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Objective: Our objective was to evaluate the diagnostic performance of the EULAR, American College of Rheumatology (ACR), and National Institute for Health and Care Excellence (NICE) criteria by using clinical experts' diagnosis of clinically relevant knee osteoarthritis (OA) as the outcome of interest. Methods: In a previous study, we recruited clinical experts to evaluate longitudinal (5‐, 8‐, and 10‐year follow‐up) clinical and radiographic data of symptomatic knees from the Cohort Hip and Cohort Knee (CHECK) study for the presence or absence of clinically relevant OA. In the current study, ACR, EULAR, and NICE criteria were applied to the same 5‐, 8‐, and 10‐year follow‐up data; then a knee was diagnosed with OA if fulfilling the criteria at one of the three time points (F1), two of the time points (F2), or at all three time points (F3). Using clinically relevant OA as the reference standard, the sensitivity, specificity, and positive and negative predictive values for the three criteria were assessed. Results: A total of 539 participants for a total of 833 examined knees were included. Thirty‐six percent of knees were diagnosed with clinically relevant OA by experts. Sixty‐seven percent to 74% of the knees received the same diagnosis (OA or non‐OA) by the three criteria sets for the different definitions (F1 to F3). EULAR consistently (F1 through F3) had the highest specificity, and NICE consistently had the highest sensitivity. Conclusion: The diagnoses only moderately overlapped among the three criteria sets. The EULAR criteria seemed to be more suitable for study enrollment (when aimed at recruiting clinically relevant OA knees), given the highest specificities. The NICE criteria, given the highest sensitivities, could be more useful for an initial diagnosis in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: We developed a smartphone application for patients with rheumatoid arthritis (RA) that allows them to self‐monitor their disease activity in between clinic visits by answering a weekly Routine Assessment of Patient Index Data 3. This study was undertaken to assess the safety (noninferiority in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28‐ESR]) and efficacy (reduction in number of visits) of patient‐initiated care assisted using a smartphone app, compared to usual care. Methods: A 12‐month, randomized, noninferiority clinical trial was conducted in RA patients with low disease activity and without treatment changes in the past 6 months. Patients were randomized 1:1 to either app‐supported patient‐initiated care with a scheduled follow‐up consultation after a year (app intervention group) or usual care. The coprimary outcome measures were noninferiority in terms of change in DAS28‐ESR score after 12 months and the ratio of the mean number of consultations with rheumatologists between the groups. The noninferiority limit was 0.5 difference in DAS28‐ESR between the groups. Results: Of the 103 randomized patients, 102 completed the study. After a year, noninferiority in terms of the DAS28‐ESR score was established, as the 95% confidence interval (95% CI) of the mean ΔDAS28‐ESR between the groups was within the noninferiority limit: −0.04 in favor of the app intervention group (95% CI −0.39, 0.30). The number of rheumatologist consultations was significantly lower in the app intervention group compared to the usual care group (mean ± SD 1.7 ± 1.8 versus 2.8 ± 1.4; visit ratio 0.62 [95% CI 0.47, 0.81]). Conclusion: Patient‐initiated care supported by smartphone self‐monitoring was noninferior to usual care in terms of the ΔDAS28‐ESR and led to a 38% reduction in rheumatologist consultations in RA patients with stable low disease activity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify barriers and solutions for the recruitment and retention of older (aged ≥65 years) people in clinical trials. DESIGN: Systematic literature review. METHODS: Three databases (Medline, Embase, and CENTRAL) were searched for articles reporting on barriers or solutions regarding the recruitment or retention of older people. Only original research articles were included. RESULTS: Fifty eligible articles were identified. Exclusion criteria were the most common cause of poor recruitment of older adults (mainly age and comorbidities). Patients' families or physicians often advised against participation (22% of included studies). Lack of interest (18%) and problems with transportation (18%) were also commonly cited as challenges. Fourteen trials (28%) reported that monitoring and adapting their recruitment methods helped, along with a flexible research team (26%) and provision of transportation (24%). Retention was impaired by death (12%), illness (8%), and loss of interest (6%). Methods with a positive effect on retention included financial incentives and regular information about the progress of the study (12%), a low staff turnover (12%), flexibility in appointment making (10%), and expression of appreciation by the staff through letters, gifts, and cards to the participants (10%). CONCLUSION: We identified several barriers and have listed potential solutions that may improve recruitment and lead to fewer dropouts in trials involving older populations. Implementation of our findings may help mitigate the manifold challenges that come with running a trial with older people. See related editorial by Robison et al. in this issue. [ABSTRACT FROM AUTHOR]

