Non-radiographic axSpA Research Articles

Treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs: British Society for Rheumatology guideline scope.

Pharmacological management has advanced considerably since the 2015 British Society for Rheumatology axial spondyloarthritis (axSpA) guideline to incorporate new classes of biologic DMARDs (bDMARDs, including biosimilars), targeted synthetic DMARDs (tsDMARDs) and treatment strategies such as drug tapering. The aim of this guideline is to provide an evidence-based update on pharmacological management of adults with axSpA (including AS and non-radiographic axSpA) using b/tsDMARDs. This guideline is aimed at health-care professionals in the UK who care directly for people with axSpA, including rheumatologists, rheumatology specialist nurses, allied health professionals, rheumatology specialty trainees and pharmacists; people living with axSpA; and other stakeholders, such as patient organizations and charities.

Impact of TNF inhibitor medication on working ability in axial spondyloarthritis: an observational national registry-based cohort study.

The aim was to investigate the effect of TNF inhibitor (TNFi) initiation on working ability and health-care resource utilization among axialSpA patients in a real-life setting. Patients with a clinical diagnosis of non-radiographic (nr-axSpA) or radiographic axial SpA initiating their first TNFi were identified from the National Register for Antirheumatic and Biologic Treatment in Finland. Sickness absences, including sick leave and disability pension, in- and outpatient days and rehabilitation rates, 1year before and after initiating the medication were retrieved from national registries. Factors affecting result variables were studied using multivariate regression analysis. Overall, 787 patients were identified. Rates of work disability days per year were 55.6 the year before treatment onset and 55.2 the year after, with significant differences between patient subgroups. The rate of sick leave decreased after starting TNFi treatment. However, the rate of disability pension continued to rise. Patients with a diagnosis of nr-axSpA experienced a decrease in overall work disability and, especially, fewer sick leaves. No sex differences were detected. TNFi interrupts the increase in work disabled days evident during the year before its initiation. However, the overall work disability remains high. Treating patients earlier in the nr-axSpA phase, regardless of sex, appears important in maintaining the ability to work.

Diagnostic value of anti-Kaiso autoantibody in axial spondyloarthritis.

Axial spondyloarthritis (axSpA) is a chronic rheumatic disease predominantly characterized by inflammation and progressive structural damage. Patients are often diagnosed very late, which delays the optimal treatment period. Early diagnosis of axSpA, especially non-radiographic axSpA (nr-axSpA), remains a major challenge. This study aimed to investigate the diagnostic value of anti-Kaiso autoantibodies in axSpA and their correlation with clinical disease indicators. Two pooled serum samples (seven patients with nr-axSpA and seven healthy controls) were profiled using HuProt arrays to investigate the diagnostic value of autoantibodies in nr-axSpA. Levels of anti-Kaiso autoantibodies in patients with axSpA and controls were determined using the Meso Scale Discovery assay system. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of anti-Kaiso autoantibodies in axSpA. Pearson's correlation was used to assess the correlation between anti-Kaiso autoantibodies and clinical parameters. Seven candidate autoantibodies were present in the serum of patients with nr-axSpA. The levels of anti-Kaiso autoantibodies were significantly higher in the nr-axSpA group than in the other groups. It can differentiate nr-axSpA from ankylosing spondylitis (AS), healthy controls, and rheumatoid arthritis. The level of early-stage AS among patients with nr-axSpA decreased when they progressed to the late stage. Of all patients with axSpA, serum anti-Kaiso autoantibody levels were positively correlated with the C-reactive protein level and the Bath Ankylosing Spondylitis Disease Activity Index score and negatively correlated with disease duration. Anti-Kaiso autoantibody may be a valuable diagnostic biomarker for early-stage AS in the nr-axSpA period and may be a potential therapeutic target.

