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
Rodrigues-Manica, S.; Sepriano, A.; Ramiro, S.; Landewe, R.; Claudepierre, P.; Molto, A.; ... ; Heijde, D. van der 2023
Objective: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to... Show moreObjective: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to investigate the association between BME patterns over time and structural lesions in patients with early axial spondyloarthritis (axSpA). Methods: Patients with axSpA from the DESIR cohort with & GE;2 consecutive magnetic resonance imaging (MRI)-SIJ were assessed at baseline, 2 and 5 years. MRI-SIJ images were divided into 8 quadrants. The association between BME and subsequent structural lesions (sclerosis, erosions, fatty lesions, and ankylosis) on MRI in the same quadrant was tested longitudinally. Additionally, patients were grouped according to the pattern of BME evo-lution across quadrants over time (no BME, sporadic, fluctuating, and persistent). The association between these patterns and 5-year imaging outcomes (eg: & GE;5 erosions and/or fatty lesions on MRI-SIJ) was tested. Results: In total, 196 patients were included. BME in each quadrant was associated with sclerosis (OR:1.9 (95%CI: 1.1;3.4)), erosions (1.9 (1.5;2.5)) and fatty lesions (1.9 (1.4;2.6)). Ankylosis was uncommon. There was a gradient between increased level of inflammation and subsequent damage: compared to the 'no BME' pattern, the sporadic (OR (95% CI): 2.1 (1.0;4.5)), fluctuating (OR:5.6(2.2;14.4)) and persistent (OR:7.5(2.8;19.6)) patterns were associated with higher structural damage on MRI-SIJ at 5-years. Conclusions: In early axSpA, inflammation on MRI-SIJ leads to damage at the quadrant level. The higher the exposure to inflammation across quadrants in the SIJs over time the higher the likelihood of subsequent struc-tural damage, suggesting a cumulative effect. Show less
Ramiro, S.; Landewe, R.; Heijde, D. van der; Sepriano, A.; FitzGerald, O.; Ostergaard, M.; ... ; Maksymowych, W.P. 2023
Objectives: To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start... Show moreObjectives: To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Methods: Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results: In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: -0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions: In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome. Show less
Capelusnik, D.; Benavent, D.; Heijde, D. van der; Landewe, R.; Poddubnyy, D.; Tubergen, A. van; ... ; Ramiro, S. 2022
Objective To summarize evidence on the relationship between early treatment (definition based on symptom/disease duration or radiographic damage) and treatment clinical response in patients with... Show moreObjective To summarize evidence on the relationship between early treatment (definition based on symptom/disease duration or radiographic damage) and treatment clinical response in patients with SpA. Methods A systematic literature review was conducted in studies on SpA patients treated with NSAIDs or biological/targeted synthetic DMARDs addressing the impact of symptom/disease duration or presence of radiographic damage on treatment response assessed by any disease activity outcome. For categorical outcomes, relative risk, relative risk ratio and number needed to treat were calculated, and for continuous outcomes, differences in differences, to compare groups stratified based on symptom/disease duration or the presence of radiographic damage. Results From the 8769 articles retrieved, 25 were included and 2 added by hand-search, all in axial SpA (axSpA), most of them with low risk of bias. Twenty-one studies compared groups based on symptom duration (n = 6) or disease duration (n = 15) and seven studies based on absence/presence of radiographic damage (two studies used two comparisons). When early axSpA was defined by symptom duration (<5 years) in randomized controlled trials, early treatment was associated with better outcomes in patients with non-radiographic axSpA [n = 2, ASAS40 relative risk ratio 5.24 (95% CI 1.12, 24.41) and 1.52 (0.60, 3.87)] but not in radiographic axSpA (n = 1) [ASAS20 0.96 (0.53-1.73)]. When early axSpA was defined based on disease duration or radiographic damage, no differences were found between groups. Conclusion Evidence towards better outcomes in early axSpA is very limited and restricted to non-radiographic axSpA and <5 years symptom duration. When early axSpA is defined based on disease duration or radiographic damage, no differences in response to treatment are found. Show less
