Objectives: To a) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; b) determine whether those thresholds... Show moreObjectives: To a) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; b) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); c) evaluate the performance of traditional health-outcomes for r-axSpA; d) explore whether thresholds are stable across contextual factors. Methods: Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an 'unacceptable work state' were calculated at baseline for four instruments assessing presenteeism and two health-outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and for predicting future AWO over 12 months. Results: Of 366 working patients, 15% reported an unacceptable work state; 6% experienced at least one AWO in 12 months. Optimal thresholds were: WPAI-presenteeism >= 40 (AUC 0.85), QQ-method <97 (0.76), WALS >= 0.75 (AUC 0.87), WLQ-25 >= 29 (AUC 0.85). BASDAI and BASFI performed similarly to the presenteeism instruments: >= 4.7 (AUC 0.82) and >= 3.5 (AUC 0.79), respectively. Thresholds for WALS and WLQ-25 were stable across contextual factors, while for all other instruments they overestimated unacceptable work state in lower educated persons. Proposed thresholds could also predict future AWO, although with lower performance, especially for QQ-method, BASDAI and BASFI. Conclusions: Thresholds of measurement instruments for presenteeism and health status to identify unacceptable work state have been established. These thresholds can help in daily clinical practice to provide work related support to r-axSpA patients at risk for AWO. Show less
Redeker, I.; Landewé, R.; Heijde, D. van der; Ramiro, S.; Boonen, A.; Dougados, M.; ... ; Kiltz, U. 2023
ObjectiveThe objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis... Show moreObjectiveThe objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) in patients with axial spondyloarthritis (axSpA).MethodsCross-sectional data collected at month 72 of the Devenir des Spondylarthropathies Indifferenciees Recentes cohort was analysed. Combining prior knowledge and observed data, probabilistic Bayesian network modelling was used to study how the interplay of different disease outcomes affects the ASAS HI, which measures disease-specific overall functioning and health. Disease outcomes comprised, among others, the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) and the Bath AS Functional Index (BASFI).ResultsData of 384 patients were analysed. The obtained structure suggests that ASAS HI is determined by both patient-reported physical function (BASFI) and disease activity (ASDAS). The parameters of the structural model show that an increase of ASDAS or BASFI by 1 unit corresponds to an increase of ASAS HI by 0.70 or 1.25 units, respectively. Moreover, the model suggests that disease activity has an indirect impact on ASAS HI via BASFI. No relationship between spinal mobility or structural damage and ASAS HI was found.ConclusionsThis is the first structural model developed to better understand the construct and the interplay between clinically relevant outcomes related to ASAS HI in axSpA patients. It shows that disease activity and physical function have a strong impact on ASAS HI, confirming it to be a valid construct of overall functioning and health in axSpA patients. Show less
Webers, C.; Grimm, S.; Tubergen, A. van; Gaalen, F. van; Heijde, D. van der; Joore, M.; Boonen, A. 2023
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
BackgroundAlthough reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational... Show moreBackgroundAlthough reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational interventions in IA is limited, but favourable results of delivery by a physiotherapist (PT) warrant the need for further research. Therefore, we aim to evaluate the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in (self-)employed people with IA compared to usual care.MethodsThis randomized controlled trial will include 140 people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who are (self-)employed and have reduced work ability (Work Ability Index – Single Item Scale (WAS) ≤ 7/10) and/or RA/axSpA related sick leave (≤ 6 months). Participants will be randomized 1:1 to the intervention or control condition (usual care). The intervention, delivered by primary care PTs, will be personalized to each patient, consisting of 10 to 21 sessions over 12 months. The intervention will be multimodal, comprising of 1) exercise therapy and a physical activity plan, 2) education/self-management support, 3) work-roadmap to guide participants in finding relevant other care, with optionally 4) online self-management course and 5) workplace examination. Assessments will be performed at baseline and after 3, 6, and 12 months. The primary outcome measure of effectiveness is work ability, as measured with the WAS at 12 months. For the cost-effectiveness analysis, the EuroQol (EQ-5D-5L), self-reported healthcare use, sick leave and productivity while at work will be used to estimate the trial based cost-utility from a societal perspective. A process evaluation, including assessments of adherence and treatment fidelity, will be undertaken using the registrations of the PTs and semi-structured interviews at 12 months follow-up in a random sample of the intervention group.DiscussionThe results of this study will provide insights in the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in people with IA and a reduced work ability. Show less
Webers, C.; Nikiphorou, E.; Boonen, A.; Ramiro, S. 2022
