Objective. To assess the association between self-reported and performance-based physical functioning and to evaluate which performance tests are most frequently impaired in patients with axial... Show moreObjective. To assess the association between self-reported and performance-based physical functioning and to evaluate which performance tests are most frequently impaired in patients with axial spondyloarthritis (axSpA).Methods. Consecutive patients with axSpA underwent standardized assessments including patient and disease characteristics; patient-reported outcomes for disease activity, functioning, depression, mobility, and physical activity; and performance tests. Patients were defined as being impaired if they were not able to perform >= 1 of the performance tests. Validated cut-offs were used to define impaired physical performance. Impairment of performance tests as well as discrimination between subgroups were analyzed.Results. A total of 200 patients (radiographic axSpA 66.5%, nonradiographic axSpA 33.5%) were included: 69% males, mean age 44.3 (SD 12.5) years, and mean symptom duration 17.9 (SD 12.6) years. The 2 most frequently impaired performance tests were the repeated chair stand test (n = 75, 37.5%) and putting on socks (n = 44, 22%). An impairment in >= 1 performance test was seen in 91 patients (45.5%). Patients with impairments were older (49.1 yrs vs 40.3 yrs); had a higher BMI (28.9 kg/m2 vs 25.8 kg/m2); a more active disease (Ankylosing Spondylitis Disease Activity Score, 3.0 vs 2.1); higher Bath Ankylosing Spondylitis Functional Index (BASFI; 5.8 vs 2.7), Bath Ankylosing Spondylitis Metrology Index (BASMI; 4.4 vs 2.7), and Assessment of Spondyloarthritis international Society Health Index scores (9.5 vs 4.9); and higher depression screen values (9-item Patient Health Questionnaire, 11.6 vs 6.5; all P < 0.01).Conclusion. Many patients with axSpA had impairments in physical performance tests. Importantly, this was frequently seen in tasks requiring coordination and muscle power of the lower extremity. Performance tests provide qualitatively different information than BASFI and BASMI assessments in patients with axSpA. Show less
To detail the unmet clinical and scientific needs in the field of rheumatology. After a 2-year hiatus due to the SARS-CoV-2 pandemic, the 22nd annual international Advances in Targeted Therapies... Show moreTo detail the unmet clinical and scientific needs in the field of rheumatology. After a 2-year hiatus due to the SARS-CoV-2 pandemic, the 22nd annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. Breakout sessions were convened with experts in five rheumatological disease-specific groups including: rheumatoid arthritis (RA), psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and connective tissue diseases (CTDs). In each group, experts were asked to identify and prioritise current unmet needs in clinical and translational research, as well as highlight recent progress in meeting formerly identified unmet needs. Clinical trial design innovation was emphasised across all disease states. Within RA, developing therapies and trials for refractory disease patients remained among the most important identified unmet needs and within lupus and spondyloarthritis the need to account for disease endotypes was highlighted. The RA group also identified the need to better understand the natural history of RA, pre-RA states and the need ultimately for precision medicine. In CTD generally, experts focused on the need to better identify molecular, cellular and clinical signals of early and undifferentiated disease in order to identify novel drug targets. There remains a strong need to develop therapies and therapeutic strategies for those with treatment-refractory disease. Increasingly it is clear that we need to better understand the natural history of these diseases, including their 'predisease' states, and identify molecular signatures, including at a tissue level, which can facilitate disease diagnosis and treatment. As these unmet needs in the field of rheumatic diseases have been identified based on consensus of expert clinicians and scientists in the field, this document may serve individual researchers, institutions and industry to help prioritise their scientific activities. 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
Heijde, D. van der; Ostergaard, M.; Reveille, J.D.; Baraliakos, X.; Kronbergs, A.; Sandoval, D.M.; ... ; Maksymowych, W.P. 2022