Benavent, D.; Capelusnik, D.; Heijde, D. van der; Landewe, R.; Poddubnyy, D.; Tubergen, A. van; ... ; Navarro-Compan, V. 2022
Aim: To identify all possible definitions of "early SpA" employed in the literature, including "early axial SpA (axSpA)" and "early peripheral SpA (pSpA)".Methods: A systematic literature review... Show moreAim: To identify all possible definitions of "early SpA" employed in the literature, including "early axial SpA (axSpA)" and "early peripheral SpA (pSpA)".Methods: A systematic literature review was conducted in Medline, EMBASE and the Cochrane Library for studies that included any mention of "early SpA" or its subtypes. The proportion of studies including a definition was calculated, and the different definitions were assessed.Results: Out of 9651 titles identified, 336 publications reporting data from 183 studies were included. Over time, an increasing number of publications were identified. In total, 114 (62%) studies reported a specific definition: 33% of them based it on symptom duration, 31% on radiographic damage, 28% on disease duration, 5% on both symptom/disease duration and radiographic damage, and 3% on other aspects. Overall, 61 (33%) studies included the term "early axSpA", whereas 60 (33%) included "early ankylosing spondylitis (AS)". Regarding the studies that referred to "early axSpA", the most used definition was symptom/disease duration <5 years, whereas for "early AS" was symptom/disease duration <10 years. After 2010, the definition of "early axSpA" based on the absence of radiographic sacroiliitis was less used compared to before 2010 (17% vs 38%).Conclusion: Over time, the term "early SpA" and its subtypes is increasingly used. More than one third of the studies did not include a definition of the term and the studies reporting one showed a large heterogeneity. These results emphasize the need for a standardised definition of early SpA. Show less
Stal, R.; Baraliakos, X.; Heijde, D. van der; Gaalen, F. van; Ramiro, S.; Berg, R. van den; ... ; Sepriano, A. 2022
Objectives To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected... Show moreObjectives To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth. Methods Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort underwent MRI (baseline, 1 year and 2 years) and ldCT (baseline and 2 years). MR images were scored by three readers for VCI and VCFD, MRI patterns were defined by presence of VCI and/or VCFD over 2 years. LdCT images were scored by two central readers for presence and size of syndesmophytes and change was calculated for new or new/grown syndesmophytes. Multilevel generalised estimated equations were used to test the associations between VCI and VCFD and syndesmophyte development. Results Fifty radiographic patients with axial spondyloarthritis were included (mean age 49 years, 86% male, 78% HLA-B27+). Absence of both VCI and VCFD protected against syndesmophyte development (ORs 0.36-0.37). Presence of VCI and/or VCFD increased the risk of syndesmophyte development (ORs 1.73-2.60). Out of all corners with a new or new/grown syndesmophyte, 47% of corners according to reader 1 and 44% according to reader 2 had neither VCI nor VCFD preceding the bone formation. Conclusions VCI and VCFD were positively associated with syndesmophyte development. This has been shown for the first time for syndesmophytes detected on ldCT and also in the thoracic spine. However, almost half of all bone formation occurred in corners without VCI or VCFD, suggesting the presence of these lesions in yearly MRIs does not fully clarify the development of syndesmophytes. Show less
Heijde, D. van der; Gensler, L.S.; Maksymowych, W.P.; Landewe, R.; Rudwaleit, M.; Bauer, L.; ... ; Deodhar, A. 2022
Background: 52-week results from C-axSpAnd demonstrated the safety and efficacy of certolizumab pegol (CZP) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective... Show moreBackground: 52-week results from C-axSpAnd demonstrated the safety and efficacy of certolizumab pegol (CZP) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammation (sacroiliitis on MRI and/or elevated C-reactive protein levels). Long-term safety and clinical outcomes, including MRI assessments, are evaluated up to 3 years for CZP-treated patients with nr-axSpA. Methods: C-axSpAnd was a phase 3 study comprising a 1-year double-blind, placebo-controlled period and 2-year open-label safety follow-up extension (SFE). At baseline, 317 patients were randomised 1:1 to placebo or CZP 200 mg every 2 weeks. Patients