To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA).
Following the EULAR Standardised Operating ...Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting.
Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures.
The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the ...Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.
Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included.
In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi.
New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety.
CRD42021257588.
To update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international Society-European Alliance of ...Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.
A systematic literature review (2016-2021) on efficacy and safety of non-pharmacological and non-biological pharmacological treatments was performed, up to 1 January 2022. The research question was formulated according to the PICO format: Population: adult patients with r-axSpA and nr-axSpA; Intervention: non-pharmacological and non-biological pharmacological treatments; Comparator: active comparator or placebo; Outcomes: all relevant efficacy and safety outcomes. Type of studies included were: randomised controlled trials (RCTs), observational studies (for efficacy of non-pharmacological treatments, and safety), qualitative studies. Cohen's effect size (ES) was calculated for non-pharmacological and risk ratio (RR) for pharmacological treatments.
Of 107 publications included, 63 addressed non-pharmacological interventions, including education (n=8) and exercise (n=20). The ES for education on disease activity, function, mobility was small to moderate (eg. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ES: 0.06-0.59). Exercise had moderate to high ES on these outcomes (eg.
0.14-1.43). Six RCTs on targeted synthetic disease-modifying antirheumatic drugs (DMARDs) showed efficacy of tofacitinib, upadacitinib and filgotinib (phase 2 only) in r-axSpA (range RR vs placebo for ASAS20: 1.91-3.10), while apremilast and nilotinib were not efficacious. Studies on conventional synthetic DMARDs (n=3), non-steroidal anti-inflammatory drugs (NSAIDs, n=8) and other drugs (n=12) did not provide new evidence on efficacy/safety (efficacy of NSAIDs confirmed; limited efficacy of short-term glucocorticoids in one RCT).
Education, exercise and NSAIDs confirmed to be efficacious in axSpA. JAKi were proved efficacious in r-axSpA.
To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).
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.
(1)
: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2)
visits every 12 weeks and treatment at the rheumatologist's discretion.
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.
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.
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 €472 compared with UC.
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.
NCT03043846.
Patients with ankylosing spondylitis (AS) have a higher prevalence of depression compared to the general population. Comorbid depression in AS likely has a multifactorial origin. While several ...disease-related and contextual factors have been associated with depressive symptoms in AS, a comprehensive model of their interrelations is currently lacking. Such a model could help understand the mechanisms leading to, or maintaining, depression in AS. The objectives of the current study were to determine which factors are associated with depressive symptoms in AS and to understand their underlying relationships.
Data from a cross-sectional survey-based multicentre study were used. Potential determinants included both contextual and disease-related factors. Depressive symptoms were assessed by the Hospital Anxiety and Depression Subscale (HADS-D). Direct and indirect associations between risk factors and the latent depressive symptom outcome were explored using structural equation modelling. A final model was selected based on model fit criteria and clinical plausibility.
Among 245 patients, median HADS-D score was 3 (interquartile range 1-6), and 44 patients (18%) had a HADS-D score ≥ 8, indicating possible depression. In the final model, contextual factors significantly associated with depressive symptoms were male gender, being employed, lower income, lower mastery and worse satisfaction with social role participation. Bath AS Disease Activity Index (BASDAI) was the only disease-related factor that was associated with depressive symptoms, acted only indirectly via mastery, and its standardized total effect on depressive symptoms was smaller than that of several contextual factors. Mastery had a central role in the path diagram and mediated the effects of BASDAI, income and satisfaction with social role participation on depressive symptoms. The final model explained 64% of the variance in the depression outcome.
Both contextual and disease-related factors are associated with depressive symptoms in AS. Mastery, the extent to which one feels in control over life and disease, has a key role in this process. Results support a relevance of self-efficacy in disease management and patient education. In order to improve patients' mental health, research is warranted whether mastery and its relation with depression can be modified.
As part of its strategic objectives for 2023, EULAR aims to improve the work participation of people with rheumatic and musculoskeletal diseases (RMDs). One strategic initiative focused on the ...development of overarching points to consider (PtC) to support people with RMDs in healthy and sustainable paid work participation.
EULAR's standardised operating procedures were followed. A steering group identified six research areas on paid work participation. Three systematic literature reviews, several non-systematic reviews and two surveys were conducted. A multidisciplinary taskforce of 25 experts from 10 European countries and Canada formulated overarching principles and PtC after discussion of the results of literature reviews and surveys. Consensus was obtained through voting, with levels of agreement obtained anonymously.
