The multi-biomarker disease activity test for assessing response to treatment strategies using methotrexate with or without prednisone in the CAMERA-II trial.

OBJECTIVES: The CAMERA-II trial compared two tight-control, treat-to-target strategies, initiating methotrexate with prednisone (MTX+pred) or MTX with placebo (MTX+plac), in early RA-patients. The multi-biomarker disease activity (MBDA) blood test objectively measures RA disease activity with a score of 1-100. In CAMERA-II, response profiles of the MBDA score, its individual biomarkers, and DAS28 were assessed. METHODS: We evaluated 92 patients from CAMERA-II of whom clinical data and serum for MBDA testing at baseline and ≥ 1 time-point from months 1, 2, 3, 4, 5, 6, 9, or 12 were available. Changes (∆) from baseline for DAS28 and MBDA score and comparisons of ∆DAS28 and ∆MBDA score over time within the MTX+pred versus the MTX+plac strategy were tested for significance with t tests. Changes in biomarker concentration from baseline to months 1-5 were tested with Wilcoxon signed rank test and tested for difference between treatment arms by Mann-Whitney U test. RESULTS: MBDA and DAS28 showed similar response profiles, with gradual improvement over the first 6 months in the MTX+plac group, and in the MTX+pred group faster improvement during month 1, followed by gradual improvement. The 12 MBDA biomarkers could be grouped into 4 categories of response profiles, with significant responses for 4 biomarkers during the MTX+plac strategy and 9 biomarkers during the MTX+pred strategy. CONCLUSIONS: MBDA tracked treatment response in CAMERA-II similarly to DAS28. More individual MBDA biomarkers tracked treatment response to MTX+pred than to MTX+plac. Four response profiles could be observed. TRIAL REGISTRATION: CAMERA-II International Standard Randomised Controlled Trial Number: ISRCTN 70365169 . Registered on 29 March 2006, retrospectively registered.

Effectiveness of Remission Induction Strategies for Early Rheumatoid Arthritis: a Systematic Literature Review.

PURPOSE OF REVIEW: To review the effectiveness of remission induction strategies compared to single csDMARD-initiating strategies according to current guidelines in early RA. RECENT FINDINGS: Twenty-nine studies, heterogeneous on, e.g., specific treatment strategy and remission outcome used, were identified. Using DAS28-remission over 12 months, 13 (76%) of 17 remission induction strategies showed significantly more patients achieving remission. Pooled relative "risk" was 1.73 [95%CI 1.59-1.88] for bDMARD-based remission induction strategies and 1.20 [95%CI 1.03-1.40] for combination csDMARD-based remission induction strategies compared to single csDMARD-initiating strategies. When additional glucocorticoid "bridging therapy" was used in single csDMARD-initiating strategies, the higher proportion patients achieving remission in remission induction strategies was no longer statistically significant (pooled RR 1.06 [95%CI 0.83-1.35]). For other remission outcomes, results were in line with above. Remission induction strategies are more effective in achieving remission compared to single csDMARD-initiating strategies, possibly more so in bDMARD-based induction strategies. However, compared to single csDMARD-initiating strategies with glucocorticoids, induction strategies may not be more effective.

Novel optical spectral transmission (OST)-guided versus conventionally disease activity-guided treatment: study protocol of a randomized clinical trial on guidance of a treat-to-target strategy for early rheumatoid arthritis.

BACKGROUND: Assessment of disease activity is a critical component of tight-control, treat-to-target treatment strategies of rheumatoid arthritis (RA). Recently, the HandScan has been validated as a novel method for objectively assessing RA disease activity in only 1.5 min, using optical spectral transmission (OST) in hands and wrists. We describe the protocol of a randomized controlled clinical trial (RCT) to investigate whether HandScan-guided treatment aimed at 'HandScan remission' (HandScan arm) is at least as effective as and more cost-effective than clinically guided treatment aimed at ACR/EULAR 2011 Boolean remission (DAS arm). METHODS/DESIGN: The study is a multi-center, double-blind, non-inferiority RCT of 18 months duration. Patients ≥ 18 years with newly diagnosed, disease-modifying antirheumatic drug (DMARD)-naïve RA according to the ACR 2010 classification criteria, will be randomized to the DAS arm or the HandScan arm. The efficacy of the arms will be compared by evaluating Health Assessment Questionnaire (HAQ) scores (primary outcome) after 18 months of DMARD therapy, aimed at remission. The equivalence margin in HAQ scores between study arms is 0.2. Secondary outcomes are differences in cost-effectiveness and radiographic joint damage between treatment arms. The non-inferiority sample size calculation to obtain a power of 80% at a one-sided p value of 0.05, with 10% dropouts, resulted in 61 patients per arm. In both arms, DMARD strategy will be intensified monthly according to predefined steps until remission is achieved; in both arms DMARDs and treatment steps are identical. If sustained remission, defined as remission that persists consistently over three consecutive months, is achieved, DMARD therapy will be tapered. DISCUSSION: The study protocol and the specifically designed decision-making software application allow for implementation of this RCT. To test a novel method of assessing disease activity and comparing (cost-)effectiveness with the contemporary method in treat-to-target DMARD strategies in early RA patients. TRIAL REGISTRATION: Dutch Trial Register, NTR6388. Registered on 6 April 2017 ( NL50026.041.14 ). Protocol version 3.0, 19-01-2017.

Can optical spectral transmission assess ultrasound-detected synovitis in hand osteoarthritis?

OBJECTIVE: To determine whether optical spectral transmission (OST) can be used to assess synovitis in hand and wrist joints of patients with hand osteoarthritis (OA). DESIGN: Hand and wrist joints of 47 primary hand OA patients with at least one clinically inflamed hand or wrist joint were assessed for synovitis by OST and ultrasound (US). Associations between standardized OST and US synovitis were studied in linear mixed effects models, across all joint types together and individually for wrist, proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints, and were adjusted for OA features that showed associations with US synovitis. Diagnostic performance was determined using receiver operator characteristic (ROC) curves analysis, with US as reference standard. RESULTS: Altogether, 6.7% of joints showed US synovitis. Statistically significant associations between OST scores and US synovitis were found for all joints combined (Δ0.37SD, p<0.001) and PIP joints (Δ0.81SD, p<0.001), but not for DIP (Δ0.14SD, p = 0.484) or wrist joints (Δ0.37SD, p = 0.178). All associations were independent of other OA features, i.e. osteophytes and dorsal vascularity. Analysis of diagnostic performance of OST, revealed an area under the ROC curve (AUC-ROC) of 0.74 for all joints together (p<0.001), 0.69 for PIP joints (p<0.001), 0.54 for DIP joints (p = 0.486), and 0.61 for wrist joints (p = 0.234). CONCLUSIONS: OST scores and US synovitis are statistically significantly associated, independent of osteophytes and dorsal vascularity. At this stage, OST performs fair in the assessment of synovitis in PIP joints of hand OA patients.

Can baseline ultrasound results help to predict failure to achieve DAS28 remission after 1 year of tight control treatment in early RA patients?

BACKGROUND: At present, there are no prognostic parameters unequivocally predicting treatment failure in early rheumatoid arthritis (RA) patients. We investigated whether baseline ultrasonography (US) findings of joints, when added to baseline clinical, laboratory, and radiographical data, could improve prediction of failure to achieve Disease Activity Score assessing 28 joints (DAS28) remission (<2.6) at 1 year in newly diagnosed RA patients. METHODS: A multicentre cohort of newly diagnosed RA patients was followed prospectively for 1 year. US of the hands, wrists, and feet was performed at baseline. Clinical, laboratory, and radiographical parameters were recorded. Primary analysis was the prediction by logistic regression of the absence of DAS28 remission 12 months after diagnosis and start of therapy. RESULTS: Of 194 patients included, 174 were used for the analysis, with complete data available for 159. In a multivariate model with baseline DAS28 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.2), the presence of rheumatoid factor (OR 2.3, 95% CI 1.1-5.1), and type of monitoring strategy (OR 0.2, 95% CI 0.05-0.85), the addition of baseline US results for joints (OR 0.96, 95% CI 0.89-1.04) did not significantly improve the prediction of failure to achieve DAS28 remission (likelihood ratio test, 1.04; p = 0.31). CONCLUSION: In an early RA population, adding baseline ultrasonography of the hands, wrists, and feet to commonly available baseline characteristics did not improve prediction of failure to achieve DAS28 remission at 12 months. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01752309 . Registered on 19 December 2012.

