Immunological biomarkers in patients with radiographic axial spondyloarthritis, an exploratory longitudinal Swedish study.

Objectives There is a need for more specific biomarkers to diagnose and predict disease course in patients with axial spondyloarthritis (axSpA). This study aimed to study immunological plasma biomarkers, at different time-points in radiographic (r)-axSpA patients overall and stratified by sex and compare these biomarker pattern in r-axSpA patients concerning disease phenotypes and disease activity. Methods Plasma samples were analysed from r-axSpA patients at and prior (Pre-Backbone) inclusion in the Backbone study. Interferon gamma, interleukin-10, -17A, -17F, -22, -23, -6, MCP-1, TNF-α, VEGF-A, MIF, IgA anti-CD74, zonulin, ESR, hsCRP, white blood cell count, and blood lipids were measured. Results Biomarker pattern discriminated significantly between r-axSpA patients in Backbone and Pre-Backbone compared with controls. When stratifying by sex, it was possible to discriminate between male and female r-axSpA patients in Backbone vs controls and between male r-axSpA patients in pre-Backbone and controls. In Backbone, markers with high discriminative capacity were MIF, IgA anti-CD74, and MCP-1. In Pre-Backbone, IL-6, TNF-α, MIF, triglycerides, cholesterol, IL-10, and zonulin displayed high discriminative capacity. Conclusion Based on their temporal pattern and mutual relationship, we suggest studying MIF, IgA anti-CD74, and MCP-1 in depth, at more time points, to further elucidate disease-driving mechanisms in this complex disease.

The cost-effectiveness of a bimekizumab versus IL-17A inhibitors treatment-pathway in patients with active axial spondyloarthritis in Scotland.

OBJECTIVE: To estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17Ai's, ixekizumab, and secukinumab, from the NHS Scotland perspective. METHODS: The axSpA treatment-pathway was modeled using a decision tree followed by a lifetime Markov model. The pathway included first- and second-line biologic disease-modifying antirheumatic drugs (bDMARD), followed by best supportive care (bDMARD, nonbiologic). Bimekizumab followed by any bDMARD ("BKZ") was compared with IL-17Ai's: secukinumab 150 mg followed by a blend ("SEC") of dose up-titration to secukinumab 300 mg and any bDMARD, or ixekizumab followed by any bDMARD ("IXE"). Transition to the next therapy was triggered by Bath Ankylosing Spondylitis Disease Activity Index-50% (BASDAI50) non-response or any-cause discontinuation. A published network meta-analysis provided efficacy data. EuroQoL-5-dimensions utilities were derived by mapping from Ankylosing Spondylitis Disease Activity Score. Costs included disease management (linked to functional limitations), biologics acquisition (list prices), administration and monitoring (NHS 2021/22). Discounting was 3.5%/year. Probabilistic results from patients with non-radiographic axSpA and ankylosing spondylitis were averaged to reflect the axSpA disease spectrum. Scenario and sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) of BKZ was £24,801/quality-adjusted life-year (QALY) vs. SEC (95% credible interval £24,163-£25,895). BKZ had similar costs (Δ -£385 [-£15,239-£14,468]) and QALYs (Δ 0.039 [-0.748-0.825]) to IXE, with £1,523 (£862-£2,222) net monetary benefit. Conclusions remained unchanged in most scenarios. Results' drivers included BASDAI50 response rate and disease management cost. LIMITATIONS: Results were based on list prices. Data concerning up-titration to secukinumab 300 mg was scarce. CONCLUSIONS: The bimekizumab treatment-pathway represents a cost-effective option across the axSpA disease spectrum in Scotland. Bimekizumab is cost-effective compared to a secukinumab-pathway that includes dose up-titration, and has similar costs and QALYs to an ixekizumab-pathway.

Different Therapeutic Response to Anti-TNF Drugs in Patients with Axial Spondyloarthritis Depending on Their Clinical Profile: An Unsupervised Cluster Analysis.

