The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire: predicting clinical arthritis development.

OBJECTIVE: There is a need to better define symptom characteristics associated with arthritis development in individuals at risk of rheumatoid arthritis (RA). We investigated whether reported symptoms in at-risk individuals could predict arthritis development and whether predictive symptoms differed between seropositive and seronegative at-risk individuals. METHOD: At-risk individuals from four cohorts (Netherlands, UK, Sweden, and Switzerland) completed the Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire. Participants had either (i) anti-citrullinated protein antibodies and/or rheumatoid factor, or (ii) relevant symptoms with or without RA antibodies. Follow up was ≥ 24 months or until clinical arthritis development. Stepwise forward selection created SPARRA prediction models for the combined group and for a seropositive subgroup. RESULTS: Of 214 participants, the mean age was 50 years, 67% were female, and 27% (n = 58) developed clinical arthritis after a median time of 7 months. Four symptoms predicted arthritis development: self-reported joint swelling, joint pain moving from side to side (combined group only), feeling pins and needles in the joints, and often feeling fatigued (predicting non-arthritis). CONCLUSION: Specific symptoms can provide useful information to estimate a person's RA risk. Differences in predictive symptoms between seropositive and seronegative at-risk individuals need to be further investigated. Future research is needed to determine whether changes in symptoms over time improve prediction and to determine the value of SPARRA in optimizing the selection of individuals who need to consult a rheumatologist.

Who stop telemonitoring disease activity and who adhere: a prospective cohort study of patients with inflammatory arthritis.

BACKGROUND: The use of frequent electronic patient reported outcome measures (ePRO's) enables monitoring disease activity at a distance (telemonitoring) in patients with inflammatory arthritis. However, telemonitoring studies report declining long-term adherence to reporting ePRO's, which may oppose the benefits of telemonitoring. Therefore, the objective was to investigate what factors are associated with (non-)adherence to telemonitoring with a weekly ePRO in patients with inflammatory arthritis (IA). METHODS: We performed a prospective cohort study in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) at Reade Amsterdam, The Netherlands. Patients telemonitored their disease activity weekly for 6 months with a modified Multidimensional Health Assessment Questionnaire completed in a smartphone application. The primary outcome was time to dropout, defined as ≥ 4 weeks of consecutively nonresponse. Based on literature and through expert meetings, a predefined set of 13 baseline factors were selected to assess the association with time to dropout through a multivariable Cox-regression analysis. RESULTS: A total of 220 consecutive patients were included (mean age 54, SD 12; 55% females; 99 RA, 81 PsA, and 40 AS). A total of 141 patients (64%) dropped out, with a median time to dropout of 17 weeks (IQR 9-26). Women had a significant higher chance to dropout over 6 months compared to men (HR 1.58, 95% CI 1.06-2.36). CONCLUSION: In the set of investigated factors, women stopped reporting the weekly ePRO sooner than men. Future focus group discussions will be performed to investigate the reasons for dropout, and in specific why women dropped out sooner. Trial registration This trials was prospectively registered at www.trialregister.nl (NL8414).

The RAPID3 questionnaire as a screening tool to reduce the number of outpatient clinic visits: a retrospective cohort study.

BACKGROUND: Treat-to-target strategies require frequent on-site evaluations of disease activity in patients with rheumatoid arthritis (RA), burdening patients and caregivers. However, this frequency may not be required in patients in a stable low disease activity state. The Routine Assessment of Patient Index Data 3 (RAPID3) is a reliable tool to detect such states in groups but has not been tested to reduce the frequency of on-site evaluations in individual patient care. In Reade, an outpatient rheumatology clinic, patients can complete the questionnaire online prior to consultation, and the results are directly fed into the electronic patient record. Focusing on low disease activity, we retrospectively studied the test characteristics of RAPID3 and its agreement with the DAS28 in our database of routine patient care. OBJECTIVE: To assess the test characteristics and agreement between de DAS28 and the RAPID3 in patients with RA, with a focus on the low disease activity categories. METHODS: We performed a retrospective database study with available clinical data collected as part of usual care from the electronic medical record at Reade Amsterdam. The dataset comprised RAPID3 assessments followed by a DAS28 within 2 weeks, obtained between June 2014 and March 2021. We dichotomized the disease activity categories for both the RAPID3 and DAS28 into low (remission and low disease activity) and high (moderate and high disease activity). With cutoff values of 2.0 for RAPID3 and 3.2 for DAS28, we calculated test characteristics and agreement (Cohen's kappa). RESULTS: A total of 5009 combined RAPID3 and DAS28 measurements were done at Reade in 1681 unique RA patients. The mean age was 60 years, and 76% of patients were female with a median disease duration of 4 years. Agreement was considered fair (kappa = 0.26). In total, 1426 (28%) of the RAPID3 measurements were classified as low and could be potentially targeted to skip their consultations. The sensitivity to detect low disease activity was 0.39, specificity was 0.93, and the positive predictive value was 0.92. CONCLUSION: We showed that when the RAPID3 classifies a patient into low disease activity state, the accuracy is 92%. Of all consultations, 28% could possibly be postponed following the screening with RAPID3.

Disease activity in women with ankylosing spondylitis remains higher under Tumour Necrosis Factor inhibitor treatment than in men: a five-year observational study.

OBJECTIVE: To assess sex differences in response, level of disease activity, and drug survival in tumour necrosis factor inhibitor (TNFi)-naïve ankylosing spondylitis (AS) patients. METHOD: Consecutive AS patients, fulfilling the modified New York criteria, were included in a prospective cohort study at initiation of the first TNFi and followed until this medication was stopped (drug survival). Disease activity scores [AS Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), and CRP] were measured at 3, 6, and 12 months, and every subsequent year, up to 5 years. The response was defined by the ASDAS-CRP response criteria (clinically important improvement: ASDAS-CRP decrease ≥ 1.1). Analyses included regression methods for repeated measurements and survival analyses. RESULTS: Overall, 356 patients were included (34% women, mean ± sd age 46 ± 12 years), with a median disease duration of 12 (interquartile range 6;20) years. Women were less likely than men to achieve a clinically important response after 6 months of TNFi treatment (47% vs 64%; relative risk 1.4, 95% confidence interval (CI) 1.1;1.9, p = 0.02], despite a lack of sex differences in mean ASDAS-CRP levels over 5 year follow-up. Adjusted models for BASDAI over 5 years showed that women had a 0.6 point higher BASDAI score than men (ß = 0.6 0.1;1.1 <0.02). Numerically, more women than men discontinued treatment over a period of 5 years (hazard ratio = 1.5, 95% CI 0.9;2.5, p = 0.15). CONCLUSION: Female AS patients show a lower response to TNFi and a higher disease activity compared to men.

Accuracy of an algorithm to identify rheumatoid arthritis in the Longitudinal Ageing Study Amsterdam population: a validation study.

Objective: In view of global ageing and the scarcity of knowledge about disease determinants in older individuals with rheumatoid arthritis (RA), an algorithm with optimal diagnostic accuracy was developed to identify RA patients in the Longitudinal Ageing Study Amsterdam (LASA).Method: Four case ascertainment algorithms were constructed and assessed for validity in LASA, an ongoing cohort study (≥ 55 years) representing the general older population of the Netherlands. Data sources used to identify the diagnosis RA were: self-reported morbidity, specialist diagnosis, and medication. A validation subsample of LASA participants was taken to verify RA diagnosis by a standard procedure using a checklist.Results: Data from 272/300 (91%) participants were verified. Four algorithms were developed: 'treatment', 'diagnosis', 'treatment or diagnosis', and 'treatment and diagnosis'. The algorithm 'treatment and diagnosis' showed the best measurement properties: specificity 100%, positive predictive value 100%, and area under the receiver operating characteristics curve 0.72. Applying this algorithm in the LASA sample (mean age 71 years) revealed a prevalence of RA of 1.0% (19/1908 participants).Conclusion: An algorithm for RA identification in the LASA population was developed, with high diagnostic accuracy. It provides an accurate tool to identify older adults with RA in LASA and, after validation, may be applicable in other large population-based studies.

Long-term effects on bone mineral density after four years of treatment with two intensive combination strategies, including initially high-dose prednisolone, in early rheumatoid arthritis patients: the COBRA-light trial.

In this study, no difference in bone loss was observed between patients with early RA initially treated with COmbinatietherapie Bij Reumatoide Artritis (COBRA) (including initially 60 mg/day prednisolone) and patients treated with COBRA-light (including initially 30 mg/day prednisolone) during 4-year observation. PURPOSE: To assess changes in bone mineral density (BMD) after 4 years in early rheumatoid arthritis (RA) patients initially treated with COBRA-light or COBRA therapy. METHODS: In a 1 year, open-label, randomised, non-inferiority trial, patients were assigned to COBRA-light (methotrexate 25 mg/week plus initially prednisolone 30 mg/day) or COBRA (methotrexate 7.5 mg/week, sulfasalazine 2 g/day plus initially prednisolone 60 mg/day) therapy. After 1 year, antirheumatic treatment was at the discretion of treating rheumatologists. BMD was measured at baseline and after 1, 2 and 4 years at hips and lumbar spine with dual-energy X-ray absorptiometry. BMD changes between treatment strategies on average over time were compared with GEE analysis. RESULTS: Data from 155 out of 162 patients could be analysed: 68% were female with a mean age of 52 (SD 13) years. Both COBRA-light and COBRA therapy showed declines in BMD at the total hip of -3.3% and -1.7%, respectively (p = 0.12), and the femoral neck, -3.7% and -3.0%, respectively (p = 0.95). At the lumbar spine, both treatment groups showed minor decline in BMD over 4 years: -0.5% and -1.0%, respectively (p = 0.10). CONCLUSION: In a treat-to-target design in early RA, over 4 years, no differences between groups were found in change in BMD at total hip, femoral neck and the lumbar spine. At the hip, bone loss was around 3% in both groups, while mild bone loss was observed at lumbar spine, both in patients starting prednisolone 60 and 30 mg/day. These data suggest that the well-known negative effects of prednisolone can be modulated by modern treatment of RA.

Microvascular changes of the retina in ankylosing spondylitis, and the association with cardiovascular disease - the eye for a heart study.

OBJECTIVE: Ankylosing spondylitis (AS) is associated with an increased risk of cardiovascular disease (CVD). Microvasculature changes can precede overt CVD, but have been studied poorly in AS. The retinal vasculature is easily accessible and changes are associated with CVD (e.g. arteriolar narrowing, venular widening, loss of tortuosity). This proof of concept study compared the retinal microvasculature of AS patients with healthy controls, and the influence of gender. METHODS: Cross-sectional case-control study comparing AS patients with healthy controls. Main inclusion criteria were: age 50-75 years, no diabetes mellitus and, for AS, fulfillment of the modified New York criteria. All subjects underwent fundus photography, analyzed with Singapore I Vessel Assessment software, and Optical Coherence Tomography Angiography (OCTA). Subjects were compared with generalized estimating equations (GEE). Multivariable analyses were adjusted for demographics and cardiovascular risk, and stratified for gender. RESULTS: Fifty-nine AS patients and 105 controls were included (50% women). Controls were significantly older than patients (68 versus 60, p<0.01), but did not differ in cardiovascular profile. Patients had a lower retinal arteriolar tortuosity (ß Ì¶-0.1, 95%CI [-0.2; -0.01], p = 0.02), and higher vessel density (ß 0.5, 95% CI [0.1; 0.9], p = 0.02). In addition, male AS patients showed a lower arteriovenular ratio compared to male controls (ß -0.03, p = 0.04, 95%CI [-0.05; -0.001]). There were no differences found between women with and without AS. CONCLUSION: This study detected several retinal microvascular changes, in AS patients compared to controls, which have been associated with CVD. Retinal imaging might be an interesting tool for future CVD screening.

Predictors of sick leave and improved worker productivity after 52 weeks of intensive treatment in patients with early rheumatoid arthritis.

Objective: To identify predictors of sick leave and improved worker productivity in patients with early rheumatoid arthritis (RA) treated for 52 weeks with intensive combination strategies. Methods: Patients with early RA were included in the COmbinatietherapie Bij Reumatoïde Artritis (COBRA)-light trial and followed for 52 weeks. As the COBRA-light strategy proved to be non-inferior to the COBRA strategy, all patients were pooled. Predictors for sick leave and improved worker productivity were assessed through a 3 month time-lag multivariable logistic generalized estimating equations model. Results: At baseline, 97 patients had a paid job, 59 had no job, and for six patients the work status was unknown. During the trial, 13 patients stopped working (8%) and six started working (4%). Only sick leave in the past 3 months predicted sick leave. By excluding this variable, patient global assessment and actual hours of sick leave became predictors. Increased worker productivity was predicted by higher patient global assessment levels, Sharp van der Heijde score ≥ 1, actual hours on sick leave, and higher worker productivity in the past 3 months. Conclusion: Sick leave and improved worker productivity were mainly predicted by non-disease-specific variables. Both outcomes can be predicted on a 3 month basis, using the outcome over the past 3 months for the next 3 months. By applying this model in daily practice, decisions for therapy change could be based not solely on disease activity but also taking into account a possible high risk for sick leave in the upcoming 3 months.

Screening instruments for identification of vulnerable older adults at the emergency department: a critical appraisal.

BACKGROUND: Early detection of vulnerable older adults at the emergency department (ED) and implementation of targeted interventions to prevent functional decline may lead to better patient outcomes. OBJECTIVE: To assess the level of agreement between four frequently used screening instruments: ISAR-HP, VMS, InterRAI ED Screener and APOP. METHODS: Observational prospective cohort study in patients ≥ 70 years attending Dutch ED. RESULTS: The prevalence of vulnerability ranged from 19% (APOP) to 45% (ISAR-HP). Overall there was a moderate agreement between the screening instruments (Fleiss Kappa of 0.42 (p<0.001)). CONCLUSION: Depending on the screening instrument used, either only a small percentage or almost as many as half of the presenting patients will be eligible for targeted interventions, leading to large dissimilarities in working processes, resources and costs.

