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Objective: To investigate a potentially primary involvement of the facet joints (FJs) in axial spondyloarthritis (axSpA) development, by studying inflammatory and structural magnetic resonance imaging (MRI) and radiographic changes in the sacroiliac joints (SIJs) and lumbar spine, focusing on FJs, in newly diagnosed radiographic axSpA over a 3 year period. Method: Twenty-four patients (14 male, 10 female; mean ± sd age 33.75 ± 8.6 years) with radiologically and MRI-confirmed axSpA according to modified New York and Assessment of SpondyloArthritis international Society criteria, with a symptom duration < 5.5 years at baseline (t0), were followed up after 3 years (t1) by rheumatologists and radiologists with axSpA MRI experience > 15 years. The Berlin MRI score was extended by an inflammation score of the lumbar FJs. Clinical assessments were performed. Results: Radiographic SIJs and syndesmophyte progression increased significantly between t0 and t1. MRI progression of the SIJs between t0 and t1 showed increasing bone marrow oedema (BME), significant fat lesion progression, and significant increases in sclerosis and erosion. In the lumbar spine, BME and fat lesions decreased while erosions in the vertebral units (VUs) significantly increased. Facet joint inflammation (FJI) in t0 significantly influenced MRI changes in VU bone proliferation at t1. Biologicals had no effect on MRI changes from t0 to t1. Conclusions: Structural MRI changes in the SIJs and lumbar VUs, and radiographic axSpA progression, developed significantly within 3 years. MRI-detected lumbar FJI in early disease is associated with MRI signs of VU bone proliferation, indicating a risk of potential ossification. [ABSTRACT FROM AUTHOR]

Objective: Inverse associations between systemic inflammation and cholesterol ('the lipid paradox') have been reported in rheumatoid arthritis (RA) and, in established axial spondyloarthritis (axSpA), but little is known about this relationship in early axSpA, which is the focus of the present study. Method: In the Swedish part of the SPondyloArthritis Caught Early (SPACE) cohort (patients with chronic back pain for ≥3 months, ≤2 years; age at onset <45 years), serum levels of total cholesterol (TC) and apolipoproteins ApoA1 and ApoB were measured at inclusion, together with parameters reflecting inflammatory disease activity [C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and sacroiliitis by magnetic resonance imaging (MRI) following Assessment of SpondyloArthritis international Society (ASAS) criteria]. All patients included in the analysis either had axSpA based on a high physician's level of confidence or fulfilled the ASAS criteria for axSpA. Associations between lipids/lipoproteins and inflammation were assessed using multivariable linear regression models. Results: In the 64 patients included, there were inverse associations for CRP with TC, ApoA1, and ApoB in age–sex-adjusted models. The negative associations with CRP remained significant for TC and ApoB in multivariable models adjusted for age, sex, BASDAI, and current smoking (p = 0.048). There were no significant associations for the lipid parameters with BASDAI or inflammation on MRI of the sacroiliac joints. Conclusion: Inverse associations between systemic inflammation and lipids, particularly TC and ApoB, are present in early axSpA, similar to those shown for other inflammatory joint diseases. These patterns must be considered when including lipids in the evaluation of cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMaterials & MethodsResultsDiscussion & ConclusionsAim of this study is to compare the thiol/disulfide variables before treatment, at the 3rd and 6th months of biologic treatment in patients with axSpA.Consecutive patients with axial spondyloarthritis to whom biologic treatment was initiated in our clinic were enrolled upon consent. Demographics, clinical characteristics, laboratory parameters and treatment agents were collected. Disease activity scores and thiol-disulfide balance parameters were recorded at baseline and 3rd, 6th months of treatment. Statistical analyses were performed in all patients and in subgroups of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients.In all patients, total thiol levels were significantly increased at 6th month in comparison to baseline values (470.5 ± 74.7 vs 491.9 ± 69.6, p = 0.047). Native thiol levels were increased at 6th month close to significance (438.9 ± 70.4 vs 458.8 ± 63.7, p = 0.060). Moderately strong negative correlations were observed between native thiol levels and disease activity parameters (BASDAI: p = 0,019; ASDAS-CRP: p = 0,035; ASDAS-ESR: p = 0,030), and between total thiol levels and disease activity parameters (BASDAI: p = 0,031; ASDAS-CRP: p = 0,020; ASDAS-ESR: p = 0,026) at 6th month evaluationOur results demonstrated oxidative stress reducing effect of biologics in axSpA patients parallel to suppression of disease activity at 6th month of the treatment. [ABSTRACT FROM AUTHOR]