Three overarching principles and 11 PtC were formulated. The PtC recognise various stakeholders are important to improving work participation. Five PtC emphasise shared responsibilities (eg, obligation to provide active support) (PtC 1, 2, 3, 5, 6). One encourages people with RMDs to discuss work limitations when necessary at each phase of their working life (PtC 4) and two focus on the role of interventions by healthcare providers or employers (PtC 7, 8). Employers are encouraged to create inclusive and flexible workplaces (PtC 10) and policymakers to make necessary changes in social and labour policies (PtC 9, 11). A research agenda highlights the necessity for stronger evidence aimed at personalising work-related support to the diverse needs of people with RMDs.
Implementation of these EULAR PtC will improve healthy and sustainable work participation of people with RMDs.
Objectives
To test the psychometric properties of the United Kingdom’s Commissioning for Quality in Rheumatoid Arthritis Patient-Reported Experience Measure (CQRA-PREM) in patients with ...spondyloarthritis (SpA) and rheumatoid arthritis (RA) and to implement this questionnaire in daily practice in the Netherlands.
Methods
After a forward-backward translation procedure into Dutch, the CQRA-PREM was tested into two quality registries in daily practice. Face validity was assessed with focus group interviews. Feasibility was evaluated through completion times and interpretability of domain scores through floor and ceiling effects. Internal consistency (Cronbach’s α coefficients) and homogeneity (corrected item-total correlations) were determined. Divergent validity was assessed by Spearman’s rank correlation coefficients (
r
s
) between the average scores of domains and outcome measures. The CQRA-PREM was implemented in daily practice, and the results were used in quality improvement cycles.
Results
Face validity of the CQRA-PREM was good. The CQRA-PREM was completed by 282 patients with SpA and 376 with RA. Median time to complete the CQRA-PREM was 4.7 min. Ceiling effects were found in three out of seven domains. Internal consistency of nearly all domains was considered good (0.65 ≤ α ≤ 0.95). Thresholds for homogeneity were exceeded within three domains (
r
p
> 0.7), suggesting item redundancy. Divergent validity showed that nearly all domains of the CQRA-PREM were at most weakly correlated with outcomes measures (− 0.3 ≤
r
s
≤ 0.3). The CQRA-PREM could identify areas of improvement for providing patient-centered care.
Conclusion
The CQRA-PREM has acceptable psychometric properties and has shown to be a useful tool in evaluating quality of care from the patients’ perspective in the Netherlands.
Trial registration
SpA-Net is registered in the Netherlands Trial Registry (NTR6740).
Key Points
• The Commissioning for Quality in Rheumatoid Arthritis Patient-Reported Experience Measure (CQRA-PREM) is a valid measure for assessing patient-centeredness of rheumatology care.
• The Dutch version of the CQRA-PREM shows acceptable psychometric properties.
• The CQRA-PREM shows to be a useful tool in Plan-Do-Check-Act quality improvement cycles in the Netherlands.
• The CQRA-PREM can be used for benchmarking and quality improvement of rheumatology services.
Abstract
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 ...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.
Trial registration
Trial registration (ASSERT):
NCT00207701
. Registered on September 21, 2005 (retrospectively registered).
Objective
To investigate willingness to pay (WTP) for treatment with infliximab by patients with ankylosing spondylitis (AS) and explore factors associated with WTP.
Methods
Data from 85 patients ...participating in the European AS Infliximab Cohort (EASIC) open‐label extension of the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) were used. WTP was included at baseline in EASIC and comprised a hypothetical scenario exploring whether the patient would be willing to pay for beneficial effects of infliximab and, if so, what amount they would be willing to pay per administration. Factors associated with WTP were explored using zero‐inflated negative binomial (ZINB) regressions.
Results
Of the 85 patients, 63 (74.1%) were willing to pay, and among these, the mean amount they were willing to pay per administration was €275 (median €100 interquartile range €50–200). Multivariable ZINB analysis showed that Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response was associated with a 7‐fold lower likelihood to pay 0 euros (odds ratio OR 0.14 95% confidence interval (95% CI) 0.03–0.71) and a 3‐fold increase in the amount willing to pay (exp(β) = 3.32 95% CI 1.44–7.69). In addition, the country of residence was associated with a lower likelihood to pay 0 euros (OR 0.07 95% CI 0.02–0.36), while increased age was associated with the amount willing to pay (exp(β) = 1.05 95% CI 1.01–1.09).
Conclusion
In a hypothetical scenario, three‐quarters of patients with AS receiving long‐term infliximab stated that they were willing to pay an out‐of‐pocket contribution for this treatment. Treatment response contributed to the willingness as well as to the amount patients were willing to pay.
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