With back pain as one of the most common complaints in the population and with no single disease feature with sufficient sensitivity and specificity to diagnose axial spondyloarthritis (axSpA) on its ...own, diagnosing axSpA can be challenging. In this article, we discuss clinical, laboratory, and imaging spondyloarthritis features that can be used in diagnosis and explain the general principles underlying an axSpA diagnosis. Moreover, we discuss three pitfalls to avoid when diagnosing axSpA: i) using classification criteria as diagnostic criteria, ii) making a diagnosis by simple counting of spondyloarthritis features, and iii) over-reliance on imaging findings. Finally, we have some advice on how to build diagnostic skills and discuss new developments that may help facilitate the diagnosis of axSpA in the future.
To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).
Pragmatic, prospective, cluster-randomised, controlled, ...open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive.
(1)
: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2)
visits every 12 weeks and treatment at the rheumatologist's discretion.
Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed.
Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC.
160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC.
TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective.
NCT03043846.
To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA).
Following the EULAR Standardised Operating ...Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting.
Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures.
The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
Objective
The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite measure of disease activity in axial spondyloarthritis. The aims of this study were to determine the most ...appropriate method for calculating the ASDAS using the C‐reactive protein (CRP) level when the conventional CRP level was below the limit of detection, to determine how low CRP values obtained by high‐sensitivity CRP (hsCRP) measurement influence ASDAS‐CRP results, and to test agreement between different ASDAS formulae.
Methods
Patients with axial spondyloarthritis who had a conventional CRP level below the limit of detection (5 mg/liter) were selected (n = 257). The ASDAS–conventional CRP with 11 different imputations for the conventional CRP value (range 0–5 mg/liter, at 0.5‐mg/liter intervals) was calculated. The ASDAS‐hsCRP and ASDAS using the erythrocyte sedimentation rate (ESR) were also calculated. Agreement between the ASDAS formulae was tested.
Results
The ASDAS‐hsCRP showed better agreement with the ASDAS‐CRP calculated using the conventional CRP imputation values of 1.5 and 2.0 mg/liter and with the ASDAS‐ESR than with other imputed formulae. Disagreement occurred mainly in lower disease activity states (inactive/moderate disease activity). When the CRP value was <2 mg/liter, the resulting ASDAS‐CRP scores may have been inappropriately low.
Conclusion
When the conventional CRP level is below the limit of detection or when the hsCRP level is <2 mg/liter, the constant value of 2 mg/liter should be used to calculate the ASDAS‐CRP score. There is good agreement between the ASDAS‐hsCRP and ASDAS‐ESR; however, formulae are not interchangeable.
Ankylosing spondylitis (AS) is a form of chronic inflammatory spondyloarthritis (SpA) that causes pain and stiffness in spines or joints. Human leukocyte antigen B27 (HLA-B27) and B60 (HLA-B60) have ...been reported as major genetic risk factors of AS. In addition, rs13202464, located on major histocompatibility complex (MHC) region, showed high sensitivity (98.7%) and specificity (98.0%) for HLA-B27.
The aim of our study is to test whether the interaction between HLA-B60 and HLA-B27 (rs13202464) can serve as a better predictor of AS. We have genotyped HLA-B60 and rs13202464 among 471 patients with AS and 557 healthy subjects. Combined risk factors were investigated to test the biological interaction.
Our results indicated that the relative risk (RR) for HLA-B27+/HLA-B60- was 152 (95% CI 91 to 255) and it increased to 201 (95% CI 85 to 475) in HLA-B27+/HLA-B60+ patients (with HLA-B27-/HLA-B60- as reference). Combinational analysis of two risk factors (HLA-B27+/HLA-B60+) showed a relative excess risk due to interaction (RERI) of 46.79 (95% CI: -117.58 to 211.16), attributable proportion (AP) of 0.23 (95% CI: -0.41 to 0.88) and a synergy index (S) of 1.31 (95% CI: 0.56 to 3.04).
In conclusion, genetic interaction analysis revealed that the interaction between HLA-B60 and HLA-B27 is a better marker for the risk of AS susceptibility in a Taiwanese population.
Objective
To investigate determinants of the physician global assessment (PhGA) of disease activity and the influence of the contextual factors on this relationship in patients with early axial ...spondyloarthritis (SpA).
Methods
Five‐year data of DESIR, a cohort of early axial SpA, were analyzed. Univariable generalized estimating equations (GEEs) were used to investigate contributory explanatory effects of various potential determinants of PhGA. Effect modification by contextual factors (age, sex, and educational level) was tested, and if significant, models were stratified. Autoregressive GEE models (i.e., models adjusted for PhGA at the previous time point) were used to confirm a longitudinal relationship.
Results
A total of 708 patients were included. Higher Bath Ankylosing Spondylitis Disease Activity Index individual questions, swollen joint count in 28 joints (SJC28), tender joint count in 53 joints, Maastricht Ankylosing Spondylitis Enthesitis Score, C‐reactive protein (CRP) level, and Bath Ankylosing Spondylitis Metrology Index score were associated with a higher PhGA. Sex and age were effect modifiers of SJC28; the contributory effect of SJC28 was largest in the younger male stratum (β = 1.07 95% confidence interval (95% CI) 0.71, 1.43), and the smallest in the older female stratum (β = 0.13 95% CI 0.04, 0.22). Autoregressive GEE models revealed the same determinants as having a longitudinal association with PhGA and the same pattern of effect modification.