Purpose: Rheumatic inflammatory diseases affecting the temporomandibular joint and the masticatory system (TMD) have been described as painful and limiting. However, the condition is often overlooked in primary care. The objective of this qualitative study was to explore and describe TMD-related experiences and perceptions of persons with rheumatic inflammatory disease, and to put this into a rehabilitation perspective. Materials and methods: Seven participants with rheumatic inflammatory disease and concomitant TMD were interviewed using a semi-structured interview guide. Giorgi's phenomenological method was used for analysis of the material. Results: The general structure of the results after phenomenological reduction indicated that the phenomenon could be described as the process of being challenged by the jaw. Five themes emerged from the analysis; 1. Physical challenges of the jaw and the struggle to retain control, 2. Shame and social challenges, 3. Worrying about the future, frustration, grief, and loss of freedom, 4. Defiance, endurance, and efforts to maintain self-esteem, and 5. Health-care experiences. Conclusions: TMD in rheumatic inflammatory diseases are complex problems associated with various challenges to the sufferer. An increased awareness of the condition and earlier interventions could reduce both suffering and worsening of the condition. IMPLICATIONS FOR REHABILITATION: The connection between the jaw and the rest of the body tends to be neglected. Questions about the jaw should be asked to detect eventual temporomandibular disorder (TMD) at an early stage to prevent worsening of the condition. Patient's experiences of TMD must be considered in the rehabilitation process. Health care providers are important for an earlier, more consistent, and more accessible diagnosis and treatment for this group of people. [ABSTRACT FROM AUTHOR]

Importance: Axial spondyloarthritis is an immune-mediated inflammatory condition involving the sacroiliac joints, spine, and peripheral joints. It affects approximately 1% of adults in the US and is associated with impaired physical function and reduced quality of life. Observations: Inflammatory chronic back pain characterized by gradual onset starting before age 45 years, prolonged morning stiffness, improvement with exercise, and lack of improvement with rest is the most common symptom of axial spondyloarthritis and affects more than 80% of patients. Patients with axial spondyloarthritis may also have inflammatory arthritis in large peripheral joints (most commonly knees) in an oligoarticular, asymmetric fashion; inflammation at tendon insertions (enthesitis); inflammatory eye disease (uveitis); psoriasis; and inflammatory bowel disease. The pathogenesis of axial spondyloarthritis may involve genetic predisposition, gut microbial dysbiosis, and entheseal trauma, with immune cell infiltration of the sacroiliac joints and entheseal insertion areas in the spine. There are currently no diagnostic criteria for axial spondyloarthritis. The diagnosis, often delayed 6 to 8 years after symptom onset, is based on history (ie, inflammatory back pain [sensitivity, 74%-81%; specificity, 25%-44%]), laboratory findings (human leukocyte antigen B27–positive [sensitivity, 50%; specificity, 90%] and elevated C-reactive protein level [sensitivity, 35%; specificity, 91%]), and imaging findings consisting of sacroiliitis on plain radiography (sensitivity, 66%; specificity, 68%) or magnetic resonance imaging (sensitivity, 78%; specificity, 88%). First-line treatments are physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). However, less than 25% of patients achieve complete symptom control with NSAIDs. Approximately 75% of patients require biologic drugs (tumor necrosis factor inhibitors [anti-TNF agents], interleukin 17 inhibitors [anti–IL-17 agents]) or targeted synthetic disease-modifying antirheumatic agents (Janus kinase [JAK] inhibitors) to reduce symptoms, prevent structural damage, and improve quality of life. Clinical trials reported that anti-TNF agents significantly improved ASAS20 (measure of pain, function, and inflammation) in 58% to 64% of patients compared with 19% to 38% for placebo. Similar outcomes were attained with anti–IL-17 agents (48%-61%, vs 18%-29% with placebo) and JAK inhibitors (52%-56%, vs 26%-29% with placebo). Anti-TNF agents, anti–IL-17 agents, and JAK inhibitors have been associated with reduced radiographic progression of axial spondyloarthritis. Conclusions: Axial spondyloarthritis predominantly affects the sacroiliac joints and spine but is also associated with extraskeletal manifestations such as uveitis, psoriasis, and inflammatory bowel disease. Physical therapy and NSAIDs are first-line treatments, but most patients require therapy with biologics (anti-TNF or anti–IL-17 agents) or JAK inhibitors to achieve improvement in signs and symptoms, inflammation control, and reduced progression of structural damage. This narrative review summarizes current evidence on the pathogenesis, epidemiology, clinical manifestations, diagnosis, and treatment of axial spondyloarthritis. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel disease (IBD) related arthritis is the most prevalent extraintestinal manifestation (EIM) of IBD, ranging between 10 and 39%. Magnetic resonance enterography (MRE) is used to assess small bowel disease involvement in Crohn's disease (CD) and can detect signs of sacroiliitis in up to 23.5% of patients. The predicting role of sacroiliitis detected on MRE is still unknown. The aim of this study is to evaluate the predictive role of sacroiliitis at MRE and other clinical features for IBD-related arthritis development in a cohort of adult patients with CD. Methods: Between December 2012 and May 2020, consecutive patients with CD who performed MRE were enrolled in the study. Patients with a previous diagnosis of IBD-related arthritis were excluded. A baseline demographics and clinical characteristics of the patients were retrospectively collected. The identification of new-onset IBD-related arthritis events during the follow-up was based on rheumatological clinical diagnosis and fulfillment of the ASAS classification criteria. Results: Ninety-five patients, mean age 43.9 years (standard deviation [SD] ± 16.6), 52.6% female were enrolled in the study with a median follow-up of 83 months (Q25:75 25:143). Six out 95 (6.3%) developed IBD-related arthritis with a mean time of 11 months (SD ± 16.8). Sacroiliitis detected on MRE was not associated with an increased risk of IBD-related arthritis (odds ratio [OR] = 2.12 [95% confidence interval (CI) 0.36, 12.53, p = 0.408]). In contrast, the presence of arthralgia and EIMs were found to be a predictor for IBD-related arthritis development (OR = 84.0 [95% CI 8.18, 862.39, p < 0.0001] and OR = 7.37 [95% CI 1.25, 43.32, p = 0.027], respectively). Conclusions: This study highlights that sacroiliitis, as assessed by MRE, was not associated with the development of IBD-related arthritis, whereas extraintestinal manifestations and arthralgia were significantly associated with later IBD-related arthritis development in patients with CD. [ABSTRACT FROM AUTHOR]