Objective. To evaluate the long-term effect of ixekizumab (IXE) on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from... Show moreObjective. To evaluate the long-term effect of ixekizumab (IXE) on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), and to identify potential predictors of progression. Methods. This study evaluates patients from COAST-V (ClinicalTrials.gov: NCT02696785, biologic disease-modifying antirheumatic drug-naive) and COAST-W (NCT02696798, tumor necrosis factor inhibitor-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with IXE (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. Results. Among patients with evaluable radiographs who were originally assigned to IXE (n = 230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of nonprogressors over 2 years was 89.6% if defined as mSASSS change from baseline < 2 and 75.7% if defined as mSASSS change from baseline <= 0. Predictors of structural progression at year 2 (mSASSS change > 0) were age >= 40, baseline syndesmophytes, HLA-B27 positivity, and male sex. Week 52 inflammation in Spondyloarthritis Research Consortium of Canada spine was also a predictor of radiographic progression at year 2 in patients with magnetic resonance imaging data in COAST-V (n = 109). Conclusion. The majority of patients with r-axSpA receiving IXE had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies. 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
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
Kiltz, U.; Wei, J.C.C.; Heijde, D. van der; Bosch, F. van den; Walsh, J.A.; Boonen, A.; ... ; Braun, J. 2021
Objective. This study evaluated the effect of ixekizumab (IXE) on self-reported functioning and health in patients with radiographic axial spondyloarthritis (r-axSpA) who were either biological... Show moreObjective. This study evaluated the effect of ixekizumab (IXE) on self-reported functioning and health in patients with radiographic axial spondyloarthritis (r-axSpA) who were either biological disease-modifying antirheumatic drug (bDMARD)-naive or failed at least 1 tumor necrosis factor inhibitor (TNFi).Methods. In 2 multicenter, randomized, double-blind, placebo-controlled, and active-controlled (bDMARD-naive only) trials, patients with r-axSpA were randomly assigned to receive 80 mg of IXE [every 2 weeks (Q2W) or every 4 weeks (Q4W)], placebo (PBO), or adalimumab (ADA; bDMARD-naive only). After 16 weeks, patients who received PBO or ADA were rerandomized to receive IXE (Q2W or Q4W) up to Week 52. Functioning and health were measured by the generic 36-item Short Form Health Survey (SF-36) and the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI). Societal health utility was assessed by the 5-level EuroQol-5 Dimension (EQ-5D-5L).Results. At Week 16, both doses of IXE in bDMARD-naive and TNFi-experienced patients resulted in larger improvement in SF-36, ASAS HI, and EQ-5D-5L versus placcbo. For SF-36, the largest improvements were seen for the domains of bodily pain, physical function, and role physical. A larger proportion of patients reaching improvement in ASAS HI >= 3 as well as an achievement of ASAS HI good health status was reported in patients treated with IXE. Improvements were maintained through Week 52.Conclusion. IXE significantly improved functioning and health as assessed by both generic and disease-specific measures, as well as societal health utility values in patients with r-axSpA, as measured by SF-36, ASAS HI, and EQ-5D-5L at Week 16, and improvements were sustained through 52 weeks. Show less
Stal, R.; Gaalen, F. van; Sepriano, A.; Braun, J.; Reijnierse, M.; Berg, R. van den; ... ; Baraliakos, X. 2020
Objectives. To evaluate the occurrence and progression of facet joint ankylosis in the whole spine using low-dose CT (IdCT) in radiographic axial spondyloarthritis (r-axSpA) and compare progression... Show moreObjectives. To evaluate the occurrence and progression of facet joint ankylosis in the whole spine using low-dose CT (IdCT) in radiographic axial spondyloarthritis (r-axSpA) and compare progression of facet joint ankylosis and syndesmophytes.Methods. Patients with r-axSpA from the Sensitive Imaging in Ankylosing Spondylitis (SIAS) cohort underwent IdCT at baseline (n = 6 0) and 2 years (n = 53) . Facet joints (right and left, levels C2-S1) were scored as ankylosed, not ankylosed or unable to assess. Joints that were frequently poorly visible (>15% missing), were excluded. Interreader reliability on the patient level was assessed with intraclass correlation coefficients (ICCs) and smallest detectable change (SDC). Ankylosis was assessed at joint level and patient level for both