Factors associated with freqeuncy and severity of COVID-19 in patients with axial spondyloarthritis

Purpose: The severe course of COVID-19 in individuals with chronic diseases has led to concerns in the management of rheumatic diseases during the pandemic therefore we aimed to define the factors associated with the frequency and severity of COVID-19 in patients with axial spondyloarthritis (axSpa) in this study.
 Materials-Methods: Patients with axSpa who were followed up in three tertiary hospitals and used their treatment regularly for at least six months were included. We assessed the relationship between axSpa associated variables such as disease duration time, radiological severity, treatment and COVID-19 outcomes.
 Results: A total of 833 patients with a mean disease duration of 109 months were analyzed; 64.5% had ankylosing spondylitis, 35.5% had non-radiographic axSpa diagnosis, and 59.4% of patients were treated with biologic agent . The frequency of COVID-19 was 23% (n: 192); only five pateints (0.5%) had a history of intensive care unit. Advanced age, hypertension (HT), and diabetes mellitus (DM) were found to be significantly more common in those with involvement in high resolution computed tomography (HRCT) (p:0.02, p:0.01, and p

Neuropathic pain in axial spondyloarthropathy is underdiagnosed and a confounding factor in biologic drug-switching decision: a cross-sectional study.

The aim of this study was to evaluate the relationship between the presence of neuropathic pain (NeP), disease activity scores and biologic drug-switching decisions in the subjects with axial spondyloarthritis (axSpA) receiving biologic treatment. PainDETECT Questionnaire was used to evaluate the presence of NeP in the patients with axSpA aged ≥18 years who had been receiving biologic treatment for at least 6 months. The relationships between disease activity scores, inflammatory markers, life quality index, biologic drug-switching decisions and the presence of NeP were analyzed. A total number of 175 patients with axSpA [ankylosing spondylitis (AS) (n:150) and non-radiographic axSpA (nr-axSpA) (n:25)] were enrolled in the study. NeP was detected in 41.7% of the patients and it was more common in females than in males (p:0.009). PainDETECT scores were positively correlated with disease activity scores, but they were not correlated with inflammatory marker levels. NeP was found to be significantly more common in whom the biologics had been switched 3 or more times (p:0.007). PainDETECT scores were higher and NeP was more prevalent (p:0.028) in the patients for whom drug-switching decisions had been made due to primary or secondary unresponsiveness. NeP is more common than estimated in the patients with axSpA and current disease activity scores are insufficient to make a distinction between NeP and inflammatory pain. NeP is a confounding factor in the evaluation of treatment response to biologic agents. In the subjects with AS and nr-axSpA with primary or secondary treatment unresponsiveness, the presence of NeP must be considered before biologic drug-switching decisions. Key Points • Neuropathic pain (NeP) is common in subjects with AxSpA treated with multiple biologic agents. • Current disease activity scores for AxSpA are insufficient to make a differentiation between NeP and inflammatory pain. • NeP is a confounding factor in the evaluation of treatment response to biologic agents. • Patients with AxSpA should be re-evaluated in terms of the presence of neuropathic pain before making biologic drug-switching decisions.

Diagnostics of Sacroiliac Joint Differentials to Axial Spondyloarthritis Changes by Magnetic Resonance Imaging.

The diagnosis of axial spondyloarthritis (axSpA) is usually based on a pattern of imaging and clinical findings due to the lack of diagnostic criteria. The increasing use of magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) to establish the diagnosis early in the pre-radiographic phase has resulted in a shift in the paradigm with an increasing frequency of axSpA diagnoses and a changed sex distribution. Non-radiographic axSpA affects males and females nearly equally, whereas ankylosing spondylitis predominantly occurs in males. The MRI-based increasing frequency of axSpA in women is mainly due to the presence of subchondral bone marrow edema (BME) on fluid-sensitive MR sequences, which may be a non-specific finding in both women and men. Due to the somewhat different pelvic tilt and SIJ anatomy, women are more prone than men to develop strain-related MRI changes and may have pregnancy-related changes. Awareness of non-specific subchondral BME at the SIJ is important as it can imply a risk for an incorrect SpA diagnosis, especially as the clinical manifestations of axSpA may also be non-specific. Knowledge of relevant MRI and clinical features of differential diagnoses is needed in the diagnostic workout of patients with suspected axSpA considering that non-SpA-related SIJ conditions are more common in patients with low back or buttock pain than axSpA sacroiliitis. The purpose of this review was to present current knowledge of the most frequent differential diagnoses to axSpA sacroiliitis by MRI taking the clinical characteristics into account.