Introduction: Combined uveitis–rheumatology clinics (combined clinics) are a relatively recent clinical care model. Here we report the demographics, ocular and systemic disease characteristics, and medications utilized in patients seen in a combined clinic at a tertiary care hospital in the USA. Methods: Medical records were reviewed of patients seen at the Combined Clinic at the University of Colorado Hospital between January 1, 2016 and November 1, 2023. Data including age, sex, referral indication, ocular and systemic inflammatory disease diagnosis, and therapies utilized were obtained. Results: A total of 171 patients were included in the study, of which 122 were diagnosed with a systemic inflammatory disease, the most common of which were spondyloarthritis and rheumatoid arthritis. Nearly half of patients referred to the combined clinic with a known ocular inflammatory disease (OID) and suspicion for a systemic process were eventually diagnosed with a systemic disease. The most common associations in patients with both OID and systemic disease were anterior uveitis with spondyloarthritis, and scleritis with rheumatoid arthritis. The most common systemic immunomodulatory therapies (IMT) used were adalimumab, methotrexate, and rituximab. Over 40% of patients underwent a change in IMT during their first evaluation. Conclusions: Most patients seen in the combined clinic had both ocular and systemic inflammatory disease and were treated with IMT. Many patients were diagnosed with a systemic inflammatory disease upon evaluation in the combined clinic, and nearly half were recommended to initiate or change IMT at their first visit. This highlights the utility of a combined clinic in the management of these complex patients, in addition to providing logistical benefits to patients and educational opportunities for trainees. [ABSTRACT FROM AUTHOR]

Objectives Reactive arthritis (ReA) provides a unique opportunity to comprehend how a mucosal infection leads to inflammatory arthritis at a distant site without the apparent invasion of the pathogen. Unfortunately, conventional stool cultures after ReA provide limited information, and there is a dearth of metagenomic studies in ReA. The objective of this study was to identify gut microbiota associated with the development of ReA. Methods Patients with ReA or undifferentiated peripheral spondyloarthritis (UpSpA) were included if they presented within 4 weeks of the onset of the current episode of arthritis. Metagenomic DNA was extracted from the stools of these patients and of 36 age- and sex-similar controls. Sequencing and analysis were done using a standard 16S ribosomal pipeline. Results Of 55 patients, there was no difference between the gut microbiota of postdiarrheal ReA (n  = 20) and of upSpA (n  = 35). Comparing the gut microbiota of patients vs healthy controls, the patients had significantly higher alpha and beta diversity measures. After stringency filters, Proteobacteria had high abundance while Firmicutes had lesser as compared with the controls. Six families were overexpressed in patients, while another five were overexpressed in controls. Sixteen genera and 18 species were significantly different between patients and controls. At the species level there was strong association of Staphylococcus aureus, Clostridium septicum Klebsiella pneumoniae, Escherichia coli, Empedobacter brevis , Roseburia hominis, Bacillus velezensis and Crassaminicella with ReA. Conclusion The microbiota of classical gut-associated ReA and upSpA is similar. Patients have higher diversities in their gut microbiota compared with healthy controls. Both known and previously unreported species associated with ReA/upSpA were identified. [ABSTRACT FROM AUTHOR]