timepoints. Syndesmophytes were assessed with CT syndesmophyte score.Results. Levels C5-T2 were difficult to assess and excluded from all further analyses. Facet joint ICCs were good to excellent for status scores (0.72-0.93) and poor to excellent for progression scores (0.10-0.91). Facet joint ankylosis was detected at every level but most frequently in the thoracic joints. In total, 48% of patients showed 2-year progression. Most progression occurred in the thoracic segment. Using SDCs as cutoff, 18% of patients had progression of facet joint ankylosis only, whereas 20% of patients had progression of syndesmophytes only.Conclusion. This is the first study evaluating facet joints in the whole spine by IdCT in r-axSpA. Facet joint ankylosis was detected most often in the thoracic spine. Assessing facet joints in addition to syndesmophytes detected substantially more patients with damage progression over two years. Show less
Bentum, R.E. van; Vodnizza, S.E.I.; Fuente, M.P.P. de la; Aldridge, F.V.; Navarro-Compan, V.; Rusman, T.R.; ... ; Horst-Bruinsma, I.E. van der 2020
Objective. Physical function in patients with axial spondyloarthritis (axSpA) is currently evaluated through questionnaires. The Ankylosing Spondylitis Performance Index (ASPI) is a performance... Show moreObjective. Physical function in patients with axial spondyloarthritis (axSpA) is currently evaluated through questionnaires. The Ankylosing Spondylitis Performance Index (ASPI) is a performance-based measure for physical functioning, which has been validated in Dutch patients with radiographic (r-) axSpA. The interrater reliability has not yet been determined. To our knowledge, this study is the first to evaluate the validity, reliability, and feasibility of the ASPI in another patient population, including both r- and nonradiographic (nr-) axSpA patients.Methods. Patients with axSpA were recruited from rheumatology clinics in Santiago, Chile. Dutch instructions were translated to Spanish by a forward-backward procedure. Study visits were performed at baseline and 1-4 weeks later. Four ASPI observers were involved, measuring the performance times of the 3 ASPI tests. Validity was assessed through a patient questionnaire (numeric rating scale 0-10: >= 6 sufficient). For reliability, intraclass correlation coefficients (ICC) were calculated (with 95% CI). Correlations between the ASPI and disease variables were tested with regression analyses.Results. Sixty-eight patients were included (57% male, 52% r-axSpA). All patients understood the Spanish instructions and considered the ASPI to reach its aim (84%) and representativeness (85%) for physical functioning. The overall interrater (n = 62) and test-retest (n = 39) reliability (ICC) of the 3 tests combined were 0.93 (0.88-0.96) and 0.94 (0.87-0.97), respectively. Eighty-two percent of the patients completed all tests and 94% finished in < 15 min (feasibility).Conclusion. This study demonstrated a high validity and feasibility in an entirely different population, with both r-axSpA and nr- axSpA. The interrater and test-retest reliability was excellent. The ASPI instructions are now available for Spanish-speaking patients. Show less
Alegria, G.C.; Voirin-Hertz, M.; Garrigues, F.; Herbette, M.; Deloire, L.; Simon, A.; ... ; Saraux, A. 2020
Objective. Lumbosacral transitional vertebras (LSTVs) are common in the general population, but their potential impact on the sacroiliac joints is unclear. We aimed to determine the prevalence of... Show moreObjective. Lumbosacral transitional vertebras (LSTVs) are common in the general population, but their potential impact on the sacroiliac joints is unclear. We aimed to determine the prevalence of LSTVs and to assess their associations with sacroiliitis by standard radiography and MRI in a population with suspected axial spondyloarthritis.Methods. The data were from the DESIR cohort of 688 patients aged 18-50 years with inflammatory low back pain for 3 months but <3 years suggesting axial spondyloarthritis. The baseline pelvic radiographs were read by two blinded readers for the presence and type (Castellvi classification) of LSTVs. Associations between LSTVs and other variables collected at baseline and at the diagnosis were assessed using the chi(2) test (or Fisher's exact test) or the Mann-Whitney test.Results. LSTV was found in 200/688 (29.1%) patients. Castellvi type was Ia in 54 (7.8%), Ib in 76 (11.0%), IIa in 20 (2.9%), IIb in 12 (1.7%), IIIa in 7 (1.0%), IIIb in 21 (3.0%) and IV in 10 (1.4%) patients. Compared with the group without LSTVs, the group with LSTVs had higher proportions of patients meeting modified New York criteria for radiographic sacroiliitis (19% vs 27%, respectively; P = 0.013) and Assessment of SpondyloArthritis international Society MRI criteria for sacroiliitis (29% vs 39%, respectively; P = 0.019).Conclusion. In patients with inflammatory back pain suggesting axial spondyloarthritis, LSTVs are associated with both radiographic and MRI sacroiliitis. Show less
