Helga Radner

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA)

Background Patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions. Objectives To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide. Methods Study design: international, cross-sectional. Patients: consecutive RA patients. Data collected: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders). Results Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)–erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%. Conclusions Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Discrepancies between patients and physicians in their perceptions of rheumatoid arthritis disease activity

OBJECTIVE Patients and physicians often differ in their perceptions of rheumatoid arthritis (RA) disease activity, as quantified by the patients global assessment (PGA) and by the evaluators global assessment (EGA). The purpose of this study was to explore the extent and reasons for this discordance. METHODS We identified variance components for the PGA and EGA in RA patients who were starting therapy with methotrexate in an academic outpatient setting. We analyzed predictors of the observed discrepancy in these measures (calculated as the PGA minus the EGA) and in their changes (calculated as the PGA(change) minus the EGA(change) ). RESULTS We identified 646 RA patients, and among them, 77.4% of the variability in the PGA and 66.7% of the variability in the EGA were explainable. The main determinants for the PGA were pain (75.6%), function (1.3%, by Health Assessment Questionnaire), and number of swollen joints (0.5%); those for the EGA were the number of swollen joints (60.9%), pain (4.5%), function (0.6%), C-reactive protein (0.4%), and the number of tender joints (0.3%). Increased pain led to a discrepancy toward worse patient perception, while increased numbers of swollen joints led to a discrepancy toward worse evaluator perception, both explaining 65% of the discordance between the PGA and the EGA. Likewise, changes in pain scores and numbers of swollen joints proved to be the main determinants for discrepant perceptions of changes in RA disease activity, explaining 34.6% and 12.5% of the discordance, respectively. CONCLUSION The most significant determinants for the cross-sectional and longitudinal discrepancy between the PGA and the EGA are pain and joint swelling, respectively. Understanding the reasons for a discordant view of disease activity will help to facilitate the sharing of decision-making in the management of RA.

Comorbidity affects all domains of physical function and quality of life in patients with rheumatoid arthritis

OBJECTIVE Comorbidities have been reported to influence physical function, but it is not clear which activities are predominantly impaired, or which other domains of health status are affected in addition to physical function. In this study, we investigated the impact of comorbidities on individual activities of daily living, and other aspects of quality of live in patients with RA. METHODS In 380 patients with established RA, we quantified comorbidity levels according to the age-adjusted Charlson Comorbidity Index (CCI(A)) and functional disability by serial measures of the HAQ over 1 year. In a subset of 185 patients, we assessed quality of life using Short Form-36 (SF-36). To analyse the relationship between comorbidities, different activities of daily living and health status, we divided patients into four subgroups of CCI(A) and performed analysis of variance (ANOVA) and multivariable general linear regression models adjusted for gender, disease duration and disease activity. RESULTS ANOVA showed significant (P < 0.03) increase of disability within each domain of HAQ with increasing level of comorbidity. Similar results were observed using the physical component score (P = 0.003) of the SF-36 and its domains, whereas mental component score (P = 0.31) and its domains were unaffected by comorbidities. In a sub-analysis stratifying patients into different levels of disease activity, we found increase in almost all domains of HAQ within respective groups of CCI(A). CONCLUSIONS Activities of daily living represented by HAQ are equally affected by comorbidities. More generally, health status was only affected with respect to its physical but not its mental domains.

Impact of comorbidity on physical function in patients with rheumatoid arthritis

Background Physical disability is a main outcome in rheumatoid arthritis (RA) which tends to increase with comorbidities. However, the extent to which comorbidities contribute to the multifactorial process of disability has not been investigated. Objective To quantify the contribution of comorbidity to physical disability in patients with RA. Methods In a prospective cohort study, age-adjusted Charlson comorbidity index (CCIA), serial measurements of disease activity and functional disability (evaluated by the Health Assessment Questionnaire Disability Index, HAQ) of 380 patients with established RA seen at an outpatient clinic over 1 year (June 2007 to July 2008) were ascertained. The association between comorbidity and physical disability was assessed using analysis of variance (ANOVA) and adjusted general linear regression models. Results Four patient groups with increasing levels of comorbidity (CCIA 0, 1–2, 3–4 and 5–9; potential range 0–38) were defined. Mean HAQ scores were significantly different across these groups (0.67, 0.80, 1.24, 1.40, respectively; p<0.001) and also when adjusted for disease activity, gender and disease duration in the regression model (0.84, 0.88, 1.14, 1.48, respectively; p<0.001). The effects of CCIA on disability were similar within different strata of disease activity: namely, remission (0.26, 0.31, 0.48 and 0.88, p<0.01); low disease activity (0.83, 0.78, 0.98 and 1.36, p<0.01); and moderate to high disease activity (1.22, 1.33, 1.70 and 1.91, p<0.01), and thus were independent of disease activity. Several sensitivity analyses, including the use of the Short Form Health Survey (SF-36), confirmed these observations. Conclusion Physical disability becomes worse with increasing levels of comorbidity, irrespective of disease activity.

