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Abstract Background Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease with challenges in diagnosis and disease activity assessment. While alterations in immunoglobulin G (IgG) N-glycosylation have been observed in varied rheumatic diseases, those in axSpA remains unclear. This study aims to explore the role of IgG N-glycan profiles in diagnosis and disease activity of axSpA. Methods A clinical case-control study was conducted involving patients with axSpA (n = 138), systemic lupus erythematosus (n = 102), rheumatoid arthritis (n = 106), osteoarthritis (n = 33), gout (n = 41) and healthy controls (n = 117). Ultra-performance liquid chromatography was employed to analyze the composition of the serum IgG N-glycome. Associations between IgG N-glycans and axSpA were investigated and compared to healthy controls and other four rheumatic diseases. The relationship among IgG N-glycosylation, disease activity, and inflammatory cytokines of axSpA patients were analyzed. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic/classification performance of IgG N-glycans to distinguish axSpA and its disease activity. Results In patients with axSpA, the abundances of IgG galactosylation and sialylation were significantly lower than healthy controls, while the abundance of fucosylation was higher than the other four studied rheumatic diseases. Additionally, two asialylated IgG N-glycans (FA2 and FA2 [3]G1) were associated with axSpA, with adjusted odds ratios (AORs) of 5.62 (95% CI: 3.41–9.24) and 0.33 (95% CI: 0.22–0.50), respectively. Notably, decreased FA2 [3]G1 emerged as a characteristic IgG N-glycan associated with all five studied rheumatic diseases, while decreased FA2BG2S2 was a unique IgG N-glycan differentiating axSpA from the other four rheumatic diseases. Furthermore, FA2 displayed positive association with disease activity indicators (ASDAS-CRP, SPARCC-SIJ and SPARCC-spine) in axSpA. IgG N-glycans, particularly FA2 [3]G1, FA2BG2S2 and FA2, demonstrated canonical correlation with inflammatory cytokines, including interleukin-23 and tumor necrosis factor α, in axSpA (r = 0.519, P = 0.017). Conclusions Specific IgG N-glycans hold potential as novel biomarkers to enhance diagnosis and disease activity assessment in axSpA management.

Abstract Background Physical activity (PA), including regular exercise, is essential for the successful management of axial spondyloarthritis (axSpA). To promote a physically active lifestyle, a digital training diary (Trainingslog) was developed in an user-centered approach by the Swiss Ankylosing Spondylitis Association (SVMB). A training diary promotes PA through feedback, goal setting and self-monitoring, which can also be used for PA counselling by physiotherapists (PT). Usability, feasibility and acceptance are essential for the successful implementation of a mobile Health Intervention such as the Trainingslog. The study objective is to evaluate the usability, feasibility and acceptance of the Trainingslog for individuals with axSpA and PTs. Methods A mixed-methods design was performed among potential end-users of the Trainingslog. Quantitative data was collected by use of questionnaires (System Usability Scale (SUS, 0-100 scale), user version of the Mobile App Rating Scale (uMARS, 5 point scale)) and number of training entries. Subsequently, qualitative data was gathered through semi-structured online focus groups or individual interviews. Results 11 PTs (9 women, mean age 52.5 [SD 15.6]) and 10 individuals with axSpA (6 women, mean age 48 [SD 13.4]) participated. The quantitative data showed mean SUS scores for usability of 82.5 [SD 21.76] for PTs and 77.0 [SD 9.34] for individuals with axSpA. The mean uMARS sector B scores for feasibility were 4.2 [SD 0.49] for PTs and 4.1 [SD 0.38] for individuals with axSpA. Acceptance, as indicated by the uMARS results (mean score > 3 in Sectors E and F for both groups), was given. But there was a lower-than-expected agreement in the training entries, with 59.86% of entries matching between the Trainingslog and the paper diary. The qualitative analysis unveiled that while usability and feasibility were good, acceptance was lower, primarily due to the use of a web-based link instead of an app version. Conclusion The Trainingslog showed a good usability and feasibility, while the acceptance was lower than expected. Acceptance could be increased by offering the Trainingslog as an app-based version, along with implementing additional recommendations for enhancement. Consequently, the Trainingslog has the potential to be applied in PA counselling by PTs or as a self-monitoring tool for individuals with axSpA.

Abstract Background Inflammatory arthritis affects approximately 2–3% of adults worldwide. For patients newly diagnosed with arthritis, effective self-management is crucial, as they often face several physiological, emotional, and social challenges. A self-management intervention called NISMA was thus developed to cater to this group. This study aimed to evaluate the feasibility and fidelity of this intervention before conducting a full-scale randomized controlled trial. Methods This feasibility study was conducted as a single-center randomized controlled trial. Twenty participants were expected to be sufficient for assessing the feasibility outcomes. The control group received only the usual care, while the intervention group received the NISMA intervention in addition, which involved individual and group sessions in a multidisciplinary setting. Feasibility was evaluated based on the recruitment, data collection, retention, and randomization processes. The patient-reported outcome measures and clinical measures were collected to review their potential for inclusion in a future randomized controlled trial. Fidelity was assessed by using documentation sheets filled in by the health professionals and audio recordings of the sessions to examine whether the intervention’s principles and components were adequately addressed. Results Among 47 eligible patients, we recruited 23 participants during a period of 4 months. The recruitment rate was 47% and the retention rate 91%. Randomization, although accepted, led to some disappointment in the control group. Data collection was effective, with only minimal missing data (

Abstract Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease primarily affecting the sacroiliac joints and spine, leading to chronic pain, fatigue, and reduced mobility. The diagnostic delay for axSpA is often long, causing significant physical, psychological, and social burdens for patients and their relatives. This study aims to explore the patient journey of individuals with axSpA and their relatives within the German healthcare system, identifying key challenges and unmet needs from symptom onset to diagnosis and treatment. A qualitative approach was employed, involving structured interviews with axSpA patients and their relatives. Participants were selected through purposive sampling to ensure diverse representation. Data collection involved individual telephone interviews, which were transcribed and analyzed using Kuckartz’s structured qualitative content analysis framework. The patient journey was characterized by four distinct phases: Time before diagnosis, Diagnosis, After the diagnosis, and Current treatment. Participants reported significant psychological and emotional burdens, with many experiences attributed to chance encounters with knowledgeable healthcare professionals. Key issues included a lack of awareness among healthcare professionals, diagnostic delays, and inadequate psychological support. The perspectives of patients and their relatives highlighted the significant psychological burden they both experience throughout the journey. This underscores the need for services that cater not only to patients but also to their relatives. The study highlights critical gaps in the current healthcare system regarding the diagnosis and care of axSpA patients. To improve care, systematic efforts are needed to enhance awareness, reduce diagnostic delays, integrate psychological support, and provide comprehensive information throughout the patient journey for both, patients and relatives. Effective care should not rely on chance; systematic improvements are necessary to ensure consistent, high-quality care.

