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This article is a response to comments on a study that investigated the effects of low-dose glucocorticoid therapy on weight and blood pressure in patients with rheumatoid arthritis. The authors performed additional analyses and found that glucocorticoid-induced weight gain was limited to the first year and then stabilized. They also addressed concerns about other adverse effects associated with long-term glucocorticoid treatment, noting that recent studies challenge the notion that low-dose glucocorticoids cause cardiovascular events, osteoporosis, or death independent of disease activity. The authors also discussed the divergence in results between their pooled analysis and another trial, and addressed concerns about the handling of missing data. [Extracted from the article]

Glucocorticoids (prednisone) are essential in the treatment of RA and other autoimmune diseases. They are widely used, but treatment guidelines advise against. This viewpoint article explains why and suggests a way forward. [ABSTRACT FROM AUTHOR]

To standardize outcome reporting in clinical trials of patients with nonspecific low back pain, an international multidisciplinary panel recommended physical functioning, pain intensity, and health-related quality of life (HRQoL) as core outcome domains. Given the lack of a consensus on measurement instruments for these 3 domains in patients with low back pain, this study aimed to generate such consensus. The measurement properties of 17 patient-reported outcome measures for physical functioning, 3 for pain intensity, and 5 for HRQoL were appraised in 3 systematic reviews following the COSMIN methodology. Researchers, clinicians, and patients (n = 207) were invited in a 2-round Delphi survey to generate consensus (≥67% agreement among participants) on which instruments to endorse. Response rates were 44% and 41%, respectively. In round 1, consensus was achieved on the Oswestry Disability Index version 2.1a for physical functioning (78% agreement) and the Numeric Rating Scale (NRS) for pain intensity (75% agreement). No consensus was achieved on any HRQoL instrument, although the Short Form 12 (SF12) approached the consensus threshold (64% agreement). In round 2, a consensus was reached on an NRS version with a 1-week recall period (96% agreement). Various participants requested 1 free-to-use instrument per domain. Considering all issues together, recommendations on core instruments were formulated: Oswestry Disability Index version 2.1a or 24-item Roland-Morris Disability Questionnaire for physical functioning, NRS for pain intensity, and SF12 or 10-item PROMIS Global Health form for HRQoL. Further studies need to fill the evidence gaps on the measurement properties of these and other instruments. [ABSTRACT FROM AUTHOR]

The Cohort Hip and Cohort Knee (CHECK) study included participants with early symptomatic osteoarthritis (OA) of the hip or knee and evaluated clinical, radiographic and biochemical variables in order to establish the course, prognosis and underlying mechanisms of early symptomatic osteoarthritis. A total of 1002 participants aged 45-65 years, with symptomatic OA characterized by pain of knee and/ or hip, entered the cohort in the period October 2002 to September 2005. They were included at or within 6 months of their first visit to the general practitioner for these symptoms. An overview of measures that are included in the study can be found on the website [www.check-research.com]. On the basis of their presenting symptoms, participants were divided into two groups. Participants with mild symptoms visited the research centre at years 0, 2, 5, 8 and 10 (variable visiting group) and participants with more serious symptoms visited the research centre each year (annual visiting group). After 7 years, only 105 participants (10%) had dropped out; their baseline characteristics did not differ significantly from those of other participants. CHECK is a valuable source of information on early symptomatic OA, that allows the examination of high-quality data on clinical, radiographic and biochemical variables. The CHECK steering group welcomes collaboration with national and international colleagues. Requests for collaboration or access to data can be sent to [checkreu@umcutrecht.nl]. [ABSTRACT FROM AUTHOR]

Patient-reported outcomes (PROs) are abundant in rheumatology and their numbers continue to increase. But which of the available measures are most important? Core outcome sets-including groups of domains and instruments for measuring them-have been defined for many rheumatic diseases, with the aim that all these outcomes should be measured in every clinical trial. The subgroup of PROs included in these core sets is, therefore, undoubtedly important. This Review summarizes the PROs included in core outcome sets developed for use in clinical trials across a wide range of rheumatic diseases. Three PROs are commonly utilized across the majority of rheumatic conditions: pain, physical functioning and the patient global assessment of disease activity. However, additional research is needed to fully understand the role of the patient global assessment of disease activity, to distinguish specific domains within the broad concept of health-related quality of life, and to work towards consensus on the choice between generic and disease-specific instruments in various contexts. [ABSTRACT FROM AUTHOR]

