Comparing clinical profiles in spondyloarthritis with Crohn's disease or ulcerative colitis: insights from the ASAS-PerSpA study.

Objectives: Assuming SpA manifestations may vary among patients with different inflammatory bowel disease (IBD) subtypes, we explored the clinical characteristics associated with the presence of Crohn's disease (CD) or ulcerative colitis (UC) in patients with spondyloarthritis (SpA). Methods: We included 3152 patients of ASAS-PerSpA study diagnosed with either axial SpA or peripheral SpA, according to their treating rheumatologist. Of these, 146 (4.6%) had confirmed IBD by endoscopy and were categorized into CD or UC groups. Demographics, clinical characteristics, treatments and patient-reported outcomes were compared between the two subgroups. Results: From 146 patients included in the current analysis, 87 (59.6%) had CD [75 (86.2%) axial SpA and 12 (13.8%) peripheral SpA], and 39 (26.7%) had UC [34 (87.2%) axial SpA and 5 (12.8%) peripheral SpA]. CD and UC groups had similar age with average of 44.9 (13.5) vs 44.0 (13.0) years, respectively, and a slight male predominance in CD (63.2%) compared with UC (51.3%). Diagnostic delay for SpA was 7.0 (6.9) years for CD and 8.8 (8.1) years for UC. Chronic back pain was the most reported symptom present in 95.4% of CD patients and 89.7% of UC patients. Both groups had similar musculoskeletal phenotyping, with higher frequency of psoriasis (15.4%) and uveitis 28.2% in UC; and higher tendency to be HLA-B27 positive in CD (51.9% in CD vs.s 39.4% in UC). Conclusion: In our analysis patients with SpA and concurrent CD or UC had mainly similar musculoskeletal phenotypes. However, they differ slightly in extra-musculoskeletal manifestations and HLA-B27 prevalence.

Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Diagnostic accuracy in axial spondyloarthritis: a systematic evaluation of the role of clinical information in the interpretation of sacroiliac joint imaging.

OBJECTIVES: Radiography and MRI of the sacroiliac joints (SIJ) are relevant for the diagnosis and classification of patients with axial spondyloarthritis (axSpA). This study aimed to evaluate the impact of clinical information (CI) on the accuracy of imaging interpretation. METHODS: Out of 109 patients referred because of suspicion of axSpA with complete imaging sets (radiographs and MRI of SIJ), 61 were diagnosed with axSpA (56%). Images were independently evaluated by three radiologists in four consecutive reading campaigns: radiographs and radiographs+MRI without and with CI including demographic data, SpA features, physical activity and pregnancy. Radiographs were scored according to the modified New York criteria, and MRIs for inflammatory and structural changes compatible with axSpA (yes/no). The clinical diagnosis was taken as reference standard. The compatibility of imaging findings with a diagnosis of axSpA (precision) before and after the provision of CI and radiologists' confidence with their findings (0-10) were evaluated. RESULTS: The precision of radiographs evaluation without versus with CI increased from 70% to 78% (p=0.008), and for radiographs+MRI from 81% to 82% (p=1.0), respectively. For CR alone, the sensitivity and specificity of radiologic findings were 51% and 94% without and 60% and 100% with CI, while, for radiographs+MRI, they were 74% and 90% vs 71% and 98%, respectively. The diagnostic confidence of radiologists increased from 5.2±1.9 to 6.0±1.7 with CI for radiographs, and from 6.7±1.6 to 7.2±1.6 for radiographs+MRI, respectively. CONCLUSION: The precision, specificity and diagnostic confidence of radiologic evaluation increased when CI was provided.

Learning imaging in axial spondyloarthritis: more than just a matter of experience.

