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
Navarro-Compán, V.; Benavent, D.; Capelusnik, D.; Heijde, D. van der; Landewé, R.B.M.; Poddubnyy, D.; ... ; Ramiro, S. 2023
Objectives To develop a consensual definition for the term ‘early axial spondyloarthritis—axSpA’—and ‘early peripheral spondyloarthritis—pSpA’.Methods The ASAS (Assessment of SpondyloArthritis... Show moreObjectives To develop a consensual definition for the term ‘early axial spondyloarthritis—axSpA’—and ‘early peripheral spondyloarthritis—pSpA’.Methods The ASAS (Assessment of SpondyloArthritis international Society-Spondyloarthritis EARly definition) steering committee convened an international working group (WG). Five consecutive steps were followed: (1) systematic literature review (SLR); (2) discussion of SLR results within the WG and ASAS community; (3) a three-round Delphi survey inviting all ASAS members to select the items that should be considered for the definition; (4) presentation of Delphi results to the WG and ASAS community and (5) ASAS voting and endorsement (2023 annual meeting).Results Following the SLR, consensus was to proceed with an expert-based definition for early axSpA (81% in favour) but not for pSpA (54% against). Importantly, early axSpA should be based on symptom duration taking solely axial symptoms into account. 151–164 ASAS members participated in the Delphi surveys. Consensus was achieved for considering the following items within early axSpA definition: duration of symptoms ≤2 years; axial symptoms defined as cervical/thoracic/back/buttock pain or morning stiffness; regardless of the presence/absence of radiographic damage. The WG agreed that in patients with a diagnosis of axSpA ‘early axSpA’ should be defined as a duration of ≤2 years of axial symptoms. Axial symptoms should include spinal/buttock pain or morning stiffness and should be considered by a rheumatologist as related to axSpA. The ASAS community endorsed this proposal (88% in favour).Conclusions Early axSpA has newly been defined, based on expert consensus. This ASAS definition should be adopted in research studies addressing early axSpA. Show less
Capelusnik, D.; Benavent, D.; Heijde, D. van der; Landewe, R.; Poddubnyy, D.; Tubergen, A. van; ... ; Ramiro, S. 2022
Objective To summarize evidence on the relationship between early treatment (definition based on symptom/disease duration or radiographic damage) and treatment clinical response in patients with... Show moreObjective To summarize evidence on the relationship between early treatment (definition based on symptom/disease duration or radiographic damage) and treatment clinical response in patients with SpA. Methods A systematic literature review was conducted in studies on SpA patients treated with NSAIDs or biological/targeted synthetic DMARDs addressing the impact of symptom/disease duration or presence of radiographic damage on treatment response assessed by any disease activity outcome. For categorical outcomes, relative risk, relative risk ratio and number needed to treat were calculated, and for continuous outcomes, differences in differences, to compare groups stratified based on symptom/disease duration or the presence of radiographic damage. Results From the 8769 articles retrieved, 25 were included and 2 added by hand-search, all in axial SpA (axSpA), most of them with low risk of bias. Twenty-one studies compared groups based on symptom duration (n = 6) or disease duration (n = 15) and seven studies based on absence/presence of radiographic damage (two studies used two comparisons). When early axSpA was defined by symptom duration (<5 years) in randomized controlled trials, early treatment was associated with better outcomes in patients with non-radiographic axSpA [n = 2, ASAS40 relative risk ratio 5.24 (95% CI 1.12, 24.41) and 1.52 (0.60, 3.87)] but not in radiographic axSpA (n = 1) [ASAS20 0.96 (0.53-1.73)]. When early axSpA was defined based on disease duration or radiographic damage, no differences were found between groups. Conclusion Evidence towards better outcomes in early axSpA is very limited and restricted to non-radiographic axSpA and <5 years symptom duration. When early axSpA is defined based on disease duration or radiographic damage, no differences in response to treatment are found. Show less
Benavent, D.; Capelusnik, D.; Heijde, D. van der; Landewe, R.; Poddubnyy, D.; Tubergen, A. van; ... ; Navarro-Compan, V. 2022
