FGF21 is a critical metabolic regulator, pivotal for fasting adaptation and directly regulated by PPARalpha in rodents. However, the physiological role of FGF21 in man is not yet defined and was investigated in our study. Serum FGF21 varied 250-fold among 76 healthy individuals and did not relate to age, gender, body mass index (BMI), serum lipids, or plasma glucose. FGF21 levels had no diurnal variation and were unrelated to bile acid or cholesterol synthesis. Ketosis induced by a 2 day fast or feeding a ketogenic diet (KD) did not influence FGF21 levels, whereas a 74% increase occurred after 7 days of fasting. Hypertriglyceridemic nondiabetic patients had 2-fold elevated FGF21 levels, which were further increased by 28% during fenofibrate treatment. FGF21 circulates in human plasma and increases by extreme fasting and PPARalpha activation. The wide interindividual variation and the induction of ketogenesis independent of FGF21 levels indicate that the physiological role of FGF21 in humans may differ from that in mice.

Objective: To develop evidence-based recommendations for the management of systemic glucocorticoid (GC) therapy in rheumatic diseases. Methods: The multidisciplinary guideline development group from 11 European countries, Canada and the USA consisted of 15 rheumatologists, 1 internist, 1 rheumatologist-epidemiologist, 1 health professional, 1 patient and 1 research fellow. The Delphi method was used to agree on 10 key propositions related to the safe use of GCs. A systematic literature search of PUBMED, EMBASE, CINAHL, and Cochrane Library was then used to identify the best available research evidence to support each of the 10 propositions. The strength of recommendation was given according to research evidence, clinical expertise and perceived patient preference. Results: The 10 propositions were generated through three Delphi rounds and included patient education, risk factors, adverse effects, concomitant therapy (ie, non-steroidal anti-inflammatory drugs, gastroprotection and cyclo-oxygenase-2 selective inhibitors, calcium and vitamin D, bisphosphonates) and special safety advice (ie, adrenal insufficiency, pregnancy, growth impairment). Conclusion: Ten key recommendations for the management of systemic GC-therapy were formulated using a combination of systematically retrieved research evidence and expert consensus. There are areas of importance that have little evidence (ie, dosing and tapering strategies, timing, risk factors and monitoring for adverse effects, perioperative GC-replacement) and need further research; therefore also a research agenda was composed.

Objective. To assess the efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis (RA).Methods. At the start of their initial treatment with a disease-modifying antirheumatic drug (DMARD), patients with early (duration <1 year) active RA were randomly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years. Radiographs of the hands and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde. Remission was defined as a Disease Activity Score in 28 joints of <2.6. Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years.Results. Of the 250 patients included, 242 completed the study and 225 had radiographs available both at baseline and at 2 years. At 2 years, the median and interquartile range (IQR) change in total Sharp score was lower in the prednisolone group than in the noprednisolone group (1.8 [IQR 0.5-6.0] versus 3.5 [IQR 0.5-10]; P ‫؍‬ 0.019). In the prednisolone group, there were fewer newly eroded joints per patient after 2 years (median 0.5 [IQR 0-2] versus 1.25 [IQR 0-3.25]; P ‫؍‬ 0.007). In the prednisolone group, 25.9% of patients had radiographic progression beyond the smallest detectable difference compared with 39.3% of patients in the no-prednisolone group (P ‫؍‬ 0.033). At 2 years, 55.5% of patients in the prednisolone group had achieved disease remission, compared with 32.8% of patients in the no-prednisolone group (P ‫؍‬ 0.0005). There were few adverse events that led to withdrawal. Bone loss during the 2-year study was similar in the 2 treatment groups.Conclusion. Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA, provided a high remission rate, and was well tolerated. Therefore, the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA.