Objectives To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial spondyloarthritis... Show moreObjectives To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial spondyloarthritis (r-axSpA). Methods Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort, inclusion criteria r-axSpA and ≥1 radiographic spinal syndesmophyte, were studied. MRI of the full spinal was performed at baseline, 1 and 2 years. PE/FJ inflammatory lesions and FJA were assessed per vertebral unit (VU) level by three readers. With multilevel time-lagged autoregressive generalised estimated equations, the association between PE/FJ inflammation and the subsequent development of FJA was investigated, taking the reader and VU levels into account. Results Out of the 58 patients with at least 2 reader scores available, mean age 49 (SD 10) years, 84% men, 59% had baseline PE inflammation, 24% had FJ inflammation and 26% had FJA. PE inflammation was more prevalent in the lower thoracic spine and FJ inflammation in the upper thoracic spine. VU with PE or FJ inflammation showed subsequent new FJA in two and one VU levels, respectively. The probability of developing FJA doubled with prior FJ inflammation. In multilevel analysis, FJ inflammation was associated with subsequent FJA (OR=3.8, 95% CI: 1.5 to 9.8), while no association was found between PE inflammation and new FJA (OR=1.2 (0.6–2.4)). Conclusions FJ inflammation is rare in severe r-axSpA, but when present, the likelihood of developing subsequent FJA is over three times higher compared with FJ without inflammation. This finding contributes to the understanding of the relationship between inflammation and ankylosis at the same anatomical location in patients with axSpA. Show less
ObjectiveTo evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and... Show moreObjectiveTo evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations.MethodsParticipants were randomly 1:1 assigned to the intervention [maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy (e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity] or usual care (care determined by clinician(s) and participants themselves). Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 [PSC1 (0–10)] at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat.Results214 participants [49% female, age 52 (S.D. 12) years], were randomized to the intervention (n = 110) or usual care (n = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (S.D. 15.1). At 52 weeks, the difference in change in PSC1 between groups favoured the intervention group [mean difference (95% CI); −1.8 (−2.4 to −1.2)]. Additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4 to 0.7.ConclusionLong-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations.Trial registrationNetherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238). Show less
Marques, M.L.; Ramiro, S.; Heijde, D. van der; Reijnierse, M.; Diekhoff, T.; Hermann, K.G.A.; ... ; Hooge, M. de 2024
Background: The Computed Tomography Syndesmophyte Score (CTSS) was developed as a reliable and sensitive tool to assess syndesmophytes in low-dose CT images of the entire spine in patients with... Show moreBackground: The Computed Tomography Syndesmophyte Score (CTSS) was developed as a reliable and sensitive tool to assess syndesmophytes in low-dose CT images of the entire spine in patients with axial spondyloarthritis (axSpA). The original paper provided sparce examples of the CTSS grades. Objectives: Provide an atlas tailored to assist readers in understanding and employing the CTSS method. Methods: In this paper, illustrations of the different grades and views of the CTSS are presented. CTSS is used to measure bone formation in the spine of patients with axial spondyloarthritis (axSpA), in the form of syndesmophytes. In both the sagittal and coronal planes, syndesmophytes can be graded from 0 to 3 over 23 vertebral units starting at C2 and ending at S1. The CTSS ranges from 0 (absence of axSpA-related syndesmophytes) to 552 (total ankylosis of the spine). Results: The current atlas contains low-dose CT images of the spine without lesions (for reference) and all grades of syndesmophytes in different planes used in the CTSS. Examples are arranged per spinal segment (cervical, thoracic and lumbar). Conclusions: These images can be used to assist any reader in the assessment of syndesmophytes on (lowdose) CT in patients with axSpA Show less
Marques, M.L.; Ramiro, S.; Lunteren, M. van; Stal, R.A.; Landewe, R.B.; Sande, M. van de; ... ; Gaalen, F.A. van 2024
Objectives To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the... Show moreObjectives To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y. Methods We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (>= 3 months, <= 2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0-not confident at all to 10-very confident). Main outcome: axSpA diagnosis with LoC >= 7 (d-axSpA) at 2y. Results In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA. Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y-d-axSpA versus 2y-d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male. Conclusion A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients. Show less
Heijde, D. van der; Molto, A.; Ramiro, S.; Braun, J.; Dougados, M.; Gaalen, F.A. van; ... ; Baraliakos, X. 2023
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... Show moreAnkylosing 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. Show less
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... Show moreWith 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) overreliance 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.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/). Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods Patients with radiographic... Show moreObjectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine lowdose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. Results Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. Conclusion In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods: Patients with... Show moreObjectives: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods: Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by & GE;2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. Results: Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. Conclusion: In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic... Show moreObjectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition.Results Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition.Conclusion In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Michielsens, C.A.J.; Bolhuis, T.E.; Gaalen, F.A. van; Hoogen, F.H.J. van den; Verhoef, L.M.; Broeder, N. den; Broeder, A.A. den 2023
Objective: In axial spondyloarthritis (axSpA), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) are recommended for use in... Show moreObjective: In axial spondyloarthritis (axSpA), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) are recommended for use in treat-to-target (T2T) strategies. However, BASDAI disease states may be a less suitable T2T instrument than ASDAS, since BASDAI contains non-disease activity related items. The objective of our study was to investigate the construct validity of BASDAI and ASDAS disease states. Method: We performed a single-centre cross-sectional study on BASDAI and ASDAS construct validity in long-term BASDAI T2T-treated axSpA patients. Our hypothesis was that BASDAI is less representative of disease activity than ASDAS owing to the focus on pain and fatigue, and missing an objective item, e.g. C-reactive protein (CRP). This was operationalized using several subhypotheses. Results: The study included 242 axSpA patients. BASDAI and ASDAS disease states showed a similar relation to Patient Acceptable Symptom State and T2T protocol adherence. The proportions of patients with high BASDAI and ASDAS disease activity fulfilling Central Sensitization Inventory and fibromyalgia syndrome criteria were similar. The correlation with fatigue was moderate for both BASDAI (Spearman's rho 0.64) and ASDAS (Spearman's rho 0.54) disease states. A high ASDAS was strongly correlated with increased CRP (relative risk 6.02, 95% CI 3.0-12.09), while this correlation was not seen for BASDAI (relative risk 1.13, 95% CI 0.74-1.74).Conclusion: Our study showed moderate and comparable construct validity for BASDAI- and ASDAS-based disease activity states, with the expected exception of association with CRP. Therefore, no strong preference can be given for either measure, although the ASDAS seems marginally more valid. Show less
Navarro-Compán, V.; Benavent, D.; Capelusnik, D.; Heijde, D. van der; Landewé, R.B.M.; Poddubnyy, D.; ... ; Ramiro, S. 2023
