ObjectiveTo demonstrate the value of diagnosing axSpA, by comparing health and costs associated with available diagnostic algorithms and perfect diagnosis.MethodsUsing data from SPACE and other... Show moreObjectiveTo demonstrate the value of diagnosing axSpA, by comparing health and costs associated with available diagnostic algorithms and perfect diagnosis.MethodsUsing data from SPACE and other cohorts, a model was developed to estimate health (quality-adjusted life-years, QALYs) and costs (healthcare consumption and work productivity losses) of different diagnostic algorithms for axSpA amongst patients with low back pain referred to a rheumatologist, over a 60-year horizon. The model combined a decision-tree (diagnosis) with a state-transition model (treatment). The three algorithms (Berlin [BER, highest specificity], Modification 1 [M1; less strict inflammatory back pain (IBP) criterion] and Modification 2 [M2; IBP not mandatory as entry criterion, highest sensitivity]) were compared. Changes in sensitivity/specificity were explored and the value of perfect diagnosis was investigated.ResultsFor each correctly diagnosed axSpA patient, up to 4.7 QALYs and €60,000 could be gained/saved, considering a societal perspective. Algorithm M2 resulted in more health and lower costs per patient (24.23 QALYs; €157,469), compared to BER (23.96 QALYs; €159,423) and M1 (24.15 QALYs; €158,417). Hypothetical improvements in M2 sensitivity resulted in slightly more value compared to improvements in specificity. Perfect diagnosis can cost €7,500 per patient and still provide enough value.ConclusionCorrect diagnosis of axSpA results in substantial health and cost benefits for patients and society. Not requiring IBP as mandatory for diagnosis of axSpA (algorithm M2) provides more value and would be preferable. A considerably more expensive diagnostic algorithm with better accuracy than M2 would still be considered good value for money. 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
A hallmark of disease pathogenesis of systemic sclerosis (SSc) is the presence of autoreactive B cell responses targeting nuclear proteins. Almost all SSc-patients harbour circulating antinuclear... Show moreA hallmark of disease pathogenesis of systemic sclerosis (SSc) is the presence of autoreactive B cell responses targeting nuclear proteins. Almost all SSc-patients harbour circulating antinuclear autoantibodies of which anti-topoisomerase 1, anti-centromere protein, anti-RNA polymerase III and anti-fibrillarin autoanti-bodies (ATA, ACA, ARA and AFA, respectively) are the most common and specific for SSc. In clinical practice, autoantibodies serve as diagnostic biomarkers and can aid in the identification of clinical phenotypes of the disease. However, factors driving disease progression in SSc are still poorly understood, and it is difficult to predict disease trajectories in individual patients. Moreover, treatment decisions remain rather empirical, with variable response rates in clinical trials due to patient heterogeneity. Current evidence has indicated that certain patients may benefit from B cell targeting therapies. Hence, it is important to understand the contribution of the antinuclear autoantibodies and their underlying B cell response to the disease pathogenesis of SSc. Show less
Marques, M.L.; Silva, N.P. da; Heijde, D. van der; Reijnierse, M.; Baraliakos, X.; Braun, J.; ... ; Ramiro, S. 2022
Objectives: To describe low dose Computed Tomography (ldCT) Hounsfield Units (HU) two-year change-from -baseline values (expressing trabecular bone density changes) and analyse their inter-reader... Show moreObjectives: To describe low dose Computed Tomography (ldCT) Hounsfield Units (HU) two-year change-from -baseline values (expressing trabecular bone density changes) and analyse their inter-reader reliability per vertebra in radiographic axial spondyloarthritis (r-axSpA). Methods: We used 49 patients with r-axSpA from the multicentre two-year Sensitive Imaging in Ankylosing Spondylitis (SIAS) study. LdCT HU were independently measured by two trained readers at baseline and two years. Mean (standard deviation, SD) for the change-from-baseline HU values were provided per vertebra by reader. Intraclass correlation coefficients (ICC; absolute agreement, two-way random effect), Bland-Altman plots and smallest detectable change (SDC) were obtained. Percentages of vertebrae in which readers agreed on the direction of change and on change >|SDC| were