particularly in the spine, sacroiliac, and peripheral joints. Recent evidence highlights early involvement of the sternoclavicular joint in SpA, which may serve as an initial indicator. Diagnosis often relies on CT and MRI, neglecting ultrasound's potential in identifying SpA‐related sternoclavicular arthritis. This review focuses on the joint's anatomy, exploring ultrasound's diagnostic and therapeutic role in SpA‐related sternoclavicular arthritis, aiming to provide insights for future ultrasound applications in SpA management. [ABSTRACT FROM AUTHOR]

Introduction: Psoriatic arthritis (PsA) is a complex condition within the Spondyloarthritis (SpA) group. Recent studies have focused on the important role of the intestinal microbiota in maintaining immunological homeostasis, highlighting how intestinal dysbiosis may act as a trigger for autoimmune diseases. Tofacitinib is a Janus kinase inhibitor (JAK-i) with proven efficacy for the treatment of both rheumatoid arthritis and PsA. However, there is a lack of data on its ability to reduce joint remission through ultrasonography (US) and the effects it might have on the composition of the gut microbiota. Methods: Here, we present a case series of seven bio-naïve PsA patients who received tofacitinib treatment and were followed up for 12 months. The clinical response was assessed using validated scores (DAPSA, ASDAS, and BASDAI), laboratory tests, and US assessment of the target joint and enthesis. Finally, we evaluated changes in the composition of the intestinal microbiota using next-generation sequencing analysis of fecal samples. Results: The patients in the study showed a significant improvement in all clinical scores used; this improvement was also confirmed by a significant reduction in the US synovitis scores. The data on the microbiota analysis suggested that the effectiveness of tofacitinib in ameliorating PsA activity was associated with a relevant modification of some gut bacterial lineages. No cases of severe adverse effects were reported. Conclusions: Treatment with tofacitinib proved to be effective, safe and capable of varying the composition of the gut microbiota by selecting bacterial strains considered beneficial in immune modulation. [ABSTRACT FROM AUTHOR]

This review examines the efficacy, safety, and pharmacokinetics of upadacitinib (UPA) for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). This review analyzes the results of multiple clinical trials and provides a comprehensive overview of UPA's effectiveness in improving disease activity, reducing symptoms, and preventing joint damage. The review also highlights the safety profile of UPA, including the increased risk of herpes zoster, non-melanoma skin cancer, and elevated creatine phosphokinase levels. In addition, the review discusses the pharmacokinetics of UPA, emphasizing its rapid absorption and limited plasma protein binding. Overall, UPA appears to be a promising therapeutic option for patients with RA, PsA, and axSpA, particularly those with inadequate response to other therapies. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a chronic illness with limited treatment options. The role of Janus kinase (JAK) inhibition as a therapeutic option has increasingly become a focus of research in recent years as they have brought a new mode of action to the clinical armamentarium. This review assesses the efficacy and safety profile of these drugs in axSpA. The current phase 2 and 3 clinical trials data are summarized across tofacitinib, upadacitinib and filgotinib. Moreover, the safety profiles of these drugs, in the context of emerging safety signals such as during the ORAL surveillance study, are reviewed. In summary, JAK inhibitors offer a novel therapeutic target for axSpA and appear to address some of the unmet needs for patients who have either failed to respond to current treatment options or in whom they are contraindicated. There is a relative lack of evidence in non-radiographic axSpA and longer-term trials are needed to establish true efficacy and safety profile in radiographic axSpA. [ABSTRACT FROM AUTHOR]

Objectives Real-world evidence is needed to inform treatment strategies for patients with PsA and axial SpA (axSpA) who have non-musculoskeletal manifestations (NMMs), various risk factors and comorbidities. International collaboration is required to ensure statistical power and to enhance generalizability. The first step forward is identifying which data are currently being collected. Across 17 registries participating in the European Spondyloarthritis Research Collaboration (EuroSpA), we aimed to map recording practices for NMMs, comorbidities and safety outcomes in patients with PsA and axSpA. Methods Through a survey with 4,420 questionnaire items, we explored the recording practices of 58 pre-defined conditions (i.e. NMMs, comorbidities and safety outcomes) covering 10 disease areas. In all registries we mapped for each condition whether it was recorded, the recording procedure and the potential to identify it through linkage to other national registries. Results Conditions were generally recorded at entry into the registry and clinical follow-up visits using a pre-specified list or a coding system. Most registries recorded conditions within the following disease areas: NMMs (number of registries, n  = 15–16), cardiovascular diseases (n  = 10–14), gastrointestinal diseases (n  = 12–13), infections (n  = 10–13) and death (n  = 14). Nordic countries had the potential for data linkage and generally had limited recording of conditions in their registry, while other countries had comprehensive recording practices. Conclusion A wide range of conditions were consistently recorded across the registries. The recording practices of many conditions and disease areas were comparable across the registries. Our findings support the potential for future collaborative research. [ABSTRACT FROM AUTHOR]