Abstract Background In SELECT-AXIS 2, upadacitinib improved the signs and symptoms of active non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks versus placebo and was well tolerated. Here, we evaluated the efficacy and safety of upadacitinib through 2 years. Methods The study enrolled eligible adult patients with a clinical diagnosis of nr-axSpA who met the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective signs of active inflammation on magnetic resonance imaging (MRI) of sacroiliac joints and/or high-sensitivity C-reactive protein. Patients were randomized 1:1 to receive double-blinded treatment with upadacitinib 15 mg once daily (QD) or placebo for 52 weeks, after which all patients received open-label treatment with upadacitinib 15 mg QD. Efficacy results over 104 weeks were reported as observed (AO) and either AO with non-responder imputation (AO-NRI; binary endpoints) or AO with mixed-effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized through week 104. Results Of 313 patients randomized and treated, 224 (continuous upadacitinib n = 117; placebo/upadacitinib n = 107) completed 104 weeks of treatment. In patients who received continuous upadacitinib, sustained improvement was observed through 2 years of treatment across efficacy endpoints including disease activity, pain, function, enthesitis, quality of life, and MRI measures of inflammation. At week 104, 57.1%, 59.0%, and 31.4% of patients achieved ASAS40 response, and low disease activity and inactive disease (as defined by Axial Spondyloarthritis Disease Activity Score), respectively (AO-NRI); week 104 outcomes were generally similar in patients who initially received placebo and were switched to upadacitinib at week 52. In total, 286 patients were exposed to ≥ 1 dose of upadacitinib, comprising 378.3 patient-years (PY) of exposure. Upadacitinib was generally well tolerated, with exposure-adjusted event rates (EAERs) for TEAEs, serious adverse events (AEs), and AEs leading to study drug discontinuation of 207.5, 8.7, and 5.3 events/100 PY, respectively. EAERs of TEAEs of special interest were broadly consistent with those reported through week 52. Conclusions Treatment with upadacitinib demonstrated consistent improvement and maintenance of treatment effect across efficacy endpoints through 2 years; no new safety signals were identified with additional exposure. Trial registration NCT04169373.

Abstract Background Axial spondyloarthritis (SpA) leads to structural bone lesions in every part of the vertebral column. These lesions are only partially visualized on conventional radiographs, omitting posterior parts of the vertebral column and the thoracic spine, that may nevertheless contribute to impaired spinal mobility and function in patients with axial SpA. Methods In this prospective and blinded investigation, we assessed the distribution of structural spinal lesions using magnetic resonance imaging (MRI) of the whole spine in 55 patients with axial SpA classified according to the Assessment in Spondyloarthritis International Society (ASAS) criteria. After assessment of spinal mobility and function two blinded radiologists independently evaluated MRIs of 23 vertebral units in every patient. Non-parametric statistical methods, Spearman‘s correlation and linear regression models were used to analyze structural lesion distribution and the relationship with clinical spinal mobility and function parameters. Results In 55 patients with axial SpA (13 females, average disease duration 14.9 years) 657 ventral and 139 dorsal vertebral body structural bone lesions and, notably, 534 facet joint lesions could be visualized. The median number of lesions per patient was higher in the thoracic (8.5, range 1.0–41.0) than in the lumbar (7.5, range 0.0-27.5) and the cervical spine (3.5, range 0.0-24.5). A negative correlation was noted between the number of osteoproliferative structural bone lesions and impairment of spinal mobility and function in univariate, but not in multivariate analyses. Conclusion MRI of the whole spine revealed a high prevalence of lesions in dorsal parts of the vertebral column and in the thoracic spine in patients with axial SpA that may not be adequately visualized on conventional radiographs. These findings could further contribute to a better understanding of reduced mobility of the spine typically associated with axial SpA and assist diagnostics.

Abstract 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 Background People with chronic inflammatory arthritis (IA) often have a reduced work ability. Consequently, they are at high risk of losing their jobs and being permanently excluded from the labor market. Therefore, we developed a new context-specific vocational rehabilitation intervention for people with IA based on the Medical Research Council’s framework for complex interventions. This intervention is called “WORK-ON” and consists of: (1) Initial assessment and goal setting by an occupational therapist experienced in rheumatology rehabilitation; (2) coordinated support from the same occupational therapist, including assistance in navigating the primary and secondary healthcare and social care systems; (3) group sessions for peer support; and (4) individually tailored consultations with physiotherapists, nurses, and/or social workers. This study investigates the feasibility of WORK-ON. Methods A 6-month single-arm feasibility study with a pre-test post-test design was conducted to evaluate recruitment, intervention fidelity and delivery, data collection, and possible outcome measures. Work ability was the primary outcome, and sick leave, quality of life, fatigue, pain, physical activity, sleep, and well-being were the secondary outcomes evaluated. Results In total, 19 participants (17 women and 2 men) with a median age of 55 years (range, 34–64) participated and completed WORK-ON. Of these, 17 participants completed patient-reported outcomes at baseline and follow-up, and the results indicated a tendency to improvement in work ability, quality of life, level of physical activity, decrease in pain, and increase in days of sick leave during the 6-month intervention period. The rehabilitation clinicians spent an average of 15.3 h per participant, and the participants spent an average of 13.5 h in the intervention. Conclusions WORK-ON is considered feasible and has the potential to increase work ability among people with IA who are concerned about their future ability to keep working. Though, an adjustment of the intervention is needed before testing in a randomized controlled trial.

Abstract Background Axial spondyloarthritis (axSpA) is a chronic inflammatory disease which mainly affects the spine and sacroiliac joints, causing longstanding back pain, stiffness, and limited mobility. AxSpA is an underrecognized disease in non-rheumatology practices because of its heterogeneous clinical features that may be difficult to identify. Main body Sports medicine practitioners are well positioned to suspect and recognize axSpA among their patients with chronic back pain and refer them to a rheumatologist. Early referral to a rheumatologist is important for timely diagnosis, prompt treatment, and improved long-term outcomes for patients with axSpA. Physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs) remain the first-line treatment for and the cornerstone of axSpA management. For patients with inadequate response to or intolerance of NSAIDs, biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs are indicated. These drugs can reduce pain, inflammation, fatigue, and disability and can improve health-related quality of life. The goal of this review is to improve awareness of axSpA among sports medicine practitioners and other non-rheumatologists so that these providers ensure timely referral of patients with suspected axSpA to rheumatologists for appropriate treatment and better outcomes. We also provide an update on current treatment possibilities for axSpA and describe how rheumatologists use treatment guidelines and disease activity measures to identify and optimally treat patients with active axSpA. Conclusion Sports medicine practitioners have an excellent opportunity to identify patients with suspected axSpA and refer them to rheumatologists in a timely manner, as well as monitor symptoms among patients diagnosed with axSpA to identify inadequately controlled disease.

Abstract Background Axial spondyloarthritis (axSpA) significantly impacts patients’ lives. The ASAS-OMERACT guideline was formulated for the multidimensional evaluation of axSpA patients, employing a specific set of tools. Given the pivotal role of patient perception, comprehensive correlation among these tools, especially concerning quality of life, may provide a clinically relevant perspective and enhance treatment efficacy in the early stages of the disease. This study aims to investigate the correlation among disease activity, functional ability, and quality of life in early-treated axSpA patients. In addition, the association between high disease activity and clinical characteristics was explored. Methods This cross-sectional study was conducted in a tertiary hospital in Thailand. Patients diagnosed with axSpA according to ASAS classification criteria and receiving treatment from rheumatologists within three years of onset of symptoms were included. Clinical and laboratory data were retrieved from a hospital database. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score with ESR or CRP (ASDAS-ESR/CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Spinal mobility was measured using the Bath Ankylosing Spondylitis Metrology Index (BASMI), while quality of life and function were evaluated using the ASAS Health Index (ASAS-HI) and Bath Ankylosing Spondylitis Functional Index (BASFI), respectively. The correlation between these measurements was analyzed using the Pearson correlation coefficient (r). Additionally, factors associated with high disease activity (ASDAS/CRP > 2.1) were explored using multivariate regression analysis. Results Sixty-six patients (41 males; mean age 49.3 ± 13.3 years) were enrolled between April to December 2022. Disease activity (ASDAS-CRP) was significantly inversely correlated with spinal mobility (BASMI), function (BASFI), and quality of life (ASAS-HI). High disease activity was associated with obesity (BMI ≥ 30 kg/m^2) and a longer duration of symptoms before treatment (≥ 2 years). Conclusion In early-treated axSpA patients, ASDAS-CRP showed significant correlations with functional ability, quality of life, and spinal mobility. High disease activity was associated with obesity and a longer pre-treatment symptom duration in our study. Early treatment may enhance patients’ function, mobility, and quality of life, with weight reduction being possibly beneficial for obese axSpA patients. Clinical trial number Not applicable.