Real-World Retention and Clinical Effectiveness of Secukinumab for Axial Spondyloarthritis: Results From the Canadian Spondyloarthritis Research Network.

Axial spondyloarthritis (axSpA) is a chronic, immune-mediated, inflammatory condition consisting of 2 clinical subsets: nonradiographic axSpA and ankylosing spondylitis, the latter having an estimated prevalence of 0.2% to 1% in Canada. Secukinumab (SEC) received Health Canada approval in 2016 for the treatment of adults with axSpA who have responded inadequately to conventional treatment, and has demonstrated efficacy and safety through extensive clinical trials. However, there is limited evidence on its real-world use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC in the Canadian axSpA population. This was an observational cohort study of Canadian patients with axSpA aged 18 to 65 years within the CanSpA network who had received treatment with SEC. Patients were indexed on the first date of SEC initiation. Retention and clinical effectiveness were assessed at 12 months postindex. Clinical effectiveness was measured as the proportion in remission and change in disease activity using multiple clinical indices. A total of 146 patients were included. Overall retention was estimated at 62.9%. Low disease activity (ie, Bath Ankylosing Spondylitis Disease Activity Index < 4) was achieved in 29.2% of patients, and 2% had achieved remission based on the Ankylosing Spondylitis Disease Activity Score. Bath Ankylosing Spondylitis Metrology Index scores improved by more than 60% from baseline to 12 months. The results of this real-world study of Canadian patients with axSpA, one of the first of its kind, support the effectiveness of SEC for treatment of axSpA. The CanSpA network presents an opportunity to continue building and improving the real-world evidence base for treatment of Canadian patients with spondyloarthritis.

JAK inhibitors, cardiovascular and thromboembolic events: what we know and what we would like to know.

JAK inhibitors (JAKinibs) have been approved for several immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis (axSpA), and non-radiographic axSpA. Although they have been proved to be very effective, some safety concerns have emerged. These mainly pertain to their profile regarding major adverse cardiovascular events (MACEs) as well as to thromboembolic events (VTEs). In fact, there are accumulating data showing that the concerns might be greater for the latter. Herein, we provide a critical analysis of the so far published major studies, discussing also some thoughts (e.g., different VTE risk across IMIDs) that could be taken into account in the interpretation of these results. In addition, we highlight the need for assessment of patients' profile for cardiovascular as well as for thromboembolic risk factors. Incorporation of the respective tools (that need further validation) should be considered in clinical practice.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

Presence of spondyloarthritis associated to higher disease activity and HLA-B27 positivity in patients with early Crohn's disease: Clinical and MRI results from a prospective inception cohort.

To determine the SpA prevalence and identify its associated factors in Crohn's disease (CD) patients receiving a systematically rheumatological and imaging assessment, including magnetic resonance imaging (MRI) of the sacroiliac joints and spine. CD patients either naive to biologics or without them for three months prior enrollment were recruited in a subgroup of the German Spondyloarthritis Inception Cohort (GESPIC-Crohn). A structured assessment of SpA manifestations was performed by a rheumatologist, including MRI of sacroiliac joints and spine. Demographic and clinical parameters including disease activity in CD (Harvey Bradshaw Index-HBI) and SpA (C-reactive protein-CRP, Bath Ankylosing Spondylitis Disease Activity Index, and Ankylosing Spondylitis Disease Activity Score) were collected. Univariable and multivariable logistic regression analyses were performed to identify factors associated with the presence of SpA. A total of 103 patients with CD were included in the cohort. The mean CD disease duration was 1.3±2.4years and 95.1% were naïve to biologics. The most frequent musculoskeletal manifestation was back pain (65.0%), followed by chronic back pain (50.5%), and arthralgia (43.7%). Prevalence of SpA was 19.4% with slightly higher proportion of axial SpA than peripheral SpA, and higher proportion of radiographic axial SpA (7.4%) than non-radiographic axial SpA (2.8%). Changes in MRI compatible with axial SpA were found in 15 (14.7%) patients, of which 9 (81.1%) patients had the clinical diagnosis of axial SpA. HLA-B27 positivity (OR 9.02, CI 95% 2.29-35.55) and higher disease activity of CD as reflected by the HBI (OR 1.14, 95%CI 1.01-1.30) were significant and independently associated with the presence of SpA. SpA was present in nearly one out of five patients with CD and it was associated with the expression of HLA-B27 and a higher clinical activity of CD. Our findings raise awareness to rheumatologists and gastroenterologists on the high concomitance between both diseases and may help to reduce the delay in SpA diagnosis.