Objective: Pain interference and pain behavior are highly relevant outcomes in patients with rheumatoid arthritis (RA). The Patient‐Reported Outcomes Measurement Information System (PROMIS) is a universally applicable set of item banks measuring patient‐reported health, and if applied as computerized adaptive tests (CATs), more efficiently and precisely than current instruments. The objective was to study the psychometric properties of the Dutch‐Flemish PROMIS pain interference (PROMIS‐PI) and the PROMIS pain behavior (PROMIS‐PB) item banks in patients with RA. Methods: A total of 2,029 patients with RA completed the full PROMIS‐PI (version 1.1, 40 items), and 1,554 patients completed the full PROMIS‐PB (version 1.1, 39 items). The following psychometric properties were studied: unidimensionality, local dependence, monotonicity and graded response model (GRM) fit, cross‐cultural validity (differential item functioning [DIF] for language [Dutch versus Flemish]), other forms of measurement invariance, construct validity, reliability, and floor and ceiling effects. Results: The PROMIS‐PI and PROMIS‐PB banks were sufficiently unidimensional (Omega‐hierarchical [Omega‐H] 0.99, 0.95, and explained common variance 0.95, 0.78, respectively), had negligible local dependence (0.3–1.4% of item pairs), good monotonicity (H 0.75, 0.46), and a good GRM model fit (no misfitting items). Furthermore, both item banks showed good cross‐cultural validity (no DIF for language), measurement invariance (no DIF for age, sex, administration mode, and disease activity), good construct validity (all hypotheses met), high reliability (>0.90 in the range of patients with RA), and an absence of floor and ceiling effects (0% minimum or maximum score, respectively). Conclusion: Both PROMIS‐PI and PROMIS‐PB banks showed good psychometric properties in patients with RA and can be used as CATs in research and clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The elderly, a population defined by an age of ≥65 years, are underrepresented in rheumatology trials, possibly due to investigators' concerns of increased premature discontinuations in higher age groups. The present study was undertaken to evaluate whether the proportion of included elderly individuals (PE) is independently associated with participant retention in rheumatology trials.Methods: Medline was searched for randomized controlled trials (RCTs) in rheumatoid arthritis (RA) and osteoarthritis (OA) of any intervention (years 2016 and 2017). PE was either extracted from the research manuscript or estimated from an assumed (truncated) normal distribution. We used mixed-effects meta-regression models including several covariates to assess whether there is an independent association between PE and participant retention. Using sensitivity analyses, we evaluated whether associations were connected to attrition due to lack of efficacy (LoE) or adverse events (AE).Results: In total, 243 RCTs comprising >48,000 participants were included. Pooled participant retention was 88%. PE was not associated with retention in the unadjusted (P = 0.97) or adjusted (all: P ≥ 0.14) models. Of all covariates, only study duration and type of intervention were associated with retention (both: P < 0.001). Post hoc analyses allowing for interaction revealed a small but statistically significant positive association between PE and retention in pharmacologic interventions and a negative association in physical/physiotherapeutic interventions (overall P for interaction = 0.05). No associations were found for PE and attrition due to LoE or AE.Conclusion: Participant retention in RA and OA trials is high and not associated with PE. These findings should motivate investigators to include more elderly participants in rheumatology trials. [ABSTRACT FROM AUTHOR]

Dr. Yun and colleagues are to be commended for their elegant observational study of the effect of rheumatoid arthritis (RA) disease activity on the chance of hospitalized infection ([1]). Quite apart from this, RA patients taking GCs may be regarded as having more severe disease, possibly introducing the same kind of heterogeneity in the study population that led the authors to exclude patients with high disease activity. They found that disease activity increases the risk of hospitalized infection and identified an independent effect of other factors, including glucocorticoids (GCs) with a dose effect. [Extracted from the article]