Objective Inflammatory spondyloarthropathies are associated with pain, fatigue, stiffness and anxiety. The National Institute for Health and Care Excellence and the EULAR provide limited lifestyle guidance for managing symptoms with inflammatory spondyloarthropathies. We investigated the combined associations of obesity and physical activity with symptom severity in inflammatory spondyloarthropathies. Methods The relationship between BMI, physical activity and symptom severity (spinal and general pain, fatigue, anxiety, mobility) was examined in people with ISpAs (n  = 1577). BMI categories were normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obese (≥30 kg/m2). Physical activity was assessed via the International Physical Activity Questionnaire (low < 600 metabolic equivalent of task (MET)-min/week, moderate ≥ 600 METs, high ≥ 3000 METs). Statistical models adjusted for confounders, including medication, estimated the likelihood (odds ratios, OR) of higher symptom severity across BMI and physical activity categories. Results Overweight and obesity, compared with normal weight, were linked to higher severity of all symptoms, with stronger associations for obesity (OR ≥ 2.34, P  < 0.001) than overweight (OR ≥ 1.37, P  ≤ 0.032). Moderate activity, compared with low, was associated with lower severity of all symptoms (OR ≤ 0.77, P  ≤ 0.032). High activity, compared with low, was associated with lower severity of fatigue, anxiety and mobility issues (OR ≤ 0.74, P  ≤ 0.029), but associations with spinal and general pain were not significant (OR ≤ 0.80, P  ≥ 0.056). No BMI-by-physical activity combinations were detected, indicating physical activity benefits all BMI groups to a similar extent. Conclusion National Institute for Health and Care Excellence and EULAR guidance for inflammatory spondyloarthropathies should emphasize maintaining a normal weight. Moderate physical activity is optimal for reducing symptom severity and should be promoted in lifestyle guidance. [ABSTRACT FROM AUTHOR]

Imaging biomarkers in axial spondyloarthritis (axSpA) are currently the most specific biomarkers for the diagnosis of this condition. Despite advances in imaging, from plain radiographs--which detect only damage--to magnetic resonance imaging (MRI)--which identifies disease activity and structural change--there are still many challenges that remain. Imaging in sacroiliitis is characterized by active and structural changes. Current classification criteria stress the importance of bone marrow edema (BME); however, BME can occur in various diseases, mechanical conditions, and healthy individuals. Thus, the identification of structural lesions such as erosion, subchondral fat, backfill, and ankylosis is important to distinguish from mimics on differential diagnosis. Various imaging modalities are available to examine structural lesions, but computed tomography (CT) is considered the current reference standard. Nonetheless, recent advances in MRI allow for direct bone imaging and the reconstruction of CT-like images that can provide similar information. Therefore, the ability of MRI to detect and measure structural lesions is strengthened. Here, we present an overview of the spectrum of current and cutting-edge techniques for SpA imaging in clinical practice; namely, we discuss the advantages, disadvantages, and usefulness of imaging in SpA through radiography, low-dose and dual-energy CT, and MRI. Cutting-edge MRI sequences including volumetric interpolated breath-hold examination, ultrashort echo time, zero echo time, and deep learning-based synthetic CT that creates CT-like images without ionizing radiation, are discussed. Imaging techniques allow for quantification of inflammatory and structural lesions, which is important in the assessment of treatment response and disease progression. Radiographic damage is poorly sensitive to change. Artificial intelligence has already revolutionized radiology practice, including protocolization, image quality, and image interpretation. [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]