Background: Lack of standardization of outcome measures limits the usefulness of clinical trial evidence to inform health care decisions. This can be addressed by agreeing on a minimum core set of outcome measures per health condition, containing measures relevant to patients and decision makers. Since 1992, the Outcome Measures in Rheumatology (OMERACT) consensus initiative has successfully developed core sets for many rheumatologic conditions, actively involving patients since 2002. Its expanding scope required an explicit formulation of its underlying conceptual framework and process. Methods: Literature searches and iterative consensus process (surveys and group meetings) of stakeholders including patients, health professionals, and methodologists within and outside rheumatology. Results: To comprehensively sample patient-centered and intervention-specific outcomes, a framework emerged that comprises three core ''Areas,'' namely Death, Life Impact, and Pathophysiological Manifestations; and one strongly recommended Resource Use. Through literature review and consensus process, core set development for any specific health condition starts by identifying at least one core ''Domain'' within each of the Areas to formulate the ''Core Domain Set.'' Next, at least one applicable measurement instrument for each core Domain is identified to formulate a ''Core Outcome Measurement Set.'' Each instrument must prove to be truthful (valid), discriminative, and feasible. In 2012, 96% of the voting participants (n5125) at the OMERACT 11 consensus conference endorsed this model and process. Conclusion: The OMERACT Filter 2.0 explicitly describes a comprehensive conceptual framework and a recommended process to develop core outcome measurement sets for rheumatology likely to be useful as a template in other areas of health care. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids. Methods: Retrospective analysis of exposure to glucocorticoids in a prospective cohort of 353 patients with rheumatoid arthritis followed from June 2001 up to November 2011 for incident cardiovascular disease in a hospital-based outpatient cohort in the Netherlands. Hazard ratios with 95%-confidence intervals were calculated for the association between different types of exposure to glucocorticoids and incident cardiovascular disease. Associations were adjusted for demographics, cardiovascular risk factors and disease related parameters. Results: Recent and current exposure to glucocorticoids were associated with incident cardiovascular disease, as was a longer duration of exposure and cumulative exposure to glucocorticoids. Adjustment for disease activity and severity negated the association. Conclusion: In observational studies the finding of incident cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids is strongly confounded by indication due to high disease activity. The adverse cardiovascular effects of glucocorticoids might be balanced by positive effects working through inflammation control. [ABSTRACT FROM AUTHOR]

Background The development and application of standardised sets of outcomes to be measured and reported in clinical trials have the potential to increase the efficiency and value of research. One of the most notable of the current outcome sets began nearly 20 years ago: the World Health Organization and International League of Associations for Rheumatology core set of outcomes for rheumatoid arthritis clinical trials, originating from the OMERACT (Outcome Measures in Rheumatology) Initiative. This study assesses the use of this core outcome set by randomised trials in rheumatology. Methods An observational review was carried out of 350 randomised trials for the treatment of rheumatoid arthritis identified through the The Cochrane Library (up to and including September 2012 issue). Reports of these trials were evaluated to determine whether or not there were trends in the proportion of trials reporting on the full set of core outcomes over time. Researchers who conducted trials after the publication of the core set were contacted to assess their awareness of it and to collect reasons for non-inclusion of the full core set of outcomes in the study. Results Since the introduction of the core set of outcomes for rheumatoid arthritis, the consistency of measurement of the core set of outcomes has improved, although variation in the choice of measurement instrument remains. The majority of trialists who responded said that they would consider using the core outcome set in the design of a new trial. Conclusions This observational review suggests that a higher percentage of trialists conducting trials in rheumatoid arthritis are now measuring the rheumatoid arthritis core outcome set. Core outcome sets have the potential to improve the evidence base for health care, but consideration must be given to the methods for disseminating their availability amongst the relevant communities. [ABSTRACT FROM AUTHOR]

The article offers information on a data collection methodology involving the Short Form-36 questionnaire (SF-36) in medical care and discusses an article published in the periodical which suggests using radar graphs also called spydergrams for plotting result of the questionnaire. It informs that spydergraph graphically depicts the data in two dimensions on a flat surface and analyzes its difficulties in quantitative interpretation.