Direct Medical Costs and Healthcare Resource Utilization of Treating Patients With Two Clinical Subtypes of Axial Spondyloarthritis in Colombia

ObjectivesThis study aimed to calculate the healthcare resource utilization and direct medical costs in patients with 2 subtypes of axial spondyloarthritis (axSpA) in a rheumatic care center in Colombia. MethodsThis is a retrospective cost-of-illness study. Patients with at least 1 medical consultation associated with an axSpA diagnosis between October 2018 and October 2019 were identified. Patients were classified as having radiographic (r-axSpA) or nonradiographic axSpA (nr-axSpA). Direct medical costs were calculated in Colombian pesos and expressed in American dollars using an exchange rate of 3263 Colombian pesos = 1 US dollar ($). Predictors of total direct costs were identified using a generalized linear model with gamma distribution and log-link. ResultsA total of 162 patients with a mean age of 49.6 years (± 13.7) were included in the study. Among these, 147 (90.7%) were considered as having r-axSpA and 15 (9.3%) nr-axSpA, with mean costs of $6600 (± 6203) and $843 (± 1135), respectively (P < .001). The total direct mean cost was calculated at $6067 (± 6144) per patient. Medication costs were the main driver of total costs (97.6%, $5921), with biologic disease-modifying antirheumatic drugs accounting for nearly 92.0% ($5582) of these costs. Rheumatologist (100%) and physiatrist (64.2%) visits were the most frequently used medical service. ConclusionsThe economic burden associated with axSpA in the Colombian setting is substantial. There is a significant difference in direct medical costs between the r-axSpA and the nr-axSpA. Health policies aimed at the comprehensive management of nr-axSpA would have an important role in the reduction of the associated direct medical costs.

Absence of overexpression of KIR3DL2 on CD4+ T cells and NK cells in patients with axial spondyloarthritis.

Dear Editor, Chan et al. described an overexpression of KIR3DL2, a receptor for HLA-B27 homodimer, on NK cells and CD4+ T cells in patients with axial SpA (axSpA) [1, 2]. HLA-B27:05 expressing cells have also been shown to promote KIR3DL2+ NK cells, with more NK cells and CD4+ T cells expressing KIR3DL2 in patients with axSpA [3]. However the overexpression of KIR3DL2 was not confirmed in another population of patients with active axSpA [4]. All these studies were conducted in patients carrying the HLA-B27 antigen. We aimed to assess the expression of KIR3DL2 in patients with axSpA, according to the presence or not of HLA B27. We included 20 patients with axSpA [16 with AS and 4 with non-radiographic axSpA (nr-axSpA)] fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria [5] and 5 healthy controls. Stratification according to the presence or not of HLA-B27 was applied. The axSpA main characteristics were: 11 HLA-B27+, 9 HLA-B27-, 14 males, mean disease duration 15.2 years and mean BASDAI of 4.7/10; all were synthetic and biologic DMARD naïve. We analysed by flow cytometry whole blood and peripheral blood mononuclear cell samples using fluorescent antibodies against CD45, CD14, CD3, CD19, CD4, CD8, gamma-delta-TCR, CD56, CD16, CD45RA, CXCR3, CCR6, KIR3DL1, KIR3DL2, IL-17A, IL-22, IL-2 and IFN-gamma. Positivity thresholds were set using control isotypes. Overnight pharmacological stimulation was performed with PMA/Ionomycin. All statistical analyses were performed using Graph Pad Prism (GraphPad Software, San Diego, CA, USA). Paired data were analysed with Wilcoxon test, and unpaired data with Mann–Whitney test. P-values <0.05 were considered to be significant. The study was approved by local ethics committee and conducted in accordance with the Declaration of Helsinki.