Objective: To assess the safety of abatacept treatment in rheumatoid arthritis (RA) using integrated data from multiple clinical trials. Methods: Data from nine double‐blind, placebo‐controlled studies of abatacept treatment (seven intravenous, two subcutaneous) in patients with RA were pooled, focusing on safety events in the double‐blind treatment period of each study. Incidence rates (IRs) of adverse events (AEs) per 100 patient‐years of exposure were calculated for abatacept‐ and placebo‐treated patients. AEs in abatacept‐treated patients were combined regardless of dose and formulation. Results: In total, 2653 patients received abatacept and 1485 received placebo, with 2357 and 1254 patient‐years of exposure, respectively. The mean (SD) durations of exposure in the abatacept and placebo groups were 10.8 (3.3) and 10.3 (3.5) months, respectively. The IRs (95% confidence interval [CI]) for serious AEs were 14.8 (13.3, 16.5) and 14.6 (12.5, 17.0) in the abatacept and placebo groups, respectively. Death occurred in 12 (0.5%) and 12 (0.8%) patients in the abatacept and placebo groups, respectively, and was most commonly caused by cardiac disorders. Malignancies were observed in 31 patients (1.2%) treated with abatacept (IR: 1.32 [95% CI: 0.90, 1.87]) versus 14 (0.9%; IR: 1.12 [0.61, 1.88]) who received placebo. Solid organ tumor was the most frequent malignancy reported in both groups (abatacept: 1.0%; IR: 1.11 [95% CI: 0.72, 1.62]; placebo: 0.8%; 0.96 [0.50, 1.67]). Conclusion: In this integrated analysis, the IRs of safety events in the abatacept and placebo groups were similar with no new safety concerns identified. [ABSTRACT FROM AUTHOR]

Objective: The Outcome Measures in Rheumatology (OMERACT) 3×3 method analyzes the occurrence of benefit and harm simultaneously at the individual patient level. We applied this method to 2 recent rheumatoid arthritis (RA) trial data sets.Methods: The Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) and the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) randomized trial outcomes for safety were defined according to OMERACT as having no adverse events (AEs), non-serious AEs, and serious AEs. Treatment efficacy was defined as good, moderate, or no response. A good treatment response without any AEs was labeled an unqualified success, and no treatment response but at least 1 AE was considered an unmitigated failure. The association between benefit and harm was assessed by chi-square or exact tests, as appropriate.Results: In TEAR, 612 of 755 patients had response data at 48 weeks: 14% of patients experienced unqualified success and 9% had unmitigated failure, with no difference between the treatment arms. Treatment response and AE rates were not correlated. In RACAT, 309 of 353 patients had response data at 48 weeks: 6% of patients experienced unqualified success and 11% had unmitigated failure, with no differences between the treatment arms. Response and AE rates were negatively correlated. The frequency of AEs and serious AEs increased as response decreased (P = 0.008).Conclusion: We found some evidence that clinical response may be reduced by the co-occurrence of AEs. [ABSTRACT FROM AUTHOR]

Objective: The Animated Activity Questionnaire (AAQ) assesses activity limitations in patients with hip/knee osteoarthritis and consists of video animations; the patients choose the animation that best matches their own performance. The AAQ has shown good validity and reliability. This study aims to evaluate cross-cultural and construct validity of the AAQ.Methods: Cross-cultural validity was assessed using ordinal logistic regression analysis to evaluate differential item functioning (DIF) across 7 languages. Construct validity was assessed by testing correlations between the AAQ and a patient-reported outcome measure (PROM) and performance-based tests.Results: Data from 1,239 patients were available. Compared to the Dutch language (n = 279), none of the 17 items showed DIF in English (n = 202) or French (n = 193), 1 item showed uniform DIF in Spanish (n = 99) and Norwegian (n = 62), and 2 items showed uniform DIF in Danish (n = 201). In all these languages, the occurrence of DIF did not influence the total score, which remained comparable with the original Dutch version. For Italian (n = 203) versus Dutch, however, 6 items showed uniform DIF, and 1 item showed nonuniform DIF, indicating some problems with the cross-cultural validity between these countries. With regard to construct validity, the correlations with PROM (0.74) and performance-based tests (0.36-0.68) were partly as expected (>0.60).Conclusion: The AAQ, an innovative tool to measure activity limitations that can be placed on the continuum between PROMs and performance-based tests, showed a good overall cross-cultural validity, and seems to have great potential for international use in research and daily clinical practice in many European countries. [ABSTRACT FROM AUTHOR]

