Identifying factors hampering physical activity in longstanding rheumatoid arthritis: what is the role of glucocorticoid therapy?

OBJECTIVES: To identify factors hampering the level of physical activity in longstanding rheumatoid arthritis (RA) patients, and to evaluate the effects of glucocorticoid therapy on physical activity. METHODS: Patient characteristics, disease characteristics and cardiovascular parameters were recorded in 170 patients, who participated in a study about glucose metabolism in longstanding RA treated with or without glucocorticoids. Disease activity scores (DAS28) were calculated and x-rays of hands and feet were taken and scored according to the Sharp van der Heijde score (SHS). Participants completed the health assessment questionnaire and short questionnaire to assess health-enhancing physical activity (SQUASH), which reflect physical disability and physical activity, respectively. Adherence rates to recommendations on physical activity were calculated, and patients were categorised as fully adhering, insufficiently adhering (adherence on less than the recommended number of days per week) or inactive (adherence on none of the days). RESULTS: Forty-four percent of the patients showed adherence to the recommended minimum level of physical activity, and 22% were classified as inactive. Higher DAS28 and SHS, glucocorticoid therapy, and presence of cardiovascular risk factors were associated with lower total SQUASH physical activity scores univariately. In a multivariate model, higher age, higher body mass index (BMI), higher DAS28, and higher SHS negatively influenced the score significantly; cardiovascular risk factors and glucocorticoid therapy were no longer significantly influencing physical activity. CONCLUSIONS: Physical activity in longstanding RA is hampered by higher age, higher BMI, higher disease activity, and more radiographic joint damage. Glucocorticoid therapy was not identified as independent risk factor in multivariate analyses.

EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases.

To develop recommendations for the management of medium to high-dose (ie, >7.5 mg but ≤100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.

Are changes in bone mineral density different between groups of early rheumatoid arthritis patients treated according to a tight control strategy with or without prednisone if osteoporosis prophylaxis is applied?

UNLABELLED: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. INTRODUCTION: This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. METHODS: Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. RESULTS: BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6% during the first year (p<0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. CONCLUSION: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids.

Toward safer treatment with glucocorticoids: via patient and rheumatologist perspectives to recommendations on monitoring for adverse events.

Glucocorticoids (GCs) play an important role in the treatment of rheumatic diseases, but adverse events (AEs) are common, particularly at high doses. By identifying perspectives of patients and rheumatologists on GC therapy reasons for concerns about GC therapy and resistance to this treatment were evaluated. Both patients and rheumatologists expressed concerns about AEs like osteoporosis, diabetes and cardiovascular diseases. These concerns and the fact that many GC-related AEs are - at least in part - preventable or treatable, underline the importance of identification of AEs. The EULAR Task Force on Glucocorticoids developed recommendations for monitoring of AEs during low-dose GC therapy in daily practice and clinical trials, which were based on literature, perspectives of patients and rheumatologists and issues such as clinical relevance. Safe treatment with low-dose GCs in daily practice can be enhanced with use of a limited set of recommendations. In clinical trials, monitoring of a more comprehensive set of AEs is recommended, because this will also contribute to the identification of the relevant AE-profile of GC therapy.

Glucose tolerance, insulin sensitivity and ß-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids.