Avidity maturation of anti–citrullinated protein antibodies in rheumatoid arthritis

OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and are present years before the onset of symptoms. The avidity of autoantibodies can have a strong impact on their effector potency. This study was undertaken to analyze the avidity of ACPAs in serum samples obtained from ACPA-positive healthy individuals (predisease), patients with early disease, and patients with established RA as well as the avidity maturation over time in samples from healthy subjects who later developed RA. METHODS We measured ACPA avidity in serum samples from ACPA-positive healthy individuals, symptomatic individuals, and patients with established RA in 5 collections from The Netherlands, Canada, and Austria. We determined the dynamics of avidity maturation of ACPAs from the predisease stage to established disease in 1 case from the native North American population and in 10 cases from a Dutch blood donor cohort. RESULTS The overall ACPA response was characterized by low-avidity antibodies. Higher-avidity ACPAs were observed in symptomatic patients only, while low-avidity ACPAs were observed in both healthy subjects and patients. In longitudinal samples obtained from subjects prior to disease onset, ACPA avidity increased over time until disease onset. No further avidity maturation was observed after disease onset. CONCLUSION Our findings indicate that avidity maturation of the ACPA response takes place prior to disease onset.

Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a systematic literature review

Background The 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) were developed to improve the identification of individuals for studies of RA. We aimed to summarise the performance of the criteria based on the published literature. Methods We performed a systematic literature search to identify all studies investigating the 2010 criteria and reporting data allowing to calculate sensitivity (SENS), specificity (SPEC), and positive and negative predictive values. Where possible, meta-analysis was performed. Results Seventeen full articles (total 6816 patients) and 17 meeting abstracts (total 4004 patients) fulfilled the inclusion criteria. Pooled sensitivity and specificity for RA (defined by different reference standards) were 0.82 (95% CI 0.79–0.84) and 0.61 (0.59–0.64). Results were comparable for different reference standards: for initiation of methotrexate pooled sensitivity was 0.85 (0.83–0.86) and specificity was 0.52 (0.49–0.54); for initiation of any disease modifying antirheumatic drug they were 0.80 (0.79–0.82) and 0.65 (0.61–0.68), respectively; and for expert opinion 0.88 (0.86–0.90) and 0.48 (0.35–0.52). No differences were observed for use of different types of joint counts. Eight studies and five meeting abstracts directly compared 1987 and 2010 criteria using different reference standards within different target populations showing higher overall sensitivity (+0.11 compared with 1987 criteria) at the cost of lower overall specificity (–0.04). Conclusions Two years after their publication, the 2010 ACR/EULAR criteria have been widely tested in the community. They are sensitive to detect cases of RA among various target populations, independent of how the latter is referenced.

Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative

Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008–09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. Results. A total of 49 242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice. Conclusions. Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice.

Remission in rheumatoid arthritis: benefit over low disease activity in patient-reported outcomes and costs

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease that causes a considerable burden for the patient and society. It is not clear yet whether aiming for remission (REM) is worthwhile, especially when compared with low disease activity (LDA).MethodsIn 356 consecutive RA patients, we obtained data on physical function (health assessment questionnaire (HAQ)), health-related quality of life (HRQoL: Short Form 36 (SF36), Short Form 6 dimensions (SF-6D), Euro QoL 5D (EQ-5D)), work productivity (work productivity and activity impairment questionnaire (WPAI)), as well as estimation of direct and indirect costs. Cross-sectionally, data were compared in patients within different levels of disease activity according to the simplified disease activity index (SDAI; remission (REM ≤3.3); n = 87; low disease activity (LDA: 3.3 < SDAI ≤11); n = 103; moderate to high disease activity (MDA/HDA) >11 n = 119) by using analyses of variance (ANOVA). Longitudinal investigations assessed patients who changed from LDA to REM and vice versa.ResultsWe found differences in patients achieving REM compared with LDA for HAQ (0.39 ± 0.58 versus 0.72 ± 68), WPAI (percentage impairment while working 11.8% ± 18.7% versus 26.8% ± 23.9%; percentage of overall activity impairment, 10.8% ± 14.1% versus 29.0% ± 23.6%)), EQ-5D (0.89 ± 0.12 versus 0.78 ± 0.6) and SF-36 (physical component score (PCS): 46.0 ± 8.6 versus 38.3 ± 10.5; mental component score (MCS): 49.9 ± 11.1 versus 47.9 ± 12.3) (P < 0.01 for all, except for SF36 MCS). Regarding costs, we found significant differences of direct and indirect costs (P < 0.05) within different levels of disease activity, with higher costs in patients with higher states of disease activity. Longitudinal evaluations confirmed the main analyses.ConclusionPatients with REM show better function, HRQoL, and productivity, even when compared with another good state, such as LDA. Also from a cost perspective, REM appears superior to all other states.

Review: treat to target in rheumatoid arthritis: fact, fiction, or hypothesis?

The treatment armamentarium for rheumatoid arthritis (RA) has grown substantially over the last 15 years since the development of targeted biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs). These drugs have broadened the treatment possibilities and changed how rheumatic disease experts approach the clinical management of RA. The goal of reducing disease activity to very low levels (or remission) is now realistic, and emerging evidence suggests that treating to achieve these targets enhances long term structural and quality of life outcomes.(1–7) Consequently, “treat to target” (TTT) has become an attractive concept in the clinical management of rheumatoid arthritis (RA). TTT is generally defined as a treatment strategy in which the clinician treats the patient aggressively enough to reach and maintain explicitly specified and sequentially measured goals, such as remission or low disease activity. TTT is proactive, has a clear endpoint (the “target”), and can be operationalized as a specific treatment algorithm, simplifying the multitude of complex medication sequences that can be used to treat active RA. The emerging TTT paradigm is supported by findings from many randomized controlled clinical trials in the last decade, not designed as TTT strategy trials, that suggest the benefits of early aggressive treatment approaches.(5, 8, 9)