Objective To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA). Methods COAST-X was a randomized,... Show moreObjective To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA). Methods COAST-X was a randomized, controlled trial conducted in patients with nonradiographic axial SpA over 52 weeks. Participants were randomized at a ratio of 1:1:1 to receive 80 mg of ixekizumab subcutaneously every 4 weeks or 2 weeks or placebo for 52 weeks. Self-reported functioning and health end points included the Medical Outcomes Study Short Form 36 (SF-36) health survey, Assessment of Spondyloarthritis International Society (ASAS) health index, and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility descriptive system. Results Compared to placebo, ixekizumab treatment resulted in improvement of SF-36 physical component summary scores from baseline, with a score of 4.7 improving to 8.9 with ixekizumab therapy every 4 weeks (P < 0.05) and a score of 9.3 with ixekizumab therapy every 2 weeks (P < 0.01); the greatest improvements were observed in the domains of physical functioning, role-physical, and bodily pain at weeks 16 and 52. A higher proportion of patients receiving ixekizumab therapy every 2 weeks reported >= 3 improvements based on the ASAS health index from baseline to weeks 16 and 52 (P < 0.05). Significantly more patients receiving ixekizumab every 4 weeks reported improvements in "good health status" on the ASAS health index (ASAS score of <= 5) at weeks 16 and 52 (P < 0.05). Patients receiving ixekizumab reported improvements on the EQ-5D-5L compared to those who received placebo at week 16 (0.11 versus 0.17 for patients receiving treatment every 4 weeks and 0.19 for patients receiving treatment every 2 weeks; P < 0.05), which remained consistent at week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen for patients who received ixekizumab therapy every 2 weeks or every 4 weeks. Conclusion In patients with nonradiographic axial SpA, therapy with ixekizumab was superior to placebo in the improvement of self-reported functioning and health at weeks 16 and 52. Show less
Hirano, F.; Landewe, R.B.M.; Gaalen, F.A. van; Heijde, D. van der; Gaujoux-Viala, C.; Ramiro, S. 2022
Objective To investigate determinants of the physician global assessment (PhGA) of disease activity and the influence of the contextual factors on this relationship in patients with early axial... Show moreObjective To investigate determinants of the physician global assessment (PhGA) of disease activity and the influence of the contextual factors on this relationship in patients with early axial spondyloarthritis (SpA). Methods Five-year data of DESIR, a cohort of early axial SpA, were analyzed. Univariable generalized estimating equations (GEEs) were used to investigate contributory explanatory effects of various potential determinants of PhGA. Effect modification by contextual factors (age, sex, and educational level) was tested, and if significant, models were stratified. Autoregressive GEE models (i.e., models adjusted for PhGA at the previous time point) were used to confirm a longitudinal relationship. Results A total of 708 patients were included. Higher Bath Ankylosing Spondylitis Disease Activity Index individual questions, swollen joint count in 28 joints (SJC28), tender joint count in 53 joints, Maastricht Ankylosing Spondylitis Enthesitis Score, C-reactive protein (CRP) level, and Bath Ankylosing Spondylitis Metrology Index score were associated with a higher PhGA. Sex and age were effect modifiers of SJC28; the contributory effect of SJC28 was largest in the younger male stratum (beta = 1.07 [95% confidence interval (95% CI) 0.71, 1.43]), and the smallest in the older female stratum (beta = 0.13 [95% CI 0.04, 0.22]). Autoregressive GEE models revealed the same determinants as having a longitudinal association with PhGA and the same pattern of effect modification. Conclusion Patients' subjective symptoms, peripheral arthritis and enthesitis, higher CRP level, and impaired spinal mobility contribute to explaining PhGA in patients with early axial SpA, irrespective of sex and age. Intriguingly, physicians consider the presence of swollen joints as more important in males than in females. Show less
Ciaffi, J.; Leeuwen, N.M. van; Boonstra, M.; Kroft, L.J.M.; Schouffoer, A.A.; Ninaber, M.K.; ... ; Vries-Bouwstra, J.K. de 2022
Objective Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc-ILD). The... Show moreObjective Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc-ILD). The aims of our retrospective observational study were to evaluate: 1) the evolution of SSc-ILD in SSc patients treated with HSCT (assessed by high-resolution computed tomography [HRCT]; a group of patients treated with CYC was included as frame of reference); 2) how results of pulmonary function tests (PFTs) are associated with HRCT findings; and 3) which factors predict ILD reduction. Methods We semiquantitatively scored total ILD extent, reticulations, and ground-glass opacities (GGO) scores at baseline and at the 1-year HRCTs of SSc patients treated with HSCT or CYC. Linear association between changes in HRCT scores and PFT results and predictors of ILD improvement were studied. Results We included 51 patients (those treated with HSCT [n = 20] and those treated with CYC [n = 31]). The mean change in total ILD score was -5.1% (95% confidence interval [95% CI] -10.2, 0.0) in the HSCT treatment group (P = 0.050), and -1.0% (95% CI -4.3, 2.3) in the CYC treatment group (P = 0.535). For all patients, the evolution of HRCT scores was weakly associated with relative changes in PFT results. In univariate logistic regression, higher ground-glass opacities, higher total ILD, and lower single-breath diffusing capacity for carbon monoxide scores at baseline predicted improvement of ILD extent after treatment, but a multivariable model could not be built to assess independency of predictors. Conclusion One year after treatment with HSCT, a nonsignificant but clear reduction of SSc-ILD extent was observed. Changes in PFT results were associated with changes in HRCT scores but the correlation was weak and cannot be considered conclusive. 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