Background: The objectives were as follows: (a) to identify, among patients with axial spondyloarthritis (axSpA), "clusters" of patients based on the presence of peripheral and extra-musculoskeletal manifestations (EMMs) and (b) to compare the effectiveness of the first anti-TNF drugs across the different clusters after 6 months of follow-up. Methods: An observational and retrospective study of 90 axSpA patients naïve to bDMARDs was conducted. An unsupervised cluster analysis using the "k-means" technique was performed using variables of peripheral and EMMs. Baseline clinical and sociodemographic characteristics were evaluated, and the response to anti-TNF treatment (considering responders as those with an improvement ≥1.1 for the Ankylosing Spondylitis Disease Activity Score (ASDAS) or ≥2.0 for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) was compared across the clusters after 6 months of follow-up. Results: Two clusters were identified: cluster 1 (n = 14), with a higher prevalence of peripheral manifestations, inflammatory bowel disease (IBD), and HLA-B27-positive status, and a lower prevalence of uveitis in comparison with cluster 2 (n = 76). Patients from cluster 1 experienced a more pronounced absolute improvement in ASDAS and BASDAI indices after 6 months. The percentage of responders after 6 months of follow-up was superior in cluster 1 compared to cluster 2 (85.7% vs. 48.7%, p = 0.011). Conclusion: This study suggests the existence of two clinical profiles in axSpA patients according to the peripheral and EMMs, with higher rates of anti-TNF effectiveness after 6 months in those with a greater presence of peripheral features.

Elevating the Standard of Care for Patients with Axial Spondyloarthritis: 'Calls to Action' from Rheumacensus, a Multistakeholder Pan-European Initiative.

INTRODUCTION: Several barriers to optimal care in axial spondyloarthritis (axSpA) exist, which is detrimental to patient outcomes. The Rheumacensus programme aimed to identify how the standard of care (SoC) and treatment ambition for patients with axSpA could be elevated, from the unique perspective of three key stakeholders from across Europe: patients, healthcare professionals (HCPs) and payors. METHODS: Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in axSpA and an area of focus, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting to generate 'Calls to Action' (CTA) to highlight the changes needed to elevate the SoC for patients with axSpA. RESULTS: The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was patient empowerment through education on the disease and treatment options available, to enable patient involvement in management and ultimately increase treatment adherence. Four key themes emerged from the Delphi process: patient empowerment, patient knowledge, patient-HCP consultations and optimal initial treatment. These themes informed 11 overarching CTA, which demonstrate the need for a multistakeholder approach to implement a paradigm shift towards patient-centred care to elevate health outcomes in patients with axSpA. CONCLUSION: Rheumacensus identified CTA to help bridge the disparities observed in axSpA care. It is now imperative for all stakeholders to take practical steps towards addressing these CTA to elevate the SoC and treatment ambition in patients with axSpA.

Axial spondyloarthritis (axSpA) is a long-term inflammatory disease involving the spine and other joints of the body as well as where tendons and ligaments attach to bone. AxSpA is associated with a significant burden to patients which can be worsened by delays in diagnosis and poor disease management. This report is about a programme called Rheumacensus which has the overall aim of improving the standard of care (SoC) for patients with axSpA. Rheumacensus brings together the points of view of three key groups involved in the care of people with axSpA: patients, payors and healthcare professionals (HCPs) from across Europe. Together, these three groups agreed to focus on patient empowerment through education on the disease and treatment options to effectively enhance treatment adherence, as a way to raise the SoC. Through a series of exercises­to agree on the current SoC and what needs to be improved­and group discussions, four themes were established which were used by the groups to help them suggest 'Calls to action' (CTA). The CTAs were ideas of how improvements could be made or what needs to be done to improve the care patients receive. The four themes were (1) patient empowerment, (2) patient knowledge, (3) patient­HCP consultation and (4) optimal initial treatment. In total, 11 CTAs were developed across these themes that provide direction and practical next steps which patients, payors and HCPs could take to drive change and make a real difference to patients by improving their care.

A Survey Exploring Inflammatory Back Pain in Patients With Inflammatory Bowel Disease.

Background Diagnostic delay of axial spondyloarthritis (axSpA) is a widely recognized issue worldwide, providing a great burden for patients with this disease. AxSpA is present in a significant proportion of patients with inflammatory bowel disease (IBD). This UK study primarily aims to identify the presence of inflammatory back pain (IBP) in patients attending IBD clinic. Further aims of this study include investigating if participants had received further referrals and diagnoses for their IBP and considering factors contributing to diagnostic delay. Methods Patients were recruited from a Royal Free London NHS Trust hospital's IBD clinic. Each participant completed a 23-question survey. The Berlin criteria were applied to the questions to investigate the presence of IBP. Further questions were asked about their IBD diagnosis and treatment, the healthcare professionals they had seen for their back pain, and other extra-articular features associated with axSpA. Results Seventy-five patients completed the online survey sent out via email. Forty percent (n = 30) of participants were female and 60% (n = 45) were male. Sixty-one percent (n = 36) of participants from the colitis clinic reported they had back pain, and 41% of the participants reported back pain for over three months. Of these, 39% (12) of participants fulfilled the Berlin criteria for IBP. Of patients experiencing back pain for over three months, we found that 10% (3) fulfilled the Berlin criteria but had not received a diagnosis for their IBP. All patients who had fulfilled the Berlin criteria but had not received a diagnosis for their IBP had seen their general practitioner (GP) and an allied healthcare professional, but not a rheumatologist. Conclusions This study highlights the presence of possibly undiagnosed axSpA in patients with IBD. The reasons for the diagnostic delay of axSpA are multifactorial. We consider specific patient characteristics, lack of awareness and education of the condition, and issues in the referral process. There is a need to improve education and awareness of axSpA, reconsider referral processes, and consider new initiatives such as joint specialty clinics to identify and treat axSpA on time.

