Do we need bone mineral density to estimate osteoporotic fracture risk? A 10-year prospective multicentre validation study

Objective Evaluate the performance of FRAX®, with and without bone mineral densitometry (BMD), in predicting the occurrence of fragility fractures over 10 years. Methods Participants aged ≥40 years at baseline, with a complete set of data and a minimum of 8.5 years of follow-up were identified from three cohorts (n=2626). Ten-year fracture risk at baseline were estimated with FRAX® and assessed by comparison with observed fractures and receiver operating characteristic analysis. Results During a mean (SD) follow-up of 9.12 (1.5) years, 178 participants suffered a major osteoporotic (MOP) fracture and 28 sustained a hip fracture. The predictive performance of FRAX® was superior to that of BMD alone for both MOP and hip fractures. The area under the curve (AUC) of FRAX® without BMD was 0.76 (95% CI 0.72 to 0.79) for MOP fractures and 0.78 (95% CI 0.69 to 0.86) for hip fractures. No significant improvements were found when BMD was added to clinical variables to predict either MOP (0.78, 95% CI 0.74 to 0.82, p=0.25) or hip fractures (0.79, 95% CI 0.69 to 0.89, p=0.72). AUCs for FRAX® (with and without BMD) were greater for men than for women. FRAX®, with and without BMD, tended to underestimate the number of MOP fractures and to overestimate the number of hip fractures in females. In men, the number of observed fractures were within the 95% CI of the number predicted, both with and without BMD. Conclusion FRAX® without BMD provided good fracture prediction. Adding BMD to FRAX® did not improve the performance of the tool in the general population.This study was supported by unrestricted grants from the Direção Geral da Saúde and Amgen, which had no role in the design of the study, the writing or review of the paper

Psychometric testing of the British English Workplace Activity Limitations Scale in four rheumatic and musculoskeletal conditions

Objectives: The aims were to validate a British English version of the Workplace Activity Limitations Scale (WALS) linguistically, then test this psychometrically in RA, axial spondyloarthritis (axSpA), OA and FM. Methods: The WALS was forward translated, reviewed by an expert panel, and cognitive debriefing interviews were conducted. Participants completed a postal questionnaire booklet. Construct (structural) validity was examined by fit to the Rasch measurement model. Concurrent validity included testing between the WALS and the Work Limitations Questionnaire-25 (WLQ-25). Two weeks later, participants were mailed a second questionnaire booklet for test–retest reliability. Results: Minor wording changes were made to the WALS, then 831 employed participants completed questionnaires: 267 men and 564 women; 53.5 (S.D. 8.9) years of age; with condition duration 7.7 (S.D. 8.0) years. The WALS satisfied Rasch model requirements, and a WALS Rasch transformation table was created. Concurrent validity was strong with the WLQ-25 (RA rs¼0.78; axSpA rs¼0.83; OA rs¼0.63; FM rs¼0.64). Internal consistency was consistent with group use (a¼0.80–0.87). Test–retest reliability was excellent, with intraclass correlation coefficient (2,1) at _0.90. Conclusion: A reliable, valid British English version of the WALS is now available for use in the UK

Not all moderate disease is the same – Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity

Background: United Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA. Methods: The study included biologic-naïve patients receiving csDMARDs only with MDA (3.2 <DAS28≤ 5.1) when recruited to the control cohort of the British Society for Rheumatology Biologics Register–RA (BSRBR-RA). Disability scores, measured using the Health Assessment Questionnaire (HAQ), were recorded every six months for three years. Trajectories of HAQ scores over follow-up were assessed using latent class growth models (LCGMs). Baseline age, gender, DAS28, symptom duration, rheumatoid factor status, number of prior csDMARDs and co-morbidities were assessed as potential predictors of group membership. Results In total, 1274 patients were included (mean age: 61 years (standard deviation: 12), 71.4% women). The best fitting model included seven HAQ trajectories. These trajectories were horizontal over follow-up and were related to baseline HAQ: very-low (6.8%, baseline (BL) HAQ: 0.22), low (11.5%, BL HAQ: 0.41), low-moderate (17.0%, BL HAQ: 0.93), moderate (13.4%, BL HAQ: 1.09), high-moderate (19.5%, BL HAQ: 1.61), severe (23.2%, BL HAQ: 1.98) and very-severe (8.6%, BL HAQ: 2.54). Higher DAS28, older age, female gender, longer disease duration and more co-morbidities were independently associated with higher HAQ trajectory group. Conclusion There is substantial heterogeneity in baseline HAQ scores in this population, and the trajectories of HAQ scores after baseline are, on average, relatively flat. As bDMARD therapy has been shown to improve HAQ scores, patients with MDA but high HAQ scores may benefit from a more aggressive approach to therapy