completing the double-blind phase who enrolled into the SFE received open-label CZP for an additional 104 weeks. Long-term safety and clinical outcomes are reported to Week 156. Continuous outcomes are presented as observed case (OC) and dichotomous outcomes as OC and with non-responder imputation. Results: 243/317 (76.7%) patients entered the SFE, during which 149 (61.3%) experienced Al treatment-emergent adverse event (TEAE); 15 (3.3/100 patient-years) experienced serious TEAEs. Continuous outcome scores (including Ankylosing Spondylitis Disease Activity Score [ASDAS]: 1.8; Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]: 2.7) at Week 52 were maintained at Week 156 (ASDAS: 1.8; BASDA1: 2.6) for the initial CZP-randomised group. Mean SPARCC MRI sacroiliac joint inflammation scores for these patients decreased at Week 52 (baseline: 7.6; Week 52: 1.7), remaining low at Week 156 (2.4).Conclusions: CZP treatment was well tolerated up to 3 years, with no new safety signals versus previous reports. Clinical outcomes achieved after 1 year were sustained to 3 years. Show less
Sepriano, A.; Ramiro, S.; Heijde, D. van der; Dougados, M.; Claudepierre, P.; Feydy, A.; ... ; Landewe, R. 2022
Objective To compare the sensitivity to change of different imaging scoring methods in patients with early axial spondyloarthritis (SpA). Methods Patients from the Devenir des Spondylarthropathies... Show moreObjective To compare the sensitivity to change of different imaging scoring methods in patients with early axial spondyloarthritis (SpA). Methods Patients from the Devenir des Spondylarthropathies Indiffererenciees Recentes (DESIR) cohort fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA were included. Radiographs and magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and spine were obtained at baseline, 1, 2, and 5 years. Each image was scored by 2 or 3 readers in 3 separate reading waves. The rate of change of outcomes measuring inflammation of the spine and SI joints (e.g., Spondyloarthritis Research Consortium of Canada [SPARCC] score) and structural damage on MRI (e.g., >= 3 fatty lesions) and radiographs (e.g., modified New York grading) was assessed using multilevel generalized estimating equation models (taking all readers and waves into account). To allow comparisons across outcomes, rates were standardized (difference between the individual's value and the population mean divided by the SD). Results In total, 345 patients were included. Inflammation detected on MRI of the SI joints (MRI-SI joints) (standardized rate range -0.278, -0.441) was more sensitive to change compared to spinal inflammation (range -0.030, -0.055). Structural damage in the SI joints showed a higher standardized rate of change on MRI-SI joints (range 0.015, 0.274) compared to radiography of the SI joints (range 0.043, 0.126). MRI-SI joints damage defined by >= 3 fatty lesions showed the highest sensitivity to change (0.274). Spinal structural damage slowly progressed over time with no meaningful difference between radiographic (range 0.037, 0.043) and MRI structural outcomes (range 0.008, 0.027). Conclusion Structural damage assessed in pelvic radiographs has low sensitivity to change, while fatty lesions detected on MRI-SI joints are a promising alternative. In contrast, MRI of the spine is not better than radiography of the spine in detecting structural changes in patients with early axial SpA. Show less
Sepriano, A.; Ramiro, S.; Landewe, R.; Molto, A.; Claudepierre, P.; Wendling, D.; ... ; Heijde, D. van der 2021
Objective To test the impact of inflammation on structural changes occurring in the sacroiliac (SI) joints and the spine detected on magnetic resonance imaging (MRI). Methods Patients with early... Show moreObjective To test the impact of inflammation on structural changes occurring in the sacroiliac (SI) joints and the spine detected on magnetic resonance imaging (MRI). Methods Patients with early axial spondyloarthritis (SpA) from the Devenir des Spondylarthropathies Indiffererenciees Recentes (DESIR) cohort were included. MRIs of the SI joints (MRI-SI joints) and spine (MRI-spine), obtained at baseline, 2 years, and 5 years, were scored by 3 central readers. Inflammation and structural damage on MRI-SI joints and MRI-spine were defined by the agreement of >= 2 of 3 readers (binary outcomes) and by the average of 3 readers (continuous outcomes). The effect of inflammation (MRI-SI joints/MRI-spine) on damage (MRI-SI joints/MRI-spine, respectively) was evaluated in 2 models: 1) a baseline prediction