Alegria, G.C.; Deloire, L.; Herbette, M.; Garrigues, F.; Gossec, L.; Simon, A.; ... ; Saraux, A. 2020
Objective. To assess associations of spinal-pelvic orientation with clinical and imaging-study findings suggesting axial SpA (axSpA) in patients with recent-onset inflammatory back pain.Methods.... Show moreObjective. To assess associations of spinal-pelvic orientation with clinical and imaging-study findings suggesting axial SpA (axSpA) in patients with recent-onset inflammatory back pain.Methods. Spinal-pelvic orientation was assessed in DESIR cohort patients with recent-onset inflammatory back pain and suspected axSpA, by using lateral lumbar-spine radiographs to categorize sacral horizontal angle (<40 degrees vs >= 40 degrees), lumbosacral angle (<15 degrees vs >= 15 degrees) and lumbar lordosis (LL, <50 degrees vs >= 50 degrees). Associations between these angle groups and variables collected at baseline and 2 years later were assessed using the chi(2) test (or Fisher's exact) and the Mann-Whitney test. With Bonferroni's correction, P < 0.001 indicated significant differences.Results. Of 362 patients, 358, 356 and 357 had available sacral horizontal angle, lumbosacral angle and LL values, respectively; means were 39.3 degrees, 14.6 degrees and 53.0 degrees, respectively. The prevalence of sacroiliitis on both radiographs and MRI was higher in the LL < 50 degrees group than in the LL >= 50 degrees group, but the difference was not statistically significant. Clinical presentation and confidence in a diagnosis of axSpA did not differ across angle groups. No significant differences were identified for degenerative changes according to sacral horizontal angle, lumbosacral angle or LL.Conclusion. Spinal-pelvic balance was not statistically associated with the clinical or imaging-study findings suggesting axSpA in patients with recent-onset inflammatory back pain. Show less
Heijde, D. van der; Braun, J.; Deodhar, A.; Baraliakos, X.; Landewe, R.; Richards, H.B.; ... ; Readie, A. 2019
Objectives. Physiotherapy is recommended in the management of people with axial spondyloarthritis (axSpA), with new insights into its preferred content and dosage evolving. The aim of this study... Show moreObjectives. Physiotherapy is recommended in the management of people with axial spondyloarthritis (axSpA), with new insights into its preferred content and dosage evolving. The aim of this study was to describe the use and preferences regarding individual and group physiotherapy among people with axSpA.Methods. A cross-sectional survey was conducted among people with axSpA living in The Netherlands (NL) and Switzerland (CH).Results. Seven hundred and thirteen people with axSpA participated (56.7% male, median age 55 years, median Assessment of Spondyloarthritis International Society Health Index score 4.2). Response rates were 45% (n = 206) in NL and 29% in CH (n = 507). Of these participants, 83.3% were using or had been using physiotherapy. Individual therapy only was used or had been used by 36.7%, a combination of individual plus land- and water-based group therapy by 29.1% and group therapy by only 5.3%. Fewer than half of the participants attending individual therapy reported active therapy (such as aerobic, muscle strength and flexibility exercises). Although the majority (75.9%) were not aware of the increased cardiovascular risk, participants showed an interest in cardiovascular training, either individually or in a supervised setting. If supervised, a majority, in CH (75.0%) more than in NL (55.7%), preferred supervision by a specialized physiotherapist.Conclusion. The majority of people with axSpA use or have used physiotherapy, more often in an individual setting than in a group setting. The content of individual therapy should be more active; in both therapy settings, aerobic exercises should be promoted. In particular, enabling people with axSpA to perform exercises independently would meet their needs and might enhance their daily physical activity. Show less
Maksymowych, W.P.; Heijde, D. van der; Baraliakos, X.; Deodhar, A.; Sherlock, S.P.; Li, D.; ... ; Kanik, K.S. 2018