The authors discuss regulatory requirements for the investigation and approval of disease-modifying anti-rheumatic drugs (DMARDs) in Europe. According to the authors, both the choice of comparator and the assessment of joint damage are influenced by the patient population studied. They cite potential indications for the use of a new agent. They point out a need for the new agent to exhibit superior efficacy to placebo in signs and symptoms for established rheumatoid arthritis cases.

The authors propose a solution to reporting response in rheumatoid arthritis (RA) clinical trials. They consider the success of the American College of Rheumatology (ACR) criteria for 20% improvement in RA disease activity (ACR20) in organizing trial reports and paving interpretation of trial data to direct patient experience. Problems with the classic type of data presentation are discussed. A discussion on the components of the proposed solution is detailed.

Abstract: Background: In the setting of multiple remission and relapse periods of a chronic disease, simple endpoint analysis does not fully capture all relevant information, and we need methods to additionally describe both the duration of remission as well as the interruptions in this desired state. Probably the two-state continuous Markov process model comprises the best mathematical approach to data analysis. However, this approach is complex and not intuitive to clinicians. In this paper we propose a simple scoring system and a graph that can enhance the information about the remission experience in a trial or cohort study. Methods: The continuity rewarded (‘ConRew’) score sums up periods in remission, and rewards extended periods by placing more value on uninterrupted periods than on interrupted periods. The ‘patient vector graph’ attempts to plot each patient''s remission experience over time as a horizontal line (the ‘vector’) that is visible when the patient is in remission, but interrupted whenever relapse occurs. In this way a pattern is formed that conveys the number of patients experiencing remission, their individual total duration and interruptions, and time when these occur. Results: In a dataset of a randomized trial in early rheumatoid arthritis, the graph clearly showed both early and late benefit of one group over the other. The scoring system demonstrated the main benefit was in the number of remission periods, not in their ‘uninterruptedness’. Conclusion: Both approaches proved feasible and added extra information. [Copyright &y& Elsevier]

Abstract: Objective: To develop a simple system to assess benefit and harm of treatment on a single scale. Harm and benefit signals from trials need to be placed in the proper perspective to decide on the value of a treatment. Several systems have been developed for assessment, but few attempt to incorporate both benefit and risk in the same metric while retaining enough simplicity to aid patients and clinicians in their decision making. Study Design and Setting: We designed a very simple 3×3 table (Outcome Measures in Rheumatology [OMERACT] 3×3) that comprises three ranks for both beneficial and harm outcomes: for benefit, these are “none,” “substantial,” and “(near) remission”; for harm, these are “none,” “severe,” and “(near) death.” Patients are ranked both for benefit and harm and subsequently counted in a 3×3 table. Results: The system was feasible when applied to one trial dataset (patient-level information) and a meta-analysis. To become applicable as a tool, several issues need to be resolved in further development, especially the definitions and cutoffs for the ranks. Conclusion: A simple 3×3 table to rank both benefit and harm outcomes is feasible. For rheumatology this will be further developed in the context of the OMERACT initiative. [Copyright &y& Elsevier]

Following a newly developed concept of health, this viewpoint suggests that the concept of frailty can usefully be defined as: the weakening of health, i.e. the resilience or capacity to cope, and to maintain and restore one's integrity, equilibrium, and sense of wellbeing in three domains: physical, mental, and social. [ABSTRACT FROM AUTHOR]

OMERACT is the acronym for an international, informally organized network initiated in 1992 aimed at improving outcome measurement in rheumatology. Chaired by an executive committee, it organizes consensus conferences in a 2-yearly cycle that circles the globe. Data driven recommendations are prepared and updated by expert working groups. Recommendations include core sets of measures for most of the major rheumatologic conditions. Since 2002 patients have been actively engaged in the process. [ABSTRACT FROM AUTHOR]

As such, it is almost certain that those who still required glucocorticoid therapy had more severe disease and that this severity was the deciding factor in determining postoperative (infection) risk, not glucocorticoid exposure. Minimizing glucocorticoid use before surgery in patients with severe rheumatoid arthritis who have been receiving long-term glucocorticoid therapy may be highly deleterious. [Extracted from the article]

Conventional graphs often include error bars around the group means. Regardless of what these bars depict, they are uninformative as to whether a difference between the groups is statistically significant.This article suggests plotting the null bar or null zone: that is, the range or area in which the means of the two groups fall if the null hypothesis of no difference cannot be rejected. The bar and zone are simply derived from the confidence interval around the difference, obtained from the t-test. [Copyright &y& Elsevier]