Aim: To identify all possible definitions of "early SpA" employed in the literature, including "early axial SpA (axSpA)" and "early peripheral SpA (pSpA)".Methods: A systematic literature review... Show moreAim: To identify all possible definitions of "early SpA" employed in the literature, including "early axial SpA (axSpA)" and "early peripheral SpA (pSpA)".Methods: A systematic literature review was conducted in Medline, EMBASE and the Cochrane Library for studies that included any mention of "early SpA" or its subtypes. The proportion of studies including a definition was calculated, and the different definitions were assessed.Results: Out of 9651 titles identified, 336 publications reporting data from 183 studies were included. Over time, an increasing number of publications were identified. In total, 114 (62%) studies reported a specific definition: 33% of them based it on symptom duration, 31% on radiographic damage, 28% on disease duration, 5% on both symptom/disease duration and radiographic damage, and 3% on other aspects. Overall, 61 (33%) studies included the term "early axSpA", whereas 60 (33%) included "early ankylosing spondylitis (AS)". Regarding the studies that referred to "early axSpA", the most used definition was symptom/disease duration <5 years, whereas for "early AS" was symptom/disease duration <10 years. After 2010, the definition of "early axSpA" based on the absence of radiographic sacroiliitis was less used compared to before 2010 (17% vs 38%).Conclusion: Over time, the term "early SpA" and its subtypes is increasingly used. More than one third of the studies did not include a definition of the term and the studies reporting one showed a large heterogeneity. These results emphasize the need for a standardised definition of early SpA. Show less
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
Webers, C.; Stolwijk, C.; Schiepers, O.; Schoonbrood, T.; Tubergen, A. van; Landewe, R.; ... ; Boonen, A. 2020
Background: Patients with ankylosing spondylitis (AS) are at increased risk of depression. This increased risk has been hypothesized to be solely secondary due to AS-related symptoms, or... Show moreBackground: Patients with ankylosing spondylitis (AS) are at increased risk of depression. This increased risk has been hypothesized to be solely secondary due to AS-related symptoms, or additionally due to a common inflammatory pathway. From a clinical perspective, it is important to know whether treatment with tumor necrosis factor alpha inhibitors reduces depressive symptoms, while from a pathophysiological point of view, it would be insightful to understand whether such an effect would be a direct result of reduced inflammation, the result of reduced AS-related symptoms, or both. The objective of this study was to evaluate the effect of infliximab on depressive symptoms in patients with AS in a randomized-controlled trial setting.Methods: Data were retrieved from a subgroup of patients from the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT). Patients were randomly allocated to infliximab (n = 16) or placebo (n = 7) until week 24, after which all received infliximab until week 54. Associations between treatment group and depressive symptoms, measured with the Center for Epidemiological Studies Depression scale (CES-D, range 0-60 (best-worst)) at baseline and over time, were explored with generalized estimating equations (GEE).Results: Mean CES-D score at baseline was 15.5 (SD 9.3) in the infliximab group and 17.3 (SD 5.7) in the placebo group. Twelve patients (52%) had a CES-D score >= 16, suggestive for clinical depression. After 24 weeks, mean CES-D had decreased to 9.5 (SD 11.4) in the infliximab group, but was 18.0 (SD 6.9) in the placebo group. GEE revealed larger improvements in depressive symptoms (B = - 6.63, 95%CI - 13.35 to 0.09) and odds of possible depression (OR = 0.02, 95%CI 0.00 to 0.72) in the infliximab group, compared to the placebo group. Both associations largely disappeared when adjusted for self-reported disease activity and/or physical function. Additional adjustment for C-reactive protein (CRP) did not change results.Conclusions: Depressive symptoms are common in patients with AS and active disease. Infliximab improves these depressive symptoms in AS when compared to placebo by improving disease symptoms. We did not find an indication for a direct link between CRP-mediated inflammation and depressive symptoms. Show less
Stolwijk, C.; Essers, I.; Bosch, F. van den; Dougados, M.; Etcheto, A.; Heijde, D. van der; ... ; ASAS-COMOSPA Study Grp 2020
Objective. To confirm validity of the Self-administered Comorbidity Questionnaire modified for patients with SpA (mSCQ), and assess whether validity improves when adding items on extra-articular... Show moreObjective. To confirm validity of the Self-administered Comorbidity Questionnaire modified for patients with SpA (mSCQ), and assess whether validity improves when adding items on extra-articular manifestations (EAMs), i.e. uveitis, psoriasis, and IBD, and osteoporosis and fractures.Methods. Data from the Assessment in SpondyloArthritis international Society COMOrbidities in SPondyloArthritis study were used. Criterion validity of presence of EAMs, osteoporosis and fractures was assessed as agreement (kappa) between patients' self-reported and physician-confirmed disease. Construct validity of the mSCQ including EAMs, osteoporosis and/or fractures (SpA-SCQ) was assessed by testing hypotheses about correlations with demographics, physical function, work ability, health utility and disease activity, and was compared with construct validity of the rheumatic disease comorbidity index.Results. In total, 3984 patients contributed to the analyses. Agreement between patient-reported and physician-reported EAMs was substantial