OBJECTIVES: To compare glucose tolerance and parameters of insulin sensitivity and ß-cell function between chronic glucocorticoid (GC)-using and GC-naive patients with rheumatoid arthritis (RA). METHODS: Frequently sampled 75 g oral glucose tolerance tests were performed in 58 chronic GC-using and 82 GC-naive patients with RA with established disease, with no known type 2 diabetes mellitus (T2DM), and 50 control subjects of comparable age with normal glucose tolerance. The associations between cumulative GC dose and disease characteristics and glucose tolerance state, insulin sensitivity and ß-cell function were tested using multivariate linear and logistic regression models, correcting for patient characteristics. RESULTS: Glucose tolerance state, insulin sensitivity and ß-cell function did not differ between the two RA populations; de novo T2DM was detected in 11% and impaired glucose metabolism in 35% of patients with RA. In patients with RA, cumulative GC dose was associated with T2DM, which seemed mostly driven by the effects of cumulative GC dose on insulin resistance; however, the association decreased when corrected for current disease activity. Patients with RA had decreased insulin sensitivity and impaired ß-cell function compared with controls, and multivariate regression analyses showed a negative association between the presence of RA and insulin sensitivity. CONCLUSIONS: GC-using and GC-naive patients with RA had comparable metabolic parameters, and had decreased insulin sensitivity and ß-cell function as compared with healthy controls. Although cumulative GC dose was shown to have a negative impact on glucose tolerance state and insulin sensitivity, confounding by indication remains the main challenge in this cross-sectional analysis.

Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice.

OBJECTIVE: To develop recommendations on monitoring for adverse events (AEs) of low-dose glucocorticoid (GC) therapy (≤7.5 mg prednisone or equivalent daily) in clinical trials and daily practice. METHODS: Literature was searched for articles containing information on incidence and monitoring of GC-related AEs using PubMed, EMBASE and Cochrane databases. Second, the authors searched for broad accepted guidelines on the monitoring of certain AEs (eg, WHO guidelines on screening for diabetes). Available data were summarised and discussed among experts (rheumatologists and patients) of the EULAR Task Force to decide which potential AEs should be monitored, how and at which interval. RESULTS: Data on monitoring proved to be scarce; most articles were focused on therapeutic effects of GCs, not on occurrence and monitoring of AEs. Most recommendations had to be based on consensus. Those for clinical trials aimed at getting insights into incidence, prevalence and clinical relevance of AEs to create a comprehensive and valid AE-profile of GC therapy. The set of AEs to monitor is therefore more extensive, and often consists of assessments at baseline and at end of trials. Recommendations for daily practice are meant to protect patients from real dangers, which can be prevented or treated. Standard care monitoring needs NOT be extended for patients on low-dose GC therapy, except for osteoporosis (follow national guidelines), and baseline assessments of ankle edema, fasting blood glucose and risk factors for glaucoma. CONCLUSION: Given the incompleteness of literature data, consensus-based recommendations on monitoring for GC-related AEs were created, separately for daily practice and clinical trials.

Patient and rheumatologist perspectives on glucocorticoids: an exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases.

OBJECTIVE: To explore perspectives among patients and rheumatologists on glucocorticoid (GC) therapy and European League Against Rheumatism (EULAR) recommendations on the management of systemic GC therapy in order to enhance implementation of the recommendations. METHODS: Rheumatologists (from eight countries) and patients (from five countries) acquainted with GCs participated in separate meetings, during which positive and negative aspects of GC therapy were discussed and possible adverse events (AEs) were ranked for importance; in addition participants were asked to evaluate the published EULAR recommendations. The reports from these meetings and themes related to implementation of the recommendations were discussed during an international forum of the experts who had formulated the recommendations and patient participants. RESULTS: In all, 140 patients (78% women; mean age 53 years; 61% patients with rheumatoid arthritis) and 110 rheumatologists (mean work experience 15 years) participated in the meetings. Osteoporosis, diabetes and cardiovascular diseases were ranked among the five most worrisome AEs by patients and rheumatologists. In both groups, there was agreement with most of the recommendations; the recommendations on GC information cards and GC use during pregnancy scored lowest. Ideas to improve implementation of the recommendations and a research agenda were generated. CONCLUSION: The patient and rheumatologist views on GCs corresponded to a large extent, reflected by concerns in both groups about osteoporosis, diabetes and cardiovascular diseases. Specific problems with the EULAR recommendations were identified and addressed to improve their implementation. This exercise shows that patient and rheumatologist perspectives should be included early in the process of formulating recommendations.