This article discusses methodological concepts and challenges underlying the interpretation of changes in plain radiographs of the joints of patients with rheumatoid arthritis. A series of consensus conferences (OMERACT [Outcome Measures in Rheumatology]) has resulted in the formulation and execution of a research agenda to harmonise reading and interpretation of films. This is important in the light of the increasing evidence that drugs can impact on the progression of joint damage. In these conferences, methodological issues have been divided according to applicability tenets summarised in the OMERACT Filter of Truth, Discrimination, and Feasibility. To pass the Filter, a measure must measure what it is supposed to measure (Truth), must discriminate between clinically relevant states (Discrimination) and be feasible in terms of costs and interpretability. ‘Truth’ issues include the choice of joints, the view and other technical specifications of the radiograph, such as which abnormalities to score, the level of aggregation of the information, culminating in the choice of the scoring system. ‘Discrimination’ issues include reproducibility and sensitivity to change. The current research agenda includes items such as defining a criterion for ‘no relevant progression’, comparison between time ordered and randomly ordered reading, further comparison of methods and subscores, and methodology around missing values. [ABSTRACT FROM AUTHOR]

Reports a study that compared the combination of sulphasalazine, methotrexate and prednisolone with sulphasalazine alone in the treatment of rheumatoid arthritis. Background; Methods; Findings; Interpretation; Discussion; References.

Objective. The effects of a 12-week treatment with modified-release prednisone (MR-pred) on the costs of drug treatment of RA were modelled.Methods. With the results of a recent randomized trial as source data, we expressed the effect of treatment (MR-pred vs placebo) on the decrease in the proportion of RA patients meeting disease activity thresholds for reimbursement of biologic treatment.Results. The results showed 11–13% more patients on MR-pred than on placebo dropped below reimbursement thresholds for the Netherlands, Belgium and the UK. Assuming 1 year of biologics cost €15 000 and MR-pred costs €1/day, €396 are saved in each patient delaying biologic treatment by 12 weeks.Conclusion. Despite a considerably higher cost than conventional prednisone, MR-pred is a cost-effective option for RA patients not on glucocorticoids who are eligible for therapy with biologic agents. [ABSTRACT FROM PUBLISHER]

The American College of Rheumatology recently published a list of five strategies (comprising four diagnostic procedures and one therapeutic approach) that they consider to be often unnecessary and thus potentially wasteful. By itself this list is useful, but finding a way to reduce wasteful strategies will be a challenge. [ABSTRACT FROM AUTHOR]

The author highlights growing interest of patient reported outcome's use in rheumatoid arthritis (RA) clinical trials and in clinical practice. He discusses several studies that determine differences between patient's and physician's assessments of disease activity, and factors that influence the two measures. It also highlights that a patient's global assessment of ≤1 on a scale of 0-10 is needed as per Boolean remission criteria of the new The American College of Rheumatology (ACR/EULAR).

A letter to the editor is presented in response to the article in the previous issue on the cost-utility analysis of the BeSt (behandelstrategietrialën voor reumatoide artritis) trial.

A letter to the editor is presented in response to the article "How antirheumatic drugs protect joints from damage in rheumatoid arthritis," by Schett and colleagues.

The author reflects on the pathophysiogical aspects of rheumatoid arthritis (RA). He challenges the traditional view of the disease and argues on the unnecessary view of J. R. Kirwan on split and on the intriguing details of the study by A. K. Brown. He views that subclinical joint information shown by ultrasound and magnetic resonance imaging (MRI) best explains the structural deterioration of RA patients.

The article reflects on a study that examines the effects of abatacept in patients with rheumatoid arthritis (RA). In this study, the author cited that abatacept has intrinsic activity in patients with RA whose methotrexate and tumor necrosis factor inhibitor therapies have failed. He also suggests that physicians should monitor patients carefully who are receiving abatacept until the drug's safety profile becomes clearer.