Background: Hypertension (HTN) is the most important modifiable risk factor for the development of cardiovascular events (CVEs). Patients with axSpA are also associated with an increased risk of future CVE. Objectives: To ascertain whether baseline early-stage HTN is a predictor of future CVE in addition to inflammation in patients with axial spondyloarthritis (axSpA). Design: A retrospective cohort study. Methods: Patients with axSpA were recruited from 2001 to 2017. Patients with at least 2 years of follow-up and without prior CVE were divided into three groups according to the calculated mean blood pressure (BP) over the first 2-year follow-up period (adjusted mean BP) (⩾140/90, 130–139/80–89, and <130/80 mm Hg). They were followed from baseline until the end of 2020 or the occurrence of a first CVE. Multivariate Cox regression analyses adjusting for baseline and time-varying variables were used to assess the relationship between mean BP and CVE. Results: Out of the 437 patients fulfilling the inclusion criteria, 49 (11.2%) and 132 (30.2%) had an adjusted mean BP ⩾ 140/90 and 130–139/80–89 mm Hg, respectively, and 256 (58.6%) were pre-HTN. After a median follow-up of 12 (7–18) years, 56 (12.8%) CVEs were documented. The incidence rates were 21.4, 14.2, and 5.9 per 1000 patient-years for the three groups, respectively. Baseline adjusted mean BP of 130–139/80–89 mm Hg was independently associated with the occurrence of CVE after adjusting for the baseline covariates as well as time-varying high inflammatory burden. Conclusion: Baseline-defined early-stage HTN carries excessive risk of developing CVE which may be due to untreated inflammatory burden. Early antihypertensive therapy should target this BP level to minimize their future risk of CVE. [ABSTRACT FROM AUTHOR]

ObjectivesMethodResultsConclusionIn axial spondyloarthritis (axSpA), patient-perceived quality of life/global functioning and health (GH) can be assessed using disease-specific [Assessment of SpondyloArthrit is international Society Health Index (ASAS-HI)] or generic [(3-level EuroQol 5 Dimensions (EQ-5D-3L)] scores. Our objectives were to explore the link between these scores and to define thresholds for good and poor GH.We conducted a post-hoc analysis of the cross-sectional ASAS-PerSpA study for patients fulfilling ASAS criteria for axSpA. The ASAS-HI and EQ-5D scores were analysed visually (distribution, scatterplot) and through Spearman correlation and agreement (deciles). To determine cut-offs for good and poor GH on EQ-5D based on the validated ≤5 and ≥12 cut-offs for ASAS-HI, respectively, receiver operating characteristics (ROC) curves and distribution-based methods were applied. Validity was assessed using crude concordance and prevalence-adjusted bias-adjusted kappa; discordance between groups was explored.In 2651 patients (median age 41.0 years, 66.5% men), the correlation between ASAS-HI and EQ-5D was high (r = −0.73) and agreement (between deciles) was moderate (weighted kappa = 0.51). Both ROC areas under the curve were 0.86; thresholds of 0.69 and 0.54 for EQ-5D were chosen for good and poor GH, respectively. Crude concordances and agreement were satisfactory (0.80–0.81 and 0.60–0.61, respectively). The EQ-5D cut-off for good GH performed better than that for poor GH.ASAS-HI and EQ-5D were highly correlated but did not fully overlap. We propose EQ-5D thresholds corresponding to the ASAS-HI thresholds for good and poor GH; however, caution is needed when assessing poor GH with EQ-5D. These findings will be useful to compare GH when only one of the outcome measures is available. [ABSTRACT FROM AUTHOR]

Objectives: The medications used for autoimmune diseases have significantly evolved in recent years, but there is limited knowledge about how treatment practices changed during pregnancy. This study aimed to describe the temporal trends of immunosuppressants, immunomodulators and biologics use during pregnancy among women with autoimmune diseases, compare their use before, during, and after pregnancy, and identify factors predicting the discontinuation of these medications during pregnancy. Methods: Using data from the Quebec Pregnancy Cohort (1998–2015), which included women under the RAMQ prescription drug plan for at least 12 months before and after pregnancy, the analysis focused on those with at least one International Classification of Diseases Ninth or Tenth Revision code in the year before pregnancy for inflammatory bowel disease, rheumatoid arthritis, spondylarthropathies, connective tissue diseases, systemic lupus erythematosus, or vasculitis. Exposure to immunosuppressants, immunomodulators and biologics were evaluated before and during the pregnancy. Discontinuation during pregnancy was defined as having no prescriptions filled during pregnancy or overlapping with the first day of gestation (1DG), given that at least one prescription was filled in the year prior to pregnancy. Generalized estimating equations were applied to estimate adjusted odds ratios (aOR) for predicting medication discontinuation during pregnancy. Results: Among 441,570 pregnant women, 3,285 had autoimmune diseases. From 1998 to 2014, the use of immunomodulators increased from 3.7% to 11.9%, immunosuppressants from 4.1% to 13.7%, and biologics from 0% to 15.6%. During pregnancy, compared to before, there was a significant decrease in exposure to immunomodulators (8.6% to 5.4%), immunosuppressants (14.2% to 8.7%), and biologics (5.1% to 4.7%). Factors influencing discontinuation varied by medication type; for immunosuppressants, prior biologics use (aOR = 2.12, 95%CI 1.16–3.85) and the year of pregnancy (aOR = 0.93, 95%CI 0.89–0.98) were key factors, while for biologics, it was only the year of pregnancy (aOR = 0.68, 95%CI 0.54–0.86). Conclusions: The use of immunomodulators, immunosuppressants, and biologics has increased over time. However, exposure during pregnancy decreased, with recent years showing a lower rate of discontinuation. Understanding the factors influencing medication discontinuation during pregnancy can improve management strategies for women with autoimmune diseases. [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]