Clinically Relevant Deficits in Performance Tests in Patients With Axial Spondyloarthritis.

To assess the association between self-reported and performance-based physical functioning and to evaluate which performance tests are most frequently impaired in patients with axial spondyloarthritis (axSpA). Consecutive patients with axSpA underwent standardized assessments including patient and disease characteristics; patient-reported outcomes for disease activity, functioning, depression, mobility, and physical activity; and performance tests. Patients were defined as being impaired if they were not able to perform ≥ 1 of the performance tests. Validated cut-offs were used to define impaired physical performance. Impairment of performance tests as well as discrimination between subgroups were analyzed. A total of 200 patients (radiographic axSpA 66.5%, nonradiographic axSpA 33.5%) were included: 69% males, mean age 44.3 (SD 12.5) years, and mean symptom duration 17.9 (SD 12.6) years. The 2 most frequently impaired performance tests were the repeated chair stand test (n = 75, 37.5%) and putting on socks (n = 44, 22%). An impairment in ≥ 1 performance test was seen in 91 patients (45.5%). Patients with impairments were older (49.1 yrs vs 40.3 yrs); had a higher BMI (28.9 kg/m2 vs 25.8 kg/m2); a more active disease (Ankylosing Spondylitis Disease Activity Score, 3.0 vs 2.1); higher Bath Ankylosing Spondylitis Functional Index (BASFI; 5.8 vs 2.7), Bath Ankylosing Spondylitis Metrology Index (BASMI; 4.4 vs 2.7), and Assessment of Spondyloarthritis international Society Health Index scores (9.5 vs 4.9); and higher depression screen values (9-item Patient Health Questionnaire, 11.6 vs 6.5; all P < 0.01). Many patients with axSpA had impairments in physical performance tests. Importantly, this was frequently seen in tasks requiring coordination and muscle power of the lower extremity. Performance tests provide qualitatively different information than BASFI and BASMI assessments in patients with axSpA.

The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences

BackgroundMale 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.MethodsWe 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.ResultsIn 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.ConclusionL 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.

Recurrence of axial spondyloarthritis among first-degree relatives in a prospective 35-year-follow-up family study

ObjectiveThe lifetime recurrence rate (RR) of axial spondyloarthritis (axSpA) among first-degree relatives (FDR) and the effect of proband’s gender, HLA-B27 and radiographic status is unclear. Our 35-year-follow-up family study has...

How good is the agreement between clinical diagnoses and classification criteria fulfilment in axial spondyloarthritis? Results from the SPARTAKUS cohort