Objectives Self-monitoring and patient-initiated care (PIC) leads to fewer outpatient clinic visits in patients with established RA with low disease activity (LDA) while healthcare outcomes are similar. This study assesses the cost-effectiveness of PIC with self-monitoring. Methods A 12-month randomized controlled trial was performed with 49 patients in the PIC with self-monitoring group (app-group) and 53 in usual care. The usual care group continued with preplanned visits. The app group had one planned follow-up visit after 12 months and monitored their RA disease activity in a smartphone app. Both groups could make additional appointments at liberty. We included adult RA patients with a disease duration of over 2 years, a disease activity score 28 (DAS28) below 3.2 that were stable on medication for at least 6 months. The effect measure, the DAS28, was measured at 12 months and healthcare resource usage and productivity losses were measured at 3, 6, 9 and 12 months. Results There was no significant difference in mean change of DAS28 (-0.04 mean difference, 95% CI: -0.39, 0.30), nor a statistically significant difference in total costs (mean difference €514, 95% CI:-€266, €3690) in the app group compared with the usual care group. The probability that the app was cost-effective was 0.37 and 0.57 at a willingness-to-pay threshold of 0 and 50 000 €/point improvement DAS28, respectively. Conclusion Although rheumatic care costs were significantly lower in the app group, total costs and effects of PIC with self-monitoring were not different from usual care in RA patients with LDA. [ABSTRACT FROM AUTHOR]

Glucocorticoids reduce disease activity and retard progression of joint damage in rheumatoid arthritis, but current recommendations discourage their use because of drug adverse effects. This study examined the effects of low-dose glucocorticoids on weight gain and hypertension, which are among the more worrisome adverse effects for patients and rheumatologists. Visual Abstract. The Effect of Low-Dose Glucocorticoids Over Two Years on Weight and Blood Pressure in Rheumatoid Arthritis: Individual Patient Data From Five Randomized Trials Glucocorticoids reduce disease activity and retard progression of joint damage in rheumatoid arthritis, but current recommendations discourage their use because of drug adverse effects. This study examined the effects of low-dose glucocorticoids on weight gain and hypertension, which are among the more worrisome adverse effects for patients and rheumatologists. Background: Weight gain and hypertension are well known adverse effects of treatment with high-dose glucocorticoids. Objective: To evaluate the effects of 2 years of low-dose glucocorticoid treatment in rheumatoid arthritis (RA). Design: Pooled analysis of 5 randomized controlled trials with 2-year interventions allowing concomitant treatment with disease-modifying antirheumatic drugs. Setting: 12 countries in Europe. Patients: Early and established RA. Intervention: Glucocorticoids at 7.5 mg or less prednisone equivalent per day. Measurements: Coprimary end points were differences in change from baseline in body weight and mean arterial pressure after 2 years in intention-to-treat analyses. Difference in the change of number of antihypertensive drugs after 2 years was a secondary end point. Subgroup and sensitivity analyses were done to assess the robustness of primary findings. Results: A total of 1112 participants were included (mean age, 61.4 years [SD, 14.5]; 68% women). Both groups gained weight in 2 years, but glucocorticoids led, on average, to 1.1 kg (95% CI, 0.4 to 1.8 kg; P  < 0.001) more weight gain than the control treatment. Mean arterial pressure increased by about 2 mm Hg in both groups, with a between-group difference of −0.4 mm Hg (CI, −3.0 to 2.2 mm Hg; P  = 0.187). These results were consistent in sensitivity and subgroup analyses. Most patients did not change the number of antihypertensive drugs, and there was no evidence of differences between groups. Limitation: Body composition was not assessed, and generalizability to non-European regions may be limited. Conclusion: This study provides robust evidence that low-dose glucocorticoids, received over 2 years for the treatment of RA, increase weight by about 1 kg but do not increase blood pressure. Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA. Methods A protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE). Results Six trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P  = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19–1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: −0.23; −0.43 to −0.03), function (HAQ −0.09; −0.18 to 0.00), and Larsen scores (–4.61; −7.52 to −1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs. Conclusion There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties. [ABSTRACT FROM AUTHOR]