Background: People with early axial spondyloarthritis experience a diagnostic delay and a similar disease burden as people with axial spondyloarthritis at a later stage of the disease. In many European countries, patients with early axial spondyloarthritis do not have access to an interdisciplinary rehabilitation team. The objective of this study was to develop a new evidence-based physiotherapist-coordinated interdisciplinary rehabilitation intervention for individuals suspected of axial spondyloarthritis. This development of the rehabilitation intervention is part of the SPINCODE project which focusses on early diagnosis and treatment for people with axial spondyloarthritis. Methods: The development of the intervention encompasses: (i) identifying the evidence base and program theories; (ii) modeling and remodeling the intervention; and (iii) describing the developed intervention. Results: The six-month SPINCODE rehabilitation intervention is a physiotherapist-coordinated, interdisciplinary, outpatient rehabilitation intervention at a specialized rheumatology hospital. The intervention consists of: (i) individual physiotherapist-coordinated consultations with assessment, goal setting, tailored physical activity support, and the defined goals, and coordination across the interdisciplinary team at the hospital and across primary and secondary healthcare levels; (ii) group sessions, encompassing patient education and peer support; and (iii) optional individual support from the interdisciplinary team. Physiotherapists from private care working with the patient enrolled in the SPINCODE study are offered digital support from the hospital-based physiotherapists. Conclusions: The developed physiotherapist-led interdisciplinary SPINCODE rehabilitation intervention is ready for feasibility testing. [ABSTRACT FROM AUTHOR]

Background/Objectives: Obesity and smoking have been related to increased disease activity in axial spondyloarthritis (axSpA), but these associations might vary depending on the composite index chosen to assess disease activity. We aimed to check this possibility. Methods: Three hundred and thirty consecutive patients were recruited from the monographic axSpA unit of a university center. To assess disease activity, BASDAI and ASDAS-CRP measurements were collected. The factors associated with the different disease activity thresholds of these instruments were analyzed using univariate and multivariate logistic regression models. Results: This study included 127 women and 203 men, with a mean age of 47.6 (SD 12.9) years, median disease duration of 8 years [IQR: 4–16], and 63% on biologic therapies. Most patients met the therapeutic goals, with a BASDAI < 4 in 187 (56.7%) and ASDAS inactive/low category in 182 (55.2%). Being male was associated with BASDAI remission (OR 2.63), but smoking reduced this likelihood (OR 0.28). Similar findings were found for ASDAS inactive disease (male: OR 2.09; smoking: OR 0.39). The variables associated with BASDAI ≥ 4 in the multivariate logistic model were the male gender (OR 0.36), age (OR 1.02), smoking (OR 2.39), and obesity (OR 2.94), whereas those associated with active/very active ASDAS categories were the male gender (OR 0.49), age (OR 1.02), and smoking (OR 2.34). However, obesity was not associated with these higher ASDAS categories (p = 0.183). Conclusions: While the association between smoking and increased disease activity was consistent across all composite activity indices, the obesity–activity relationship was only apparent through the BASDAI. [ABSTRACT FROM AUTHOR]

Objective: To develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA). Method: A joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated. Results: A total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients' values and willingness as well as the objective of testing in the local context. Conclusion: This guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from. [ABSTRACT FROM AUTHOR]

