2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.

Predictive value of gastrointestinal symptoms and patient risk factors for NSAID-associated gastrointestinal ulcers defined by endoscopy? Insights from a pooled analysis of two naproxen clinical trials.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain and rheumatic conditions. To facilitate patient management, we determined the predictive value of gastrointestinal (GI) symptoms and risk factors for the development of NSAID-associated GI injuries. METHODS: Post-hoc analysis of pooled data from naproxen treatment arms of two identical, randomized, double-blind, controlled phase 3 trials in arthritis patients at risk of GI adverse events. Endoscopic incidence of GI ulcers at baseline, and 1, 3, and 6 months was employed as a surrogate parameter for GI injury. For GI symptom analysis, Severity of Dyspepsia Assessment questionnaire was used. For GI risk factor analysis, the high risk factors: previous GI injury, concomitant selective serotonin reuptake inhibitors or corticosteroids, ulcer history, concomitant low-dose aspirin, and age >65 years were employed. RESULTS: Data of 426 naproxen patients were analyzed. Distribution of GI symptoms between patients with and without ulcer was similar; about one third of patients developing an ulcer reported no GI pain symptoms. GI symptoms experienced under naproxen treatment were thus not indicative of GI injury. The proportion of patients developing an ulcer increased with the number of risk factors present, however, about a quarter of patients without any of the analyzed risk factors still developed an ulcer. CONCLUSION: GI symptoms and the number of risk factors are not reliable predictors of NSAID-induced GI injury to decide which patients need gastroprotection and will lead to a large group of patients with GI injuries. A preventive rather than reactive approach should be taken.

Relative Impact of Pain and Disease Activity on Improvements in Fatigue: Results From 2 Baricitinib Phase 3 Clinical Trials.

BACKGROUND/OBJECTIVE: Fatigue is common in patients with rheumatoid arthritis (RA). We assessed the relative impact of pain and disease activity on improvements in fatigue in 2 phase 3 baricitinib clinical trials. METHODS: RA-BEAM (NCT01710358) and RA-BEACON (NCT01721044) were randomized, double-blind, placebo-controlled studies in adults with moderate to severe RA. RA-BEAM assessed baricitinib + methotrexate (MTX) and adalimumab + MTX in patients with prior inadequate response/intolerance (IR) to MTX (MTX-IR). RA-BEACON assessed patients with IR to ≥1 biologic disease-modifying antirheumatic drug (bDMARD-IR). Measures included the Functional Assessment of Chronic Illness Therapy-Fatigue scale, Clinical Disease Activity Index (CDAI) for RA, and pain visual analog scale (VAS). Analyses were implemented separately for each study. RESULTS: Significant improvements were seen in disease activity and pain, which were greater with baricitinib versus adalimumab. A statistically significant improvement was seen in fatigue with both active treatments versus placebo. Moderate correlations were observed between improvements in disease activity and fatigue and between improvements in pain and fatigue in both MTX-IR and bDMARD-IR patients. Reductions in pain (≥50%) and remission or low disease activity (CDAI ≤10) had significant associations with fatigue improvement at week 24. In mediation analysis, improvements in fatigue attributable to CDAI and pain VAS in MTX-IR patients were 31% and 52%, respectively, for baricitinib, and 30% and 47%, respectively, for adalimumab. In bDMARD-IR patients, improvement in fatigue was attributed 48% to CDAI and 48% to pain VAS. CONCLUSIONS: In both MTX-IR and bDMARD-IR patients, a large proportion of improvements in fatigue across treatment arms were accounted for by improvements in pain and disease activity.

Fatigue is associated with disease activity in some, but not all, patients living with rheumatoid arthritis: disentangling "between-person" and "within-person" associations.