Objective: To describe the perception of the current role of systemic glucocorticoids in the management of rheumatoid arthritis (RA) by examining their importance and the current level of evidence in recent guidelines, and to identify open questions to be addressed in future guidelines and research projects.Methods: We conducted a systematic literature review using the databases Ovid Embase, PubMed Medline, and Cochrane Library for guidelines on the pharmacologic treatment of RA. Retrieved articles were evaluated regarding their quality using the Appraisal of Guidelines for Research and Evaluation II tool and scrutinized for all relevant information concerning the use of glucocorticoids.Results: All guidelines agree that glucocorticoids, especially if given at low doses and for a short duration, are an appropriate option in the treatment of RA. However, many recommendations remain vague, as reliable and detailed evidence is scarce. Important aspects of glucocorticoid therapy are partially or completely neglected, and the existing nomenclature is not used uniformly. Quality evaluation revealed flaws in many articles, concerning not only glucocorticoid-specific recommendations but also guideline quality in general.Conclusion: Current recommendations for use of glucocorticoids in the management of RA are suboptimal. More rigorous evaluation of doses, timing, and duration of their use is needed. Existing nomenclature on glucocorticoid therapy should be used uniformly. [ABSTRACT FROM AUTHOR]

Objective To investigate whether remission at single and consecutive visits predicts good outcome in early rheumatoid arthritis (RA). Methods The presence of remission according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and other criteria (Boolean clinical, Clinical Disease Activity Index, Disease Activity Score [DAS], DAS in 28 joints, and Routine Assessment of Patient Index Data 3) was assessed in early RA patients during the first year of the Combination Therapy for Rheumatoid Arthritis light trial. Likelihood ratios were used to assess whether meeting the remission criteria at single visits (13, 26, 39, or 52 weeks) and consecutive visits (13 and 26, 26 and 39, or 39 and 52 weeks) predicted good outcome in the second year (52-104 weeks). Good outcome was defined for function (Health Assessment Questionnaire score consistently ≤0.5 and no deterioration), radiographic damage progression (no deterioration in Sharp/van der Heijde scores), and both ('overall good outcome'). Results Of the original 164 trial patients, 144 had evaluable data. In the second year, good functional outcome was observed in 35%, good radiographic outcome in 79%, and both in 28% of the patients. Almost all criteria predicted good functional and good overall outcome, at both single and consecutive visits; only single DAS remission did not significantly predict good overall outcome ( P = 0.07). Sustained remission periods resulted in higher likelihood ratios than remission at single visits. None of the criteria predicted good radiographic outcome. Conclusion Early RA patients who reached remission according to ACR/EULAR and other criteria during short or sustained periods were likely to retain good physical function in the subsequent months. Sustained remission periods were a stronger predictor than remission at single visits. However, in the setting of low overall damage progression, (sustained) remission was not predictive of good radiographic outcome. [ABSTRACT FROM AUTHOR]

Objective: To further simplify the simple erosion narrowing score (SENS) by removing scored areas that contribute the least to its measurement precision according to analysis based on item response theory (IRT) and to compare the measurement performance of the simplified version to the original.Methods: Baseline and 18-month data of the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial were modeled using longitudinal IRT methodology. Measurement precision was evaluated across different levels of structural damage. SENS was further simplified by omitting the least reliably scored areas. Discriminant validity of SENS and its simplification were studied by comparing their ability to differentiate between the COBRA and sulfasalazine arms. Responsiveness was studied by comparing standardized change scores between versions.Results: SENS data showed good fit to the IRT model. Carpal and feet joints contributed the least statistical information to both erosion and joint space narrowing scores. Omitting the joints of the foot reduced measurement precision for the erosion score in cases with below-average levels of structural damage (relative efficiency compared with the original version ranged 35-59%). Omitting the carpal joints had minimal effect on precision (relative efficiency range 77-88%). Responsiveness of a simplified SENS without carpal joints closely approximated the original version (i.e., all Δ standardized change scores were ≤0.06). Discriminant validity was also similar between versions for both the erosion score (relative efficiency = 97%) and the SENS total score (relative efficiency = 84%).Conclusion: Our results show that the carpal joints may be omitted from the SENS without notable repercussion for its measurement performance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the longitudinal relationship between disease activity and self-reported physical activity (PA) in patients with early rheumatoid arthritis during the first year of treatment with combination therapy.Methods: PA was measured with the Short Questionnaire to Assess Health-Enhancing Physical Activity at baseline, 13 weeks, 26 weeks, and 52 weeks after start of treatment in the context of the Combinatietherapie Bij Reumatoïde Artritis-Light trial. The reported PA classified patients as meeting or not meeting the World Health Organization (WHO) PA guideline (cutoff: 150 minutes of moderate-to-intense activity per week). Other measurements included the Disease Activity Score (DAS). Since both treatment arms showed equal treatment effect, these were analyzed as 1 group with simple before-after analyses and generalized estimating equations (GEE).Results: In these analyses, 140 patients (86% of the trial population, 66% women, mean age 52 years) with complete data were included. At entry, 69% of the patients met the WHO PA guideline, increasing to 90% at week 13, and remaining stable at 89% after 1 year (P < 0.001). Mean DAS improved from 4.0 to 1.8 during the first year of treatment (P < 0.001). In GEE analyses, DAS decreases were significantly associated with PA increases (P = 0.008). Patients with clinically relevant responses (expressed as DAS remission, European League Against Rheumatism good response or American College of Rheumatology criteria for 70% improvement response) showed higher PA levels compared to nonresponders, regardless of the definition of response, for both the WHO and Dutch PA guideline.Conclusion: Early rheumatoid arthritis patients using combination therapy improved both disease activity and PA, a beneficial effect persisting for at least 1 year. [ABSTRACT FROM AUTHOR]