computed. Results: Overall, 1,053 (98% of all possible) vertebrae were assessed by each reader both at baseline and two years. Over two years, HU mean change values varied from-23 to 28 and 29 for reader 1 and 2, respectively. Inter-reader reliability of the two-year change-from-baseline values per vertebra was excellent: ICC:0.91-0.99; SDC:6-10; Bland-Altman plots were homoscedastic, with negligible systematic error between readers. Readers agreed on the direction of change in 88-96% and on change >|SDC| in 58-94% of vertebrae, per vertebral level, from C3 to L5. Overall, similar results were obtained across all vertebrae. Conclusion: LdCT measurement of HU is a reliable method to assess two-year changes in trabecular bone density at each vertebra from C3-L5. Being reliable across all vertebrae, this methodology can aid the study of trabecular bone density changes over time in r-axSpA, a disease affecting the whole spine. Show less
A hallmark of disease pathogenesis of systemic sclerosis (SSc) is the presence of autoreactive B cell responses targeting nuclear proteins. Almost all SSc-patients harbour circulating antinuclear... Show moreA hallmark of disease pathogenesis of systemic sclerosis (SSc) is the presence of autoreactive B cell responses targeting nuclear proteins. Almost all SSc-patients harbour circulating antinuclear autoantibodies of which anti-topoisomerase 1, anti-centromere protein, anti-RNA polymerase III and anti-fibrillarin autoantibodies (ATA, ACA, ARA and AFA, respectively) are the most common and specific for SSc. In clinical practice, autoantibodies serve as diagnostic biomarkers and can aid in the identification of clinical phenotypes of the disease. However, factors driving disease progression in SSc are still poorly understood, and it is difficult to predict disease trajectories in individual patients. Moreover, treatment decisions remain rather empirical, with variable response rates in clinical trials due to patient heterogeneity. Current evidence has indicated that certain patients may benefit from B cell targeting therapies. Hence, it is important to understand the contribution of the antinuclear autoantibodies and their underlying B cell response to the disease pathogenesis of SSc. Show less
Objectives: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). Methods: Patients... Show moreObjectives: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). Methods: Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cere-brovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. Results: A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival. Conclusion: The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates. Show less
ObjectivesTo analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE).MethodsPatients... Show moreObjectivesTo analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE).MethodsPatients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders.ResultsA total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29–2.67) and more specifically CVD (HR 2.17, 1.41–3.33) and organic brain syndrome (HR 2.11, 1.19–3.74) accounted as independent prognostic factors for poor survival.ConclusionThe presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates. 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
Wang, Q.K.; Runhaar, J.; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bierma-Zeinstra, S.M.A.; CREDO Expert Grp 2022
Objective: To internally and externally validate our diagnostic criteria of early stage knee osteoarthritis (OA) in the CHECK and OAI cohorts. Design: We applied two previously developed diagnostic... Show moreObjective: To internally and externally validate our diagnostic criteria of early stage knee osteoarthritis (OA) in the CHECK and OAI cohorts. Design: We applied two previously developed diagnostic models to all knees in CHECK and OAI cohorts to calculate probabilities of early stage knee OA at baseline. Knees were categorized into three groups based on probability: 'no OA' (probability <= 30%), 'uncertain' (probability between 30% and 70%) and 'early stage OA' (probability >= 70%). To validate the diagnosis, we obtained OA related outcome measures at 10-year follow-up in the CHECK cohort, and at 8-9-year follow-up in the OAI cohort. We compared outcome measures between 'no OA' and 'early stage OA' knees, and between 'no OA' and 'uncertain' knees using generalized estimating equations. Results: In CHECK (n = 1042 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher Kellgren & Lawrence (KL) grade, and higher rates of joint space narrowing (JSN) progression after 10 years, compared to 'no OA' knees. In OAI (n = 2937 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher KL grade, and higher rates of KL and JSN progression after 8-9 years, compared to 'no OA' knees. Smaller, but still significant differences between 'uncertain' and 'no OA' knees were observed in both cohorts. Conclusions: These results support internal and external validity of the two sets of diagnostic criteria for early stage knee OA. (C) 2022 The Author(s). Published by Elsevier Inc. Show less