Objectives To develop a consensual definition for the term ‘early axial spondyloarthritis—axSpA’—and ‘early peripheral spondyloarthritis—pSpA’.Methods The ASAS (Assessment of SpondyloArthritis... Show moreObjectives To develop a consensual definition for the term ‘early axial spondyloarthritis—axSpA’—and ‘early peripheral spondyloarthritis—pSpA’.Methods The ASAS (Assessment of SpondyloArthritis international Society-Spondyloarthritis EARly definition) steering committee convened an international working group (WG). Five consecutive steps were followed: (1) systematic literature review (SLR); (2) discussion of SLR results within the WG and ASAS community; (3) a three-round Delphi survey inviting all ASAS members to select the items that should be considered for the definition; (4) presentation of Delphi results to the WG and ASAS community and (5) ASAS voting and endorsement (2023 annual meeting).Results Following the SLR, consensus was to proceed with an expert-based definition for early axSpA (81% in favour) but not for pSpA (54% against). Importantly, early axSpA should be based on symptom duration taking solely axial symptoms into account. 151–164 ASAS members participated in the Delphi surveys. Consensus was achieved for considering the following items within early axSpA definition: duration of symptoms ≤2 years; axial symptoms defined as cervical/thoracic/back/buttock pain or morning stiffness; regardless of the presence/absence of radiographic damage. The WG agreed that in patients with a diagnosis of axSpA ‘early axSpA’ should be defined as a duration of ≤2 years of axial symptoms. Axial symptoms should include spinal/buttock pain or morning stiffness and should be considered by a rheumatologist as related to axSpA. The ASAS community endorsed this proposal (88% in favour).Conclusions Early axSpA has newly been defined, based on expert consensus. This ASAS definition should be adopted in research studies addressing early axSpA. Show less
Koppejan, H.; Beyrend, G.; Hameetman, M.; Abdelaal, T.; Toes, R.E.M.; Gaalen, F.A. van 2023
Objective: Mass cytometry (MC) immunoprofiling allows high-parameter phenotyping of immune cells. We set to investigate the potential of MC immuno-monitoring of axial spondyloarthritis (axSpA)... Show moreObjective: Mass cytometry (MC) immunoprofiling allows high-parameter phenotyping of immune cells. We set to investigate the potential of MC immuno-monitoring of axial spondyloarthritis (axSpA) patients enrolled in the Tight Control SpondyloArthritis (TiCoSpA) trial. Methods: Fresh, longitudinal PBMCs samples (baseline, 24, and 48 weeks) from 9 early, untreated axSpA patients and 7 HLA-B27+ controls were analyzed using a 35-marker panel. Data were subjected to HSNE dimension reduction and Gaussian mean shift clustering (Cytosplore), followed by Cytofast analysis. Linear discriminant analyzer (LDA), based on initial HSNE clustering, was applied onto week 24 and 48 samples. Results: Unsupervised analysis yielded a clear separation of baseline patients and controls including a significant difference in 9 T cell, B cell, and monocyte clusters (cl), indicating disrupted immune homeostasis. Decrease in disease activity (ASDAS score; median 1.7, range 0.6-3.2) from baseline to week 48 matched significant changes over time in five clusters: cl10 CD4 Tnai cells median 4.7 to 0.02%, cl37 CD4 T-em cells median 0.13 to 8.28%, cl8 CD4 Tcm cells median 3.2 to 0.02%, cl39 B cells median 0.12 to 2.56%, and cl5 CD38+ B cells median 2.52 to 0.64% (all p<0.05). Conclusions: Our results showed that a decrease in disease activity in axSpA coincided with normalization of peripheral T- and B-cell frequency abnormalities. This proof of concept study shows the value of MC immuno-monitoring in clinical trials and longitudinal studies in axSpA. MC immunophenotyping on a larger, multi-center scale is likely to provide crucial new insights in the effect of anti-inflammatory treatment and thereby the pathogenesis of inflammatory rheumatic diseases. Show less
Koppejan, H.; Beyrend, G.; Hameetman, M.; Abdelaal, T.; Toes, R.E.M.; Gaalen, F.A. van 2023