Objectives To assess the impact on patient outcomes of the spondyloarthritis (SpA) and inflammatory bowel disease (IBD) multidisciplinary team (MDT) meetings in a large university hospital. Methods A single-centre retrospective observational case-note review was conducted assessing the outcome of all 226 cases discussed at the SpA–IBD MDT meetings in a large UK university hospital between 2017 and 2022. Results A total of 226 patients were discussed. It was deemed that 97% of MDT meetings helped to improve communication between teams, and 100% were educational. A total of 57% of discussions led to an instant change of disease management, while 40% of discussions resulted in a treatment plan that avoided the use of dual advanced therapy. This improved patient safety by reducing immunosuppression. The MDT meetings were highly cost and time efficient; 125 referrals between specialists were avoided, and in 51 cases there was a significant chance of reducing future drug costs. A timely investigation or appointment was arranged following 50% of MDT discussions, helping to clarify the diagnosis and optimize patient care. Nine percent of meetings enabled drugs to be prescribed to patients that are not yet licensed for the other speciality, thereby improving treatment options available in the management of complex cases. Conclusion The MDT meetings have been beneficial for patients, the clinical team and the institution. This approach might be considered by other rheumatology and gastroenterology departments. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the prevalence of late-onset axial spondyloarthritis (lo-axSpA) and to identify clinical, laboratory, and imaging features associated with this phenotype. Methods: This single-center, observational study included patients diagnosed with axSpA from the "Reuma-check" SpA program. Patients with a symptom onset ≥ 45 years were classified as lo-axSpA, as opposed to early-onset axSpA (eo-axSpA, onset < 45 years). The prevalence of lo-axSpA was calculated, and lo-axSpA and eo-axSpA were compared in terms of clinical, laboratory and imaging characteristics. Factors associated with lo-axSpA were analyzed with univariable followed by multivariable logistic regression. Results: A total of 126 patients were included, 35 (28%) were lo-axSpA. Comparing lo-axSpA vs. eo-axSpA, significant differences were observed: higher female prevalence in lo-axSpA vs. eo-axSpA (51% vs. 29%), lower NSAID response (52% vs. 73%), increased skin psoriasis prevalence (42% vs. 17%,), and shorter diagnosis delay (40 vs. 93 months). In the multivariable analysis, male sex and diagnosis delay were independently and inversely associated with lo-axSpA (OR 0.2, 95% CI 0.06–0.8 and OR 0.9, 95% CI 0.96–0.99, respectively), while psoriasis was associated with a higher odds for lo-axSpA (OR 4.8, 95% CI 1.1–29). Conclusion: lo-axSpA was present in more than a quarter of the patients. Although recall bias in the symptom duration cannot be excluded, the presentation with lo-axSpA seems to be associated with distinct features, being more frequent in females and more associated with psoriasis and with a shorter diagnostic delay. Key Points • Late-onset axSpA (≥ 45Y) is observed in 28% in our cohort, a higher frequency than previously reported. • Female sex and psoriasis are associated with a higher likelihood for late-onset axSpA. [ABSTRACT FROM AUTHOR]

Purpose: To determine the performance of T2* cartilage mapping in diagnosing and assessing disease activity in early axial spondyloarthritis (axSpA), and to investigate the interaction of cartilage damage with clinical characteristics, sacroiliitis MRI scorings, and diffusion metrics. Materials and methods: This prospective study included 83 axSpA patients and 37 no-axSpA patients. Clinical characteristics, the Assessment of SpondyloArthritis International Society-defined active sacroiliitis on MRI, and T2* SIJs values were recorded. In axSpA, disease activity was evaluated using the ankylosing spondylitis disease activity score-C-reactive protein; active sacroiliitis was evaluated using Spondyloarthritis Research Consortium of Canada, intravoxel incoherent motion, and diffusion kurtosis imaging; chronic sacroiliitis was assessed using composite structural damage score (CSDS) and structural score fat. Mann–Whitney U-test, Kruskal–Wallis test with false discovery rate (FDR), ROC curve, and linear regression were used for statistical analysis. Results: AxSpA patients had significantly higher T2*SIJs values than no-axSpA patients. (22.86 ± 2.42 ms vs 20.36 ± 1.30 ms, p < 0.001). The combination of T2*SIJs values and active sacroiliitis on MRI had the highest AUC for identifying axSpA. T2*SIJs values were significantly different between the inactive and very high, moderate and very high, high and very high, as well as inactive and high disease activity groups (all pFDR < 0.05). Dk (β = 0.48) and CSDS (β = 0.48) were independently associated with T2*SIJs values. Conclusion: T2* values may be a promising biomarker for diagnosing and differentiating disease activity in early axSpA. Both acute and chronic sacroiliitis influence cartilage properties. Clinical relevance statement: Sacroiliac joint cartilage abnormalities can be quantified with T2* relaxation time and allow better characterization of early axSpA. Key Points: T2* mapping may have value in evaluating axSpA. The combination of T2* values and active sacroiliitis on MRI enhances diagnostic performance for axSpA. Abnormalities measured with T2* values correlate with disease activity, acute sacroiliitis, and degree of structural damage. [ABSTRACT FROM AUTHOR]