BACKGROUND: Previous research has shown an unclear and inconsistent association between fatigue and disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to explore differences in "between-person" and "within-person" associations between disease activity parameters and fatigue severity in patients with established RA. METHODS: Baseline and 3-monthly follow-up data up to one-year were used from 531 patients with established RA randomized to stopping (versus continuing) tumor necrosis factor inhibitor treatment enrolled in a large pragmatic trial. Between- and within-patient associations between different indicators of disease activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], swollen and tender joint count [ SJC and TJC], visual analog scale general health [VAS-GH]) and patient-reported fatigue severity (Bristol RA Fatigue Numerical Rating Scale) were disaggregated and estimated using person-mean centering in combination with repeated measures linear mixed modelling. RESULTS: Overall, different indices of disease activity were weakly to moderately associated with fatigue severity over time (ß's from 0.121 for SJC to 0.352 for VAS-GH, all p's < 0.0001). Objective markers of inflammation (CRP, ESR and SJC) were associated weakly with fatigue within patients over time (ß's: 0.104-0.142, p's < 0.0001), but not between patients. The subjective TJC and VAS-GH were significantly associated with fatigue both within and between patients, but with substantially stronger associations at the between-patient level (ß's: 0.217-0.515, p's < 0.0001). Within-person associations varied widely for individual patients for all components of disease activity. CONCLUSION: Associations between fatigue and disease activity vary largely for different patients and the pattern of between-person versus within-person associations appears different for objective versus subjective components of disease activity. The current findings explain the inconsistent results of previous research, illustrates the relevance of statistically distinguishing between different types of association in research on the relation between disease activity and fatigue and additionally suggest a need for a more personalized approach to fatigue in RA patients. Trial registration Netherlands trial register, Number NTR3112.

Model-based cost-effectiveness analyses comparing combinations of urate lowering therapy and anti-inflammatory treatment in gout patients.

OBJECTIVES: To assess the cost-effectiveness of various combinations of urate lowering therapy (ULT) and anti-inflammatory treatment in the management of newly diagnosed gout patients, from the Dutch societal perspective. METHODS: A probabilistic patient-level simulation estimating costs and quality-adjusted life years (QALYs) comparing gout and hyperuricemia treatment strategies was performed. ULT options febuxostat, allopurinol and no ULT were considered. Flare treatments naproxen, colchicine, prednisone, and anakinra were considered. A Markov Model was constructed to simulate gout disease. Health states were no flare, and severe pain, mild pain, moderate pain, or no pain in the presence of a flare. Model input was derived from patient level clinical trial data, meta-analyses or from previously published health-economic evaluations. The results of probabilistic sensitivity analyses were presented using incremental cost-effectiveness ratios (ICERs), and summarized using cost-effectiveness acceptability curves (CEACs). Scenario analyses were performed. RESULTS: The ICER for allopurinol versus no ULT was €1,381, when combined with naproxen. Febuxostat yielded the highest utility, but also the highest costs (€4,385 vs. €4,063 for allopurinol), resulting in an ICER of €25,173 when compared to allopurinol. No ULT was not cost-effective, yielding the lowest utility. For the gout flare medications, comparable effects on utility were achieved. Combined with febuxostat, naproxen was the cheapest option (€4,404), and anakinra the most expensive (€4,651). The ICER of anakinra compared to naproxen was €818,504. Colchicine and prednisone were dominated by naproxen. CONCLUSION: Allopurinol and febuxostat were both cost-effective compared to No ULT. Febuxostat was cost-effective in comparison with allopurinol at higher willingness-to-pay thresholds. For treating gout flares, colchicine, naproxen and prednisone offered comparable health economic implications, although naproxen was the favoured option.

Co-Design of a Disease Activity Based Self-Management Approach for Patients with Rheumatoid Arthritis.

OBJECTIVE: The systematic development of an intervention to improve disease activity-based management of rheumatoid arthritis (RA) in daily clinical practice that is based on patient-level barriers. METHODS: The self-management strategy was developed through a step-wise approach, in a process of co-design with all stakeholders and by addressing patient level barriers to RA management based on disease activity. RESULTS: The resulting DAS-pass strategy consists of decision supportive information and guidance by a specialised rheumatology nurse. It aims to increase patients' knowledge on DAS28, to empower patients to be involved in disease management, and to improve patients' medication beliefs. The decision supportive information includes an informational leaflet and a patient held record. The nurse individualises the information, stimulates patients to communicate about disease activity, and offers the opportunity for questions or additional support. CONCLUSION: The DAS-pass strategy was found helpful by stakeholders. It can be used to improve RA daily clinical practice. Our systematic approach can be used to improve patient knowledge and self-management on other RA related topics. Also, it can be used to improve the management of other chronic conditions. We therefore provide a detailed description of our methodology to assist those interested in developing an evidence-based strategy for educating and empowering patients.