Dakkak, Y.J.; Wouters, F.; Matthijssen, X.M.E.; Reijnierse, M.; Helm-van Mil, A.H.M. van der 2022
Objective The relationship between functional disability and magnetic resonance imaging (MRI) inflammation has been studied for the hands, but has not been well established for the feet, even... Show moreObjective The relationship between functional disability and magnetic resonance imaging (MRI) inflammation has been studied for the hands, but has not been well established for the feet, even though walking difficulties are common. Therefore, our objective was to study whether walking difficulties were associated with MRI inflammation at metatarsophalangeal (MTP) joints in early arthritis patients, at diagnosis and during 24 months of follow-up. Methods A total of 532 consecutive patients presenting with early arthritis reported on the presence and severity of walking difficulties (Health Assessment Questionnaire question 4a, scale 0-3), and underwent unilateral contrast-enhanced MRI of MTP joints 1-5 at baseline. In total, 107 patients had clinical and MRI data at follow-up (4, 12, and 24 months). MRI inflammation (synovitis, tenosynovitis, and osteitis) was scored in line with the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. At baseline, the association of walking disability with MRI inflammation was assessed using regression. Longitudinally, the association between a change in walking disability with a change in MRI inflammation was studied with linear mixed models. Results At baseline, 81% of patients with walking disabilities had MRI inflammation at MTP joints, versus 68% without walking disabilities (P < 0.001). Total MRI inflammation (i.e., the sum of tenosynovitis, synovitis, and osteitis) was associated with severity of walking disability (beta = 0.023, P < 0.001). Studying the MRI features separately, tenosynovitis, synovitis, and osteitis were all univariably associated with severity of walking disability (P < 0.001, P < 0.001, and P = 0.014, respectively). In multivariable analysis, the association was strongest for tenosynovitis. During follow-up, a decrease in MTP inflammation was associated with a decrease in walking disability (beta = 0.029, P = 0.001); in multivariable analyses only, tenosynovitis was independently associated (beta = 0.073, P = 0.049). Conclusion Of the different inflamed tissues in MTP joints, predominantly MRI-detected tenosynovitis was associated with walking disabilities. Likewise a reduction in tenosynovitis related to a decrease in walking disabilities. These results increase our understanding of the involvement of tenosynovitis in walking disabilities in early arthritis. 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
Beest, S. van; Kroon, H.M.; Reijnierse, M.; Rosendaal, F.R.; Kloppenburg, M.; Kroon, F.P.B. 2021
Objective To investigate the two-year course of pain and osteoarthritic features on magnetic resonance imaging (MRI) in the thumb base. Methods Patients in the Hand Osteoarthritis in Secondary Care... Show moreObjective To investigate the two-year course of pain and osteoarthritic features on magnetic resonance imaging (MRI) in the thumb base. Methods Patients in the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort who had received radiographic examination, MRI, and clinical examination of the right thumb base at baseline and who had a 2-year follow-up period were studied. Pain on palpation of the thumb base was assessed on a 0-3 scale. MRIs were analyzed with the Outcome Measures in Rheumatology (OMERACT) thumb base osteoarthritis MRI scoring system for synovitis, bone marrow lesions (BMLs), subchondral bone defects, cartilage space loss, osteophytes, and subluxation. Radiographs were assessed for osteophytes and joint space narrowing. We studied the associations of changes in synovitis and BMLs with changes in pain using a logistic regression model adjusted for radiographic damage, with values expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Of 165 patients, 83% were women and the mean age was 60.7 years. At baseline, 65 patients had thumb base pain. At 2-year follow-up, pain had decreased in 32 patients and increased in 33 patients. MRI features remained stable in most patients. Structural MRI features generally deteriorated, while synovitis and BMLs improved in some individuals and deteriorated in others. Change in radiographic osteophytes rarely occurred (n = 10). Increased synovitis (odds ratio [OR] 3.4 [95% CI 1.3-9.3]) and increased BMLs (OR 5.1 [95% CI 2.1-12.6]) were associated with increased pain. Decreased BMLs appeared to be associated with decreased pain (OR 2.7 [95% CI 0.8-8.9]), and reductions in synovitis occurred too infrequently to calculate associations. Conclusion Over 2 years, thumb base pain fluctuated, while MRI features changed in a minority of patients with hand osteoarthritis. Changes in synovitis and BMLs were associated with changes in pain on palpation, even after adjustment for radiographic damage. Show less