Abstract Background Spondyloarthritis (SpA) encompasses a spectrum of immune-mediated inflammatory conditions primarily affecting the axial skeleton, including sacroiliitis and spondylitis, each with distinct features. This study aimed to investigate imaging disparities, focusing on sacroiliac magnetic resonance and spine radiography, across phenotypes and between males and females in axial SpA. Method A cross-sectional study was conducted to assess clinical data, laboratory findings, magnetic resonance imaging (MRI) scores of sacroiliac joints using the Spondyloarthritis Research Consortium of Canada (SPARCC) and Sacroiliac Joint Structural Score (SSS), and cervical and lumbar spine radiographs utilizing the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The study aimed to compare these parameters between two groups: axial spondyloarthritis (axSpA, radiographic and non-radiographic) and axial psoriatic arthritis (axPsA), as well as between males and females. Results Ninety-four patients were included, with 62 patients in the axSpA group and 32 patients in the axPsA group. There were no differences in disease activity, mobility, radiographic damage in the spine (Modified Stoke Ankylosing Spondylitis Spine Score– mSASSS), or sacroiliac magnetic resonance imaging (MRI) scores (Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index - SPARCC and Sacroiliac Joint Structural Score - SSS) between the two phenotypes. Regarding sex, in imaging exams, men had higher mSASSS (p = 0.008), SSS (p = 0.001), and fat metaplasia (MG) score based on SSS (p = 0.001), while women had significantly higher SPARCC scores (p = 0.039). In the male group, the presence of HLA-B27 allele had an impact on more structural lesions on MRI (SSS), p = 0.013. Conclusion In this study, imaging of sacroiliac joints and spine in patients with axial SpA did not show differences in phenotypes but did reveal differences based on sex, which may have an impact on future diagnostic recommendations. Further studies are needed to confirm these findings.

Abstract Background Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often needing prolonged medication treatment for effective management. Maintaining drug retention is essential for both achieving disease control and improving patients' quality of life. This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients. Methods A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. Pain Catastrophizing Scale (PCS) was employed to assess pain catastrophizing. Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention. Results In the PsA group, patients early discontinuing therapy showed higher baseline disease activity as well as higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted the treatment. Multivariable analysis confirmed pain catastrophizing as an independent predictor of drug suspension within two years. In axSpA, drug discontinuation was associated with female gender, shorter disease duration, higher baseline disease activity as well as elevated levels of pain catastrophizing. Univariable analysis supported the role of pain catastrophizing, including its domains, as predictors of treatment interruption. However, limited events in axSpA patients precluded a multivariate analysis. Conclusion This prospective study emphasizes the impact of pain catastrophizing on drug retention in patients with PsA and axSpA.

Abstract Objective To evaluate the efficacy and safety of mind-body exercise (MBE) interventions, including Tai Chi, Yoga, Pilates, and Qigong, in patients with axial spondyloarthritis (axSpA), a systematic review and meta-analysis was conducted. Methods Eight electronic databases were searched from their inception to May 2024. RevMan 5.4 and Stata 16.0 software were used for statistical analysis. Outcome measures included Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Visual Analog Scale (VAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL) Scale, and adverse events. The methodological quality of the included studies was evaluated using the Cochrane risk of bias (RoB) tool (2.0). The certainty of evidence for each outcome was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results Of the 330 studies retrieved, 15 studies satisfied the criteria for meta-analysis. Compared with the controls, MBE interventions significantly improved physical function (measured by BASFI, MD = -0.76, 95% CI: -1.01 to -0.50, P

Abstract Background Differentiating between degenerative disc disease (DDD), diffuse idiopathic skeletal hyperostosis (DISH), and axial spondyloarthritis (axSpA) represents a diagnostic challenge in patients with low back pain (LBP). We aimed to evaluate the distribution of inflammatory and degenerative imaging features in a real-life cohort of LBP patients referred to a tertiary university rheumatology center. Methods In a retrospective cross-sectional analysis of patients referred for LBP, demographics, symptom information, and available imaging were collected. SpA-like changes were considered in the spine in the presence of one of the following lesions typically related to SpA: erosions, sclerosis, squaring, and syndesmophytes on conventional radiographs (CR) and bone marrow oedema (BMO), erosions, sclerosis, and fat lesions (FL) on MRI. SIJ CR were graded per New York criteria; on MRIs, SIJs were evaluated by quadrant for BMO, erosions, FL, sclerosis and ankylosis, similar to the approach used by the Berlin SIJ MRI scoring system. The final diagnosis made by the rheumatologist was the gold standard. Data were presented descriptively, by patient and by quadrant, and compared among the three diagnosis groups. Results Among 136 referred patients, 71 had DDD, 38 DISH, and 27 axSpA; median age 62 years [IQR55-73], 63% males. On CR, SpA-like changes were significantly higher in axSpA in the lumbar (50%, vs. DDD 23%, DISH 22%), in DISH in the thoracic (28%, vs. DDD 8%, axSpA 12%), and in DDD in the cervical spine (67% vs. DISH 0%, axSpA 33%). On MRI, BMO was significantly higher in DISH in the thoracic (37%, vs. DDD 22%, axSpA 5%) and equally distributed in the lumbar spine (35-42%). FL were significantly more frequently identified in DISH and axSpA in the thoracic (56% and 52%) and DDD and axSpA in the lumbar spine (65% and 74%, respectively). Degenerative changes were frequent in the three groups. Sacroiliitis (NY criteria) was identified in 49% (axSpA 76%, DDD 48%, DISH 29%). Conclusion A significant overlap was found among DDD, DISH, and axSpA for inflammatory and degenerative imaging features. Particularly, SpA-like spine CR features were found in one-fourth of patients with DISH, and MRI BMO was found in one-third of those patients.

Abstract Background In spondyloarthritides (SpA) and fibromyalgia (FM), patients suffer from generalized pain. The impact of FM on PRO validated in SpA has not been systematically studied. Objective Study the performance of PROs developed for SpA in patients with primary (p) FM without chronic inflammatory-rheumatic disease vs. SpA without and with concomitant (c) FM. Methods Patients with pFM, axSpA or PsA and indication for treatment adaptation were prospectively included. Standardized PROs were assessed: BASDAI, ASDAS-CRP, DAPSA, patient´s global assessment, BASFI, LEI, MASES, SPARCC Enthesitis Score and FIQ. Results 300 patients were included (100/diagnosis). More males were found in axSpA vs. PsA and pFM group (67, 33 and 2/100, respectively), while 12 axSpA (axSpA+) and 16 PsA (PsA+) patients had cFM. pFM patients showed significantly higher scores in all assessments vs. axSpA or PsA, with exception of ASDAS-CRP (3.3 ± 0.6 in FM vs. 3.1 ± 1.0 in axSpA) and duration of low lumbar morning stiffness. Similar results were also found in the subanalysis of female patients only. In addition, patients with axSpA + or PsA + showed no differences to patients with pFM, while significantly higher scores were found for FM, axSpA + and PsA + for almost all FIQ items compared to axSpA- or PsA-. Conclusions PROs originally developed for axSpA or PsA need to be interpreted differently in the presence or absence of cFM. ASDAS-CRP and duration of lumbar morning stiffness were not affected by cFM. FM-specific questionnaires also showed high scores in patients with SpA with cFM but not in those without.