Arthropathies are common in past populations and can be categorized into two groups: those with predominant bone production (e.g., osteoarthritis) and those with significant bone loss (e.g., erosive arthropathies). The former is frequent in the archaeological record, whereas the latter are uncommon. We present a Post‐Medieval male individual, recovered in the Convent of the Holy Spirit (Loures, Portugal), with multiple articular and entheseal bone changes, particularly extensive periarticular, marginal, and subchondral erosive processes, often exposing trabecular bone. Proliferative lesions and extensive ankylosis are also observed in the synovial joints. These pathological changes affect both the axial and peripheral skeleton in a polyarticular, bilateral, and asymmetric pattern. Given that the appendicular skeleton, particularly the hands and feet, are the most affected areas, the most probable diagnosis is a peripheral spondyloarthropathy such as psoriatic arthritis or reactive arthritis. This case study is the first archaeological instance of psoriatic arthritis or reactive arthritis described in Portugal, highlighting the importance of a differential diagnosis and the need for reflection when pathological changes characteristics overlap, advocating for a broader diagnostic approach. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the effectiveness and drug retention rate of secukinumab (SCK) in axial spondyloarthritis (ax-SpA) within a multicentric real-life cohort. Methods: Data from patients with ax-SpA treated with SCK at five Italian centers were collected retrospectively, excluding those with a diagnosis of Psoriatic Arthritis. Evaluations were conducted at baseline and at 3, 6, 12, 18, and 24 months. Assessments included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), BASDAI, and ASDAS-CRP. Results: Seventy-one ax-SpA patients (57.7% female, mean age: 53.86 ± 12.67 years) were enrolled. Baseline mean BASDAI was 6.2 ± 1.4 and ASDAS-CRP was 2.9 ± 1.3. Significant improvements in BASDAI and ASDAS-CRP were observed over time, with BASDAI reducing to 3.5 ± 1.9 (p < 0.0001) and ASDAS-CRP to 1.7 ± 0.9 (p < 0.0001) at 24 months. The follow-up duration averaged 20.46 ± 13.46 months. By the end of follow-up, 29.5% of patients discontinued SCK. The two-year retention rate was 72%. Dropout risk was higher in patients with fibromyalgia (HR: 2.896, p = 0.026). No significant retention differences were found based on sex, age, enthesitis, radiographic disease, combination with cDMARDs, SCK dosage, or previous bDMARD exposure. Lower ASDAS-CRP at the study's end was noted in patients without fibromyalgia (1.4 vs. 2.5, p < 0.001). Conclusions: SCK showed rapid and lasting effectiveness for ax-SpA with a favorable retention rate, though fibromyalgia may reduce treatment persistence. [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 estimate objective cut‐off values for Bath ankylosing Spondylitis Disease Activity Index (BASDAI) corresponding to Ankylosing Spondylitis Disease Activity Score with CRP (ASDAS) cut‐off values (1.3, 2.1, and 3.5), and for interval changes (ΔBASDAI) corresponding to ΔASDAS (1.1 and 2). Methods: In this multicentric study, adult patients with active axial spondyloarthritis (axSpA) treated with either tofacitinib 5 mg twice daily or adalimumab 40 mg subcutaneously fortnightly were recruited. Available paired data on BASDAI and ASDAS and paired interval change of these parameters (taken at least 3‐months apart) were analyzed. Cut‐off values for BASDAI were determined from a multinomial logistic regression and that for ΔBASDAI were determined with ordinal logistic regression with predicted probabilities. Diagnostics were assessed with correct classification rate (CRR), polychoric correlations (PCC), Goodman and Kruskal Gamma (GKG), and Matthew's correlation coefficient (MCC). Results: Total 962 observations of paired data and 670 interval change data were available from 266 patient (mean age 35 years, mean disease duration 7 years, mean BASDAI 2.7, and mean ASDAS 2.1). Following ASDAS classes were observed: inactive disease 131 (13.6%), moderate disease activity 322 (33.5%), high disease activity 420 (43.65%), and very high disease activity 89 (9.25%). The three cut‐offs generated for BASDAI were 0.8, 2.5, and 6 for BASDAI and those for ΔBASDAI were 2 and 4. The CRR for BASDAI cut‐offs was 65.59 and that for ΔBASDAI was 54.9. For the BASDAI cut‐offs, both PCC and GKG showed high values (> 0.85) and the MCC was 0.471. Conclusion: In patients with axSpA, without any clinical or serological confounders, BASDAI values 0.8, 2.5, and 6 corresponded to ASDAS‐CRP values 1.3, 2.1, and 3.5, respectively, and ΔBASDAI values of 2 and 4 correspond to ΔASDAS cut‐offs of 1.1 and 2. [ABSTRACT FROM AUTHOR]