Common Functional Ability Score for Young People With Juvenile Idiopathic Arthritis.

OBJECTIVE: As young people enter adulthood, the interchangeable use of child and adult outcome measures may inaccurately capture changes over time. This study aimed to use item response theory (IRT) to model a continuous score for functional ability that can be used no matter which questionnaire is completed. METHODS: Adolescents (ages 11-17 years) in the UK Childhood Arthritis Prospective Study (CAPS) self-completed an adolescent Childhood Health Assessment Questionnaire (CHAQ) and a Health Assessment Questionnaire (HAQ). Their parents answered the proxy-completed CHAQ. Those children with at least 2 simultaneously completed questionnaires at initial presentation or 1 year were included. Psychometric properties of item responses within each questionnaire were tested using Mokken analyses to assess the applicability of IRT modeling. A previously developed IRT model from the Pharmachild-NL registry from The Netherlands was validated in CAPS participants. Agreement and correlations between IRT-scaled functional ability scores were tested using intraclass correlations and Wilcoxon's signed rank tests. RESULTS: In 303 adolescents, the median age at diagnosis was 13 years, and 61% were female. CHAQ scores consistently exceeded HAQ scores. Mokken analyses demonstrated high scalability, monotonicity, and the fact that each questionnaire yielded reliable scores. There was little difference in item response characteristics between adolescents enrolled in CAPS and Pharmachild-NL (maximum item residual 0.08). Significant differences were no longer evident between IRT-scaled HAQ and CHAQ scores. CONCLUSION: IRT modeling allows the direct comparison of function scores regardless of different questionnaires being completed by different people over time. IRT modeling facilitates the ongoing assessment of function as adolescents transfer from pediatric clinics to adult services.

Two parallel short forms to measure disease- and treatment-associated knowledge in rheumatoid arthritis: application of item response theory.

OBJECTIVE: The aim was to develop two disease- and treatment-related knowledge about RA (DataK-RA) short forms using item response theory-based linear optimal test design. METHODS: We used the open source Excel add-in solver to program a linear optimization algorithm to develop two short forms from the DataK-RA item bank. The algorithm was instructed to optimize precision (i.e. reliability) of the scores for both short forms, subject to a number of constraints that served to ensure that each short form would include unique items and that the short forms would have similar psychometric properties. Agreement among item response theory scores obtained from the different short forms was assessed using the Bland-Altman method and Student's paired t-test. Construct validity and relative efficiency of the short forms was evaluated by relating the score to age, sex and educational attainment. RESULTS: Two short forms were derived from the DataK-RA item bank that satisfied all content constraints. Both short forms included 15 unique items and yielded reliable scores (r > 0.70), with low ceiling and floor effects. The short forms yielded statistically indistinguishable mean scores according to Student's paired t-test and Bland-Altman analysis. Scores on short forms 1 and 2 were associated with age, sex and educational attainment to a similar extent. CONCLUSION: In this study, we developed two DataK-RA short forms with unique items, yet similar psychometric properties, that can be used to assess patients pre- and post-test interventions aimed at improving disease-related knowledge in RA patients.

Cost-Effectiveness of a JAK1/JAK2 Inhibitor vs a Biologic Disease-Modifying Antirheumatic Drug (bDMARD) in a Treat-to-Target Strategy for Rheumatoid Arthritis.