Hilberdink, B.; Carbo, M.; Paap, D.; Arends, S.; Vlieland, T.V.; Giesen, F. van der; ... ; Weely, S. van 2022
Objective: Since decades, supervised group exercise (SGE) is recommended for people with axial spondyloarthritis (axSpA). This study examines if weekly SGE contributes to fulfillment of exercise... Show moreObjective: Since decades, supervised group exercise (SGE) is recommended for people with axial spondyloarthritis (axSpA). This study examines if weekly SGE contributes to fulfillment of exercise recommendations in axSpA patients. Methods: Cross-sectional data from three studies with axSpA patients in The Netherlands, including two with outpatient populations (n = 196 and n = 153) and one with SGE participants (n = 128), were analysed. Sociodemographic and disease characteristics, SGE participation, health status (ASAS Health Index), spinal mobility and fulfillment of the recommendations for leisure-time aerobic (>= 150 min/week moderate-intensity or >= 75 min/week vigorous-intensity) and strength and mobility (>= 2 sessions/week) exercise (measured with SQUASH-questionnaire) were assessed. Differences between patients with and without SGE were analysed. Results: In the two outpatient populations (n = 349), 17 patients (5%) used SGE. The SGE participants (n = 145) were significantly older, had longer disease duration, were less frequently employed, used less medication and had worse spinal mobility than patients without SGE (n = 332). There were no significant differences in health status. Patients with SGE fulfilled the moderate-intensity aerobic (89 % vs. 69%) and strength and mobility (44 % vs. 29%) exercise recommendations more often than patients without SGE, but the aerobic exercise recommendation was less often fulfilled with vigorous-intensity exercise (5 % vs. 12%). Conclusion: SGE is used by just few, especially older, axSpA patients and contributes to fulfilling recommendations for moderate-intensity, mobility and strength exercise. Both in patients with and without SGE, only a minority fulfilled the recommendations for vigorous-intensity, strength and mobility exercises. Therefore, future promotion of exercise should focus on implementing these types of exercise. Show less
Kroon, F.P.B.; Heijde, D. van der; Maxwell, L.J.; Beaton, D.E.; Abishek, A.; Berenbaum, F.; ... ; Kloppenburg, M. 2021
Objective: Physical function is one of the Outcome Measures in Rheumatology (OMERACT) core outcome domains for hand osteoarthritis studies. Our aim was to select appropriate instrument(s) to... Show moreObjective: Physical function is one of the Outcome Measures in Rheumatology (OMERACT) core outcome domains for hand osteoarthritis studies. Our aim was to select appropriate instrument(s) to measure this domain, as part of the development of a core outcome measurement set.Methods: Following the OMERACT Filter 2.1 instrument selection process, the (function subscale of) the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA) and Michigan Hand Outcomes Questionnaire (MHQ) were assessed for domain match, feasibility, truth and discrimination. Data gathered from available literature, working group and patient surveys, and additional analyses in two hand osteoarthritis cohorts were used to inform a consensus process.Results were summarized in Summary of Measurements Properties tables and reviewed by the OMERACT technical advisory group. Results: MHQ passed the assessment of domain match and feasibility by the working group and patient research partners. For AUSCAN important limitations in feasibility were noted, but domain match was good. FIHOA did not pass the assessment and was not taken through the follow-up assessment. Based on published literature, reliability and construct/longitudinal validity of both MHQ and AUSCAN fulfilled OMERACT standards. While clinical trial discrimination and thresholds of meaning were good for AUSCAN, results for MHQ were ambiguous.Conclusion: MHQ was provisionally endorsed as OMERACT core outcome measure for the core domain physical function. While AUSCAN may have better metric properties than MHQ, it received provisional endorsement as a second measure of function due to important feasibility issues. A research agenda to merit full endorsement was set. (c) 2021 The Author(s). Published by Elsevier Inc. Show less