Biological disease-modifying antirheumatic drugs (bDMARDs) have taken up an important role in the management of axial spondyloarthritis. Once stable remission or low disease activity has been... Show moreBiological disease-modifying antirheumatic drugs (bDMARDs) have taken up an important role in the management of axial spondyloarthritis. Once stable remission or low disease activity has been achieved with bDMARDs, it may be possible to maintain this state with lower levels of these drugs. Studies consis-tently demonstrate that tapering of tumor necrosis factor alpha inhibitors (TNFi) is not inferior to full-dose continuation in terms of maintaining treatment response, while data for tapering of interleukin-17 inhibi-tors (IL-17i) is lacking. Complete discontinuation of TNFi and IL-17i, however, often results in relapse and should not be recommended at this moment. Clear safety benefits of tapering or discontinuation have not been shown, although studies were typically not designed to address this. Current evidence does not sup-port specific tapering or discontinuation strategies, although stepwise disease activity-guided regimens do allow for a more personalized approach and might be preferred. The definition of what constitutes an appropriate disease state to initiate tapering or discontinuation is unclear, and requires further study. Also, reliable predictors of successful tapering and discontinuation have not yet been identified. Fortuna-tely, if tapering or discontinuation fails, most patients are able to regain disease control when reverted to the original bDMARD regimen. Finally, most patients indicate that, when asked, they would be willing to try tapering if the rationale is clear and if it is in their best interests. The decision to taper or discontinue should be made through shared decision-making, as this could improve the likelihood of success. (c) 2022 Les Auteurs. Publie par Elsevier Masson SAS au nom de Societe franc,aise de rhumatologie. Cet article est publie en Open Access sous licence CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Webers, C.; Kiltz, U.; Braun, J.; Heijde, D. van der; Boonen, A. 2022
Objective To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. Methods Data from the observational... Show moreObjective To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. Methods Data from the observational Assessment of SpondyloArthritis international Society Health Index Validation Study were used. Patients were assessed at baseline and after initiation of NSAIDs/conventional synthetic DMARDs (csDMARDs)/TNF inhibitors (TNFis). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale depression subscale [HADS-D; 0-21 (best-worst)]. Covariables included demographics and disease characteristics, including disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS)/BASDAI]. The change in HADS-D from baseline was compared between treatments (NSAIDs/csDMARDs/TNFis) with analysis of variance and multivariable regression analysis. Results A total of 304 patients were included; 102/45/157 initiated NSAIDs/csDMARDs/TNFis and 260 (85%) / 44 (15%) had axial/peripheral SpA. At baseline, the mean HADS-D was 6.9 (s.d. 4.2); 126 (42%) were possibly depressed (HADS-D >= 8) and 66 (22%) were probably depressed (HADS-D >= 11). At follow-up, depressive symptoms significantly improved in all treatment groups. In multivariable regression without disease activity measures, initiating TNFis compared with NSAIDs was associated with greater improvement in depressive symptoms [beta = -1.27 (95% CI -2.23, -0.32)] and lower odds of possible depression at follow-up [odds ratio 0.47 (95% CI 0.23, 0.94)]. This association was attenuated after additional adjustment for disease activity (ASDAS/BASDAI) but not CRP. csDMARDs did not differ from NSAIDs regarding their effect on HADS-D. Between-drug class results were confirmed in axial SpA (axSpA), although less clear in peripheral SpA. Conclusion Treatment of active SpA also improves depressive symptoms. Especially in axSpA, TNFis have a greater effect than NSAIDs, which is mainly explained by a stronger effect on disease activity. We found no evidence for a direct link between CRP-mediated inflammation and depressive symptoms in SpA. Show less
A clinical guideline is a document with the aim of guiding decisions based on evidence regarding diagnosis, management and treatment in specific areas of healthcare. Specific to rheumatic and... Show moreA clinical guideline is a document with the aim of guiding decisions based on evidence regarding diagnosis, management and treatment in specific areas of healthcare. Specific to rheumatic and musculoskeletal diseases (RMDs), adherence to clinical guidelines recommendations impacts the outcomes of people with these diseases. However, currently, the implementation of recommendations is less than optimal in rheumatology.The WHO has described the implementation of evidence-based recommendations as one of the greatest challenges facing the global health community and has identified the importance of scaling up these recommendations. But closing the evidence-to-practice gap is often complex, time-consuming and difficult. In this context, the implementation science offers a framework to overcome this scenario. This article describes the principles of implementation science to facilitate and optimise the implementation of clinical recommendations in RMDs. Embedding implementation science methods and techniques into recommendation development and daily practice can help maximise the likelihood that implementation is successful in improving the quality of healthcare and healthcare services. Show less
Khidir, S.J.H.; Boeren, A.M.P.; Boonen, A.; Jong, P.H.P. de; Mulligen, E. van; Helm-van Mil, A.H.M. van der 2022