OBJECTIVE: Reliable interpretation of imaging findings is essential for the diagnosis of axial spondyloarthritis (axSpA) and requires a high level of experience. We investigated experience-dependent differences in diagnostic accuracies using X-ray (XR), MRI and CT. METHODS: This post hoc analysis included 163 subjects with low back pain. Eighty-nine patients had axSpA, and 74 patients had other conditions (mechanical, degenerative or non-specific low back pain). Final diagnoses were established by an experienced rheumatologist before the reading sessions. Nine blinded readers (divided into three groups with different levels of experience) scored the XR, CT and MRI of the sacroiliac joints for the presence versus absence of axSpA. Parameters for diagnostic performance were calculated using contingency tables. Differences in diagnostic performance between the reader groups were assessed using the McNemar test. Inter-rater reliability was assessed using Fleiss kappa. RESULTS: Diagnostic performance was highest for the most experienced reader group, except for XR. In the inexperienced and semi-experienced group, diagnostic performance was highest for CT&MRI (78.5% and 85.3%, respectively). In the experienced group, MRI showed the highest performance (85.9%). The greatest difference in diagnostic performance was found for MRI between the inexperienced and experienced group (76.1% vs 85.9%, p=0.001). Inter-rater agreement was best for CT in the experienced group with κ=0.87. CONCLUSION: Differences exist in the learnability of the imaging modalities for axSpA diagnosis. MRI requires more experience, while CT is more suitable for inexperienced radiologists. However, diagnosis relies on both clinical and imaging information.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

OBJECTIVE: To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. METHODS: Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. RESULTS: Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. CONCLUSIONS: Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

Association of nociplastic and neuropathic pain components with the presence of residual symptoms in patients with axial spondyloarthritis receiving biological disease-modifying antirheumatic drugs.

OBJECTIVE: To evaluate the association of nociplastic (NoP) and neuropathic pain (NP) components with residual symptoms in patients with radiographic axial spondyloarthritis (r-axSpA) receiving biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: 78 patients with r-axSpA from the GErman SPondyloarthritis Inception Cohort receiving a bDMARD for at least 3 months were included in this analysis. The Widespread Pain Index (WPI) and the PainDETECT (PD) questionnaire were used to quantify the NoP and the NP components, respectively. Axial Spondyloarthritis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were used as measures of residual symptoms. C reactive protein (CRP) was used as a measure of systemic inflammatory activity. Univariable and multivariable regression analyses of disease activity were performed. The regions of the WPI score and items of the PD score were used for cluster analyses. RESULTS: Linear multivariable regression analysis showed that WPI and PD were independently associated with ASDAS (b=0.1, 95% CI 0.04 to 0.17, and b=0.05, 95% CI 0.02 to 0.08, respectively) and BASDAI (b=0.24, 95% CI 0.08 to 0.39, and b=0.17, 95% CI 0.1 to 0.25, respectively) in r-axSpA patients receiving stable treatment with bDMARDs. Furthermore, WPI and PD were found to be significantly associated with the presence of relevant residual symptoms as defined by BASDAI ≥4 (OR 1.93, 95% CI 1.09 to 4.15, and OR 1.32, 95% CI 1.04 to 1.85, respectively). The effects were present also in patients with normal level of CRP. Cluster analysis revealed three distinct pain distribution profiles and four specific sensory symptom constellations allowing differentiation of different pain subtypes. CONCLUSION: Both NoP and NP components seem to be associated with residual symptoms in patients with r-axSpA receiving treatment with bDMARDs.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial.

OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.

Goodbye to the term 'ankylosing spondylitis', hello 'axial spondyloarthritis': time to embrace the ASAS-defined nomenclature.

Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs. The Assessment of SpondyloArthritis international Society, representing a worldwide group of experts reached consensus on changes in the nomenclature pertaining to axial spondyloarthritis (axSpA), such as the terminology of diagnosis and of assessment of disease activity tools. These are important changes in the field, as experts in axSpA are now in agreement that the term axSpA is the overall term for the disease. A further differentiation, of which radiographic versus non-radiographic is only one aspect, may be relevant for research purposes. Another important decision was that the terms AS and radiographic axSpA (r-axSpA) can be used interchangeably, but that the preferred term is r-axSpA. Based on the decision that axSpA is the correct terminology, a proposal was made to officially change the meaning of the ASDAS acronym to 'Axial Spondyloarthritis Disease Activity Score'. In addition, for simplification it was proposed that the term ASDAS (instead of ASDAS-CRP) should be preferred and applied to the ASDAS calculated with C reactive protein (CRP). It is hoped that these changes will be used consequently for education, in textbooks, manuscripts and presentations.