model (the effect of baseline inflammation on damage assessed at 5 years); and 2) a longitudinal model (the effect of inflammation on structural damage assessed during a 5-year period). Results A total of 202 patients were included. Both the presence of bone marrow edema on MRI-SI joints and on MRI-spine at baseline were predictive of 5-year damage (>= 3 fatty lesions) on MRI-SI joints (odds ratio [OR] 4.2 [95% confidence interval (95% CI) 2.4, 7.3]) and MRI-spine (OR 10.7 [95% CI 2.4, 49.0]), respectively, when adjusted for C-reactive protein level. The association was also confirmed in longitudinal models (when adjusted for Ankylosing Spondylitis Disease Activity Score) both in the SI joints (OR 5.1 [95% CI 2.7, 9.6]) and spine (OR 15.6 [95% CI 4.8, 50.3]). Analysis of other structural outcomes (i.e., erosions) on MRI-SI joints yielded similar results. In the spine, a significant association was found for fatty lesions but not for erosions and bone spurs, which occurred infrequently over time. Conclusion We found a predictive and longitudinal association between inflammation detected on MRI and several types of structural damage detected on MRI in patients with early axial SpA, which adds to the evidence for a causal relationship. Show less
Boel, A.; Navarro-Compan, V.; Boonen, A.; Mease, P.; Kiltz, U.; Dougados, M.; ... ; Heijde, D. van der 2021
Objective. Advances in the field of axial spondyloarthritis (axSpA) and the methodology to develop core sets have led the Assessment of SpondyloArthritis international Society (ASAS) group to... Show moreObjective. Advances in the field of axial spondyloarthritis (axSpA) and the methodology to develop core sets have led the Assessment of SpondyloArthritis international Society (ASAS) group to update the ASAS-Outcomes in Rheumatology (OMERACT) core set. An important aspect was to ensure it would be applicable to the entire spectrum of axSpA. The first step was to define the most relevant disease domains.Methods. A 3-round Delphi survey was conducted to gather opinions of 188 patients and 188 axSpA experts to define the most relevant disease domains to be included in the core set. The Delphi survey evaluated 2 separate research settings: (1) studies assessing symptom-modifying therapies; and (2) studies evaluating disease-modifying therapies. Importance of the domains was rated on a 1-9 Likert scale. A domain was considered for inclusion if, for both stakeholder groups, >= 70% of participants scored the domain as critical (7-9) and <= 15% scored it as not important (1-3) after 3 rounds.Results. A total of 132 (70%) patients and 135 (72%) experts completed at least 1 round. After 3 rounds, 7 domains (pain, physical function, stiffness, disease activity, mobility, overall functioning and health, peripheral manifestations) were selected for the symptom-modifying therapies setting. For the disease-modifying therapies setting, 6 domains (physical function, disease activity, mobility, structural damage, extramusculoskeletal manifestations, peripheral manifestations) were selected. All domains selected by experts were also selected by patients. Patients selected all offered domains except emotional function.Conclusion. This study provides the domains selected by patients and axSpA experts that should be considered for the core set for axSpA. Show less
Objective To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with... Show moreObjective To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist. Methods Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters. Results The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist's diagnosis as well as with the classification criteria was found. Conclusion These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations. Show less
Objectives. To determine quantitative SI joint MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial SpA (axSpA) and that predict... Show moreObjectives. To determine quantitative SI joint MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial SpA (axSpA) and that predict clinical diagnosis.Methods. The Assessment of SpondyloArthritis international Society (ASAS) MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises where (A) 169 cases and 7 central readers; (B) 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SI joint quadrants or slices with bone marrow oedema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with >= 95% specificity were analysed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPVs/NPVs) and selecting cut-offs with PPV >= 95%.Results. Active