Gouty arthritis: decision-making following dual-energy CT scan in clinical practice, a retrospective analysis.

To establish whether dual-energy CT (DECT) is a diagnostic tool, i.e., associated with initiation or discontinuation of a urate lowering drug (ULD). Secondly, to determine whether DECT results (gout deposition y/n) can be predicted by clinical and laboratory variables. Digital medical records of 147 consecutive patients with clinical suspicion of gout were analyzed retrospectively. Clinical data including medication before and after DECT, lab results, and results from diagnostic joint aspiration and DECT were collected. The relationship between DECT results and clinical and laboratory results was evaluated by univariate regression analyses; predictors showing a p < 0.10 were entered in a multivariate logistic regression model with the DECT result as outcome variable. A backward stepwise technique was applied. After the DECT, 104 of these patients had a clinical diagnosis of gout based on the clinical judgment of the rheumatologist, and in 84 of these patients, the diagnosis was confirmed by demonstration of monosodium urate (MSU) crystals in synovial fluid (SF) or by positive DECT. After DECT, the current ULD was modified in 33 (22.4%) of patients; in 29 of them, ULD was started and in 1 it was intensified. Following DECT, the current ULD was stopped in three patients. In the multivariable regression model, cardiovascular disease (OR 3.07, 95% CI 1.26-7.47), disease duration (OR 1.008, 95% CI 1.001-1.016), frequency of attack (OR 1.23, 95% CI 1.07-1.42), and creatinine clearance (OR 2.03, 95% CI 0.91-1.00) were independently associated with positive DECT results. We found that the DECT result increases the confidence of the prescribers in their decision to initiation or discontinuation of urate lowering therapy regimen in of mono- or oligoarthritis. It may be a useful imaging tool for patients who cannot undergo joint aspiration because of contraindications or with difficult to aspirate joints, or those who refuse joint aspiration. We also suggest the use of DECT in cases where a definitive diagnosis cannot be made from signs, symptoms, and MSU analysis alone.

Efficacy and safety of selective glucocorticoid receptor modulators in comparison to glucocorticoids in arthritis, a systematic review.

BACKGROUND: Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking. OBJECTIVE: To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis. METHODS: A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results. RESULTS: A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety. CONCLUSION: Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance.

Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique.

OBJECTIVES: In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. METHODS: In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. RESULTS: At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. CONCLUSIONS: In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.

Economic evaluation of a tight-control treatment strategy using an imaging device (handscan) for monitoring joint inflammation in early rheumatoid arthritis.

OBJECTIVES: To evaluate the cost-effectiveness of a tight-control treatment strategy using the handscan (TCHS) compared to using only clinical assessments (TC) and compared to a general non-tight-control treatment strategy (usual care; UC) in early rheumatoid arthritis (RA). METHODS: Data from 299 early RA patients from the CAMERA trial were used. Clinical outcomes were extrapolated to Quality Adjusted Life Years (QALYs) and costs using a Markov model. Costs and QALYs were compared between the TC and UC treatment strategy arm of the CAMERA trial and a simulated tight-control treatment strategy using the handscan (TCHS). Incremental Cost-Effectiveness Ratios (ICERs) were calculated and several scenario analyses performed. All analyses were performed probabilistically to obtain confidence intervals and costs-effectiveness planes and acceptability curves. RESULTS: In TCHS, €4,660 (95% CI -€11,516 to €2,045) was saved and 0.06 (95% CI 0.01 to 0.11) QALYs were gained when compared to UC, with an ICER of €77,670 saved per QALY gained. Ninety-one percent (91%) of simulations resulted in less costs and more QALYs. TCHS resulted in comparable costs or even limited savings €642 (95% CI -€6,903 to €5,601)) and comparable QALYs to TC. In all scenario analyses, TCHS and TC were found to be cost effective as compared to UC. CONCLUSIONS: A tight-control treatment strategy is highly cost-effective compared to a non-tight-control approach in early RA. Using the handscan as a monitoring device might facilitate implementation of tight-control treatment strategy at comparable costs and with comparable effects. This approach should be investigated further.

Psychological factors associated with response to treatment in rheumatoid arthritis.

This paper presents a comprehensive review of research relating psychological domains with response to therapy in patients with rheumatoid arthritis. A holistic approach to the disease was adopted by incorporating not only disease activity but also dimensions of the impact of disease on patients' lives. Psychological distress, including depression and anxiety, is common among patients with rheumatoid arthritis and has a significant negative impact on response to therapy and on patients' abilities to cope with chronic illness. Evidence regarding the influence of positive psychological dimensions such as acceptance, optimism, and adaptive coping strategies is scarce. The mechanisms involved in these interactions are incompletely understood, although changes in neuro-endocrine-immune pathways, which are common to depression and rheumatoid arthritis, seem to play a central role. Indirect psychological influences on therapeutic efficacy and long-term effectiveness include a myriad of factors such as adherence, placebo effects, cognition, coping strategies, and family and social support. Data suggest that recognition and appropriate management of psychological distress may improve response to treatment and significantly reduce disease burden.

The separate impact of tight control schemes and disease activity on quality of life in patients with early rheumatoid arthritis: results from the CAMERA trials.

OBJECTIVES: To examine in patients with early rheumatoid arthritis (RA) whether quality of life (QoL), independently of disease activity, is affected by tight control treatment strategy schemes. METHODS: In the Computer Assisted Management in Early RA (CAMERA) trials, patients with early RA, disease duration <1 year, no prior use of DMARDs) had been randomised to a methotrexate (MTX)-based tight control strategy or usual care (CAMERA study) or to 10 mg/d prednisone or placebo both added from start to a MTX-based tight control strategy (CAMERA-II study). In either study, randomisation to the more intensive strategy resulted in lower disease activity. To assess QoL, the 'Influence of Rheumatic Diseases on General Health and Lifestyle' questionnaire (IRGL) was used. Baseline and 1- and/or 2-year measurements were analysed with regression analyses with the IRGL (sub)scales as outcome variables and treatment strategy and disease activity assessing 28 joints (DAS28) as independent variables, correcting for baseline values of each scale and possible confounders (gender, age, rheumatoid factor status). RESULTS: There was no clear association between either of the treatment strategies and QoL, but a decrease in DAS28 was associated with improvement in the majority of QoL (sub)scales. CONCLUSIONS: No independent effect of the specific tight control strategies schemes on QoL was found, while there was a clear disease activity related effect. Thus frequent outpatient visits or the inclusion of prednisone in a tight control strategy did not negatively influence QoL.

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.

How to perform local soft-tissue glucocorticoid injections?

Inflammation of periarticular soft-tissue structures such as tendons, tendon sheaths, entheses, bursae, ligaments and fasciae is the hallmark of many inflammatory rheumatic diseases, but inflammation or rather irritation of these structures also occurs in the absence of an underlying rheumatic disease. In both these primary and secondary soft-tissue lesions, local glucocorticoid injection often is beneficial, although evidence in the literature is limited. This chapter reviews local injection therapy for these lesions and for nerve compression syndromes.

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.

