Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm® - and placebo-controlled trial (BRIDGE).

BACKGROUND: Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient. OBJECTIVES: To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm® , in adults with moderate-to-severe chronic plaque psoriasis. METHODS: In this phase III, double-blind, placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012-000055-13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of 'clear' or 'almost clear' in the Physician's Global Assessment (PGA) at week 16. RESULTS: In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm® ; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm® : P < 0·001). Overall, 33% of patients treated with LAS41008 were 'clear' or 'almost clear' in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm® . Most treatment-related adverse events were classed as 'mild' in severity. CONCLUSIONS: LAS41008 (DMF) is effective in the treatment of adults with moderate-to-severe chronic plaque psoriasis.

Affective disorders in general practice. Treatment of 6000 patients with fluvoxamine.

A total of 6258 patients seen in general practice complaining of low mood with or without associated somatic symptoms was studied. The mean patient entry score on the Montgomery-Asberg Depression Rating Scale (MADRS) was 29.69 (moderately severe depressive disorder). Three-quarters (73%) of the patients were female, average age was 46.1 years, and a reactive element was considered to be present in 43%. Patients received fluvoxamine, a novel anti-depressant, over a treatment period of 6 weeks, dosage starting at either 50 or 100 mg at night increasing after the first week, if necessary, to a maximum of 300 mg per day. Results were analyzed for 5625 patients. Efficacy of treatment was assessed using the MADRS, Psychosomatic Symptom Scale and Clinical Global Impression scales. During treatment, there was a marked improvement in mood and a parallel improvement in somatic symptoms; there was no difference in overall response between those with or without somatic symptoms. By Week 6, patients had improved by approximately 65%, with suicidal ideation being most marked at 81%. Patient compliance was good, the most commonly reported unwanted effect being nausea. In overdoses up to 2 g fluvoxamine no lasting toxic effects were observed. In an 'elderly' sub-group of 1096 patients aged 60 years and over, efficacy and the incidence of unwanted effects were similar, but the drop-out rate due to intolerance was greater than in the younger age sub-group.