Effect of vitamin D supplementation on health status in non-vitamin D deficient people with type 2 diabetes mellitus.

OBJECTIVE: Increased levels of depressive symptoms, fatigue or pain (all dimensions of reduced health-related quality of life (HRQOL)) are common in people with type 2 diabetes mellitus (DM). Earlier studies have reported associations between low vitamin D status and fatigue and depressive symptoms. The aim of the present study was to examine the effects of vitamin D supplementation on dimensions of HRQOL in people with type 2 DM. DESIGN: Randomised, double-blind, placebo-controlled trial. METHODS: The effect of monthly cholecalciferol 50,000 IU vs placebo on HRQOL was assessed in 275 adults with type 2 DM derived from general practices. HRQOL at baseline and after six months using the Short Form 36 Health Survey (SF-36) was collected. Linear regression analyses were used to compare the change in HRQOL over time between the vitamin D and placebo group. RESULTS: 187/275 (68%) completed baseline and follow-up SF-36 and were included in the analysis. Median serum 25-hydroxyvitamin D almost doubled in the intervention group compared to that in the placebo group (58.5-106.0 nmol/L vs 60.0-61.5 nmol/L, respectively). A small significant difference (adjusted B: -8.90; 95% CI: -17.16 to -0.65) between both groups was seen concerning the SF-36 domain role limitations due to physical problems in disadvantage of the vitamin D group. CONCLUSIONS: Six months of vitamin D supplementation did not improve HRQOL in non-vitamin D-deficient people with type 2 DM managed on oral antidiabetic therapy.

Indirect costs account for half of the total costs of an osteoporotic fracture: a prospective evaluation.

UNLABELLED: Data on direct and indirect costs of clinical fractures in 116 osteoporotic patients 50 years and older were prospectively collected using cost diaries. Indirect costs accounted for roughly half of the total costs, with a contribution of at least 81% of these costs in employed patients. INTRODUCTION: The aim of this prospective study was to gain insight into the current total costs of clinical fractures in osteoporotic patients aged 50 years and older. METHODS: In a study in the Netherlands, patients prospectively filled out cost diaries every 3 months, during 1 year after a clinical fracture. Primary analyses were performed on those patients with all four cost diaries returned. In-depth analyses of indirect costs were performed, dividing results for employed and unemployed patients. Sensitivity analyses using imputation techniques were performed on patients who returned two or three diaries RESULTS: Of the 116 included patients, 69 completed all four diaries, 24 only two or three, and 23 patient completed one or no diaries. For all fractures, approximately 50% of the total costs were due to indirect costs; employed patients contributed for at least 81% of the indirect cost. Humerus fractures were most expensive with a total 1-year cost of €16.841 per patient. Indirect costs in the group with clinical spine fractures were highest (12.522), accounting for 89.1% of the total costs for this fracture. CONCLUSION: Indirect costs account for roughly half of the total costs of clinical fractures, which are largely related to sick leave. When performing cost analyses in fracture patients, we advise a societal perspective in which indirect costs are also considered, and to apply a patient derived prospective data collection method to get a 'true' and complete image of the total costs due to clinical fractures.

The effect of biological agents on work participation in rheumatoid arthritis patients: a systematic review.

This study reviewed the effect of biological agents on participation in paid work among patients with rheumatoid arthritis (RA). A systematic literature search was performed to identify published articles reporting the effect of biological agents on employment status, sick leave and/or presenteeism. The quality of included articles was assessed according to the guidelines as proposed by the Dutch Cochrane Centre. Narrative summaries were used to present the data separately for randomised controlled trials (RCTs) as well as controlled and uncontrolled cohort studies. 19 studies (six uncontrolled cohorts, seven controlled cohorts and six RCTs) were included, in which 11 259 patients were treated with biological agents. Employment status improved in four out of 13 studies, absence from work in all 10 studies and presenteeism in seven out of nine studies that reported this outcome. For absenteeism and presenteeism the statistical significance of change or difference was not always provided and results within studies were sometimes conflicting when using different time frames or alternative outcomes. The large heterogeneity in terms of population, design, analyses and most important in outcome measures limits interpretation of the data. RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying antirheumatic drugs (DMARD), continuing the failing DMARD, the general population or the situation before the start of biological agents. The effect on employment status was more conflicting, but 50% of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status.