Abstract Objective Define the prevalence and location of inflammatory and structural lesions on magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and radiographic axial spondyloarthritis (r-axSpA) with neck pain as leading clinical symptom. Methods Patients with diagnosis of RA and r-axSpA were consecutively included if they had chronic (> 3 months) neck pain. Clinical assessment, neck pain questionnaires and MRIs of the cervical spine (CS) were performed. Results 107 patients (59 RA and 48 r-axSpA) were included. While there was no difference in the Northwick-Park-Neck-Pain-questionnaire, patients with RA reported higher neck pain compared to r-axSpA on a numeric rating scale (5.0 ± 3.6 vs. 3.0 ± 3.1; p = 0.003). Inflammatory lesions occurred predominantly in the craniocervical area in RA and in the lower CS segments in r-axSpA. Bone marrow edema (BME) was more frequent in axSpA (BME-score axSpA/RA: 0.35vs0.17; p

Abstract Background The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. Methods An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele’s presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of

Abstract Background We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi). Methods Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA. Results This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200–2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678–1.455), after adjusting for other baseline characteristics. Conclusions The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.

Abstract Background There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). Methods The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. Results A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. Conclusions Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

Abstract Background We report long-term, end-of-study program safety outcomes from 25 randomized clinical trials (RCTs) in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) [including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] who received ≥ 1 dose of Ixekizumab (IXE) over 5 years (PsO) or up to 3 years (PsA, axSpA). Methods This integrated safety analysis consists of data from patients who received any dose of IXE, across 25 RCTs (17 PsO, 4 PsA, 4 axSpA). Rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and selected adverse events (AEs) of interest were analyzed for all pooled studies by years of therapy and overall, through March 2022. Results were reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) overall and at successive year intervals. Results Six thousand eight hundred ninety two adult patients with PsO, 1401 with PsA, and 932 with axSpA (including AS and nr-axSpA), with a cumulative IXE exposure of 22,371.1 PY were included. The most commonly reported TEAE across indications was nasopharyngitis (IRs per 100 PY: 8.8 (PsO), 9.0 (PsA), 8.4 (axSpA)). SAEs were reported by 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8). Forty-five deaths were reported (PsO, n = 36, IR 0.2; PsA, n = 6, IR 0.3; axSpA, n = 3, IR 0.1). TEAEs did not increase during IXE exposure: IRs per 100 PY, PsO: 88.9 to 63.2 (year 0–1 to 4–5), PsA: 87 to 67.3 (year 0–1 to 2–3), axSpA: 82.1 to 55.4 (year 0–1 to > = 2). IRs per 100 PY of discontinuation from IXE due to AE were 2.9 (PsO), 5.1 (PsA), and 3.1 (axSpA). IRs per 100 PY of injection site reactions were 5.9 (PsO), 11.6 (PsA) and 7.4 (axSpA); Candida: 1.9 (PsO), 2.0 (PsA), and 1.2 (axSpA); depression, major adverse cerebro-cardiovascular events and malignancies: ≤ 1.6 across all indications. Adjudicated IRs per 100 PY of inflammatory bowel disease were ≤ 0.8 across indications (0.1 [PsO]; 0.1 [PsA]; 0.8 [axSpA]). Conclusions In this integrated safety analysis, consisting of over 22,000 PY of exposure, the long-term safety profile of IXE was found to be consistent with previous, earlier reports, with no new safety signals identified. Trial registration NCT registration numbers for RCTs included in this integrated analysis can be found in Additional File 1.

Abstract Introduction Ankylosing spondylitis(AS) is a chronic inflammatory rheumatic disease primarily affecting the spine and sacroiliac joints. While biologic disease-modifying antirheumatic drugs(bDMARDs) and targeted synthetic DMARDs(tsDMARDs) are popular treatments for AS, there is limited research on their combined use. This study examined a cohort of AS patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib in conjunction with bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach. Methods In this study, we retrospectively collected the electronic medical records (EMR) of 15 adult patients with AS who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between January 2018 and June 2022. All patients had received at least one bDMARD treatment for more than three months and still exhibited moderate to high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment. Treatment was continued for a minimum of 12 weeks following the initiation of combination therapy. Changes in ASDAS-CRP and BASDAI scores at week 12 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, and 12 were also collected and analyzed. Results After 12 weeks of treatment, the overall ASDAS-CRP score decreased significantly from a baseline of 3.82 ± 1.47 (2.83 ~ 4.99) to 1.47 ± 0.48 (0.75 ~ 2.44), with remission achieved by 7 patients (46.7%) and low disease activity achieved by 5 patients (33.3%). The overall BASDAI score also showed significant improvement, decreasing from a baseline of 5.11 ± 1.42 (3.25 ~ 7 0.75) to 1.28 ± 0.70(0.20 ~ 2.55). Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation. Conclusion To a certain extent, our findings provide some evidence supporting the efficacy and safety of the combination of bDMARD and JAK inhibitor tofacitinib in AS patients with inadequate response to bDMARD monotherapy. It effectively controls disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.

Abstract Background The role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease combined with axial spondyloarthritis (axSpA) is gaining widespread interest. Aims This study was conducted to investigate the clinical and fecal microbiota characteristics of patients with both ulcerative colitis (UC) and axSpA. Methods Clinical data were collected from patients with UC. Patients were divided into the axSpA and non-axSpA groups according to human leukocyte antigen-B27 serology and sacroiliac joint imaging results. We obtained fecal specimens from 14 axSpA and 26 non-axSpA patients. All samples underwent 16S ribosomal DNA sequencing. Results Seventy-three patients with UC were included in this study, and the axSpA incidence was 19.2%. This incidence was significantly higher in patients with C-reactive protein > 10 mg/L. Firmicutes and Faecalibacterium abundances were decreased, and Proteobacteria and Escherichia_Shigella abundances were increased in the axSpA group compared with those of the non-axSpA group. Indicator analysis showed that Escherichia_Shigella was more likely to be an indicator species of axSpA. Additionally, many biosynthetic and metabolic pathways, including glutathione metabolism, fatty acid degradation, geraniol degradation, and biosynthesis of siderophore group nonribosomal peptides, were upregulated in the axSpA group. Conclusion Patients with UC have a high axSpA incidence, which may be related to the relative abundances of Escherichia_Shigella in these patients. The abundances of various biosynthetic and metabolic pathways of the fecal flora were upregulated in patients with axSpA.