Introduction: Pain in both peripheral and axial joints is a major symptom in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Emerging evidence demonstrates pain mechanisms, beyond those related to inflammation or joint damage, based on aberrant processing of nociceptive stimuli peripherally as well as centrally. The Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway has been implicated in the processing of pain beyond its role in mediating inflammation and inhibitors of this pathway approved for the treatment of axSpA and PsA have been shown to alleviate a broad array of pain outcomes in both axial and peripheral joints. Areas covered: We review recent definitions and standardization of the nomenclature for categorizing chronic pain according to causality, assessment tools to evaluate nociplastic pain, the pathophysiologic role of JAK-STAT signaling in nociplastic pain, evidence for the presence of nociplastic pain in axSpA and PsA, and the impact of JAK inhibitors (JAKi) on pain outcomes in clinical trials (PubMed: 01/01/2019-04/01-2024). Expert opinion: Nociplastic pain assessment has been confined almost entirely to the use of a limited number of questionnaires in cross-sectional studies of these diseases. Though effective for alleviating pain, it is unclear if JAKi specifically impact nociplastic pain. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA). Methods. This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data. Agreement was defined as = 2/3 clinical experts with a rating of = -1 or = 1, and high confidence agreement as = -2 or = 2. The association of clinical features and both global assessments was tested with modified Poisson regression models. Results. Two hundred seventy-two of 303 cases (89.8%) achieved agreement with clinical data alone. Adding imaging data affected agreement in 38.9% (118/303) and directionality of agreement in 23.4% (71/303). Agreement was facilitated in 26/31 cases and lost in 21/272 cases. Of those 71 cases that changed directionality, 33 changed from axial disease being absent to present and 38 from present to absent. The final model had an area under the receiver-operating characteristic (AUROC) curve of 0.93 and 3 factors were independently associated with expert agreement (HLA-B27: relative risk [RR] 1.41, 95% CI 1.14-1.74; pain improvement with activity: RR 1.27, 95% CI 1.05-1.54; and bone marrow edema on MRI: RR 4.08, 95% CI 2.91-5.73). Conclusion. The addition of imaging data affected directionality and improved high confidence agreement of expert assessment of axial disease. These results underscore the integral role of MRI in the determination of axial disease in JSpA. [ABSTRACT FROM AUTHOR]

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]

Background: Patients with Rheumatic and Musculoskeletal Diseases, including axial spondyloarthritis (axSpA), may suffer from stressors like pain and functional impairments leading to limitations in their self-perceived health status. The COping with Rheumatic Stressors (CORS) questionnaire was developed to analyze how patients cope with these stressors. The CORS is currently not available in German. Objective: First, to translate, cross-culturally adapt and to linguistically validate the original Dutch CORS into German. Second, to test the pre-final German translation through cognitive debriefing in patients with axSpA. Methodology: The original Dutch CORS underwent a multistep cross-cultural adaptation process, as described by Beaton. It was first independently translated into German by bilingual Dutch-German lay and expert translators. Subsequently, it was translated back from the German version into Dutch. Remaining discrepancies were resolved by a scientific committee, resulting in a pre-final German version. This version was then tested through cognitive debriefing by 10 patients with axSpA across a broad spectrum of sociodemographic backgrounds. Results: Forward and backward translations of the CORS revealed minor discrepancies, mainly based on the degree of formal versus informal language usage, minor semantic errors or unusual syntax, which led to minor modifications in the wording. Reviewed by the scientific committee, the pre-final consensus German version was linguistically validated by cognitive debriefing by 10 patients with axSpA. Cognitive debriefing confirmed and ensured closest linguistic validity for German in Germany and highest equivalence to the Dutch original version. Conclusion: The German CORS was shown to have high cross-cultural and face validity for the assessment of coping with rheumatic stressors. Key messages: • Cognitive debriefing revealed that the German CORS is highly relevant for patients with axSpA. • The German CORS has high cross-cultural validity to assess coping with rheumatic stressors. • The German CORS has closest linguistic validity and highest equivalence to the Dutch original version [ABSTRACT FROM AUTHOR]

Objectives To (i) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; (ii) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); (iii) evaluate the performance of traditional health-outcomes for r-axSpA; and (iv) explore whether thresholds are stable across contextual factors. Methods Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an 'unacceptable work state' were calculated at baseline for four instruments assessing presenteeism and two health outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and for predicting future AWO over 12 months. Results Of 366 working patients, 15% reported an unacceptable work state; 6% experienced at least one AWO in 12 months. Optimal thresholds were: WPAI-presenteeism ≥40 (AUC 0.85), QQ-method <97 (0.76), WALS ≥0.75 (AUC 0.87), WLQ-25 ≥ 29 (AUC 0.85). BASDAI and BASFI performed similarly to the presenteeism instruments: ≥4.7 (AUC 0.82) and ≥3.5 (AUC 0.79), respectively. Thresholds for WALS and WLQ-25 were stable across contextual factors, while for all other instruments they overestimated unacceptable work state in lower educated persons. Proposed thresholds could also predict future AWO, although with lower performance, especially for QQ-method, BASDAI and BASFI. Conclusions Thresholds of measurement instruments for presenteeism and health status to identify unacceptable work state have been established. These thresholds can help in daily clinical practice to provide work-related support to r-axSpA patients at risk for AWO. [ABSTRACT FROM AUTHOR]