Objectives: Cross-sectional studies have shown that rheumatoid arthritis is more prevalent among people with a lower educational attainment. No longitudinal data are present on educational... Show moreObjectives: Cross-sectional studies have shown that rheumatoid arthritis is more prevalent among people with a lower educational attainment. No longitudinal data are present on educational attainment in the at-risk phase of clinically suspect arthralgia (CSA). We therefore analysed the association between educational attainment and progression from CSA to inflammatory arthritis (IA), and performed mediation analysis with subclinical joint inflammation to elucidate pathways of this association. Methods: A total of 521 consecutive patients presenting with CSA were followed for IA development during median 25 months. Educational attainment was defined as low (lower secondary vocational education), intermediate or high (college/university education). Subclinical inflammation in hand and foot joints was measured at presentation with contrast enhanced 1.5 T-MRI. Cox-regression was used to analyse IA development per educational attainment. A three-step mediation analysis evaluated whether subclinical joint inflammation was intermediary in the path between educational attainment and IA development, before and after age correction. Association between educational attainment and IA development was verified in an independent CSA cohort. Results: Low educational attainment was associated with increased IA development (HR = 2.35, 95% CI = 1.27, 4.33, P = 0.006), independent of BMI and current smoking status (yes/no). Moreover, patients with a low educational attainment had higher levels of subclinical inflammation, which also was associated with IA development. Partial mediation effect of subclinical inflammation was observed in the relationship between education and IA development. Low educational attainment was also associated with increased IA development in the validation cohort (HR = 5.72, 95% CI = 1.36, 24.08, P = 0.017). Conclusion: This is the first study providing evidence that lower educational attainment is associated with a higher risk of progressing from arthralgia to IA. This effect was partially mediated by subclinical joint inflammation. Show less
Terpstra, S.E.; Stadt, L. van de; Boonen, A.; Damman, W.; Rosendaal, F.; Kloppenburg, M. 2022
Objectives: Data on work participation impairment and related societal costs for patients with hand osteoarthritis (OA) are scarce. Therefore, we aimed to investigate the association of hand OA... Show moreObjectives: Data on work participation impairment and related societal costs for patients with hand osteoarthritis (OA) are scarce. Therefore, we aimed to investigate the association of hand OA with work limitations and costs of productivity loss in paid and unpaid work. Methods: We used data from the Hand Osteoarthritis in Secondary Care cohort, including patients with hand OA diagnosed by their treating rheumatologist. Using the validated Health and Labour Questionnaire, we assessed experienced unpaid and paid work restrictions, unpaid work replacement by others and inefficiency and absence during paid work related to hand OA over the last 2 weeks. Societal costs (euro) per hour of paid and unpaid work were estimated using Dutch salary data in 2019. Results: 381 patients were included (mean age 61 years, 84% women, 26% high education level, 55% having any comorbidity). Replacement of unpaid work by others due to hand OA was necessary for 171 out of 381 patients (45%). Paid work was reported by 181/381 patients (47%), of whom 13/181 (7%) reported absenteeism, 28/181 (15%) unproductive hours at work and 120/181 (66%) paid work restrictions due to hand OA. Total estimated work-related societal costs per patient with hand OA (381 patients) were euro94 (95% CI 59 to 130) per 2 weeks (euro2452, 95% CI 1528 to 3377 per year). Conclusions: Hand OA is associated with impairment in paid and unpaid work participation, which translates into substantial societal costs of lost productivity. These results highlight the importance of adequate hand OA treatment. Show less
Navarro-Compan, V.; Boel, A.; Boonen, A.; Mease, P.J.; Dougados, M.; Kiltz, U.; ... ; Heijde, D. van der 2022
Objectives: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis ... Show moreObjectives: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA). Methods: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS. Results: The updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments. Conclusions: The selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials. Show less
Kiltz, U.; Boonen, A.; Heijde, D. van der; Bautista-Molano, W.; Vargas, R.B.; Chiowchanwisawakit, P.; ... ; Braun, J. 2022
Objective: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health... Show moreObjective: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). Method: First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. Results: The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. Conclusions: An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health. Show less
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
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
Molto, A.; Lopez-Medina, C.; Bosch, F.E. van den; Boonen, A.; Webers, C.; Dernis, E.; ... ; Dougados, M. 2021
Objectives To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).Methods Pragmatic, prospective, cluster... Show moreObjectives To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).Methods Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) >= 2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive.Interventions (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion.Main outcome Percentage of patients with a >= 30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed.Statistical analysis Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC.Results 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by >= 30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved euro472 compared with UC.Conclusion TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. 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
Background Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses... Show moreBackground Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses.Objectives To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain.Methods The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously.Results Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9).Conclusion Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP. 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
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
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
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