Objectives: To compare reliabilities of assessing synovitis in hand osteoarthritis (OA) using Magnetic Resonance Imaging (MRI) with/without gadolinium (Gd). Methods: Three readers scored synovitis... Show moreObjectives: To compare reliabilities of assessing synovitis in hand osteoarthritis (OA) using Magnetic Resonance Imaging (MRI) with/without gadolinium (Gd). Methods: Three readers scored synovitis on non-enhanced two-dimensional (2D) proton density (PD)weighted MRI and Gd-enhanced (3D) MRI of hand joints in 20 patients. Inter-reader reliabilities were examined. Results: Reliability was good for Gd-enhanced MRI, but poor for non-enhanced PD-weighted MRI (intraclass correlation coefficient 0.83 and 0.21, respectively). Agreement between the two sequences was poor (weighted kappa 0.18). Conclusion: Gd-enhanced MRI was more reliable than PD-weighted MRI for assessing synovitis. Gd-enhancement, but also resolution and tissue contrast, might have contributed to this. (c) 2021 Elsevier Inc. All rights reserved. Show less
Zhao, S.S.; Nikiphorou, E.; Boonen, A.; Lopez-Medina, C.; Dougados, M.; Ramiro, S. 2021
Objective: To examine whether associations between socioeconomic factors and work outcomes in spondyloarthritis (SpA) differ across axial (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA... Show moreObjective: To examine whether associations between socioeconomic factors and work outcomes in spondyloarthritis (SpA) differ across axial (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), and whether associations for individual-level socioeconomic factors are modified by country-level factors. Methods: Patients with a physician diagnosis of SpA within working age (18-65 years) were included. Associations between individual-(age, gender, education, marital status) and country-level factors (Human Development Index, Health Care Expenditure (HCE), Gross Domestic Product, percentage unemployed) with work outcomes (employment status, absenteeism, presenteeism) were assessed using multivariable mixed-effects models. Associations between individual factors and outcomes were compared according to SpA phenotypes and country-level factors using interaction terms. Results: A total of 3835 patients (mean age 42 years, 61% males) from 23 countries worldwide were included (66% axSpA, 10% pSpA, 23% PsA). Being employed was associated with gender (male vs. female OR 2.5; 95%CI 1.9-3.2), education (university vs. primary OR 3.7; 2.9-4.7), marital status (married vs. single OR 1.3; 1.04-1.6), and age in a non-linear manner. University (vs primary) education was associated with lower odds of absenteeism (OR 0.7; 0.5-0.96) and presenteeism (OR 0.5; 0.3-0.7). Associations were similar across SpA phenotypes. Higher HCE was associated with more favourable work outcomes, e.g., higher odds of employment (OR 2.5; 1.5-4.1). Gender discrepancy in odds of employment was greater in countries with lower socioeconomic development. Conclusion: Higher educational attainment and higher HCE were associated with more favourable work outcomes, independently of SpA phenotype. The disadvantageous effect of female gender on employment is particularly strong in countries with lower socioeconomic development. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Show less
Capelusnik, D.; Ramiro, S.; Schneeberger, E.E.; Citera, G. 2021