Abstract Background Identifying axial spondyloarthritis (axSpA) activity early and accurately is essential for treating physicians to adjust treatment plans and guide clinical decisions promptly. The current literature is mostly focused on axSpA diagnosis, and there has been thus far, no study that reported the use of a radiomics approach for differentiating axSpA disease activity. In this study, the aim was to develop a radiomics model for differentiating active from non-active axSpA based on fat-suppressed (FS) T2-weighted (T2w) magnetic resonance imaging (MRI) of sacroiliac joints. Methods This retrospective study included 109 patients diagnosed with non-active axSpA (n = 68) and active axSpA (n = 41); patients were divided into training and testing cohorts at a ratio of 8:2. Radiomics features were extracted from 3.0 T sacroiliac MRI using two different heterogeneous regions of interest (ROIs, Circle and Facet). Various methods were used to select relevant and robust features, and different classifiers were used to build Circle-based, Facet-based, and a fusion prediction model. Their performance was compared using various statistical parameters. p

Abstract Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil’s subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Abstract Background TNF-α inhibitor (TNFi) serum trough levels have previously been found to be related to disease activity in axial spondyloarthritis (axSpA). However, most research regarding serum trough levels has been conducted in patients who only recently started TNFi therapy. Therefore, our objective was to explore TNFi serum trough level measurements in relation to disease activity and BMI in the total axSpA population in daily clinical practice, also including patients on long-term TNFi therapy. Methods Consecutive patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were approached for a TNFi serum trough level measurement during their regular outpatient visit at the UMCG. Spearman’s correlation coefficient was used to analyse the relation of serum trough levels with disease activity and BMI. Logistic regression was performed to analyse the relation between therapeutic drug levels and disease activity, corrected for potential confounders, including BMI. Results Thirty-four patients on adalimumab and 21 patients on etanercept were included. Mean age was 45 ± 12 years, 47% were male, median BMI was 26.4 (IQR 23.9–32.5) and median treatment duration was 41 months (range 2–126). According to definitions of Sanquin, 47% of patients had therapeutic serum trough levels. No significant correlations were found between TNFi levels and disease activity (ASDAS-CRP: adalimumab: ρ = -0.16, p = 0.39; etanercept: ρ = -0.29, p = 0.20). TNFi levels were moderately correlated with BMI (adalimumab: ρ = -0.48, p = 0.004; etanercept: ρ = -0.50, p = 0.021). Patients with active disease (ASDAS ≥ 2.1) showed higher BMI than patients with inactive disease (median 29.7 vs. 24.6, p = 0.015). In multivariable regression analyses, BMI was identified as the only confounder for the relationship between therapeutic drug levels and ASDAS. Conclusion In this cross-sectional, observational study of axSpA patients mainly on long-term treatment with TNFi, higher BMI was significantly associated with lower adalimumab and etanercept serum trough levels and higher disease activity.

Abstract Background Although reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational interventions in IA is limited, but favourable results of delivery by a physiotherapist (PT) warrant the need for further research. Therefore, we aim to evaluate the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in (self-)employed people with IA compared to usual care. Methods This randomized controlled trial will include 140 people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who are (self-)employed and have reduced work ability (Work Ability Index – Single Item Scale (WAS) ≤ 7/10) and/or RA/axSpA related sick leave (≤ 6 months). Participants will be randomized 1:1 to the intervention or control condition (usual care). The intervention, delivered by primary care PTs, will be personalized to each patient, consisting of 10 to 21 sessions over 12 months. The intervention will be multimodal, comprising of 1) exercise therapy and a physical activity plan, 2) education/self-management support, 3) work-roadmap to guide participants in finding relevant other care, with optionally 4) online self-management course and 5) workplace examination. Assessments will be performed at baseline and after 3, 6, and 12 months. The primary outcome measure of effectiveness is work ability, as measured with the WAS at 12 months. For the cost-effectiveness analysis, the EuroQol (EQ-5D-5L), self-reported healthcare use, sick leave and productivity while at work will be used to estimate the trial based cost-utility from a societal perspective. A process evaluation, including assessments of adherence and treatment fidelity, will be undertaken using the registrations of the PTs and semi-structured interviews at 12 months follow-up in a random sample of the intervention group. Discussion The results of this study will provide insights in the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in people with IA and a reduced work ability. Trial registration This study is registered in the International Clinical Trial Registry Platform (ICTRP) under number NL9343.

Abstract Objective To investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA). Methods We investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every other week for 12 and 6 weeks, respectively, and thereafter ADA to week 48. Serum concentrations of degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), type X (C10C) collagen; metabolite of C-reactive protein (CRPM), prolargin (PROM), citrullinated vimentin (VICM), calprotectin (CPa9-HNE); and formation of type II (PRO‑C2), III (PRO‑C3), and VI (PRO‑C6) turnover of type IV collagen (PRO-C4) were measured at baseline and weeks 6 or 12, 24, and 48. The pharmacodynamic effect and treatment response to ADA was evaluated by linear mixed models, and correlations between biomarkers and clinical scores were assessed by Spearman’s correlation. Results C1M, C3M, C4M, C6M, CRP, PRO-C4, and CPa9-HNE levels declined after 6 or 12 weeks in patients receiving ADA compared to placebo (all p

Abstract Background Axial spondyloarthritis (axSpA) is known to be associated with several extra-skeletal manifestations (ESM), including the inflammatory skin disease psoriasis. It is important to recognize and diagnose psoriasis timely in axSpA in order to provide optimal treatment and outcome for both axSpA and psoriasis. Methods In this observational study, all patients from the Dutch Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort included before June 2016 were sent a questionnaire with self-screening psoriasis questions including prototypical color pictures. Results Of the 592 questionnaires sent, 448 (75.7%) were eligible for analysis. Of these 448 respondents, 58 (13%) had a positive self-screening for psoriasis symptoms, currently or in the past. In 28 (48%) of 58 patients, psoriasis diagnosis could be verified by medical records, resulting in a psoriasis prevalence rate of 6.3%. In comparison with patients with a confirmed psoriasis diagnosis, patients reporting psoriasis symptoms without a verified diagnosis mentioned more mild than moderate-severe psoriasis symptoms (25% vs. 3%, p = 0.02), and their psoriasis lesions were less often located on the torso area (3% vs. 18%, p = 0.04), the intergluteal cleft (0% vs. 25%, p = 0.02), and legs (7% vs. 43%, p

Abstract Background The psychological burden in people with inflammatory arthritis is substantial, yet little is known about the disease-related affect experienced by individuals with axial Spondyloarthritis (axial SpA). The aim of this study was to conduct a qualitative evidence synthesis and a review of social media to explore the emotional impact of living with axial SpA. Methods We searched nine databases for studies reporting qualitative data about participants’ emotional experience of living with axial SpA. In addition, we searched social media platforms for posts from people with axial SpA based in the UK that offered insights into emotional responses to living with the condition. We employed a thematic approach to synthesise the data. Results We included 27 studies (1314 participants; 72% men) in our qualitative evidence synthesis and developed seven descriptive themes from the data: 1) delayed diagnosis: a barrier to emotional wellbeing; 2) disruptive symptoms: a source of mood swings; 3) work disability: a loss of self-esteem; 4) obstacles in interpersonal relationships: a trigger of distress; 5) taking up exercise: personal pride or unwelcomed reminders; 6) anti-TNF therapy: hope reignited despite concerns and 7) a journey of acceptance: worry mixed with hope. Posts extracted from social media fora (537; 48% from women) for the most part supported the seven themes. One additional theme—COVID-19, uncertainty and anxiety during the pandemic, was developed, reflecting common emotions expressed during the UK’s first wave of the coronavirus pandemic. Conclusion This study highlights a preponderance of negative affect experienced by people living with axial SpA, conditioned through existing and anticipated symptoms, failed expectations, and lost sense of self. Given the bidirectional relationships between negative emotions and inflammation, negative emotions and perceptions of pain, and the influence of affect in self-care behaviours, this finding has important implications for treatment and management of people with axial SpA.