ObjectiveMass cytometry (MC) immunoprofiling allows high-parameter phenotyping of immune cells. We set to investigate the potential of MC immuno-monitoring of axial spondyloarthritis (axSpA)... Show moreObjectiveMass cytometry (MC) immunoprofiling allows high-parameter phenotyping of immune cells. We set to investigate the potential of MC immuno-monitoring of axial spondyloarthritis (axSpA) patients enrolled in the Tight Control SpondyloArthritis (TiCoSpA) trial.MethodsFresh, longitudinal PBMCs samples (baseline, 24, and 48 weeks) from 9 early, untreated axSpA patients and 7 HLA-B27+ controls were analyzed using a 35-marker panel. Data were subjected to HSNE dimension reduction and Gaussian mean shift clustering (Cytosplore), followed by Cytofast analysis. Linear discriminant analyzer (LDA), based on initial HSNE clustering, was applied onto week 24 and 48 samples.ResultsUnsupervised analysis yielded a clear separation of baseline patients and controls including a significant difference in 9 T cell, B cell, and monocyte clusters (cl), indicating disrupted immune homeostasis. Decrease in disease activity (ASDAS score; median 1.7, range 0.6–3.2) from baseline to week 48 matched significant changes over time in five clusters: cl10 CD4 Tnai cells median 4.7 to 0.02%, cl37 CD4 Tem cells median 0.13 to 8.28%, cl8 CD4 Tcm cells median 3.2 to 0.02%, cl39 B cells median 0.12 to 2.56%, and cl5 CD38+ B cells median 2.52 to 0.64% (all p<0.05).ConclusionsOur results showed that a decrease in disease activity in axSpA coincided with normalization of peripheral T- and B-cell frequency abnormalities. This proof of concept study shows the value of MC immuno-monitoring in clinical trials and longitudinal studies in axSpA. MC immunophenotyping on a larger, multi-center scale is likely to provide crucial new insights in the effect of anti-inflammatory treatment and thereby the pathogenesis of inflammatory rheumatic diseases. Show less
Stal, R.; Ramiro, S.; Baraliakos, X.; Braun, J.; Reijnierse, M.; Berg, R. van den; ... ; Gaalen, F.A. van 2023
Objectives: To assess construct validity of the CT Syndesmophyte Score (CTSS) for the measurement of structural spinal damage in patients with radiographic axial spondyloarthritis. Methods: Low... Show moreObjectives: To assess construct validity of the CT Syndesmophyte Score (CTSS) for the measurement of structural spinal damage in patients with radiographic axial spondyloarthritis. Methods: Low-dose CT and conventional radiography (CR) were performed at baseline and 2 years. CT was assessed with CTSS by two readers and CR with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by three readers. Two hypotheses were tested: (1) syndesmophytes scored with CTSS are also detected with mSASSS at baseline or 2 years later; (2) CTSS is non-inferior to mSASSS in correlations with spinal mobility measures. Presence of a syndesmophyte was determined per reader per corner for all anterior cervical and lumbar corners on CT at baseline and CR at baseline and 2 years. Correlations of CTSS and mSASSS with six spinal/hip mobility measurements plus Bath Ankylosing Spondylitis Metrology Index (BASMI) were tested. Results: Data from 48 patients (85% male, 85% HLA-B27+, mean age 48 years) were available for hypothesis 1 and 41/48 were available for hypothesis 2. At baseline, syndesmophytes were scored with CTSS in 348 (reader 1, 38%) and 327 (reader 2, 36%) corners out of 917. Of these, depending on reader pairs, 62%-79% were also seen on CR at baseline or after 2 years. CTSS correlated well (r(s)0.46-0.73), and with higher correlation coefficients than mSASSS (r(s)0.34-0.64), with all spinal mobility measures and BASMI. Conclusions:The good agreement between syndesmophytes detected by CTSS and mSASSS and the strong correlation of CTSS with spinal mobility support the construct validity of the CTSS. Show less
Marques, M.L.; Silva, N.P. da; Heijde, D. van der; Stal, R.; Baraliakos, X.; Braun, J.; ... ; Gaalen, F.A. van 2023
Objective: To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases... Show moreObjective: To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation at the same vertebra. Methods: Whole spine (C3-L5) data from patients included in the multicentre 2-year Sensitive Imaging in Ankylosing Spondylitis cohort was used. Two readers measured baseline TBD by Hounsfield units (HU) on low-dose CT (ldCT). Baseline MRI bone marrow oedema (BME) status scores and ldCT syndesmophyte formation and/or growth change-from-baseline scores were assessed by three and two readers, respectively. Average of readers' continuous measurements or readers' agreement in binary scores generated within the same vertebra (1-present in >= 1 quadrant/0-absent in all quadrants) were used. Multilevel generalised estimating equations models were used, the unit of analysis being the vertebra. Results: In 50 patients with r-axSpA, TBD HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant confounder-adjusted association was found between inflammation and lower TBD (regression coefficient=-51; 95% CI-63 to -39). TBD was not associated with 2-year syndesmophyte formation or growth (adjusted OR 1.00; 95% CI 0.99 to 1.00). Conclusion: In r-axSpA, while vertebral inflammation was associated with lower vertebral TBD, lower vertebral TBD itself did not increase the risk for new bone formation at the same vertebra. In preventing syndesmophyte progression, targeting local inflammation seems more important than targeting vertebral trabecular bone loss. Show less