Objectives To study the agreement between clinical axial spondyloarthritis (axSpA) diagnoses and fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) axSpA and modified New York (mNY) classification criteria, and to compare disease/health status between axSpA subtypes. Method Patients with prevalent, clinical axSpA attending a rheumatology clinic were enrolled in a cross-sectional study. Assessments included physical evaluation, laboratory testing, questionnaires, and appropriate imaging, allowing classification. Standard axSpA outcome measures were compared between patients fulfilling mNY/radiographic versus non-radiographic axSpA (r-axSpA/nr-axSpA) criteria. Results Of 239 consecutively included patients, 141 fulfilled ASAS r-axSpA and/or mNY criteria, while 57 fulfilled nr-axSpA criteria. The agreement between r-axSpA and mNY criteria fulfilment was 94%. The positive predictive value (PPV) of a clinical ankylosing spondylitis (AS) diagnosis for mNY criteria fulfilment was 71%; the PPV of an undifferentiated axSpA (u-axSpA) diagnosis for fulfilment of nr-axSpA criteria was 30% and 40% for mNY criteria. Patients with r-axSpA/AS were older, more often men, and had longer disease duration, more uveitis, and worse spinal mobility than nr-axSpA patients, who had more enthesitis and dactylitis. Conclusion We found an overall good concordance between clinical axSpA diagnoses and classification criteria fulfilment, with 83% fulfilling ASAS axSpA and/or mNY criteria. Regarding axSpA subtypes, the concordance was weaker, and although the ICD-10 code for AS correctly identified patients meeting mNY criteria in 71% of cases, one-third of mNY-positive patients lacked an AS diagnosis. Moreover, clinical u-axSpA diagnoses could not serve as a proxy to identify nr-axSpA, highlighting the importance of thorough classification in research on axSpA subtypes.

Factors associated with atherosclerosis in radiographic and non-radiographic axial spondyloarthritis. A multicenter study on 838 patients

To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA). This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection. 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients. Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.

OP0149 RADIOGRAPHIC PROGRESSION FROM NON-RADIOGRAPHIC TO RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: RESULTS FROM A 5-YEAR MULTICOUNTRY PROSPECTIVE OBSERVATIONAL STUDY

BackgroundPatients (pts) with axial spondyloarthritis (axSpA) are classified into radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) based on the presence or absence of radiographic sacroiliitis. Approximately 20% to 80% of newly diagnosed axSpA pts have nr-axSpA and 8% to 40% progress to r-axSpA over the next 2 to 10 years.ObjectivesTo evaluate progression from nr-axSpA to r-axSpA over 5 years in a prospective multicentre cohort.MethodsPROOF was a global, real-world, prospective, observational study conducted in rheumatology clinical practices in 29 countries across 6 different geographic regions.1 The study enrolled adults with chronic back pain for ≥3 months and onset before 45 years of age. This analysis included pts diagnosed with axSpA who also fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA. Study visits occurred at baseline (BL) and yearly thereafter. Baseline and follow-up radiographs of sacroiliac joints (SIJ) were evaluated for pts with initial nr-axSpA diagnosis independently by 2 central readers according to the modified New York criteria. In the case of disagreement on the classification (nr- or r-axSpA), images were adjudicated by a third reader. Radiographic progression from nr-axSpA to r-axSpA over 5 years was evaluated by Kaplan-Meier analysis. Cox proportional hazards regression analyses for time to radiographic progression from nr-axSpA to r-axSpA were conducted. For model 1, ‘imaging arm vs clinical arm’ was used as an independent variable, and for model 2, ‘active inflammation on magnetic resonance imaging highly suggestive of sacroiliitis associated with SpA’ was used. Further, potential predictive factors included in the models were age, gender, back pain duration, number of SpA parameters, smoking status, CRP, good response to NSAIDs, HLA-B27 status, and current use of NSAIDs and TNF inhibitors.ResultsAmong 2633 enrolled pts, 2165 (82%) were diagnosed with axSpA and fulfilled the ASAS classification criteria. Among these, 1612 (74%) were classified as having r-axSpA (1050 [65%]) or nr-axSpA (562 [35%]) by central reading. The majority of nr-axSpA pts (77%) fulfilled the ASAS classification criteria due to positive findings on imaging (plus ≥1 SpA feature) and 23% were classified according to the clinical arm. A total of 246 nr-axSpA pts who had ≥1 follow-up SIJ radiograph were included in this analysis. Among these 246 pts, progression from initial nr-axSpA to r-axSpA at any of the follow-up visits was observed in 40 pts (16%) over 5 years. Mean time to radiographic progression was 2.4 years (ranging from 0.9 to 5.1 years) in descriptive analysis (Kaplan-Meier curve shown in Figure 1). In model 1 of the Cox regression analysis, male gender (hazard ratio [HR]: 3.16 [95% CI: 1.22–8.17]; P=0.0174), fulfilment of the imaging arm (HR: 6.64 [1.37–32.25]; P=0.0188), and good response to NSAIDs, (HR: 4.66 [1.23–17.71]; P=0.0237), were significantly associated with progression to r-axSpA (Figure 1). In model 2, HLA-B27 positivity showed a significant association with progression (HR: 3.99 [1.10–14.49]; P=0.0353; Figure 1).ConclusionIn this study, 16% of nr-axSpA pts progressed to r-axSpA within 5 years. The mean time to disease progression was 2.4 years. Predictors of radiographic progression were male gender, good response to NSAIDs, and fulfilment of the imaging arm as well as HLA-B27 positivity.