Objetive: The aim of this study was to investigate whether peripheral arthritis together with disease activity independently contribute to functional impairment over time in patients with axSpA and... Show moreObjetive: The aim of this study was to investigate whether peripheral arthritis together with disease activity independently contribute to functional impairment over time in patients with axSpA and to evaluate if there are contextual factors modifying this relationship.Material and methods: Patients with axial spondyloarthritis from the ESPAXIA cohort were followed-up annually over a mean of 3.7 years. Physical function was assessed by the self-reported questionnaire BASFI, disease activity by ASDAS and peripheral arthritis was also recorded. Generalized estimating equations (GEE) were used to investigate longitudinal association between peripheral arthritis, ASDAS and BASFI as the outcome. Autoregressive models (adjusted for BASFI 1 year earlier) were run to allow for a truly longitudinal interpretation. Interactions between each of ASDAS and peripheral arthritis with contextual factors (age, gender, educational level, smoking, job type) were tested.Results: 185 patients (77 % male, mean (SD) age 42 (13) years old and mean disease duration (SD) of 9.4 (9.6) years) were included. ASDAS and peripheral arthritis independently contributed to explaning BASFI over time. Contextual factors did not modify either of the relationships. A true longitudinal relation was proven with the autoregressive GEE model, showing that, adjusted for age, gender, spinal mobility and use of NSAIDs, an increase of one ASDAS unit led to a BASFI 0.48 units higher (ss 0.48 [95%CI 0.39, 0.57]), and the presence of peripheral arthritis, to a BASFI 0.44 units higher (ss 0.44 [95%CI 0.08, 0.8]). Conclusion: Peripheral arthritis and higher disease activity independently lead to more functional impairment in axSpA over time. Contextual factors do not modify these relationships.(c) 2021 Elsevier Inc. All rights reserved. Show less
King, L.K.; Epstein, J.; Cross, M.; Buzzi, M.; Buttel, T.; Cembalo, S.M.; ... ; Guillemin, F. 2021
Objective: Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Out-come Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify... Show moreObjective: Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Out-come Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify and define relevant domains of flare in KHOA.Methods: Guided by OMERACT Filter 2.1, candidate domains were identified from data generated in inter-views, in English or French, with persons with KHOA and health professionals (HPs) who treat OA. The first and second rounds of an online Delphi process with patients and HPs, including researchers, selected rele-vant domains. The third round provided agreement on the selected domains and their definitions. At the vir-tual OMERACT 2020 workshop, the proposed domains and their definitions were discussed in facilitated breakout groups with patients and HPs. Participants then voted, with consensus set at >= 70%.Results: Qualitative interviews characterizing OA flare were completed with 29 persons with KHOA and 16 HPs. Content was analyzed and grouped into nine clusters. These candidate domains were included in two Delphi rounds, completed by 91 patients and 165 HPs then 50 patients and 116 HPs, per round, respectively. This resulted in selecting five relevant domains. A final Delphi round, completed by 38 patients and 89 HPs, provided agreement on these domains and their definitions. The OMERACT virtual vote included 27 patients and 106 HPs. The domains and their definitions were endorsed with >= 98% agreement. Domains include: Pain, Swelling, Stiffness, Psychological aspects, and Impact of symptoms, all defined "during flare".Conclusion: Using OMERACT methodology, we have developed five domains of KHOA flare that were highly endorsed by patients and HPs. (c) 2021 Elsevier Inc. All rights reserved. Show less
Toupin-April, K.; Decary, S.; Wit, M. de; Meara, A.; Barton, J.L.; Fraenkel, L.; ... ; Tugwell, P. 2021
Objective: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions.Methods: The process followed... Show moreObjective: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions.Methods: The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating whiteboard videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set.Results: A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1-Knowledge of options, their potential benefits and harms; 2-Chosen option aligned with each patient's values and preferences; 3-Confidence in the chosen option; 4-Satisfaction with the decision-making process; 5-Adherence to the chosen option and 6-Potential negative consequences of the SDM intervention.Conclusion: We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set.Clinical significance: Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers.(c) 2021 Elsevier Inc. All rights reserved. Show less
Sepriano, A.; Ramiro, S.; Heijde, D. van der; Dougados, M.; Claudepierre, P.; Feydy, A.; ... ; Landewe, R. 2020