Marques, M.L.; Silva, N.P. da; Heijde, D. van der; Stal, R.; Baraliakos, X.; Braun, J.; ... ; Gaalen, F.A. van 2023
Objective To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases... Show moreObjective To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation at the same vertebra.Methods Whole spine (C3–L5) data from patients included in the multicentre 2-year Sensitive Imaging in Ankylosing Spondylitis cohort was used. Two readers measured baseline TBD by Hounsfield units (HU) on low-dose CT (ldCT). Baseline MRI bone marrow oedema (BME) status scores and ldCT syndesmophyte formation and/or growth change-from-baseline scores were assessed by three and two readers, respectively. Average of readers’ continuous measurements or readers’ agreement in binary scores generated within the same vertebra (1—present in ≥1 quadrant/0—absent in all quadrants) were used. Multilevel generalised estimating equations models were used, the unit of analysis being the vertebra.Results In 50 patients with r-axSpA, TBD HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant confounder-adjusted association was found between inflammation and lower TBD (regression coefficient=−51; 95% CI−63 to −39). TBD was not associated with 2-year syndesmophyte formation or growth (adjusted OR 1.00; 95% CI 0.99 to 1.00).Conclusion In r-axSpA, while vertebral inflammation was associated with lower vertebral TBD, lower vertebral TBD itself did not increase the risk for new bone formation at the same vertebra. In preventing syndesmophyte progression, targeting local inflammation seems more important than targeting vertebral trabecular bone loss. Show less
Ramiro, S.; Nikiphorou, E.; Sepriano, A.; Ortolan, A.; Webers, C.; Baraliakos, X.; ... ; Heijde, D. van der 2022
Objectives To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). Methods Following the EULAR... Show moreObjectives To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). Methods 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. Results 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. Conclusions The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA. Show less
Jong, H.M.Y. de; Winter, J.J.H. de; Horst-Bruinsma, I.E. van der; Schaardenburg, D.J. van; Gaalen, F.A. van; Tubergen, A.M. van; ... ; Sande, M.G.H. van de 2022
Objective As first-degree relatives (FDRs) of HLA-B27-positive patients with axial spondyloarthritis (SpA) have an increased risk of developing axial SpA, the objectives were 1) to evaluate the... Show moreObjective As first-degree relatives (FDRs) of HLA-B27-positive patients with axial spondyloarthritis (SpA) have an increased risk of developing axial SpA, the objectives were 1) to evaluate the presence of highly specific imaging features as well as clinical signs of SpA at baseline and after 1 year of follow-up, and 2) to describe the evolution toward clinical disease within 1 year of follow-up in a cohort of seemingly healthy FDRs of HLA-B27-positive axial SpA patients. Methods The Pre-SpA cohort is a 5-year prospective inception cohort of seemingly healthy FDRs of HLA-B27-positive axial SpA patients. Clinical and imaging features were collected and recorded. Results At baseline, 19% of the FDRs reported inflammatory back pain, 32% current arthralgia, 3% arthritis (ever), 5% enthesitis (ever), and 1% dactylitis (ever), and 3% had an extraarticular manifestation. C-reactive protein level was elevated in 16%, and erythrocyte sedimentation rate was elevated in 7%. On magnetic resonance imaging (MRI) views of sacroiliac joints, 10% had a Spondyloarthritis Research Consortium of Canada score of >= 2, 4% had a score of >= 5, and 4% had deep lesions. In total, 1% fulfilled the modified New York criteria for radiographic sacroiliitis. Clinical, MRI, and acute phase findings were equally distributed between HLA-B27-positive and -negative FDRs. After 1 year of follow-up, clinical parameters did not change on the group level, but 6% of the FDRs were clinically diagnosed with axial SpA, of whom 86% were HLA-B27-positive. Conclusion Features associated with SpA or imaging abnormalities were found in up to 32% of seemingly healthy FDRs, with an equal distribution between HLA-B27-positive and -negative FDRs. Progression to clinical axial SpA within 1 year of follow-up was mainly observed in HLA-B27-positive FDRs. Show less