Objective Microangiopathy and dysregulation of the immune system play important roles in the pathogenesis of systemic sclerosis (SSc). Factors that trigger vascular injury in SSc have not been... Show moreObjective Microangiopathy and dysregulation of the immune system play important roles in the pathogenesis of systemic sclerosis (SSc). Factors that trigger vascular injury in SSc have not been elucidated so far. We undertook this study to evaluate whether sex or expression of specific antinuclear autoantibodies might associate with the degree of microangiopathy through performance of a systematic review that summarizes what is known about these associations.Methods A standardized search of PubMed, Embase, Web of Science, and the Cochrane Library were performed to identify studies that described autoantibodies in SSc patients and microangiopathy and, for the second search, those that described sex and microangiopathy.Results We included 11 studies that described the relationship between SSc-specific autoantibodies and microangiopathy and 6 studies that reported on the association between sex and microangiopathy. Contradictory results were found on the association between SSc-specific autoantibodies and microangiopathy, and no association was found between sex and microangiopathy based on the current literature.Conclusion Based on this review of the literature, we can conclude that sex does not seem to influence degree of microangiopathy in SSc, while results on association between SSc-specific autoantibodies and degree of microangiopathy were inconclusive. Show less
Bakker, M.M.; Putrik, P.; Rademakers, J.; Laar, M. van de; Vonkeman, H.; Kok, M.R.; ... ; Boonen, A. 2021
Objective To identify and describe health literacy profiles of patients with rheumatic diseases and explore whether the identified health literacy profiles can be generalized to a broader... Show moreObjective To identify and describe health literacy profiles of patients with rheumatic diseases and explore whether the identified health literacy profiles can be generalized to a broader rheumatology context.Methods Patients with rheumatoid arthritis, spondyloarthritis, and gout from 3 hospitals in different regions in The Netherlands completed the Health Literacy Questionnaire (HLQ). Hierarchical cluster analysis was used to identify patients' health literacy profiles based on 9 HLQ domains. A multinomial regression model with the identified health literacy profiles as the dependent variable was fitted to assess whether patients with a given disease type or attending a given hospital were more likely to belong to a specific profile.Results Among 895 participating patients, the lowest mean HLQ domain scores (indicating most difficulty) were found for "critical appraisal," "navigating the health system," and "finding good health information." The 10 identified profiles revealed substantial diversity in combinations of strengths and weaknesses. While 42% of patients scored moderate to high on all 9 domains (profiles 1 and 3), another 42% of patients (profiles 2, 4, 5, and 6) clearly struggled with 1 or several aspects of health literacy. Notably, 16% (profiles 7-10) exhibited difficulty across a majority of health literacy domains. The probability of belonging to one of the profiles was independent of the hospital where the patient was treated or the type of rheumatic disease.Conclusion Ten distinct health literacy profiles were identified among patients with rheumatic diseases, independent of disease type and treating hospital. These profiles can be used to facilitate the development of health literacy interventions in rheumatology. Show less
Siviero, P.; Limongi, F.; Gesmundo, A.; Zambon, S.; Cooper, C.; Dennison, E.M.; ... ; European Project Osteoarthrit Res 2021
Objective To assess the psychometric properties of 8 pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) item banks in a clinical sample of children with juvenile idiopathic... Show moreObjective To assess the psychometric properties of 8 pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) item banks in a clinical sample of children with juvenile idiopathic arthritis (JIA).Methods A total of 154 Dutch children (mean +/- SD age 14.4 +/- 3.0 years; range 8-18 years) with JIA completed 8 pediatric version 1.0 PROMIS item banks (anger, anxiety, depressive symptoms, fatigue, pain interference, peer relationships, physical function mobility, physical function upper extremity) twice and the Pediatric Quality of Life Inventory (PedsQL) and the Childhood Health Assessment Questionnaire (C-HAQ) once. Structural validity of the item banks was assessed by fitting a graded response model (GRM) and inspecting GRM fit (comparative fit index [CFI], Tucker-Lewis index [TLI], and root mean square error of approximation [RMSEA]) and item fit (S-X-2 statistic). Convergent validity (with PedsQL/C-HAQ subdomains) and discriminative validity (active/inactive disease) were assessed. Reliability of the item banks, short forms, and computerized adaptive testing (CAT) was expressed as the SE of theta (SE[theta]). Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) and smallest detectable change.Results All item banks had sufficient overall GRM fit (CFI >0.95, TLI >0.95, RMSEA <0.08) and no item misfit (all S-X-2 P > 0.001). High correlations (>0.70) were found between most PROMIS T scores and hypothesized PedsQL/C-HAQ (sub)domains. Mobility, pain interference, and upper extremity item banks were able to discriminate between patients with active and inactive disease. Regarding reliability, PROMIS item banks outperformed legacy instruments. Post hoc CAT simulations outperformed short forms. Test-retest reliability was strong (ICC >0.70) for all full-length item banks and short forms, except for the peer relationships item bank.Conclusion The pediatric PROMIS item banks displayed sufficient psychometric properties for Dutch children with JIA. PROMIS item banks are ready for use in clinical research and practice for children with JIA. Show less
Stadt, L.A. van de; Kroon, F.P.B.; Kloppenburg, M. 2020
Objective Supervised group exercise (SGE) has been proven effective in patients with axial spondyloarthritis (SpA), but its contents and dosage do not always comply with current scientific insight.... Show moreObjective Supervised group exercise (SGE) has been proven effective in patients with axial spondyloarthritis (SpA), but its contents and dosage do not always comply with current scientific insight. This aim of this study was to describe axial SpA patients' satisfaction with currentSGEand perspective on potential evidence-basedSGEenhancements. Methods Patients with axial SpA who participated inSGEin 4 regions in The Netherlands (n = 118) completed a cross-sectional survey on their satisfaction with features of their currentSGE(8 questions scored on a 3-point Likert scale; 1 overall grade, scored according to an 11-point scale) and their perspective on the introduction of appropriately dosed cardiorespiratory and strengthening exercise, monitoring of exercise intensity, periodic reassessments, patient education, and supervision by physical therapists with specific expertise (4 dichotomous questions and one 5-point Likert scale). Results Most patients were satisfied with the current total intensity (84 of 112 patients [75%]), duration (93 of 111 patients [84%]), and load (89 of 117 patients [76%]) of the program and the proportion of mobility (102 of 114 patients [90%]), strengthening (90 of 115 patients [78%]), and cardiorespiratory exercise (82 of 114 patients [72%]). The median overall grade of the program was a 7 (interquartile range 7-8). Most patients agreed with the implementation of more frequent (home) exercise (73 of 117 patients [62%]), heart-rate monitoring (97 of 117 patients [83%]), and annual reassessments (97 of 118 patients [82%]), whereas 50% agreed with the introduction of patient education (37 of 74 patients). The majority found supervision by therapists specializing in axial SpA to be of high importance (105 of 118 patients [89%]). Conclusion The majority ofSGEparticipants with axial SpA were satisfied with currentSGEbut also agreed with enhancements in line with scientific evidence. Current satisfaction levels indicate that a planned implementation strategy, including education and addressing potential barriers and facilitators for the uptake of enhancements, is warranted. Show less
Nordal, E.; Pistorio, A.; Rygg, M.; Giancane, G.; Maghnie, M.; Iorgi, N. di; ... ; Paediat Rheumatology Int Trials 2020
Objective To study growth and puberty in a multinational longitudinal prospective cohort of children with juvenile dermatomyositis (DM). Methods Children from 31 countries who were ages DM in... Show moreObjective To study growth and puberty in a multinational longitudinal prospective cohort of children with juvenile dermatomyositis (DM). Methods Children from 31 countries who were ages DM in active phase were studied, and analyses of height, weight, and pubertal development were conducted in those who had follow-up visits during a 2-year period and for whom anthropometric data was available. Results A total of 196 of 275 children (71%) were included. We found a significant reduction in parent-adjusted height Z score over time in female patients (P < 0.0001) and male patients (P = 0.001), but with catch-up growth at the final study visit. Median body mass index Z score peaked at 6 months (P < 0.0001) and was still significantly above baseline at the final study visit, which was at a median of 26 months after baseline (P = 0.007), with no difference between sexes. Female patients with a disease duration >= 12 months after onset had significantly lower parent-adjusted height Z score (P = 0.002) and no 2-year catch-up growth. At the final study visit, growth failure was seen in 20 of 97 female patients (21%) and in 11 of 73 male patients (15%). Height deflection ( increment height Z score less than -0.25/year) was observed in 29 of 116 female patients (25%) and 25 of 80 male patients (31.3%). Delayed puberty was seen in 20 of 55 female patients (36.4%) and in 11 of 31 male patients (35.5%). Children in early pubertal stage at baseline had the highest risk of growth failure. Conclusion Juvenile DM in the active phase and/or its treatment has a significant impact on growth and puberty in affected children. Children with recent onset of puberty or previous growth failure have the highest risk of delayed pubertal development and further growth retardation. Show less
Ramiro, S.; Heijde, D. van der; Sepriano, A.; Lunteren, M. van; Molt?, A.; Feydy, A.; ... ; Claudepierre, P. 2019