or structural lesions typical of axSpA on MRI had PPVs >= 95% for clinical diagnosis of axSpA. Cut-offs that best reflected a definite active lesion typical of axSpA were either >= 4 SI joint quadrants with BME at any location or at the same location in >= 3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of >= 3 SI joint quadrants with erosion or >= 5 with fat lesions, erosion at the same location for >= 2 consecutive slices, fat lesions at the same location for >= 3 consecutive slices, or presence of a deep (i.e. >1 cm depth) fat lesion.Conclusion. We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPVs for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research. Show less
Nikiphorou, E.; Boonen, A.; Fautrel, B.; Richette, P.; Landewe, R.; Heijde, D. van der; Ramiro, S. 2021
Objectives: To investigate the impact of clinical and socioeconomic factors on work disability (WD) in early axial spondyloarthritis (axSpA). Methods: Patients from the DESIR cohort with a clinical... Show moreObjectives: To investigate the impact of clinical and socioeconomic factors on work disability (WD) in early axial spondyloarthritis (axSpA). Methods: Patients from the DESIR cohort with a clinical diagnosis of axSpA were studied over 5 years. Time to WD and potential baseline and time-varying predictors were explored, with a focus on socioeconomic (including ethnicity, education, job-type, marital/parental status) and clinical (including disease activity, function, mobility) factors. Univariable analyses, collinearity and interaction tests guided subsequent multivariable time-varying Cox survival analyses. Results: From 704 patients eligible for this study, the estimated incidence of WD among those identified as at risk (n = 663, 94%), and across the five years of DESIR, was 0.05 (95% CI 0.03, 0.06) per 1000 person-days. Significant differences in baseline socioeconomic factors, including lower educational status and clinical measures, including worse disease activity, were seen in patients developing WD over follow-up, compared with those who never did. In the main multivariable model, educational status was no longer predictive of WD, whereas the AS disease activity score (ASDAS) and the BASFI were significantly and independently associated with a higher hazard of WD [HR (95%CI) 1.79 (1.27, 2.54) and 1.42 (1.22, 1.65), respectively]. Conclusion: WD was an infrequent event in this early axSpA cohort. Nevertheless, clinical factors were among the strongest predictors of WD, over socioeconomic factors, with worse disease activity and function independently associated with a higher hazard of WD. Disease severity remains a strong predictor of adverse work outcome even in early disease, despite substantial advances in therapeutic strategies in axSpA. Show less
Taylor, P.C.; Heijde, D. van der; Landewe, R.; McCue, S.; Cheng, S.; Boonen, A. 2021
Objective. To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with active ankylosing spondylitis (AS).Methods. This phase III, multicenter, double... Show moreObjective. To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with active ankylosing spondylitis (AS).Methods. This phase III, multicenter, double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01583374) randomized patients with active AS (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily for 24 weeks, followed by a long-term extension phase (up to 5 yrs). The primary endpoint was Assessment of the Spondyloarthritis international Society 20 (ASAS20) response at Week 16. The effect of treatment on radiographic outcomes after 104 weeks was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).Results. In total, 490 patients with active AS were randomized in the study (placebo: n = 164; apremilast 20 mg twice daily: n = 163; apremilast 30 mg twice daily: n = 163). The primary endpoint of ASAS20 response at Week 16 was not met (placebo: 37%; apremilast 20 mg twice daily: 35%; apremilast 30 mg twice daily: 33%; P = 0.44 vs placebo). At Week 104, mean (SD) changes from baseline in mSASSS were 0.83 (3.6), 0.98 (2.2), and 0.57 (1.9) in patients initially randomized to placebo, apremilast 20 mg twice daily, and apremilast 30 mg twice daily, respectively. The most frequently reported adverse events through Week 104 were diarrhea, nasopharyngitis, upper respiratory infection, and nausea.Conclusion. No clinical benefit was observed with apremilast treatment in patients with active AS. The safety and tolerability of apremilast were consistent with its known profile. Show less
