Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA.

Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.

Once-weekly administration of etanercept 50 mg improves patient-reported outcomes in patients with moderate-to-severe plaque psoriasis.

OBJECTIVE: To assess baseline patient-reported outcomes (PROs) and PRO improvement in patients with psoriasis administered etanercept 50 mg once weekly (QW). METHODS: Adult patients with moderate-to-severe plaque psoriasis participated in a 12-week, double-blind, controlled trial in which they received etanercept 50 mg QW (n = 96) or placebo QW (n = 46), followed by a 12-week, open-label extension in which they received etanercept 50 mg QW (etanercept-etanercept, n = 90; placebo-etanercept, n = 36). Patients completed the Dermatology Life Quality Index (DLQI), EuroQoL-5D (EQ-5D) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at baseline and subsequent study visits. RESULTS: At baseline, DLQI and EQ-5D scores indicated significant quality of life (QoL) impairment, and FACIT-F scores suggested more fatigue than in the general population. At week 12, etanercept 50 mg QW provided statistically significantly (p < 0.05) and clinically meaningfully greater improvement in DLQI and EQ-5D utility scores than placebo, but not in FACIT-F scores. After 24 weeks of etanercept, the mean DLQI suggested psoriasis had a small effect on QoL, while EQ-5D and FACIT-F scores were comparable to population norms. CONCLUSIONS: Patients with moderate-to-severe psoriasis entered this trial with serious PRO impairment. At week 12, etanercept 50 mg QW provided significant QoL improvements compared with placebo. After 24 weeks of etanercept, the patients' serious PRO impairment had largely abated.

Etanercept in the longterm treatment of patients with ankylosing spondylitis.

OBJECTIVE: To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS). METHODS: A 96-week open-label extension study, which followed a 12-week double-blind placebo-controlled trial, was designed to provide longterm efficacy and safety data, including radiographic outcomes, for patients treated with etanercept 25 mg twice weekly (NCT00421980). In all, 81 patients were enrolled (96% of the participants from the double-blind study). Key efficacy measures included improvement using the Assessment in Ankylosing Spondylitis 20% (ASAS20) criteria, the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) method. Paired t tests were used to test within-group changes from baseline. RESULTS: The percentage of responders, by ASAS20 criteria, remained relatively constant in patients who received etanercept during the 12-week double-blind study (60% at Week 0 and 83% at Week 96 of the open-label extension); more patients from the placebo group became responders after being switched to etanercept (23% and 74%, respectively). A similar trend was also observed using the ASAS40 and ASAS5/6 criteria, the BASFI, and the BASDAI. Most patients had no change from baseline in mSASSS values. Etanercept was well tolerated; the most frequent adverse events were injection site reactions (n=30; 37.0%) and headache (n=18; 22.2%), and the most frequent infections were upper respiratory tract infections (n=43; 53.1%) and flu syndrome (n=22; 27.2%). CONCLUSION: For 2 years, etanercept was clinically effective and well tolerated, with no unexpected safety findings.

Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: The EFICA study.

BACKGROUND: Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients admitted to intensive and coronary care units (ICU/CCU). Observational data may improve disease management and guide the design of clinical trials. AIMS: EFICA is an observational study of the clinical profile, management and survival of ADHF patients admitted to ICU/CCU. METHODS: The study included 599 patients admitted to 60 ICU/CCUs across France. Relevant data was recorded during hospitalisation. Survival was assessed at 4 weeks and 1 year. RESULTS: The main cause of ADHF was ischaemic heart disease (61%); 29% of patients had cardiogenic shock. Mortality was 27.4% at 4 weeks and 46.5% at 1 year, increasing to 43.2% and 62.5%, respectively, when including pre-admission deaths. Shock patients had the highest [57.8% vs. 15.2% without shock (p < 0.001)] and patients with hypertension and pulmonary oedema had the lowest 4-week mortality: (7%). Pre-admission NYHA class III-IV heart failure, not initial clinical presentation, influenced 1-year mortality. CONCLUSION: ADHF is a heterogeneous syndrome. Based on initial clinical presentation, three entities with distinct features and outcome may be described: cardiogenic shock, pulmonary oedema with hypertension, and 'decompensated' chronic heart failure. This should be taken into account in future observational studies, guidelines and clinical trials.