BACKGROUND: Baricitinib is a janus kinase (JAK1/JAK2) inhibitor developed for the treatment of patients suffering from rheumatoid arthritis (RA). Treating RA to the target of remission is current common practice. Cost-effectiveness of different treat-to-target (T2T) strategies, especially ones including new treatments is important for development and preference policy for treatment centers. European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) guidelines are currently unclear about preference between a JAK1/JAK2 versus a biological disease-modifying antirheumatic drug (bDMARD). OBJECTIVE: The main goal of this paper was to evaluate the cost-effectiveness of baricitinib versus first biological for methotrexate inadequate responders in a T2T strategy using a Markov model that incorporates hospital costs as well as societal costs. Costs and utilities over five years were compared between the two strategies. METHODS: A Monte Carlo simulation model was developed to conduct cost-utility analysis from the societal perspective over 5 years. Health states were based on the DAS28-erythrocyte sedimentation rate (ESR) categories. Effectiveness of baricitinib was retrieved from randomized controlled trials. Effectiveness of all other treatments, health state utilities, medical costs, and productivity loss were retrieved from the Dutch RhEumatoid Arthritis Monitoring (DREAM) cohorts. Annual discount rates of 1.5% for utility and 4% for costs were used. Probabilistic sensitivity analysis was employed to incorporate uncertainty and assess robustness of the results. RESULTS: Probabilistic sensitivity analysis results showed the baricitinib strategy yielded lower costs and higher utility over a 5-year period. Scenario analyses showed the baricitinib strategy to be cost-effective in both the moderate and severe RA populations. CONCLUSION: Results suggest that the use of a JAK1/JAK2 inhibitor instead of a bDMARD in a T2T approach is cost-effective in csDMARD refractory RA patients.

Disease activity-based management of rheumatoid arthritis in Dutch daily clinical practice has improved over the past decade.

To re-evaluate the adherence to clinical practice guidelines recommended disease activity-based management of rheumatoid arthritis (RA) in daily clinical practice, among Dutch rheumatologists in the past decade. In 2007, disease activity was measured in only 16% of outpatient visits. All rheumatologists that participated in the 2007 study were invited to re-enter our study in 2016/2017. If necessary, data were supplemented with data from other rheumatologists. For all 26 rheumatologists who agreed to participate in our study, data were collected from 30 consecutive patients that visited the outpatient clinic. Per patient, data from four consecutive rheumatologist outpatient visits were collected. Since 2007, disease activity was measured more frequently in Dutch daily clinical practice, increasing from 16 to 79% of visits (2440/3081 visits). In addition, intensification of medication based on disease activity scores increased from 33 to 50% of visits (260/525 visits). DAS/DAS28 was the most frequently used disease activity measure (1596/2440 visits). There was a wide variation among rheumatologists in measuring disease activity and intensification of medication, 20-100% and 0-75% respectively. Over the past years, there has been a large improvement in disease activity assessment in daily clinical practice. Disease activity-based medication intensifications, also called tight control or treat to target, increased to a lesser extent. Large variation between different rheumatologists and clinics indicates that there is still room for improvement. Key Points • Following guideline dissemination disease activity is assessed more frequently (79%). • There is large variation between rheumatologists, indicating room for improvement. • Finding factors that explain variation is necessary to improve tight control in daily practice.

A goal management intervention for patients with polyarthritis and elevated levels of depressive symptoms: a quasiexperimental study.

Purpose: Goal was to establish whether an intervention that aims to increase goal management competencies is effective in decreasing elevated levels of depressive symptoms and increasing well-being in patients with polyarthritis.Materials and methods: Eighty-five persons with polyarthritis and elevated levels of depressive symptoms participated in the goal management intervention consisting of six group-based meetings. A quasiexperimental design with baseline measurement, follow-up at 6 months and a reference group of 151 patients from an observational study was applied. Primary outcome was depression; secondary outcomes were anxiety, purpose in life, positive affect, satisfaction with participation, goal management strategies, and arthritis self-efficacy. A linear mixed model procedure was applied to evaluate changes in outcomes.Results: No improvement was found for depressive symptoms and no changes were found for the secondary outcomes, except for positive affect that improved in the intervention group. This increase was mediated by an increase in goal adjustment. Furthermore, goal maintenance decreased and self-efficacy for other symptoms increased in the intervention group.Conclusion: This study indicates that interventions designed to aid patients with arthritis with goal management skills are potentially helpful for increasing positive affect, although further studies are needed.Implications for rehabilitationPeople with polyarthritis have to manage their disease in combination with possibly conflicting roles and personal goals, resulting in an ongoing process of finding equilibrium in a constantly changing situation.Based on a person-focused view, the program Right on Target focused on coping with threatened activities and life goals due to arthritis.The program consisted of six group-based meetings led by a trained nurse and a personal trajectory wherein participants were stimulated to try out various behavioral options related to an own threatened activity in concordance with their personal goals.The program seemed effective in increasing flexible goal adjustment and self-efficacy and participants experienced more positive affect directly after the program and at 6-month follow-up.