Calibration of FRAX ® 3.1 to the Dutch population with data on the epidemiology of hip fractures.

UNLABELLED: The FRAX tool has been calibrated to the entire Dutch population, using nationwide (hip) fracture incidence rates and mortality statistics from the Netherlands. Data used for the Dutch model are described in this paper. INTRODUCTION: Risk communication and decision making about whether or not to treat with anti-osteoporotic drugs with the use of T-scores are often unclear for patients. The recently developed FRAX models use easily obtainable clinical risk factors to estimate an individual's 10-year probability of a major osteoporotic fracture and hip fracture that is useful for risk communication and subsequent decision making in clinical practice. As of July 1, 2010, the tool has been calibrated to the total Dutch population. This paper describes the data used to develop the current Dutch FRAX model and illustrates its features compared to other countries. METHODS: Age- and sex-stratified hip fracture incidence rates (LMR database) and mortality rates (Dutch national mortality statistics) for 2004 and 2005 were extracted from Dutch nationwide databases (patients aged 50+ years). For other major fractures, Dutch incidence rates were imputed, using Swedish ratios for hip to osteoporotic fracture (upper arm, wrist, hip, and clinically symptomatic vertebral) probabilities (age- and gender-stratified). The FRAX tool takes into account age, sex, body mass index (BMI), presence of clinical risk factors, and bone mineral density (BMD). RESULTS: Fracture incidence rates increased with increasing age: for hip fracture, incidence rates were lowest among Dutch patients aged 50-54 years (per 10,000 inhabitants: 2.3 for men, 2.1 for women) and highest among the oldest subjects (95-99 years; 169 of 10,000 for men, 267 of 10,000 for women). Ten-year probability of hip or major osteoporotic fracture was increased in patients with a clinical risk factor, lower BMI, female gender, a higher age, and a decreased BMD T-score. Parental hip fracture accounted for the greatest increase in 10-year fracture probability. CONCLUSION: The Dutch FRAX tool is the first fracture prediction model that has been calibrated to the total Dutch population, using nationwide incidence rates for hip fracture and mortality rates. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Dutch FRAX tool a good candidate for implementation into clinical practice.

The use of conventional disease-modifying anti-rheumatic drugs in established RA.

Conventional disease-modifying anti-rheumatic drugs (DMARDs) are the main tool to treat any form of rheumatoid arthritis (RA). Over the years, treatment strategies and use of DMARDs have changed. 'Tight control' and 'treat-to-target' are now the present paradigms. Combining DMARDs and adapting their dosages to obtain the best (clinical) result in individual RA patients with the least amount of medication has been and is studied worldwide. Literature results are mainly on early RA however, and they do not necessarily also apply to patients with established RA. Methotrexate (MTX) is the key conventional DMARD also for the treatment of established RA, and MTX often has to be combined with other DMARDs to reach low disease activity. However, there is lack of data on combination DMARD strategies and on how to treat best individual patients with established RA. In this review, we address these uncertainties and give an overview of available data.

Glucocorticoids in rheumatoid arthritis: lessons from the Utrecht study.

The lessons from the Utrecht study on glucocorticoid therapy in early rheumatoid arthritis and of the spin-off and follow-up studies are reviewed. The data indicate that: glucocorticoids are DMARDs, the joint-sparing effect is predominantly on erosions, glucocorticoids do not influence the percentage of patients developing erosive disease, and the gain in joint-sparing effect persists after the stop of treatment. Further lessons are that the size of the joint-sparing effect and the (presumed) size of the symptomatic effect of glucocorticoids depend on co-therapies. Additional DMARDs must be added to glucocorticoids for maximum effect on radiographic progression. Finally, low-dose glucocorticoids are safer than often thought.

Glucocorticoids in rheumatology: indications and routes of administration.

This paper in short reviews general indications, doses and routes of administration of glucocorticoid therapy in rheumatology. It presents greater detail concerning intralesional and intra-articular glucocorticoid injections.