Abstract Background In patients with rheumatic diseases, the use of biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) after discontinuation of tumor necrosis factor inhibitors (TNFi) is known to be effective. However, data on the use of TNFi after discontinuation of non-TNFi bDMARDs or tsDMARDs (non-TNFi) are scarce. This study assessed the 4-years golimumab retention in patients with rheumatic diseases when used after discontinuation of non-TNFi. Methods Adults with rheumatoid arthritis (RA; n = 72), psoriatic arthritis (PsA; n = 30) or axial spondyloarthritis (axSpA; n = 23) who initiated golimumab after discontinuation of non-TNFi from the Spanish registry of biological drugs (BIOBADASER) were analyzed retrospectively. The retention rate (drug survival or persistence) of golimumab up to 4 years was evaluated. Results The golimumab retention rate was 60.7% (51.4–68.8) at year 1, 45.9% (36.0–55.2) at year 2, 39.9% (29.8–49.7) at year 3 and 33.4% (23.0–44.2) at year 4. Retention rates did not differ significantly whether golimumab was used as second, third, or fourth/subsequent line of therapy (p log-rank = 0.462). Golimumab retention rates were higher in axSpA or PsA patients than in RA patients (p log-rank = 0.002). When golimumab was administered as third or fourth/subsequent line, the 4-years retention rate after discontinuation of non-TNFi was similar to that after discontinuation of TNFi. Conclusion In patients who discontinued non-TNFi, most of whom received golimumab as third/subsequent line of therapy, one-third of patients remained on golimumab at year 4. Retention rates were higher in patients with axSpA and PsA than in those with RA.

Abstract Background Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here. Methods In the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0–8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0–72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0–24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0–69). Results Overall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, − 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], − 1.23 [2.81] vs − 0.37 [1.90] with placebo) was sustained through week 104 (− 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104). Conclusion Structural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years. Trial registration ClinicalTrials.gov, NCT02696031.

Abstract Background We sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity. Methods We studied biologic-treatment-naïve AS and healthy control (HC) patients’ sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters in protein–protein interaction networks and Ingenuity Pathway Analysis (IPA) for upstream regulators. Lasso regression analysis was performed for diagnosis. Results Of the 1317 proteins detected in our diagnosis and monitoring analyses, 367 and 167 (317 and 59, FDR-corrected q

Abstract Background Predicting radiographic progression in axial spondyloarthritis (axSpA) remains limited because of the complex interaction between multiple associated factors and individual variability in real-world settings. Hence, we tested the feasibility of artificial neural network (ANN) models to predict radiographic progression in axSpA. Methods In total, 555 patients with axSpA were split into training and testing datasets at a 3:1 ratio. A generalized linear model (GLM) and ANN models were fitted based on the baseline clinical characteristics and treatment-dependent variables for the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) of the radiographs at follow-up time points. The mSASSS prediction was evaluated, and explainable machine learning methods were used to provide insights into the model outcome or prediction. Results The R 2 values of the fitted models were in the range of 0.90–0.95 and ANN with an input of mSASSS as the number of each score performed better (root mean squared error (RMSE) = 2.83) than GLM or input of mSASSS as a total score (RMSE = 2.99–3.57). The ANN also effectively captured complex interactions among variables and their contributions to the transition of mSASSS over time in the fitted models. Structural changes constituting the mSASSS scoring systems were the most important contributing factors, and no detectable structural abnormalities at baseline were the most significant factors suppressing mSASSS change. Conclusions Clinical and radiographic data-driven ANN allows precise mSASSS prediction in real-world settings. Correct evaluation and prediction of spinal structural changes could be beneficial for monitoring patients with axSpA and developing a treatment plan.

Abstract Background In patients with axial spondyloarthritis, vertebral fracture risk is elevated and not always correlated with bone mineral density (BMD). Trabecular bone score (TBS) may offer some advantages in the assessment of vertebral fracture risk in these patients. The primary objective of this study was to compare TBS and BMD between axial spondyloarthritis patients depending on their vertebral fracture status. Secondary objectives were to estimate the prevalence of morphometric vertebral fractures, and to explore factors associated with fracture, as well as the interference of syndesmophytes on BMD and TBS. Methods A cross-sectional study was conducted. Data were collected on demographic and clinical characteristics, lab results, imaging findings and treatment. Statistical analysis was performed using SPSS v.13 statistical software. Results Eighty-four patients (60 men and 24 women; mean age of 59 years) were included. Nearly half (47.6%) of them had lumbar syndesmophytes. The rate of morphometric fracture was 11.9%. TBS showed a higher area under the curve (0.89) than total hip, femoral neck and lumbar BMD (0.80, 0.78, and 0.70 respectively) for classifying patients regarding their fracture status. Nonetheless, the differences did not reach statistical significance. Syndesmophytes affected lumbar spine BMD (p

Abstract Objectives To analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine). Methods Patients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years. Results Mean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14–0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52–1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24–0.77 and 0.85, 95% CI 0.51–1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12–0.80 versus OR 0.56, 95% CI 0.26–1.24 for the cervical and lumbar spine, respectively). Conclusion Disease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.

Abstract Background Involving patients and members of the public in healthcare planning is beneficial for many reasons including that the outcomes focus on topics relevant to service users. The National Early Inflammatory Arthritis Audit (NEIAA) aims to improve care quality for patients with inflammatory arthritis. Case study This paper presents a case study detailing how the NEIAA Patient Panel worked with NEIAA governance groups, the National Rheumatoid Arthritis Society and the National Axial Spondyloarthritis Society to co-create an outpatient clinic visit framework for rheumatology professionals. A framework was co-created, divided into nine sections: pre-appointment preparation, waiting area (face-to-face appointments), face-to-face consultations, physical examination, establishing a forward plan, post consultation, annual holistic reviews, virtual appointments and key considerations. Providing insight into how the multi-disciplinary team can meet the diverse needs of patients with inflammatory arthritis, this framework now informs the teaching content about people who live with physical and mental disability for Year 3 and 4 undergraduate medical students at King’s College London. Conclusion Patients play an important role in helping to address gaps in health service provision in England/Wales. The co-production of a clinic visit framework, informed by their own lived experience and their own expectations can lead to improved and relevant outcomes for the benefit of patients and raises awareness to medical students what matters to patients with physical disabilities when attending outpatient care.

Abstract Objectives To investigate longitudinal relationship between serum uric acid (SUA) and disease activity among Chinese males with axial spondyloarthritis (axSpA). Methods Two-year data from the NASA study cohort of male patients with axial spondyloarthritis were analyzed. Patients global assessment of disease activity (PtGA), BASDAI, ASDAS-CRP, BASFI, and SF-36 were used as the outcomes. The autoregressive Generalized Estimation Equation (GEE) model was used to investigate the longitudinal relationship between SUA and the above outcomes. Age and gender and symptom duration were tested as effect modifiers or confounders. Results In total, 102 male axSpA patients were included, 33.3% of who were hyperuricemia at baseline. Over time,serum uric acid levels associated with the global assessment of patient global assessment of disease activity (PtGA)[P=0.041, β=-2.059,95%CI(-4.032, -0.086)], SF-36: Vitality (VT) [P=0.01, β=1.751, 95%CI (0.415,3.087)], SF-36: Social Functioning (SF)[P=0.002, β= 2.968,95%CI (1.067,4.869)]). And these relationgships were independent of age, symptom duration, baseline uric acid levels, and medication use. Conclusions In summary, SUA levels is longitudinally related to PtGA and mental health assessment. Age, gender and symptom duration do not have an impact on the relationships.