Marques, M.L.; Silva, N.P. da; Heijde, D. van der; Reijnierse, M.; Baraliakos, X.; Braun, J.; ... ; Ramiro, S. 2022
Objective: Studying vertebral bone loss in radiographic axial spondyloarthritis (r-axSpA) has been challenging due to ectopic bone formation. We cross-sectionally analysed low-dose CT (ldCT)... Show moreObjective: Studying vertebral bone loss in radiographic axial spondyloarthritis (r-axSpA) has been challenging due to ectopic bone formation. We cross-sectionally analysed low-dose CT (ldCT) trabecular bone density Hounsfield units (HU) measurements and calculated inter-reader reliability at the vertebral level in patients with r-axSpA. Methods: LdCT scans of 50 patients with r-axSpA from the sensitive imaging in ankylosing spondylitis study, a multicentre 2-year prospective cohort were included. Trabecular bone HU taken from a region of interest at the centre of each vertebra (C3-L5) were independently assessed by two trained readers. HU mean (SD), and range were provided at the vertebral level, for each reader and centre separately. Inter-reader reliability and agreement were assessed using intraclass correlation coefficients (ICC; single measurements, absolute agreement, two-way mixed effects models); smallest detectable difference and Bland-Altman plots. Results: Overall, 1100 vertebrae were assessed by each reader. HU values decreased from cranial to caudal vertebrae. For readers 1 and 2 respectively, the highest mean (SD) HU value was obtained at C3 (354(106) and 355(108)), and the lowest at L3 (153(65) and 150 (65)). Inter-reader reliability was excellent (ICC(2,1):0.89 to 1.00). SDD varied from 4 to 8. For most vertebrae, reader 1 scored somewhat higher than reader 2 (mean difference of scores ranging from -0.6 to 2.9 HU). Bland-Altman plots showed homoscedasticity. Conclusion: LdCT measurement of HU is a feasible method to assess vertebral bone density in r-axSpA with excellent inter-reader reliability from C3 to L5. These results warrant further validation and longitudinal assessment of reliability. Show less
Stal, R.; Sepriano, A.; Gaalen, F.A. van; Baraliakos, X.; Berg, R. van den; Reijnierse, M.; ... ; Heijde, D. van der 2022
Objectives In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased... Show moreObjectives In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased the risk of the other lesion. Methods Patients with r-axSpA underwent low-dose CT (ldCT) and MRI of the whole spine at baseline and 2 years. On ldCT, vertebrae were scored for presence and size of syndesmophytes; facet joints were assessed for ankylosis. MR images were assessed for inflammation. Two hypotheses were tested: (i) presence of FJA is associated with new syndesmophyte(s) on the same vertebral unit (VU) 2 years later, and (ii) presence of bridging syndesmophyte(s) is associated with new FJA on the same VU 2 years later. Two generalized estimating equations models were tested per hypothesis using increase of FJA/syndesmophytes (model A) or presence of FJA/syndesmophytes (model B) as outcome, adjusted for inflammation at baseline. Secondary analyses tested the hypotheses with outcomes on adjacent VUs and dose-response effects. Results Fifty-one patients were included (mean age 49, 84% male, 82% HLA-B27(+)). Baseline bridging syndesmophytes occurred more often (range: 10-60% per VU) than FJA (range: 8-36%). Odds ratios (ORs) (95% CI) for presence of bridging syndesmophytes on development of FJA were 3.55 (2.03, 6.21) for model A and 3.30 (2.14, 5.09) for model B. ORs for presence of baseline FJA on new syndesmophytes were 1.87 (1.20, 2.92) for model A and 1.69 (0.88, 3.22) for model B. Secondary analyses yielded positive ORs for both hypotheses. Conclusions Bone formation in vertebrae and in facet joints influence each other's occurrence, with the effect of syndesmophytes being larger than that of FJA. Show less