Radiographic Progression in Sacroiliac Joints in Patients With Axial Spondyloarthritis: Results From a Five-Year International Observational Study.

OBJECTIVE: To evaluate progression from nonradiographic (nr-) to radiographic axial spondyloarthritis (r-axSpA) over 5 years in patients with recently diagnosed (≤1 year) axSpA fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. METHODS: A prospsective, observational study (Patients with Axial Spondyloarthritis: Multi-Country Registry of Clinical Characteristics) was conducted in rheumatology practices in 29 countries. Baseline and follow-up radiographs of sacroiliac joints were centrally evaluated by three readers according to the grading system of the modified New York criteria for patients initially classified as nr-axSpA. Radiographic progression from nr-axSpA to r-axSpA was evaluated by Kaplan-Meier analysis. Cox proportional regression analyses for progression from nr-axSpA to r-axSpA were also conducted. RESULTS: Among 2,165 patients with axSpA, 1,612 (74%) were classified as having r-axSpA (1,050 [65%]) or nr-axSpA (562 [35%]) by central reading. Of 246 patients with nr-axSpA (mean [SD] symptom duration: 4.4 [6.2] years) who had at least one follow-up sacroiliac joint radiograph, progression from nr-axSpA to r-axSpA at any follow-up visit was observed in 40 patients (16%) over 5 years. Mean time to radiographic progression was 2.4 years (ranging from 0.9 to 5.1 years). Progression to r-axSpA was associated with male sex (hazard ratio [HR] 3.16 [95% CI 1.22-8.17]), fulfillment of the imaging arm of the ASAS classification criteria (HR 6.64 [1.37-32.25]), and good response to nonsteroidal anti-inflammatory drugs (HR 4.66 [1.23-17.71]). CONCLUSION: 16% of patients with nr-axSpA progressed to r-axSpA within 5 years. Male sex, fulfillment of the imaging arm of the ASAS criteria, and good response to nonsteroidal anti-inflammatory drugs were predictors of radiographic progression in patients with recently diagnosed axSpA.

Sex-specific diagnostic efficacy of MRI in axial spondyloarthritis: challenging the 'One Size Fits All' notion.

OBJECTIVES: Sex-specific differences in the presentation of axial spondyloarthritis (axSpA) may contribute to a diagnostic delay in women. The aim of this study was to investigate the diagnostic performance of MRI findings comparing men and women. METHODS: Patients with back pain from six different prospective cohorts (n=1194) were screened for inclusion in this post hoc analysis. Two blinded readers scored the MRI data sets independently for the presence of ankylosis, erosion, sclerosis, fat metaplasia and bone marrow oedema. Χ2 tests were performed to compare lesion frequencies. Contingency tables were used to calculate markers for diagnostic performance, with clinical diagnosis as the standard of reference. The positive and negative likelihood ratios (LR+/LR-) were used to calculate the diagnostic OR (DOR) to assess the diagnostic performance. RESULTS: After application of exclusion criteria, 526 patients (379 axSpA (136 women and 243 men) and 147 controls with chronic low back pain) were included. No major sex-specific differences in the diagnostic performance were shown for bone marrow oedema (DOR m: 3.0; f: 3.9). Fat metaplasia showed a better diagnostic performance in men (DOR 37.9) than in women (DOR 5.0). Lower specificity was seen in women for erosions (77% vs 87%), sclerosis (44% vs 66%), fat metaplasia (87% vs 96%). CONCLUSION: The diagnostic performance of structural MRI markers is substantially lower in female patients with axSpA; active inflammatory lesions show comparable performance in both sexes, while still overall inferior to structural markers. This leads to a comparably higher risk of false positive findings in women.