Taking the patient and the patient's perspective into account to improve outcomes of care of patients with musculoskeletal diseases.

Patient-reported outcome measures are commonly used in the assessment of patients with musculoskeletal diseases. The present review provides an overview of historic and recent developments, including core set recommendations for assessing patient-reported outcomes in patients with fibromyalgia, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The evidence supporting commonly used patient-reported outcomes measures is reviewed. Furthermore, various methodological approaches that can be utilized to evaluate validity and measurement precision of patient reported outcomes are introduced. Commonly used methods based on the classical test theory as well as modern approaches based on item response theory will be discussed. The review finally describes the increasing use of item response theory-based approaches used in patient-reported outcomes assessment in the musculoskeletal diseases.

[The next step in the treatment of immune diseases: jakinibs, inhibitors of the intracellular Janus kinase]. / Nieuwe stap in behandeling van immuunziekten.

The next step in the treatment of immune diseases: jakinibs, inhibitors of the intracellular Janus kinase The intracellular Janus kinase (JAK) and the signal transduction and activator of transcription (STAT) proteins are involved in the whole spectrum of immune-mediated diseases. Currently, agents are developed that influence the JAK-STAT mechanism. JAK inhibitors (jakinibs) have only recently made their way into clinical practice. These agents exhibit both similarities and differences in terms of effectiveness and safety. In the coming years, results from basic and clinical research will improve our knowledge of these agents. For patients who suffer from immune-mediated diseases, their introduction appears to be a breakthrough that will offer new treatment options. One advantage over biologicals is that jakinibs can be taken orally. As with all new innovative medicines, with jakinibs one cannot escape a discussion over costs as well. The balance between the added value of jakinibs compared to biologicals, and the actual purchase prices for each of these treatment modalities, will influence the eventual positioning of jakinibs.

Predictors of biologic-free disease control in patients with rheumatoid arthritis after stopping tumor necrosis factor inhibitor treatment.

BACKGROUND: The aim of this study was to identify predictors of prolonged disease control after discontinuation of tumor necrosis factor inhibitor (TNFi) treatment in patients with rheumatoid arthritis (RA). METHODS: Post-hoc analysis of 439 RA patients (67.3% rheumatoid factor positive) with longstanding RA in remission or with stable low disease activity, randomized to stopping TNFi treatment in the multicenter POET trial. Prolonged acceptable disease control was defined as not restarting TNFi treatment within 12 months after stopping. Baseline demographic and disease-related variables were included in univariate and multivariate logistic regression analysis for identifying predictors of relapse. RESULTS: One year after baseline, 220 patients (50.1%) had not restarted TNFi treatment. Use of an anti-TNF monoclonal antibody (versus a receptor antagonist, OR = 2.41; 95% CI: 1.58-3.67), ≤10 yrs. disease duration (OR = 2.15; 95% CI: 1.42-3.26) and low or moderate multi-biomarker disease activity (MBDA) scores (OR = 2.00; 95% CI: 1.10-3.64) at baseline were independently predictive of successful TNFi discontinuation (area under the receiver operating characteristic curve = 0.66; 95% CI: 0.61-0.71). Results were similar when using no physician-reported flare as the criterion. TNFi-free survival was significantly different for patient groups based on the number of predictors present, ranging from 21.4% of patients with no predictor present to 66.7% of patients with all three predictors present. CONCLUSION: Patients using an anti-TNF monoclonal antibody, with shorter disease duration and low or moderate baseline MBDA score are most likely to achieve prolonged disease control after TNFi discontinuation. TRIAL REGISTRATION: Netherlands Trial Register NTR3112, 21 October 2011.

Long-term clinical, functional, and cost outcomes for early rheumatoid arthritis patients who did or did not achieve early remission in a real-world treat-to-target strategy.