Piriformis syndrome as an overlooked cause of pain in a patient with axial spondyloarthritis: a case report.

Piriformis syndrome is a neuromuscular disorder characterized by hip, buttock, and leg pain. Axial spondyloarthritis is a rheumatic disease primarily affecting the sacroiliac joint and the spine. Due to their anatomical proximity, the potential relationship between piriformis syndrome and sacroiliitis has been discussed for some time. However, literature review revealed that there is no study on piriformis syndrome in individuals with axial spondyloarthritis. Here, we present the case of a 30-year-old female with axial spondyloarthritis who developed severe low back, hip, and buttock pain that persisted despite initial treatment for axial spondyloarthritis. We first re-evaluated her condition through physical examination, magnetic resonance imaging, and an injection test for piriformis syndrome. Following a comprehensive assessment, the patient was diagnosed with both axial spondyloarthritis and piriformis syndrome. Subsequently, a tailored treatment plan was devised, addressing both conditions, and after a 3-month course of treatment, we obtained significant reduction in pain of the patient. This is the first case report in literature, where we used injection test to confirm the diagnosis of the piriformis syndrome in a patient with axial spondyloarthritis. We therefore strongly advocate considering piriformis syndrome as a potential etiology for pain in individuals with axial spondyloarthritis consistently. This recognition is important as piriformis syndrome does not respond adequately to non-steroidal anti-inflammatory drugs and may lead to unnecessary use of biological disease-modifying antirheumatic drugs. Timely identification and intervention are imperative in ensuring optimal patient care.

Is sarcopenia a real concern in ankylosing spondylitis? A systematic literature review.

PURPOSE: Sarcopenia is a condition defined as loss of muscle mass and strength, associated with poor functional performance and disability. Sarcopenia can be exacerbated or worsened in presence of inflammation, sedentary lifestyle and cytokine imbalance, thus it frequently occurs in people affected by rheumatic diseases. This systematic literature review aims to explore the association between sarcopenia and spondyloarthritis (SpA) and its most frequent manifestation, i.e. ankylosing spondylitis (AS). METHODS: The Scopus, PubMed, and Web of Science databases were searched for articles on muscle mass, muscle strength and axial SpA, from any date to November 2023. Only studies written in English were considered. The methodological quality of the studies included in the review was evaluated using the Newcastle-Ottawa Scales for observational studies and for case-control studies. RESULTS: 190 papers were retrieved from the searches, 14 of which met the inclusion criteria. Rather than diagnosis of sarcopenia, pre-sarcopenia or probable sarcopenia were frequent in people with AS, with a great reduction especially of muscle strength. The pre-sarcopenia status appears to be related to high AS disease activity, suggesting that chronic inflammation resulting in pain, less movement and decreased physical activity could play a role in the muscle heath of AS patients. CONCLUSIONS: Our review confirms the existence of an association between AS and loss of muscle strength-likely sarcopenia-already at a young age. Preventive and early strategies should be adopted to ensure successful aging for individuals with AS.

Safety Profile of Upadacitinib up to 5 Years in Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis: An Integrated Analysis of Clinical Trials.

INTRODUCTION: This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]). METHODS: Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY). RESULTS: A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases. CONCLUSION: Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified. TRIAL REGISTRATION: SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.

Psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis are a group of diseases that cause pain and inflammation of the joints and/or spine. Safety data were combined from five studies: two in psoriatic arthritis, two in ankylosing spondylitis, and one in non-radiographic axial spondyloarthritis. Patients were treated with upadacitinib or adalimumab for up to 5 years. Adalimumab was only used for patients participating in one of the two psoriatic arthritis studies. Side effects from treatment were more common in patients with psoriatic arthritis than those with ankylosing spondylitis and non-radiographic axial spondyloarthritis; more patients with psoriatic arthritis had side effects with upadacitinib than adalimumab. A similar number of patients across treatment groups and diseases had side effects that made them stop treatment. The number of cancer cases (except cancer of the upper layer of the skin), cardiovascular issues, and blood clots were similar between the upadacitinib and adalimumab groups in psoriatic arthritis and across diseases. Serious infections, painful rashes that cause blisters (herpes zoster, also commonly referred to as shingles), low levels of white blood cells, and cancer of the upper layer of the skin were more common with upadacitinib than adalimumab in patients with psoriatic arthritis; overall, these events occurred more often with upadacitinib in patients with psoriatic arthritis than with ankylosing spondylitis and non-radiographic axial spondyloarthritis. Our results showed that the safety of upadacitinib was generally similar across diseases, and patients could tolerate it well for up to 5 years. No new safety risks were found with upadacitinib treatment.

Drug Survival, Effectiveness and Safety of Secukinumab in Axial Spondyloarthritis up to 4 Years: A Real-Life Single Center Experience.

(1) Objective: The main aims of our study were to explore the drug survival and effectiveness of secukinumab in patients with axial spondyloarthritis (axSpA). (2) Methods: We underwent a retrospective analysis of consecutive axSpA treated with secukinumab as a first line of biologics or at switch in a biologic-experienced population. Efficacy data, indicating improvement in inflammation parameters (such as C-reactive protein and erythrocyte sedimentation rate) and disease activity scores (such as Ankylosing Spondylitis Disease Activity Score [ASDAS-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and patient-reported outcomes (pain), were assessed at 6, 12, 24, 36 and 48 months. The drug survival rate, dropout rate and discontinuation reasons (efficacy versus safety) of secukinumab were assessed in subgroup analysis (axSpA with and without exposure to biologics). (3) Results: In total, 46 patients were exposed to the IL-17A inhibitor secukinumab. The drug survival for axSpA patients 59.7% at 12 months and 31.3% at 24 months. There were no statistically significant differences in the median drug survival between biologic-naïve versus biologic-experienced subgroups. (4) Conclusions: Secukinumab has demonstrated effectiveness and safety in treating a cohort of axSpA patients in real-world settings, with a notable retention rate of the drug.

Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy.

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.

Early identification of golimumab-treated patients with higher likelihood of long-term retention.

Background: The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications. Objectives: To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions. Design: Retrospective non-interventional database analysis. Methods: Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated. Results: 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]). Conclusion: With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab.

Short-term effectiveness of guselkumab in psoriatic arthritis patients and suggestive features of axial involvement: results from a real-life multicentre cohort.

OBJECTIVE: To evaluate the short-term effectiveness of guselkumab in patients with psoriatic arthritis (PsA) and suggestive features of axial involvement in a prospective "real-life" multicentre cohort. METHODS: Between June 2022 and June 2023, PsA patients with axial involvement were evaluated if treated at least for 4 months with guselkumab. The effectiveness was evaluated by BASDAI, ASDAS, DAPSA, and achievement of BASDAI ≤ 4, also exploiting predictive factors. In a group of patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. RESULTS: Sixty-seven patients with PsA and suggestive features of axial involvement (age 53.4 ± 11.2 years, male sex 26.9%) were treated with guselkumab. After 4 months, a significant reduction of BASDAI, ASDAS, and DAPSA was observed. A ΔBASDAI of -2.11 ± 0.43 was estimated assessing the mean difference values before and after guselkumab administration and 52.2% of patients reached a BASDAI ≤ 4. In 27 patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. A reduction of 0.80 or larger of the sacroiliac joint lesion score was observed in the majority of patients (70.3%) based on MRI improvements, paralleling with the clinical response.No life-threatening side effects were recorded; 17.9% of patients reported minor adverse events mainly injection site reactions. CONCLUSIONS: The short-term effectiveness of guselkumab in patients with PsA and suggestive features of axial involvement was shown. Although further studies are needed, our multicentre "real-life" study may suggest the clinical usability of guselkumab in this context.

Costotransverse joint ankylosis and their association with syndesmophyte progression in patients with radiographic axial spondyloarthritis.