Abstract Objectives To determine whether acetabular dysplasia is associated with hip pain at physical examination among adults with recent-onset inflammatory back pain (IBP) suggesting axial spondyloarthritis (axSpA). Methods This cross-sectional ancillary study was conducted on the prospective DESIR cohort, which enrolled patients aged 18–50 years who had recent-onset IBP. Two readers used antero-posterior pelvic radiographs to assess the Tönnis angle, acetabular angle (AA), lateral centre-edge angle (LCEA), and femoral head extrusion index (FHEI). Abnormality of one or more of these four variables defined acetabular dysplasia. Hip pain upon physical examination was assessed based on Ritchie’s articular index. Results The overall prevalence of acetabular dysplasia was 22% (139/636). The proportion of females was higher in the group with acetabular dysplasia. Hip pain was found in 21% (29/139) of patients with versus 12% (59/497) without acetabular dysplasia (OR, 1.96; 95% CI, 1.20 to 3.20); the association was significant in males (OR, 3.14; 95% CI, 1.44 to 6.86) but not females (OR, 1.39; 95% CI, 0.74 to 2.62). Results were similar when acetabular dysplasia was defined on the basis of LCEA alone (OR, 2.15; 95% CI, 1.18 to 2.62). Conclusion Among patients with recent-onset IBP suggesting axSpA, acetabular dysplasia was significantly associated with hip pain in males. Hip pain related to acetabular dysplasia might result in overdiagnosis of hip involvement by axSpA.

Abstract Background Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease affecting the spine and sacroiliac joints. To investigate whether there are differences in inflammatory and chronic structural damages, as assessed by a semiquantitative MRI scoring method, between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) patients with active inflammation at baseline, and to evaluate the treatment response in these patients after 3 months of tumor necrosis factor-alpha (TNF-α) inhibitor treatment. Methods Fifty-eight axSpA patients with active inflammation were included in the study. The patients were divided into nr-axSpA group and AS group. MRI examinations of the sacroiliac joints were performed before and after treatment. Inflammatory and structural damages in these patients were assessed using the established Spondyloarthritis Research Consortium of Canada (SPARCC) inflammation and sacroiliac joint structural (SSS) scoring methods, which are two MRI-based scoring methods. The SPARCC score, SSS score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were compared between the two groups. Results At baseline, SPARCC scores for patients in the nr-axSpA and AS groups did not differ significantly (P > 0.05); however, SSS scores for fat metaplasia, erosion, and backfill for patients in the AS group were significantly higher (P < 0.001). Compared with baseline, SPARCC scores were significantly decreased in both groups after treatment (P < 0.001); however, after treatment, no statistically significant difference was found regarding SPARCC scores between the AS and nr-axSpA groups. Compared with baseline, a significant increase in the SSS scores for fat metaplasia and backfill (P < 0.001) and a significant decrease in the SSS scores for erosion (P < 0.001) were observed in all axSpA patients. Changes in the SPARCC score was inversely correlated with the changes in the SSS score for fat metaplasia (r = − 0.634, P < 0.001). Changes in the SSS score for backfill were positively correlated with the changes in the SSS score for fat metaplasia (r = 0.277, P < 0.05) and inversely correlated with those for erosion (r = − 0.443, P < 0.001). Conclusion The SPARCC and SSS scoring systems can be used to assess inflammatory and chronic structural damages as well as treatment responses in patients with axSpA. More severe structural damages were seen in AS patients. TNF-α inhibitor treatment for 3 months could effectively reduce inflammation in axSpA patients.

Abstract Background Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis. Methods We analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed. Results In L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease. Conclusion L and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis.

Abstract Background Increased cancer-risk has been reported with rheumatoid arthritis and systemic lupus erythematosus, but the risk is poorly studied in ankylosing spondylitis (AS). Conflicting data in AS have been reported in Asia and Europe, with lack of US population-based studies. Our objective is to study the prevalence of cancer in patients with AS in the US. Methods Using the Explorys database, we performed a cross-sectional study. Data from AS patients and controls were stratified by 2 rheumatology visits, age groups, clinical characteristics, and frequency of cancers. The data were analyzed using a series of chi-square tests of independence as well as logistic regression to test for association between AS and cancer. Results 1410 AS patients (12.88%) had cancer. Female AS patients had a lower prevalence of cancer compared to controls (OR 0.840, 95% CI [0.769, 0.916]), while male AS patients had no statistically significant difference (OR 1.011, 95% CI [0.929, 1.099]). Among patients with AS, Skin cancers (squamous cell, malignant melanoma, and basal cell) and head and neck cancers were significantly increased. Conclusion Our study demonstrated that the prevalence of “any-type-cancer” was not increased in AS patients compared to controls with no rheumatic disease. Skin, head, and neck cancers were more frequently seen in AS patients.

Abstract Background Axial spondyloarthritis (axSpA) is associated with an increased risk of cardiovascular disease. We aimed to evaluate the effect of tumor necrosis factor inhibitors (TNFis) on the risk of cardiovascular disease in patients with axSpA. Methods This retrospective study included 450 patients with axSpA without pre-existing cardiovascular disease. The outcome was incident cardiovascular disease (myocardial infarction or stroke) after the diagnosis of axSpA. The effect of TNFis on cardiovascular risk was analyzed in the total study population and in an inverse probability of treatment weighting (IPTW)-adjusted population. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular disease, according to exposure to TNFis. Results Of the 450 patients, 233 (51.8%) and 217 (48.2%) patients were and were not exposed to TNFis, respectively. Twenty cardiovascular diseases occurred during 2868 person-years of follow-up (incidence rate: 6.97/1000 person-years). In the total study population, exposure to TNFis was associated with a reduced cardiovascular risk when adjusted for traditional cardiovascular risk factors (HR 0.30, 95% CI 0.10–0.85, p = 0.024). However, when time-averaged erythrocyte sedimentation rate and C-reactive protein were additionally adjusted, this association was attenuated and lost statistical significance (HR 0.37, 95% CI 0.12–1.12, p = 0.077). Furthermore, in the IPTW-adjusted population, exposure to TNFis showed no significant reduction in cardiovascular risk (HR 0.60, 95% CI 0.23–1.54, p = 0.287). Conclusions Although controlling inflammation through TNFis could be beneficial in cardiovascular risk reduction, our data indicate no TNFi-specific reduction in cardiovascular risk in patients with axSpA.

Abstract Background Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA. Methods We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman’s correlations were performed with ECM biomarkers and clinical scores. Results Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001). Conclusions Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions.

Abstract Background In patients with axial spondyloarthritis (axSpA), magnetic resonance imaging (MRI) is used to detect bone marrow edema (BME) in sacroiliac joints (SIJ) but SIJ BME are also detected in the population. Not much is known about sex differences in that regard. Objective To explore sex-specific differences associated with the extent of BME in the SIJ suggestive of axSpA in a general population cohort study. Methods Taking advantage of 793 recently evaluated MRIs of subjects < 45 years taking part in the SHIP cohort, we used negative-binomial (NB) count data regression to analyze factors associated with the extent of SIJ BME. Predictors were explored by model-based boosting (MBB), a machine learning approach. Results Estimates of NB regression showed strong effects of sex in interaction with age, BMI, back pain, and particularly HLA-B27. The NB regression model showed incidence rate ratios (IRR) for the main effect of sex (females vs. males): 0.94 [95% CI: 0.63; 1.41], HLA-B27: 4.32 [2.09; 9.8], and for the interaction of sex to HLA-B27: 0.22 [0.06; 0.75]. According to MBB, HLA-B27 positivity, BMI, current smoking, back pain in the last 3 months, the interaction of sex and HLA-B27, and delivery in the last 12 months were of highest importance to explain the extent of SIJ BME. Conclusions Different factors were associated with the extent of SIJ BME in females and males. Most importantly, HLA-B27 was relevant only in males but not in females in whom a postpartal state was important. This finding may be relevant for the pathogenesis of axSpA.