Objective To investigate which factors are associated with treatment intensification (TI) in axial SpA (axSpA) patients with high disease activity (HDA). Methods Patients with axSpA and HDA [Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1] from the Dutch SpA-Net registry were included. TI was defined as: (i) higher dose or shorter interval of the same drug, (ii) switch from current drug to another due to inefficacy or (iii) addition of a new drug. Only anti-inflammatory drugs were considered. Primary determinants considered were ASDAS, Assessment of SpondyloArthritis international Society Health Index (ASAS HI) and physician global assessment (PhGA). Acceptable symptom state according to patient (PASS-patient) or physician (PASS-physician) were included in sensitivity analyses. Patient-centred and physician-centred logistic regression models were used to investigate the association between potential determinants and TI. Results In total, 121 patients with HDA were included. TI was conducted in a minority (41/121, 33.9%), and mainly involved a switch or addition of a drug. In multivariable regression analyses, a higher ASDAS was associated with TI in the patient-centred model [odds ratio (OR)ASDAS = 1.94 (95% CI 1.00–3.74)]. However, in the physician-centred model, this association attenuated, and PhGA or PASS-physician were the primary factors associated with TI [ORPhGA = 1.71 (1.24–2.34); ORPASS-physician = 94.95]. Interestingly, patient-centred factors (ASAS HI/PASS-patient/education level) did not contribute to TI. Conclusion In practice, treatment is intensified in a minority of axSpA patients with HDA. Physician-centred factors are associated with the decision to change treatment, independently of disease activity or patient perspective. Further research is needed to better understand these decisions. [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]

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]

Objectives: To assess the longitudinal association between physical activity and global functioning in patients with axial spondyloarthritis (axSpA), and to identify the subtype of physical activity that is longitudinally related to global functioning. Method: Physical activity was measured using Global Physical Activity Questionnaire. Global functioning was assessed using the Assessment of SpondyloArthritis international Society Health Index (ASAS HI). The amount and subtype (work, transport, and recreation) of physical activity, disease activity, and ASAS HI were assessed at baseline, and at 1 and 2 year follow-up. Physical activity levels were categorized as low, moderate, or high. The longitudinal association between physical activity and ASAS HI scores was analysed using a generalized estimating equation. Results: The study evaluated 160 patients. Univariate analysis identified physical activity at moderate level and higher, Ankylosing Spondylitis Disease Activity Score (ASDAS), and syndesmophyte number as being longitudinally associated with ASAS HI over 2 years. Multivariate analysis identified physical activity at moderate level and higher as being longitudinally associated with ASAS HI. Physical activity above moderate levels was associated independently with good global functioning. In the analysis stratified by radiographic axSpA and non-radiographic axSpA, a positive association between physical activity and global functioning was observed in both groups. Only recreational activity, but not work- and transport-related activity, showed an independent longitudinal relationship with the ASAS HI score. Conclusions: Physical activity at moderate level and higher was associated independently with global functioning in axSpA. Therefore, patients should maintain physical activity above moderate levels to preserve global function. [ABSTRACT FROM AUTHOR]