AB0830 Turkish translation and cross-cultural adaptation of the modified Short QUestionnaire to Assess Health-enhancing physical activity (mSQUASH).

BackgroundThe Short Questionnaire to Assess Health-enhancing physical activity (SQUASH) is a validated tool measuring the duration, frequency, and intensity of physical activity. The modified version of the SQUASH (mSQUASH) has been developed, in collaboration between spondyloarthritis (SpA) experts and axial (ax)SpA patients, to better address the needs of these patients in the assessment physical activity (1).ObjectivesTo translate and cross-cultural adapt the mSQUASH into Turkish as well as its cognitive debriefing to test the conceptual equivalence of the translated version among patients with axSpA.MethodsThe mSQUASH was translated into Turkish by 2 bilingual translators, native speakers of Turkish one from medical (informed) and the other is without medical background (uninformed). The consensus on forward-translation was reached by the team included two rheumatologist (GA and LK) and the translators. Backward-translation into Dutch was performed by 2 bilingual translators, native speakers of Dutch and who were blinded to the original mSQUASH version. After the review of the Turkish version by an expert committee that included translators, two patients and the research team a pre-final version was prepared. This version was used in a field-test with cognitive debriefing and involved a sample of 10 axSpA patients (7 radiographic- and 3 non-radiographic axSpA patients) with variation in gender, age, disease duration, and educational background. The final Turkish mSQUASH version was reached after the patients were interviewed to check understandability, interpretation and cultural relevance of the translation. The whole process was performed according to the Beaton method (Figure 1) (2).Figure 1.Flow-chart of the translation and cross-cultural adaptation processResultsAfter the forward-backward translation process, small incompatibilities were resolved during the expert committee meeting. For example: `Ander transport (heen en terug)` was translated as `Diğer hedeflere (gidip gelmek)`. The meaning in English is `Other transport (round trip)’. This item questions the way of going to other places and the discrepancy raised whether to use `transportation` or the `target` as the title. To make it culturally adaptable consensus reached to use a word equivalent to `the target` which is semantically equal to the Dutch version. A total of 10 patients with axSpA [7 females, mean (SD) age of 38 (10)] participated in the field test. Mean (SD) time to complete the mSQUASH was 6.1 (2.4) minutes. Cognitive debriefing showed that items of the mSQUASH are clear, relevant, understandable, and easy to complete. None of the patients indicate any important aspect of physical activity that is missing from the questionnaire items. During the cognitive debriefing, 2 patients suggested a change in the wording of one item to make it more suitable to the Turkish culture. This item inquires after sport activities and patients raised the concern that the example activities, ice-skating, tennis, handball are not culturally suitable. According to their comments these items were replaced by other examples such as football.ConclusionThe final Turkish version of the mSQUASH showed acceptable linguistic validity and can be used in both clinical practice and for research purposes. However, to implement the Turkish version of the mSQUASH, further assessment of its psychometric properties (validity and reliability) is needed.

Heterogeneity of axial spondyloarthritis: genetics, sex and structural damage matter

ObjectiveAxial spondyloarthritis (axSpA) comprises both radiographic and non-radiographic disease. However, the paucity of specific objective measures for the disease and current classification criteria showing suboptimal specificity contribute to disease heterogeneity...