Objective To determine the effect of a multidisciplinary lifestyle program in patients with RA with low–moderate disease activity. Methods In the 'Plants for Joints' (PFJ) parallel-arm, assessor-blind randomized controlled trial, patients with RA and 28-joint DAS (DAS28) ≥2.6 and ≤5.1 were randomized to the PFJ or control group. The PFJ group followed a 16-week lifestyle program based on a whole-food plant-based diet, physical activity and stress management. The control group received usual care. Medication was kept stable 3 months before and during the trial whenever possible. We hypothesized that PFJ would lower disease activity (DAS28). Secondary outcomes included anthropometric, metabolic and patient-reported measures. An intention-to-treat analysis with a linear mixed model adjusted for baseline values was used to analyse between-group differences. Results Of the 83 people randomized, 77 completed the study. Participants were 92% female with mean (s. d.) age of 55 (12) years, BMI of 26 (4) kg/m2 and mean DAS28 of 3.8 (0.7). After 16 weeks the PFJ group had a mean 0.9-point greater improvement of DAS28 vs the control group (95% CI 0.4, 1.3; P  < 0.0001). The PFJ intervention led to greater decreases in body weight (difference –3.9 kg), fat mass (–2.8 kg), waist circumference (–3 cm), HbA1c (–1.3 mmol/mol) and low-density lipoprotein (–0.32 mmol/l), whereas patient-reported outcome measures, blood pressure, glucose and other lipids did not change. Conclusion The 16-week PFJ multidisciplinary lifestyle program substantially decreased disease activity and improved metabolic status in people with RA with low–moderate disease activity. Trial Registration International Clinical Trials Registry Platform; https://www.who.int/clinical-trials-registry-platform ; NL7800. [ABSTRACT FROM AUTHOR]

Objectives To identify highly ranked features related to clinicians' diagnosis of clinically relevant knee OA. Methods General practitioners (GPs) and secondary care physicians (SPs) were recruited to evaluate 5–10 years follow-up clinical and radiographic data of knees from the CHECK cohort for the presence of clinically relevant OA. GPs and SPs were gathered in pairs; each pair consisted of one GP and one SP, and the paired clinicians independently evaluated the same subset of knees. A diagnosis was made for each knee by the GP and SP before and after viewing radiographic data. Nested 5-fold cross-validation enhanced random forest models were built to identify the top 10 features related to the diagnosis. Results Seventeen clinician pairs evaluated 1106 knees with 139 clinical and 36 radiographic features. GPs diagnosed clinically relevant OA in 42% and 43% knees, before and after viewing radiographic data, respectively. SPs diagnosed in 43% and 51% knees, respectively. Models containing top 10 features had good performance for explaining clinicians' diagnosis with area under the curve ranging from 0.76–0.83. Before viewing radiographic data, quantitative symptomatic features (i.e. WOMAC scores) were the most important ones related to the diagnosis of both GPs and SPs; after viewing radiographic data, radiographic features appeared in the top lists for both, but seemed to be more important for SPs than GPs. Conclusions Random forest models presented good performance in explaining clinicians' diagnosis, which helped to reveal typical features of patients recognized as clinically relevant knee OA by clinicians from two different care settings. [ABSTRACT FROM AUTHOR]

The authors analyze a study which showed that it is possible to stop a risky and expensive treatment for patients with rheumatoid arthritis once an initial response has been obtained. They think that the study raises three questions, including the need for patients to take biological therapy, another treatment effect hidden within the trial results and the cost effectiveness of biological therapy. They also mention other treatments used in the study, such as glucocorticoids and methotrexate.

Summary: What is known: Currently, medication bottles with an electronic cap are frequently used to measure medication adherence. This system is termed medication event monitoring system (MEMS). To our knowledge, the optimal method to summarize data from MEMS has not yet been determined. Objective: Look for best practices on how to quantify adherence data from MEMS. Methods: Review of PubMed, Embase and Cochrane databases for the articles on medication adherence with MEMS. Results: Of 1493 identified articles, 207 were included in this review. The MEMS cap was used for a median of 3 months (IQR: 4; range: 1 week to 24 months) in various health conditions. Many different outcome measures were used. Most studies computed an adherence score, expressed as the percentage of days on which the correct dose of medication was taken. The threshold to mark people as adherent was most frequently, arbitrarily, set at 80% (range: 67%‐95%). We found no data to support a specific threshold. Discussion: Although the commonly used definition of adherence has face validity, we found no validation studies, and not all studies used the same cut‐off for adherence. Ideally, a cut‐off should be defined and validated in the context of the specific drug and its pharmacokinetic and dynamic characteristics, and perhaps other contextual factors, rather than generically. In addition, there was large heterogeneity in the definition of what "correct intake" of medication is. What is new and conclusion: Outcome measures for MEMS data lacked standardization, and no demonstrable effort to validate any definition against a relevant clinical outcome is available. Consensus on the definition of adherence is urgently needed. Outcome measures for Medication Event Monitoring System (MEMS) data lacked standardization and no demonstrable effort to validate any definition against a relevant clinical outcome is available. A consensus effort on the definition of adherence is urgently needed. [ABSTRACT FROM AUTHOR]

The author talks about the study conducted to evaluate the effectiveness of spleen tyrosine kinase (Syk) in the suppression of rheumatoid arthritis (RA). The data collected from a 3-month methotrexate (MTX) failure trial suggested the ineffectiveness of fostamatinib in patients with relatively treatment-resistant disease. According to the author, the findings suggest that Syk kinase inhibition with fostamatinib is unreliable.