Objective: Although the Computer Assisted Management in Early Rheumatoid Arthritis Trial-II (CAMERA-II) showed favorable clinical effects in the most intensive methotrexate (MTX)-based strategy with prednisone (MTX ± prednisone) compared to that with placebo (MTX + placebo), this beneficial difference was only seen in 1 of the 3 analyses of remission. Our objective was to investigate whether the Continuity Rewarded (ConRew) score and a simple sum score would better reveal differences regarding remission between the 2 treatment arms of CAMERA-II. Furthermore, we investigated whether the patient vector graph, which plots on patient level, would add visual information on remission compared to a conventional box plot only, which displays data on the group level.Methods: The ConRew method, which awards continuous periods of remission with a higher score, was applied, in addition to a simple sum score of remission periods of 4 weeks. A patient vector graph was compared with box plots.Results: Both the mean ± SD simple sum score and the ConRew score of remission were significantly higher (favorable) in the MTX + prednisone strategy group versus the MTX + placebo group, respectively: 9 ± 7 versus 12 ± 8; P = 0.003, and 23 ± 16 versus 17 ± 14; P = 0.004. The patient vector graphs show a visual pattern of more and longer periods of remission in the MTX + prednisone strategy and visually add information to the box plots.Conclusion: The simple sum of remission periods, the ConRew score, and the patient vector graph add understanding and discrimination to the analysis of the remission outcome in CAMERA-II. [ABSTRACT FROM AUTHOR]

The author comments on getting patients involved in their rheumatology experience. Topics covered include the important role of clinicians in educating patients regarding how to effectively manage their health conditions. Also mentioned is the need for clinicians to help their patients understand the effects of inflammatory arthritis.

Objective: To investigate whether remission at single and consecutive visits predicts good outcome in early rheumatoid arthritis (RA).Methods: The presence of remission according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and other criteria (Boolean clinical, Clinical Disease Activity Index, Disease Activity Score [DAS], DAS in 28 joints, and Routine Assessment of Patient Index Data 3) was assessed in early RA patients during the first year of the Combination Therapy for Rheumatoid Arthritis light trial. Likelihood ratios were used to assess whether meeting the remission criteria at single visits (13, 26, 39, or 52 weeks) and consecutive visits (13 and 26, 26 and 39, or 39 and 52 weeks) predicted good outcome in the second year (52-104 weeks). Good outcome was defined for function (Health Assessment Questionnaire score consistently ≤0.5 and no deterioration), radiographic damage progression (no deterioration in Sharp/van der Heijde scores), and both ("overall good outcome").Results: Of the original 164 trial patients, 144 had evaluable data. In the second year, good functional outcome was observed in 35%, good radiographic outcome in 79%, and both in 28% of the patients. Almost all criteria predicted good functional and good overall outcome, at both single and consecutive visits; only single DAS remission did not significantly predict good overall outcome (P = 0.07). Sustained remission periods resulted in higher likelihood ratios than remission at single visits. None of the criteria predicted good radiographic outcome.Conclusion: Early RA patients who reached remission according to ACR/EULAR and other criteria during short or sustained periods were likely to retain good physical function in the subsequent months. Sustained remission periods were a stronger predictor than remission at single visits. However, in the setting of low overall damage progression, (sustained) remission was not predictive of good radiographic outcome. [ABSTRACT FROM AUTHOR]