OBJECTIVE: To retrospectively compare the long-term clinical, functional, and cost outcomes for early RA patients (symptoms < 1 year) who did or did not achieve early remission in a treat-to-target strategy. METHOD: Five-year data of 471 patients included in the DREAM remission induction cohort were used. Patients were treated according to a pre-specified 28-joint Disease Activity Score (DAS28) remission driven step-up treatment strategy starting with methotrexate, addition of sulfasalazine, and exchange of sulfasalazine for biological medication in case of failure. Two- and 3-year healthcare costs were available for selected subsamples of patients only. RESULTS: DAS28 remission was achieved in 27.7%, 38.2%, and 51.6% of patients at 2, 3, and 6 months, respectively. Achieving DAS28 remission at 2, 3, or 6 months was consistently associated with significantly lower DAS28 and Health Assessment Questionnaire-Disability scores at 1, 3, and 5 years of follow-up (all P values < 0.02). Patients in remission at 2, 3, or 6 months also had significantly lower medication costs per patient over the first 2 and 3 years of treatment, mainly due to lower biologic use, but differences in total healthcare resource costs (hospital admissions plus consultations) were less pronounced. Mean total medication and total healthcare resource costs at 3 years were €1131 and €1757 for patients in remission at 6 months vs. €7533 (P < 0.01) and €2202 (P = 0.09) for those not in remission. CONCLUSION: Achieving early remission was associated with beneficial clinical outcomes for early RA patients and lower costs in the long term. Key Points • Previous studies in rheumatoid arthritis patients have demonstrated that early good response is associated with sustained remission and better long-term clinical outcomes. • This study extents these findings by examining the long-term benefits of achieving early remission on clinical, patient-reported, and economic outcomes in a real-world cohort of patients with very early rheumatoid arthritis treated according to treat-to-target principles. • The findings of this study clearly demonstrate that aiming for early remission in rheumatoid arthritis patients is beneficial in the long-term in terms of better clinical and functional outcomes and lower healthcare costs.

A systematic literature review of patient-reported outcome measures used in gout: an evaluation of their content and measurement properties.

BACKGROUND: Gout is a common, monosodium urate crystal-driven inflammatory arthritis. Besides its clinical manifestations, patients often also suffer from pain, physical impairment, emotional distress and work productivity loss, as a result of the disease. Patient-reported outcome measures (PROMs) are commonly used to assess these consequences of the disease. However, current instrument endorsements for measuring such outcomes in acute and chronic gout clinical settings are based on limited psychometric evidence. The objective of this systematic literature review was to identify currently available PROMs for gout, and to critically evaluate their content and psychometric properties, in order to evaluate the current status regarding PROMs for use in gout patients. METHODS: Systematic literature searches were performed in the PubMed and EMBASE databases. The methodological quality of included papers was appraised using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist, and evaluation of measurement properties (reliability, responsiveness, construct validity, floor and ceiling effects) was done in accordance with published quality criteria. Item content was appraised by linking health concepts to the International Classification of Functioning Disability and Health (ICF) framework. RESULTS: In total, 13 PROMs were identified, of which three were targeted specifically at gout patients. The majority of the PROMs were rated positively for content validity. For most instruments, limited evidence was available for construct validity and reliability. Instruments to assess pain scored well on responsiveness and floor and ceiling effects, but not much is known about their reliability in gout. CONCLUSIONS: The physical functioning subscale of the SF-36v2 (Short Form-36 item version 2) is the only PROM that had sufficient supporting evidence for all its psychometric properties. Many of the commonly used PROMs in gout are currently not yet well supported and more studies on their measurement properties are needed among both acute and chronic gout populations.

Psychometric properties and cross-language equivalence of the revised Bristol Rheumatoid Arthritis Fatigue and the Rheumatoid Arthritis Impact of Disease scales in rheumatoid arthritis.

