Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

PURPOSE: This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. METHODS: This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. RESULTS: The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. DISCUSSION: Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. CONCLUSIONS: Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.

Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on epidemiology and phenotype of osteoarthritis.

Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.

How to define responders in osteoarthritis.

BACKGROUND: Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures. SCOPE: Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis. FINDINGS: The ESCEO considers that the major challenges in DMOAD development are the absence of a precise definition of the disease, particularly in the early stages, and the lack of consensus on how to detect structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over time and should predict disease progression and outcomes such as joint replacement. CONCLUSION: The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space narrowing >0.5 mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement. On-going research using techniques such as magnetic resonance imaging and biochemical markers may allow the identification of these patients earlier in the disease process.

[Heart rate and functional impairment are predictors of outcome in heart failure patients in the real world. Data from the Austrian Heart Failure registry]. / Ruhepuls und funktionelle Einschränkungen als prognostische Parameter bei herzinsuffizienten Patienten im tatsächlichen Leben. Daten aus dem Herzinsuffizienz-Register der ÖKG.

PURPOSE: Elevated heart rate (70 beats per minute-bpm or more) is a predictor of impaired prognosis in patients with ischemic heart failure. The Austrian Working Group on Heart Failure has established a registry in May 2006 for all patients referred to dedicated heart failure clinics with a planned follow-up after 12 ± 3 months. Here we report an analysis of the prognostic impact of elevated heart rate at referral in a well-defined cohort of heart failure patients. METHODS: Between May 2006 and October 2009 1904 patients have been documented in the Austrian Heart Failure Registry. One thousand threehundred and sixty three patients (72%) had sinus rhythm at referral. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare overall and cardiovascular mortality between high (70 bpm or more) and low heart-rate groups. Patients who were lost-to-follow-up (n = 166) were censored at the time of last contact. RESULTS: At baseline in 793 patients (58%) heart rate has been elevated (70 bpm or more) while in 562 patients it has been below 70 bpm, in 8 patients no baseline heart rate has been recorded. Groups were equally balanced regarding age, gender and cardiovascular risk factors with the exception of smokers (more active smokers in the high heart-rate group: 23 vs 14%; p = 0.001) and valvular cause of heart failure (more frequent in the high heart-rate group: 3% vs 1%; p = 0.012). Patients in the high heart-rate group had significantly higher median NT-pro-BNP (1470 pg/ml, IQR 499-4188 pg/ml) compared to patients in the low heart-rate group (784 pg/ml, IQR 314-2162 pg/ml; p < 0.001). NYHA functional classes III and IV have been more frequent in the high heart-rate group than in the low heart-rate group (32% and 22%, respectively; p < 0.001) while reduced left ventricular ejection fraction (39% or less) has been more frequent in the high heart-rate group than in the low heart-rate group (71% and 61%, respectively; p < 0.001). In the high heart-rate group treatment with beta-blockers has been less frequent than in the low heart rate group (76% and 86%, respectively; p < 0.01) while dosage of beta-blocker therapy has been comparable in both groups. Of the 75 patients who died within 3.5 years 38 deaths had a cardiovascular cause. Cox proportional hazards analysis revealed that high NYHA functional class (III and IV) and elevated heart rate (70 bpm or more) were the best predictors of overall mortality while cardiovascular mortality could best be predicted by NYHA functional classes III and IV. CONCLUSION: Higher NYHA-functional classes and elevated heart rate are predictors of adverse outcome in chronic heart failure patients.

Extent and time course of pain intensity upon treatment with a topical diclofenac sodium patch versus placebo in acute traumatic injury based on a validated end point: post hoc analysis of a randomized placebo-controlled trial.

OBJECTIVE: To investigate the extent and time course of pain intensity upon treatment with a topical diclofenac patch compared with placebo in acute traumatic sport injury based on a validated and established end point. METHODS: Post hoc analysis of a randomized, placebo-controlled, double-blind, multicentre, 1-week study in 120 patients with traumatic blunt soft tissue injury. Visual analogue scale (VAS) scores (in millimetres) for pain on movement were analysed. The mean absolute VAS changes in pain intensity from baseline over the study course were calculated for the diclofenac patch formulation (active) and placebo; mean differences between active and placebo were assessed twice daily during the first 3 days after enrolment and then once daily up to day 7. RESULTS: The diclofenac patch was consistently superior to placebo in relieving pain. The mean differences compared with placebo were greatest on day 2 (23.6 - 30.6 mm, p < 0.0001) and day 3 (24.5 - 24.6 mm, p < 0.0001). Diminishing differences were observed over the study course. CONCLUSION: The investigated diclofenac sodium patch provides clinically relevant pain relief in patients with acute traumatic injuries. Maximum effects versus placebo are detected at 2 - 3 days post-injury. This analysis may serve as useful information for the planning of clinical trials in acute traumatic injury.