Objective: In postpartum healthy women, inflammatory lesions of the sacroiliac joint (SIJ) can appear and mimic sacroiliitis. However, the impact of delivery on imaging abnormalities in women with axial spondyloarthritis (axSpA) is unknown. Thus, this study aimed to evaluate the impact of delivery on SIJ imaging in early axSpA. Method: Women with axSpA from the French prospective cohort DESIR were included, with a follow-up of 5 years. Demographic and disease characteristics, and SIJ imaging abnormalities at baseline, were described in all women and then according to nulliparous status. Changes on imaging over time were analysed in the 38 women who were nulliparous at baseline and had their first pregnancy with delivery during follow-up. Results: At baseline, nulliparous women were younger and had a higher educational level than other women with axSpA. The presence of sacroiliitis on magnetic resonance imaging (MRI) and X-ray was more frequent in nulliparous women (16.9% vs 9.9% and 33.8% vs 19.4%, respectively). When focusing on first incident deliveries, these patients had more sacroiliitis on X-ray and MRI at baseline than nulliparous patients at the end of follow-up, but lower Ankylosing Spondylitis Disease Activity Score–C-reactive protein (ASDAS-CRP). Only the modified New York score on the left SIJ was statistically different after delivery. Conclusion: Pregnancy with delivery does not seem to aggravate imaging in women with. Following axSpA patients who had their first delivery showed a mild increase in left sacroiliitis on X-ray after delivery, but without other signs of structural or inflammatory aggravation on imaging. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the health status and functional impairments in patients with axial spondyloarthritis (axSpA) using the Assessment of SpondyloArthritis International Society Health Index (ASAS-HI) and Environmental Factors (ASAS-EF) Index, and to evaluate the correlation of these indices with established clinical parameters. METHODS: This cross-sectional study included 91 patients diagnosed with axSpA at the Rheumatology Department between November 2017 and July 2018. Participants were evaluated using ASAS-HI, ASAS-EF, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, and Health Assessment Questionnaire (HAQ). Descriptive statistics and correlation analyses were performed to examine relationships between these indices and various clinical and demographic variables. RESULTS: The study found that 49.5% of patients had a BASDAI score >4, indicating high disease activity. The mean ASASHI score was 6.8, reflecting moderate to severe functional impairment in the study population. Significant positive correlations were observed between ASAS-HI and BASFI, BASDAI, spinal pain, and HAQ scores (p<0.05). However, no significant correlations were found between ASAS-HI and ASQoL, disease duration, CRP, or ESR. ASAS-EF was also positively correlated with BASFI, BASDAI, spinal pain, and HAQ scores. CONCLUSION: The ASAS-HI and ASAS-EF indices effectively evaluate health status and functional impairments in patients with axSpA. The significant correlations with established clinical parameters highlight the indices' utility in capturing the multifaceted impact of axSpA, emphasizing the importance of comprehensive disease assessment in guiding targeted interventions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess patient activation using patient activation measure 13 (PAM-13) in systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and axial spondyloarthritis (axSPA). Patients and methods: A cross-sectional study was conducted involving patients with three rheumatological conditions (SLE, PsA, and axSPA). Patients were contacted either at the clinic or through social media platforms. Data, including demographics, PAM 13, Arabic compliance questionnaire for rheumatology (ACQR), and disease-related activity scores, were collected electronically. The analyses included Chi-squared tests, linear regression, and binary logistic regression. Results: Overall, 418 patients were recruited (SLE = 323, PsA = 65, and axSPA = 30), with a mean (±SD) age of 42 ± 11 years and a female predominance (88%). PAM-13 scores did not significantly differ between the rheumatological disorders. Patients with axSPA showed significantly higher compliance than those with SLE or PsA (p = 0.012). In regression models, patients with PsA were more likely to be in activation level 1, with an OR of 2.890 (95% CI: 1.044–8.000, p = 0.0041), whereas patients with axSPA were more likely to be in activation level 4, with an OR of 2.460 (95% CI: 1.122–5.393, p = 0.025). The SLEDAI score was inversely related to the PAM-13 score (Pearson's correlation coefficient = −0.221, p < 0.001). Conclusions: This study explored the levels of activation and medication compliance in different rheumatological conditions. Larger studies are needed to confirm these findings and explore the challenges and opportunities for improving compliance and activation. [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]

Abstract 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.

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]

Introduction: The aim of the study was to systematically assess the efficacy and safety of tumor necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i), and Janus kinase inhibitors (JAKi) in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Register of Clinical Trials, and Scopus to find randomized controlled trials in patients with nr-axSpA published until June 2023. Stata 17.0 software and Review Manager 5.4 software were used for data analysis. The results for binary and continuous variables were expressed as the values of odds ratio and mean difference and their 95% confidence interval, respectively. Results: For Assessment of SpondyloArthritis International Society Response Criteria for 40% improvement (ASAS40), the efficacy of the 12 interventions ranked as follows: certolizumab pegol (CZP) 200 mg every 2 weeks (Q2W) > CZP 400 mg Q4W > golimumab (GOL) > bimekizumab (BKZ) > adalimumab (ADA) > upadacitinib (UPA) > etanercept (ETN) > brodalumab (BRO) > ixekizumab (IXE) > secukinumab (SEC) 150 mg no loading (NL) > SEC 150 mg loading dose (LD) > placebo (PBO). For assessment of ASAS20, the NMA results were ranked as follows: GOL > CZP 400 mg Q4W> BKZ> ADA > UPA > CZP 200 mg Q2W > ETN > BRO > SEC 150 mg NL > SEC 150 mg LD > PBO, and GOL > ADA > PBO > UPA > SEC 150 mg NL > BKZ > IXE > SEC 150 mg LD > ETN > CZP 200 mg Q2W for adverse events. Conclusions: Most TNFi may be more effective than JAKi and IL-17i. They were all well tolerated. However, the efficacy and safety of TNFi/IL-17i/JAKi remain to be further analyzed in studies with larger sample sizes and longer follow-up times. [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]

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]

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]

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]

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]

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]