Conclusion
Patients’ subjective symptoms, peripheral arthritis and enthesitis, higher CRP level, and impaired spinal mobility contribute to explaining PhGA in patients with early axial SpA, irrespective of sex and age. Intriguingly, physicians consider the presence of swollen joints as more important in males than in females.
Background
Axial spondyloarthritis (axSpA) is a common inflammatory arthritis of the sacroiliac joints and the spine. The best‐known and most studied form of axSpA is ankylosing spondylitis.
Design
...In this review, we provide a brief overview of the pathophysiology of axSpA. In addition, we performed a quantitative text analysis of reviews on the pathogenesis of axSpA published in the last 10 years to establish the current consensus in various fields of research into the pathogenesis of axSpA.
Results
There appears to be broad consensus on genetic risk factors and the involvement of the immune system in the initiation phase of the disease although little consensus was found on which specific immune cells drive disease. Moreover, despite relatively little data available, alterations in the microbiome are commonly thought to be involved in disease. Abnormal bone formation is the most prominent pathogenic factor thought to be involved in disease progression.
Conclusion
So, although the pathophysiology of axSpA remains incompletely understood, the progress in recent years in several fields of research in axSpA including genetics, diagnosis, imaging and therapeutics, hold great promise for the future.
Patients with spondyloarthritis with radiographic sacroiliitis are traditionally classified according to the modified New York (mNY) criteria as ankylosing spondylitis (AS) and more recently ...according to the Assessment of SpondyloArthritis international Society (ASAS) criteria as radiographic axial spondyloarthritis (r-axSpA).
To investigate the agreement between the mNY criteria for AS and the ASAS criteria for r-axSpA and reasons for disagreement.
Patients with back pain ≥3 months diagnosed as axSpA with radiographic sacroiliitis (mNY radiographic criterion) were selected from eight cohorts (ASAS, Esperanza, GESPIC, OASIS, Reuma.pt, SCQM, SPACE, UCSF). Subsequently, we calculated the percentage of patients who fulfilled the ASAS r-axSpA criteria within the group of patients who fulfilled the mNY criteria and vice versa in six cohorts with complete information.
Of the 3882 patients fulfilling the mNY criteria, 93% also fulfilled the ASAS r-axSpA criteria. Inversely, of the 3434 patients fulfilling the ASAS r-axSpA criteria, 96% also fulfilled the mNY criteria. The main cause for discrepancy between the two criteria sets was the reported age at onset of back pain.
Almost all patients with axSpA with radiographic sacroiliitis fulfil both ASAS and mNY criteria, which supports the interchangeable use of the terms AS and r-axSpA.
To compare the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) with the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) for conventional radiographs (CR) in patients with ankylosing ...spondylitis (AS).
Patients with AS in the Sensitive Imaging in Ankylosing Spondylitis cohort had lateral cervical and lumbar spine CR and whole spine ldCT at baseline and 2 years. CR and ldCT images were scored by two readers, paired by patient, blinded to time order, per imaging modality. For the total score analysis, we used average scores of readers per corner on CR or quadrant on ldCT. For the syndesmophyte analysis we used individual reader and consensus scores, regarding new or growing syndesmophyte at the same corner/quadrant.
50 patients were included in the syndesmophyte analysis and 37 in the total score analysis. Mean (SD) status scores for mSASSS (range 0-72) and CTSS (range 0-552) at baseline were 17.9 (13.8) and 161.6 (126.6), and mean progression was 2.4 (3.8) and 17.9 (22.1). Three times as many patients showed new or growing syndesmophytes at ≥3 quadrants on ldCT compared with ≥3 corners on CR for individual readers; for consensus this increased to five times. In 50 patients, 36 new or growing syndesmophytes are seen on CR compared with 151 on ldCT, most being found in the thoracic spine.
ldCT, covering the whole spine, detects more progression in the form of new and growing syndesmophytes in patients with AS compared with CR, which is limited to the cervical and lumbar spine. Most progression occurred in the thoracic spine.
Abstract
Objectives
To investigate the determinants of patient well-being over time, and the influence of age, gender and education in patients with early axial spondyloarthritis (axSpA).
Methods
...Five-year data from DESIR, a cohort of early axSpA, were analysed. The outcome was the BAS-G over 5 years. Generalized estimating equations (GEE) were used to test the relationship between potential explanatory variables from five outcome domains (disease activity, physical function, spinal mobility, structural damage and axial inflammation) and BAS-G over time. Longitudinal relationships were analysed using an autoregressive GEE model. Age, gender and educational level were tested as effect modifiers or confounders.
Results
A total of 708 patients were included. Higher BASDAI questions on fatigue β (95% CI): 0.17 (0.13, 0.22), back pain 0.51 (0.46, 0.56), peripheral joint pain 0.08 (0.04, 0.12) and severity of morning stiffness 0.08 (0.03–0.13), and higher BASFI 0.14 (0.08, 0.19) were associated with a higher BAS-G. In the autoregressive model, the same variables except for morning stiffness were associated with a worsening in BAS-G. Age, gender and educational level were neither effect modifiers nor confounders.
Conclusion
A higher level of back pain is associated with a worsening of patient well-being, as are, though to a lesser extent, higher levels of fatigue, peripheral joint pain and physical disability. Age, gender and educational level do not have an impact on these relationships.
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