Objective: To assess if an integrated longitudinal analysis using all available imaging data affects the precision of estimates of change in patients with axial spondyloarthritis (axSpA), with... Show moreObjective: To assess if an integrated longitudinal analysis using all available imaging data affects the precision of estimates of change in patients with axial spondyloarthritis (axSpA), with completers analysis as reference standard.Methods: Patients from the DESIR cohort fulfilling the ASAS axSpA criteria were included. Radiographs and MRIs of the sacroiliac joints and spine were obtained at baseline, 1, 2 and 5 years. Each image was scored by 2 or 3 readers in 3 'reading-waves' (or campaigns). Each outcome was analyzed: i. According to a 'combination algorithm' (e.g. '2 out of 30 for binary scores); and ii. Per reader. Change over time was analyzed with generalized estimating equations by 3 approaches: (a)'integrated-analysis' (all patients with >1 score from >1 reader from all waves); (b1)Completers-only analysis (patients with 5-year follow-up, using scores from individual readers); (b2)Completers analysis using a 'combination algorithm' (as (b1) but with combined scores). Approaches (b1) and (b2) were considered the 'reference'.Results: In total, 413 patients were included. The 'integrated analysis' was more inclusive with similar levels of precision of the change estimates as compared to both completers analyses. In fact, for low-incident outcomes (e.g.% mNY-positive over 5-years), an increased incidence was 'captured', with more precision, by the 'integrated analysis' compared to the completers analysis with combined scores (% change/year (95%CI): 1.1 (0.7; 1.5) vs 1.2 (0.5; 1.8), respectively).Conclusion: An efficient and entirely assumption-free 'integrated analysis' does not jeopardize precision of the estimates of change in imaging parameters and may yield increased statistical power for detecting changes with low incidence. (C) 2020 The Authors. Published by Elsevier Inc. Show less
Romao, V.C.; Humby, F.; Kelly, S.; Cicco, M. di; Mahto, A.; Lazarou, I.; ... ; Pitzalis, C. 2020
Background: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naive... Show moreBackground: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naive early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures.Methods: Patients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6months and radiographic progression (>= 1-unit-increase in Sharp van der Heijde [SvdH] score) at 12months.Results: EORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p<0.05) and power-Doppler (p<0.01) synovitis and SvdH (p<0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p<0.001), whereas EORA presented only mild decreases in synovitis (p<0.05), sublining macrophage (p<0.05) and T cell scores (p<0.05), with no significant changes in lining macrophages, B cells or plasma cells.Conclusion: Early EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes. (C) 2020 Elsevier Inc. All rights reserved. Show less
Mulligen, E. van; Weel, A.E.A.M.; Kuijper, T.M.; Hazes, J.M.W.; Helm-van Mil, A.H.M. van der; Jong, P.H.P. de 2020
Objectives: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment.Methods: Data were used from... Show moreObjectives: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment.Methods: Data were used from the TARA trial; a multicenter, randomized controlled trial in which RA patients, with a well-controlled disease (DAS <= 2.4 and SJC <= 1) for at least 6 months, gradually tapered their DMARDs. PROMs of patients with a flare (DAS>2.4 and/or SJC>1) were compared every three months before and after a flare with their own norm values. Linear Mixed Models were used to investigate whether a disease flare influenced functional ability (HAQ-DI), fatigue (BRAF-MDQ), quality of life (EQ-5D and SF36), anxiety and depression (HADS), morning stiffness, general health (GH) and worker productivity, and if so, the duration was determined. For unemployment and sick leave we used descriptive statistics.Results: A flare negatively influenced GH, morning stiffness, HAQ-DI, EQ-5D, BRAF-MDQ and the SF36 physical component scale and this effect lasted >3 months. Except for the HAQ-DI, effect sizes exceeded the minimum clinically important differences (MCIDs). For the physical outcomes effects lasted >6 months. Worker productivity was not significantly affected by a flare.Conclusion: A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients. (C) 2020 The Author(s). Published by Elsevier Inc. Show less