The article reflects on biologics' cost-effectiveness as first-line treatment of rheumatoid arthritis (RA). It is informed that the biologics are priced at the maximum level the market will bear. It is also said that the number of diseases, which can be treated with biologics has increased substantially.

The article discusses the need to conduct large, simple, pragmatic trials for the treatment of rheumatoid arthritis due to lack of enough evidence that will guide the choice of treatment for this disease. The pragmatic trials must be designed to determine the best way to treat rheumatoid arthritis as well as how to approach comorbidity and how patients should be monitored.

A letter to the editor in response to the article "Infliximab and Methotrexate As Induction Therapy in Patients With Early Rheumatoid Arthritis" in a 2007 issue and a response by A. E. van der Bijl et al. to the letter are presented.

Presents a letter to the editor in response to the article "Risk of cardiovascular events and rofecoxib: cumulative meta-analysis," by Peter J¨ni and colleagues in the December 4, 2004 issue.

Comments on pharmaceutical clinical research. Evidence of bias in some trials due to pressure from sponsors; Efforts of editors of medical journals to make requirements for study authors more stringent; Suggestion that masked analyses should be used.

Discusses two studies that describe how selective cyclo-oxygenase-2 (COX-2) inhibition can reduce the incidence of major gastrointestinal complications caused by non-steroidal anti-inflammatory drugs (NSAID). Findings of the CLASS study of celecoxib versus ibuprofen or diclofenac in osteoarthritis and rheumatoid arthritis, and the VIGOR study of rofecoxib versus naproxen in rheumatoid arthritis; Finding that the prevention of cardiovascular events is at the cost of significant gastrointestinal toxicity; Indications for the clinician.

Comments on the value of magnetic resonance imaging (MRI) in the management of rheumatoid arthritis. Reference to research by Mette Klarlund and colleagues comparing MRI with conventional radiography, technetium scintigraphy, and clinical assessment of inflammation; Discussion of whether MRI satisfies the criteria for a useful clinical measurement; View that MRI has a limited role in the assessment of arthritis.

Objective The aim of this study was to investigate the effect of treat-to-target combination therapy with intensification at 13 weeks in early RA. Methods Early RA patients were classified as being at high or low risk of worsening RA based on disease activity and prognostic factors. High-risk patients received COBRA-light (prednisolone 30 mg/day tapered to 7.5 mg/day, MTX increasing to 25 mg/week), and low-risk patients received MTX monotherapy increasing to 25 mg/week. The primary outcome (target) was DAS44 < 1.6 or EULAR good response at 26 weeks. At 13 weeks, non-responders were randomized to (open-label) intensification [high-risk patients: prednisolone 60 mg/day tapered to 7.5 mg/day, addition of SSZ (2 g/day) and HCQ (400 mg/day); low-risk patients: prednisolone 30 mg/day tapered to 7.5 mg/day] or continuation. Results In the high-risk group (n  = 150), 110 patients (73%) reached the target at 13 weeks, and 9 dropped out. Non-responders were randomized to intensification (n  = 15) or continuation (n  = 16), and after 26 weeks, 12 (80%) vs 7 (44%) of these, respectively, reached the target [difference: 36%, (95% CI 2%, 71%); P  = 0.04]. In the low-risk group (n  = 40), 17 (43%) reached the target. Non-responders were randomized to intensification (n  = 8) or continuation (n  = 7); 4 vs 3, respectively, reached the target. Adverse event rates were higher in the high-risk group, and higher in the intensification subgroup of that group. Serious adverse events were rare. Protocol violations were frequent and mostly led to mitigation of actual treatment intensification. Conclusion Initial combination therapy was very successful in high-risk RA, and early intensification was beneficial in patients not reaching the strict target. The low-risk group was too small for drawing conclusions. In routine practice, adherence to early intensification based on strict targets is difficult. Trial registration Netherlands Trial Register (NTR), NL4393, https://www.trialregister.nl/. [ABSTRACT FROM AUTHOR]