Sepriano, A.; Ramiro, S.; Wichuk, S.; Chiowchanwisawakit, P.; Paschke, J.; Heijde, D. van der; ... ; Maksymowych, W.P. 2021
Objective To investigate whether tumor necrosis factor inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (SpA) and whether this is coupled to their... Show moreObjective To investigate whether tumor necrosis factor inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (SpA) and whether this is coupled to their effect on inflammation.Methods Patients with axial SpA fulfilling the modified New York criteria were included in a prospective cohort (the ALBERTA Follow Up Research Cohort in Ankylosing Spondylitis Treatment). Spine radiographs, performed every 2 years for up to 10 years, were scored by 2 central readers, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS was evaluated with generalized estimating equations by testing the interaction between TNFi and Ankylosing Spondylitis Disease Activity Score (ASDAS) at the start of each 2-year interval (t). If significant, the association between ASDAS at t and mSASSS at the end of the interval (t+1) was assessed in 1) patients treated with TNFi at all visits, 2) patients treated with TNFi at some visits, and 3) patients who were never treated with TNFi. In addition, the association between TNFi at t and mSASSS at t+1 (adjusting for ASDAS at t) was also tested (direct effect).Results In total, 314 patients were included. A gradient was seen for the effect of ASDAS at t on mSASSS at t+1 (interaction P = 0.10), with a higher progression in patients never treated with TNFi (beta = 0.41 [95% confidence interval (95% CI) 0.13, 0.68]) compared to those continuously treated (beta = 0.16 [95% CI 0.00, 0.31]) (indirect effect). However, TNFi also directly slowed progression, as treated patients had on average an mSASSS 0.85 units lower at t+1 compared to untreated patients (beta = -0.85 [95% CI -1.35, -0.35]).Conclusion Our findings indicate that TNFi reduce spinal radiographic progression in patients with radiographic axial SpA, which might be partially uncoupled from their effects on inflammation as measured by the ASDAS. Show less
Protopopov, M.; Proft, F.; Sepriano, A.; Landewe, R.; Heijde, D. van der; Maksymowych, W.P.; ... ; Poddubnyy, D. 2021
Background Limited information is available on the impact of treatment with a tumor necrosis factor inhibitor (TNFi) on structural lesions in patients with recent-onset axial spondyloarthritis ... Show moreBackground Limited information is available on the impact of treatment with a tumor necrosis factor inhibitor (TNFi) on structural lesions in patients with recent-onset axial spondyloarthritis (axSpA). We compared 2-year structural lesion changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) of patients with recent-onset axSpA receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). We also evaluated the relationship between the Ankylosing Spondylitis Disease Activity Score (ASDAS) and change in MRI structural parameters. Methods The difference between etanercept (EMBARK) and control (DESIR) in the net percentage of patients with structural lesion change was determined using the SpondyloArthritis Research Consortium of Canada SIJ Structural Score, with and without adjustment for baseline covariates. The relationship between sustained ASDAS inactive disease, defined as the presence of ASDAS < 1.3 for at least 2 consecutive time points 6 months apart, and structural lesion change was evaluated. Results This study included 163 patients from the EMBARK trial and 76 from DESIR. The net percentage of patients with erosion decrease was significantly greater for etanercept vs control: unadjusted: 23.9% vs 5.3%; P = 0.01, adjusted: 23.1% vs 2.9%; P = 0.01. For the patients attaining sustained ASDAS inactive disease on etanercept, erosion decrease was evident in significantly more than erosion increase: 34/104 (32.7%) vs 5/104 (4.8%); P < 0.001. A higher proportion had erosion decrease and backfill increase than patients in other ASDAS status categories. However, the trend across ASDAS categories was not significant and decrease in erosion was observed even in patients without a sustained ASDAS response. Conclusions These data show that a greater proportion of patients achieved regression of erosion with versus without etanercept. However, the link between achieving sustained ASDAS inactive disease and structural lesion change on MRI could not be clearly established. Show less
Sepriano, A.; Ramiro, S.; Wichuk, S.; Chiowchanwisawakit, P.; Paschke, J.; Heijde, D. van der; ... ; Maksymowych, W.P. 2021