Objective: To evaluate the sociodemographic characteristics and disease‐related factors associated with diagnostic delay in Canadian patients with axial spondyloarthritis (axSpA). Methods: Data from 542 Canadian patients who participated in the International Map of Axial Spondyloarthritis online survey were analysed. Diagnostic delay was calculated as the difference between age at diagnosis and age at onset of the first symptoms reported by participants. Univariate and multivariate analyses were used to evaluate possible factors associated with diagnostic delay. Results: The mean age (± SD) of the surveyed participants was 44.3 ± 13.9 years and 63.1% were female. The average diagnostic delay was 9.0 ± 10.5 years (median, 5.0 years; interquartile range, 1.0–13.8). In the multivariate regression analysis, the three variables most strongly associated with longer diagnostic delay were use of nonsteroidal anti‐inflammatory drugs (NSAIDs) (B = 2.991; 95% CI = 1.075–4.909), medium or high functional limitation (B = 1.541; 95%CI = 0.186–2.896), and number of HCPs seen before diagnosis (B = 1.524, 95%CI = 1.072–1.977). Conclusion: Diagnostic delay continues to be a barrier to optimal care for Canadian axSpA patients. Significant diagnostic delay, associated with a high number of HCP visits prior to diagnosis, high use of NSAIDs, and marked functional limitation in daily life, illustrate the convoluted axSpA patient journey. [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]

Objective: To compare the accuracy and reliability of detecting the intensity of spinal inflammation on short tau inversion recovery (STIR) with the apparent diffusion coefficient (ADC) values of the active magnetic resonance imaging (MRI) lesions in axial spondyloarthritis (axSpA). Materials and methods: Fifty active lesions in the STIR sequence of spinal MRI were identified. With reference to sites of active lesions in STIR, the corresponding region of interest (ROI) on the ADC map was drawn to determine the maximum ADC (ADC max ), mean ADC (ADC mean ), normalized maximum (nADC max ), and mean (nADC mean ). Four independent readers scored the identified active lesions as "intense" or "non-intense" according to the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. They were compared to various ADC parameters for assessment of accuracy and reliability. Regression analyses were used to adjust potential factors that could affect ADC. Results: Significant differences were found in ADC max between "intense" and "non-intense" lesions scored by three of the four readers (1,405.7 ± 271.4 vs. 1,165.8 ± 223.8, p = 0.01; 1,420.7 ± 272.1 vs. 1,209.0 ± 248.5, p = 0.01; 1,438.0 ± 307.2 vs. 1,213.6 ± 231.0, p = 0.01). Only one reader could differentiate a difference in "intense" and "non-intense" lesions with respect to ADC mean (899.2 ± 248.3 vs. 711.0 ± 222.6, p = 0.01) and nADC mean (4.4 ± 2.1 vs. 3.4 ± 1.4, p = 0.05). Inter-reader agreements were slight to moderate (kappa = 0.07–0.45). Reliability substantially improved when only the lowest and highest 25th percentiles of ADC values were included (kappa = 0.17–0.75). Regression analyses showed that the "intense" lesions were associated with higher ADC values after adjustment for confounders. Conclusion: Reading of STIR MRI is limited by the lack of ability in differentiating subtle differences of spinal inflammation. ADC could be an alternative method. [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]

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]

Objectives: This study aimed to evaluate the rate of successful transitions, identify factors associated with early versus late transitions, and diagnosis and treatment changes after transition into adult rheumatology. Patients and methods: In this retrospective study, patients with childhood-onset rheumatic diseases who transitioned from pediatric to adult rheumatology care between January 2013 and January 2023 were screened for a successful transition. Successful transitions were defined as maintaining annual visits to the adult rheumatology clinic after transition. Early transition was defined as less than three months between the last pediatric and first adult rheumatology visits. Results: Out of 2,552 referred patients, 210 (8.2%) patients (117 females, 93 males; mean age: 25.2±5.6 years; range, 18 to 44 years) transitioned successfully. Juvenile idiopathic arthritis and familial Mediterranean fever were the most prevalent rheumatic diseases. The median transition time was four months (interquartile range, 1 to 13 months) in patients with successful transition, and the early transition rate was 46.7%. Receiving biologic disease-modifying antirheumatic drugs was found to be associated with early transition (28.6% vs. 17.0%, p=0.040), and higher education levels and familial Mediterranean fever diagnosis were found to be associated with late transition. The treatment was changed for about half of the patients after transition to adult rheumatology. Patients with juvenile idiopathic arthritis were reclassified in 25 (31.6%) patients as rheumatoid arthritis, in 22 (27.8%) patients as ankylosing spondylitis, in 20 (25.3%) patients as nonradiographic axial spondyloarthritis, and in eight (10.1%) patients as psoriatic arthritis. Conclusion: A successful transition to adult rheumatology is essential for adolescents and young adults with childhood-onset rheumatic diseases. The successful transition rate in this study was relatively low, highlighting the need for standardized transition programs. [ABSTRACT FROM AUTHOR]