Abstract Background Barriers and facilitators to physical activity in inflammatory arthritis can be assessed through the Inflammatory arthritis FAcilitators and Barriers (IFAB) questionnaire. The objective was to measure the correlation between IFAB and self-reported physical activity levels. Methods This was an international, multicentric, cross-sectional study in 2019–20. Consecutive spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients completed the 10-item IFAB, which ranges from − 70 to 70 with lower scores indicating more barriers. Physical activity was measured by the IPAQ-S questionnaire, steps per day collected by smartphone, and psychological readiness to change by stages of behaviour change. Spearman correlations and multivariable linear regression were calculated. Results Of 245 patients included, 150 were analysed: 69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA. Mean age was 48.6 years (standard deviation, SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. Barriers to physical activity were moderate: mean IFAB, 6 (SD 19.2); 39 (26%) patients scored less than − 5, corresponding to significant barriers. The mean physical activity was 2837 (SD 2668, median 1784) MET-minutes per week. The IPAQ-S questionnaire was correlated with the IFAB (rho 0.28, p

Abstract Background Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP). Methods C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value

Abstract Background Little evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA. Methods We prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score). Results A total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls (p = 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36–15.1, p = 0.014), age (per 10-year increase OR 1.05, 1.02–1.68, p = 0.007), and BMI (OR 0.77, 0.63–0.9, p = 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls (p = 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8–25.3, p = 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement. Conclusions Improving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are less prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement. Study registration Protocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010).

Abstract Background Anterior uveitis (AU) is the most frequent extra-articular feature of axial spondyloarthritis (axSpA). We aimed to assess and compare the incidence of AU in axSpA patients treated with anti-TNF or anti-IL17A. Methods We systematically reviewed PubMed, EMBase, and Cochrane from inception to May 3, 2020, and searched for placebo-controlled and head-to-head randomized controlled trials (RCTs) assessing anti-TNF monoclonal antibodies (mAb) or soluble receptor fusion protein or anti-IL17A in patients with axSpA according to ASAS criteria and reporting safety data on AU. Data were extracted following a predefined protocol. We did pairwise and network meta-analyses for the primary outcome of AU flares (relapse or de novo) incidence and estimated summary odds ratios (ORs). We assessed the quality of evidence using the Cochrane risk-of-bias 2.0 tool. We ranked treatments according to their effectiveness in preventing AU flare using the P-score. Results We identified 752 citations and included 33 RCTs, comprising 4544 treated patients (anti-TNF mAb 2101, etanercept [ETN] 699, anti-IL17A 1744) and 2497 placebo-receiving patients. Incidence of uveitis was lower with anti-TNF mAb versus placebo (OR = 0.46; CI 95% [0.24; 0.90]) and versus anti-IL17A (OR = 0.34; CI 95% [0.12; 0.92]. According to the P-score, the ranking from the most to the least preventive treatment of uveitis flare was as follows: anti-TNF mAb, ETN, placebo, and anti-IL17A. Conclusion In RCTs assessing anti-TNF and anti-IL17A in axSpA, incident uveitis are rare events. However, this network meta-analysis demonstrates that anti-TNF mAb are associated with a lower incidence of uveitis compared to placebo and anti-IL17A.

Abstract Background Enthesitis is a hallmark of spondyloarthritis (SpA) with a substantial impact on quality of life. Reports of treatment effectiveness across individual enthesitis sites in real-world patients with axial SpA (axSpA) are limited. We investigated the evolution of enthesitis following tumor necrosis factor inhibitor (TNFi) initiation in axSpA patients, both cumulatively and at specific axial and peripheral sites. Methods AxSpA patients in the Swiss Clinical Quality Management Registry were included if they initiated a TNFi, had an available Maastricht Ankylosing Spondylitis Enthesitis Score, modified to include the plantar fascia (mMASES, 0–15), at start of treatment and after 6 and/or 12 months and ≥12 months follow-up. Logistic regression models were utilized to analyze explanatory variables for enthesitis resolution. Results Overall, 1668 TNFi treatment courses (TCs) were included, of which 1117 (67%) had active enthesitis at baseline. Reduction in mMASES at the 6- and 12-month timepoints was experienced in 72% and 70% of TCs, respectively. Enthesitis resolution at 6/12 months occurred in 37.9%/43.0% of all TNFi TCs and 40.7%/50.9% of first TNFi TCs. At 6 months, a significant reduction in the frequency of enthesitis was observed at all sites, except for the Achilles tendon and plantar fascia among first TNFi TCs, while at 12 months, reduction was significant at all sites in both TC groups. Enthesitis resolved in 60.3–77% across anatomical sites, while new incident enthesitis occurred in 4.0–13.5% of all TNFi TCs at 12 months. Both baseline and new-incident enthesitis occurred most frequently at the posterior superior iliac spine and the fifth lumbar spinous process. Younger age and lower mMASES at baseline were predictors of complete enthesitis resolution, while female sex and second- or later-line TNFi treatment were associated with persistence of enthesitis at 12 months. Conclusion In real-world axSpA patients treated with a TNFi, enthesitis improved in the majority of patients across all anatomical sites. Significant improvement at the Achilles and plantar fascia entheses was observed only at 12 months. Complete and site-specific enthesitis resolution occurred in ≥40% and ≥60% of TCs evaluated at 12 months, with a low incidence of new site-specific enthesitis. Trial registration Not applicable.

Abstract Background Informative serum biomarkers for monitoring inflammatory activity and treatment responses in axial spondyloarthritis (axSpA) are lacking. We assessed whether Lipocalin 2 (LCN2) and Oncostatin M (OSM), both having roles in inflammation and bone remodeling, may accurately reflect chronic joint inflammation and treatment response in axSpA. Previous reports in animal models showed involvement of LCN2 and OSM in joint/gut inflammation. We asked whether they also play a role in human axSpA. Methods We analyzed a longitudinal observational axSpA cohort (286 patients) with yearly clinical assessments and concurrent measurements of serum LCN2 and OSM (1204 serum samples) for a mean of 4 years. Biomarker levels were correlated with MRI scoring and treatment response. Results Persistent and transient elevation of LCN2 and OSM were observed in axSpA patients. Persistent elevation of LCN2 or OSM, but not CRP, correlated with sacroiliac joint (SIJ) MRI SPARCC scores (Pearson’s correlation p = 0.0005 and 0.005 for LCN2 and OSM respectively), suggesting that LCN2/OSM outperforms CRP as reflective of SIJ inflammation. We observed both concordant and discordant patterns of LCN2 and OSM in relationship to back pain, the cardinal clinical symptom in axSpA. Twenty-six percent (73/286) of the patients remained both clinically and serologically active (CASA). Sixty percent (173/286) of the patients became clinically quiescent, with back pain resolved, but 53% (92/173) of them were serologically active (CQSA), indicating that pain control may not indicate control of joint inflammation, as reflected by positive MRI imaging of SIJ. With respect to treatment responses, transient elevation of LCN2 or OSM over time was predictive of better response to all treatments. Conclusion In axSpA, persistent LCN2 and/or OSM elevation reflects chronic SIJ inflammation and suboptimal treatment response. In our cohort, half of the currently deemed clinically quiescent patients with back pain resolved continued to demonstrate chronic joint inflammation. LCN2 and OSM profiling outperforms CRP as a predictive measure and provides an objective assessment of chronic local inflammation in axSpA patients.