Background: Abnormal new bone formation can occur not only in the vertebral body but also can occur in facet, costovertebral, and costotransverse joints in radiographic axial spondyloarthritis (r-axSpA) patients. Little is known about the association between syndesmophyte progression and paravertebral joint ankylosis in r-axSpA. Objectives: Costotransverse joint ankylosis in r-axSpA patients was measured. Furthermore, the association between syndesmophyte progression for 2 years assessed by computed tomography syndesmophyte score (CTSS) and facet, costovertebral, and costotransverse joints ankylosis were evaluated. Design: Single-center, prospective, cohort study. Methods: Whole spine CT images taken at baseline and 2-year follow-up were used to calculate the CTSS of the vertebral body. In addition, ankylosis of the facet/costovertebral/costotransverse joints was scored. CTSS (range, 0-552) and facet joint ankylosis (range, 0-46) were assessed at 23 vertebral units. Costovertebral joints at T1-T12 (range, 0-48) and costotransverse joints at T1-T10 (range, 0-20) were also assessed by independent two readers. Intraclass correlation coefficients (ICC) were calculated to determine inter-reader reliability. Odds ratios (OR) were calculated to identify the associations between syndesmophyte progression and the baseline status of facet, costovertebral, and costotransverse joints. Results: In all, 50 patients with r-axSpA were included. Readers 1 and 2 identified C7-T3 (facet joints), T5-T7 and T12 (costovertebral joints), and T8-T9 (costotransverse joints), as common sites of ankylosis at baseline and at 2-year follow-up. The ICCs for the facet, costovertebral, and costotransverse joints at baseline were 0.876, 0.952, and 0.753, respectively. OR of baseline costovertebral and costotransverse joint ankylosis for predicting syndesmophyte progression of the vertebral body was 4.644 [95% confidence interval (CI), 2.295-9.398] and 1.524 (95% CI, 1.036-2.244), respectively. Conclusion: Costotransverse joint ankylosis in r-axSpA patients can be measured semi-quantitatively on whole spine CT, and ankylosis of the costotransverse and costovertebral joints predicts the progression of syndesmophytes.Trial registration: Not applicable.

Disease activity and widespread pain are main contributors to patient-reported global health in axial spondyloarthritis: an analysis of 6064 patients.

Global health (GH) and health-related quality of life are patient priorities in axial spondyloarthritis (axSpA). Our objective was to assess the relative importance of disease-related factors including disease activity, and patient-related factors including comorbidities, to explain GH in axSpA. Post hoc cross-sectional analyses of 4 sets (COMOSPA, PERSPA, COMEDSPA, and DESIR) of patients fulfilling ASAS criteria for axSpA. GH was assessed through the ASAS Health Index (ASAS-HI) or the EuroQoL-5D-3L (EQ-5D). Disease-related factors included disease activity (ASDAS, psoriasis, arthritis, enthesitis, and CRP), disease duration, diagnostic delay, bamboo spine, and treatment. Non-disease-related factors included sociodemographic characteristics, comorbidities and chronic widespread pain. Multivariable logistic and linear regressions and partial variances (R2) were applied to identify independent determinants of GH. In 6064 patients (range 284-2756 across datasets), mean age ranged 38.9-45.8 years, 51-68% were male. GH was generally moderate: median ASAS-HI ranged 5.0-7.0. GH was explained by ASDAS (range of odds ratios, OR, 2.60-4.48) and chronic widespread pain (range of OR 2.19-8.39); other determinants included comorbidities and sociodemographic characteristics. Only 47-57% of the total variance in GH could be explained by the models; disease activity (partial variance, 16-26%) and chronic widespread pain (partial variance 12-15%) were the key contributing variables. A wide range of disease and non-disease-related variables usually collected in studies could only explain 47-57% of the variability in GH. Among these, disease activity and chronic widespread pain were most relevant and of similar magnitude of importance. These findings will be helpful for shared decision-making.

Evaluation of a hybrid telehealth care pathway for patients with axial spondyloarthritis including self-sampling at home: results of a longitudinal proof-of-concept mixed-methods study (TeleSpactive).

Patients with axial spondyloarthritis (axSpA) require close monitoring to achieve the goal of sustained disease remission. Telehealth can facilitate continuous care while relieving scarce healthcare resources. In a mixed-methods proof-of-concept study, we investigated a hybrid telehealth care axSpA pathway in patients with stable disease over 6 months. Patients used a medical app to document disease activity (BASDAI and PtGA bi-weekly, flare questionnaire weekly). To enable a remote ASDAS-CRP (TELE-ASDAS-CRP), patients used a capillary self-sampling device at home. Monitoring results were discussed and a decision was reached via shared decision-making whether a pre-planned 3-month on-site appointment (T3) was necessary. Ten patients completed the study, and eight patients also completed additional telephone interviews. Questionnaire adherence was high; BASDAI (82.3%), flares (74.8%) and all patients successfully completed the TELE-ASDAS-CRP for the T3 evaluation. At T3, 9/10 patients were in remission or low disease activity and all patients declined the offer of an optional T3 on-site appointment. Patient acceptance of all study components was high with a net promoter score (NPS) of +50% (mean NPS 8.8 ± 1.5) for self-sampling, +70% (mean NPS 9.0 ± 1.6) for the electronic questionnaires and +90% for the T3 teleconsultation (mean NPS 9.7 ± 0.6). In interviews, patients reported benefits such as a better overview of their condition, ease of use of telehealth tools, greater autonomy, and, most importantly, travel time savings. To our knowledge, this is the first study to investigate a hybrid approach to follow-up axSpA patients including self-sampling. The positive results observed in this scalable proof-of-concept study warrant a larger confirmatory study.

To be or not to B27 positive: implications for the phenotypes of axial spondyloarthritis outcomes. Data from a large multiracial cohort from the Brazilian Registry of Spondyloarthritis.

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.

Axial Spondyloarthritis: an overview of the disease.

Axial Spondyloarthritis (axSpA) is a chronic, inflammatory, immune-mediated rheumatic disease that comprises two subsets, non-radiographic and radiographic axSpA, and belongs to a heterogeneous group of spondyloarthritides (SpA). Over the years, the concept of SpA has evolved significantly, as reflected in the existing classification criteria. Considerable progress has been made in understanding the genetic and immunological basis of axSpA, in studying the processes of chronic inflammation and pathological new bone formation, which are pathognomonic for the disease. As a result, new medication therapies were developed, which bring more effective ways for disease control. This review presents a brief overview of the literature related to these aspects of disease after summarising the available information on the topic that we considered relevant. Specifically, it delves into recent research illuminating the primary pathological processes of enthesitis and associated osteitis in the context of inflammation in axSpA. The exploration extends to discussion of inflammatory pathways, with a particular focus on Th1/Th17-mediated immunity and molecular signaling pathways of syndesmophyte formation. Additionally, the review sheds light on the pivotal role of cytokine dysregulation, highlighting the significance of the IL-23/17 axis and TNF-α in this intricate network of immune responses which is decisive for therapeutic approaches in the disease.

Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation.

OBJECTIVE: There is an increased risk for cardiovascular disease (CVD) in patients with radiographic axial spondyloarthritis (r-axSpA). In this cross-sectional study, we aimed to, overall and stratified by sex, (i) compare ultrasound derived carotid intima media thickness (cIMT), between patients and controls, and (ii) investigate associations between cIMT, clinical disease activity and inflammation-related laboratory markers in patients with r-axSpA. METHOD: In total, 155 patients diagnosed with r-axSpA using the modified New York criteria and 400 controls were included. Bilateral carotid ultrasound, laboratory testing, and questionaries were acquired. Disease-specific assessments were carried out for patients. Linear regression analysis was used to assess associations. RESULTS: Linear regression analyses showed that patients with r-axSpA had increased mean cIMT compared to controls (mean ± SD, 0.8 ± 0.1 mm vs 0.7± 0.1 mm, respectively, unstandardized ß (95% CI) -0.076 (-0.10, -0.052), P < 0.001) adjusted for smoking status and age. Linear regression analyses for patients with r-axSpA showed that only males presented significant associations between cIMT and inflammation-related laboratory markers, white blood cell (WBC) count (mean ± SD, 6.8 ± 1.6 109/L) and monocytes (0.6 ± 0.2 109/L); WBC count (unstandardized ß (95% CI) 0.019 (0.0065, 0.031), P = 0.003, R2 = 0.57) and monocytes (0.13 (0.0047, 0.26), P = 0.041, R2 = 0.55), adjusted for age, smoking status, body mass index, hypertension, dyslipidemia, diabetes mellitus, ASDAS-CRP, and treatment with DMARDs and glucocorticoids. No significant association was found between cIMT and clinical disease activity assessed by ASDAS-CRP. CONCLUSION: Patients with r-axSpA had significantly increased cIMT compared to controls. In male patients, higher WBC and monocyte count were associated with an increase in cIMT suggesting the role of inflammation in the development of atherosclerosis. Key Points •Carotid intima-media thickness was increased in patients with radiographic axial spondyloarthritis compared to controls. •White blood cell and monocyte counts were associated with carotid intima-media thickness in male patients with radiographic axial spondyloarthritis.