Differential glucocorticoid metabolism in patients with persistent versus resolving inflammatory arthritis

Introduction: Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis. In the inflamed synovium, cortisol is generated from cortisone by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. The objective of this study was to determine the role of endogenous glucocorticoid metabolism in the development of persistent inflammatory arthritis. Methods: Urine samples were collected from patients with early arthritis (symptoms ≤12 weeks duration) whose final diagnostic outcomes were established after clinical follow-up and from patients with established rheumatoid arthritis (RA). All patients were free of disease-modifying anti-rheumatic drugs at the time of sample collection. Systemic measures of glucocorticoid metabolism were assessed in the urine samples by gas chromatography/mass spectrometry. Clinical data including CRP and ESR were also collected at baseline. Results: Systemic measures of 11β-HSD1 activity were significantly higher in patients with early arthritis whose disease went on to persist, and also in the subgroup of patients with persistent disease who developed RA, when compared with patients whose synovitis resolved over time. We observed a significant positive correlation between systemic 11β-HSD1 activity and ESR/CRP in patients with established RA but not in any of the early arthritis patients group. Conclusions: The present study demonstrates that patients with a new onset of synovitis whose disease subsequently resolved had significantly lower levels of systemic 11β-HSD1 activity when compared with patients whose synovitis developed into RA or other forms of persistent arthritis. Low absolute levels of 11β-HSD1 activity do not therefore appear to be a major contributor to the development of RA and it is possible that a high total body 11β-HSD1 activity during early arthritis may reduce the probability of disease resolution

Biologics registers in RA: methodological aspects, current role and future applications

The beginning of the 21st century saw a biopharmaceutical revolution in the treatment of inflammatory rheumatic diseases, particularly rheumatoid arthritis. The fast-evolving use of biologic therapies highlighted the need to develop registers at national and international levels with the aim of collecting long-term data on patient outcomes. Over the past 15 years, many biologics registers have contributed a wealth of data and provided robust and reliable evidence on the use, effectiveness and safety of these therapies. The unavoidable challenges posed by the continuous introduction of new therapies, particularly with regard to understanding their long-term safety, highlights the importance of learning from experience with established biologic therapies. In this Perspectives article, the role of biologics registers in bridging the evidence gap between efficacy in clinical trials and real-world effectiveness is discussed, with a focus on methodological aspects of registers, their unique features and challenges and their role going forward

Validity of a2-component imaging-derived disease activity score (2C-DAS28) for improved assessment of synovitis in early rheumatoid arthritis

Objectives. Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. Methods. Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). Results. Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (test log-likelihood <2.6, P < 0.01), Larsen score and presence of erosions. Conclusion. A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established

Sick leave and work disability in patients with early arthritis

We studied the occurrence of sick leave and work disability, the presence of workplace adaptations and the usage of professional guidance related to working problems in patients with early arthritis. Inclusion criteria were arthritis symptoms of less than 2 years duration and a paid job at the time of diagnosis. Assessments were done in connection with an early arthritis clinic (EAC) at entry into the cohort and 12 months thereafter by means of a questionnaire comprising questions on sick leave (absenteeism from work reported to the employer), work disability (receiving a full or partial work disability pension), unemployment, work adaptations and professional guidance related to working problems. Fifty-seven of the 69 participants (83%) had an arthritis symptom duration of <6 months. The number of patients with sick leave due to arthritis in the past 12 months decreased from 28 (41%) at study entry to 18 (26%) after 12 months of follow-up. The number of patients receiving a work disability pension increased from 5 (7%) at study entry to 13 (19%) after 12 months of follow-up (10 partial and 3 full). Sick leave in the 12 months before study entry appeared to be the most important predictor of the institution or increase in a work disability pension (odds ratio, 16.1; 95%CI, 1.8–142.8). Between study entry and follow-up, the number of patients with workplace adaptations increased from 20 (29%) to 28 (42%), whereas the number of patients receiving vocational guidance decreased from 48 (70%) to 36 (52%). In patients with early arthritis and a paid job, arthritis-related sick leave was common and occurred in part before patients entered the EAC and a diagnosis was made. About 20% of the patients became permanently work disabled, with partial work disability being more common than full work disability. Considerable proportions of patients received workplace adaptations and professional guidance with working problems