OBJECTIVE: To assess psychometric properties and cross-language measurement equivalence of six versions of the Bristol Rheumatoid Arthritis Fatigue Scale (BRAF-MDQ) and the Rheumatoid Arthritis Impact of Disease Score (RAID in rheumatoid arthritis (RA). METHODS: Both questionnaires were completed by French (n = 206), German (n = 206), Dutch (n = 317), Spanish (n = 157), Swedish (n = 170) and UK (n = 210) RA patients. The presence of cross-language differential item functioning (DIF) was examined using the generalized partial credit model. The impact of DIF on the item and total scores was examined by comparing DIF unadjusted and DIF adjusted expected item and scale scores. IRT-based methods were used to assess psychometric properties of the instruments. RESULTS: 11 of the 20 BRAF-MDQ (55%) and 4 of the 7 RAID items (57%) exhibited significant DIF in at least one of the six countries. The mean number of items with DIF per country was 2.6 for BRAF-MDQ and 1.1 for RAID. However, the impact of DIF on the total RAID and BRAF-MDQ scores, as well as the BRAF subscales, was found to be negligible at the group level. Only for the BRAF physical subscale was there evidence of minor DIF. Marginal reliabilities of BRAF-MDQ (0.93) and RAID (0.89) were excellent, and precise scores could be obtained across the spectrum of disease impact and fatigue scores measured by these PROMs. CONCLUSION: This study supports the cross-language measurement equivalence of BRAF-MDQ and RAID and provides further support for the psychometric properties of these measures in RA.

Development and validation of a patient-reported gout attack intensity score for use in gout clinical studies.

OBJECTIVE: Inflammation-related symptoms such as pain, swelling and tenderness of the affected joint are frequently assessed using 5-point diary rating scales in gout clinical trials. Combining these into a single gout attack symptom intensity score may be a useful summary measure for these data, which is potentially more responsive to change compared with the individual components. The objective of this study was to develop a patient-reported gout flare intensity score, the Gout Attack Intensity Score (GAIS), for use in clinical studies, that includes components for gout-related pain, swelling and tenderness. METHODS: Data from a randomized controlled trial comparing anakinra to standard of care for the treatment of acute gout attacks were used for this study. A 7-day flare diary was completed by patients, including questions relating to intensity of pain, swelling and tenderness (5-point rating scales). Scalability of these items was assessed using Mokken Scale Analysis, and reliability using greatest lower bound reliability coefficients. Known-groups validity was evaluated, as well as the responsiveness to change and the presence of floor and ceiling effects. RESULTS: Scalability of the single items was supported, and GAIS scores were reliable (greatest lower bound >0.80). GAIS scores demonstrated responsiveness to change with high effect sizes (>0.8), and discriminated better between responders and non-responders compared with its single-item components. No floor and ceiling effects were found. CONCLUSION: The GAIS seems to be a reliable and responsive instrument for assessing patient-reported gout attack intensity that may be used in gout clinical studies.

Anakinra for the treatment of acute gout flares: a randomized, double-blind, placebo-controlled, active-comparator, non-inferiority trial.

OBJECTIVES: To evaluate the efficacy and safety of anakinra in treating acute gout flares in a randomized, double-blind, placebo-controlled, active comparator, non-inferiority (NI) trial. METHODS: Patients with a crystal-proven acute gout flare were randomized (1: 1) to treatment with anakinra or treatment as usual (free choice: either colchicine, naproxen or prednisone). The primary end point was the change in pain between baseline and the averaged pain score on days 2-4 measured on a five-point rating scale. NI of anakinra would be established if the upper bound of the 95% CI of the numeric difference in changed pain scores between treatment groups did not exceed the NI limit of 0.4 in favour of treatment as usual, in the per-protocol (PP) and intention-to-treat (ITT) populations, assessed in an analysis of covariance model. Secondary outcomes included safety assessments, improvement in pain, swelling, tenderness and treatment response after 5 days, assessed using linear mixed models and binary logistic regression models. RESULTS: Forty-three patients received anakinra and 45 treatment as usual. Anakinra was non-inferior (mean difference; 95% CI) to treatment as usual in both the PP (-0.13; -0.44, 0.18) and ITT (-0.18; -0.44, 0.08) populations. No unexpected or uncommon (serious) adverse events were observed in either treatment arm. Analyses of secondary outcomes showed that patients in both groups reported similar significant reductions in their gout symptoms. CONCLUSION: Efficacy of anakinra was shown to be non-inferior to treatment as usual for the treatment of acute gout flares, suggesting that anakinra is an effective treatment alternative for acute gout flares. TRIAL REGISTRATION: Het Nederlands Trial Register, www.trialregister.nl, NTR5234.

International Consortium for Health Outcome Measurement Set of Outcomes That Matter to People Living With Inflammatory Arthritis: Consensus From an International Working Group.

OBJECTIVE: The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. RESULTS: The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. CONCLUSION: We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.