to almost perfect (uveitis kappa = 0.81, IBD kappa = 0.73, psoriasis kappa = 0.86). Agreement for osteoporosis (kappa = 0.38) and fractures (kappa = 0.39) was fair. As hypothesized, the mSCQ correlated moderately to weakly with age, physical function, work limitations and health utility, and very weakly with disease activity. In contrast to our hypothesis, adding EAMs, osteoporosis and/or fractures to the mSCQ decreased correlations with several external constructs, especially among patients with peripheral SpA. Correlations with the different constructs were stronger for the both mSCQ and SpA-SCQ (r(BASFI) = 0.34; r(EQ-5D) = -0.33) compared with the rheumatic disease comorbidity index (r(BASFI) = 0.24; r(EQ-5D) = -0.21).Conclusion. The mSCQ is a valid self-report instrument to assess the influence of comorbidities on health outcomes in patients with SpA. Adding EAMs and/or osteoporosis or fractures does not improve validity of the mSCQ. Show less
BACKGROUND & AIMS: Telemedicine can be used to monitor determinants and outcomes of patients with chronic diseases, possibly increasing the quality and value of care. Telemedicine was found to... Show moreBACKGROUND & AIMS: Telemedicine can be used to monitor determinants and outcomes of patients with chronic diseases, possibly increasing the quality and value of care. Telemedicine was found to reduce outpatient visits and hospital admissions for patients with inflammatory bowel diseases (IBD). We performed a full economic evaluation of telemedicine interventions in patients with IBD, comparing the cost-utility of telemedicine vs standard care.METHODS: We performed a randomized trial of 909 patients with IBD at 2 academic and 2 non-academic hospitals in The Netherlands. Patients were randomly assigned to groups that received telemedicine (myIBDcoach; n = 465) or standard outpatient care (n = 444) and followed for 12 months. Costs were measured from a societal perspective. Direct healthcare costs were based on actual resource use. Indirect costs comprised self-reported hours sick leave from work, intervention costs (annual license fee of (sic)40 per patient [$45]), and utility costs (assessed using EQ5D). Cost-utility and uncertainty were estimated using the non-parametric bootstrapping method.RESULTS: Telemedicine resulted in lower mean annual costs of (sic)547/patient [$612] (95% CI, (sic)1029-2143 [$1150-2393]; mean costs of (sic)9481 [$10,587] for standard care and (sic)8924 [$9965] for telemedicine) without changing quality adjusted life years. At the Dutch threshold of (sic)80,000 [$89,335] per quality adjusted life year, the intervention had increased incremental cost-effectiveness over standard care in 83% of replications and an incremental net monetary benefit of (sic)707/patient [$790] (95% CI, (sic)1241-2544 [$1386-2841]).CONCLUSIONS: Telemedicine with myIBDcoach is cost saving and has a high probability of being cost effective for patients with IBD. This self-management tool enables continuous registration of quality indicators and (patient-reported) outcomes and might help reorganize IBD care toward value-based healthcare. Show less
Kiltz, U.; Landewe, R.B.M.; Heijde, D. van der; Rudwaleit, M.; Weisman, M.H.; Akkoc, N.; ... ; Braun, J. 2020
Objectives The Assessment of SpondyloArthritis International Society (ASAS) aimed to develop a set of quality standards (QS) to help improve the quality of healthcare provided to adult patients... Show moreObjectives The Assessment of SpondyloArthritis International Society (ASAS) aimed to develop a set of quality standards (QS) to help improve the quality of healthcare provided to adult patients affected by axial spondyloarthritis (axSpA) worldwide.Methods An ASAS task force developed a set of QS using a stepwise approach. First, key areas for quality improvement were identified, discussed, rated and agreed on. Thereafter, areas were prioritised and statements for the most important key areas were phrased on consensus. Appropriate quality measures were defined to allow quantification of the QS at the community level.Results The ASAS task force, consisting of 20 rheumatologists, two physiotherapists and two patients, selected and proposed 34 potential key areas for quality improvement which were then commented by 140 ASAS members and patients. Within that process three new key areas came up, which led to a re-evaluation of all 37 key areas by 120 ASAS members and patients. Five key areas were identified as most important to determine quality of care: referral including rapid access, rheumatology assessment, treatment, education/self-management and comorbidities. Finally, nine QS were agreed on and endorsed by the whole ASAS membership.Conclusions ASAS successfully developed the first set of QS to help improving healthcare for adult patients with axSpA. Even though it may currently not be realistic to achieve the QS in all healthcare systems, they provide high-quality of care framework for patients with axSpA that should be aimed for. Show less
Boel, A.; Molto, A.; Heijde, D. van der; Ciurea, A.; Dougados, M.; Gensler, L.S.; ... ; Ramiro, S. 2019
