Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial.

BACKGROUND: Oral finasteride is a well-established treatment for men with androgenetic alopecia (AGA), but long-term therapy is not always acceptable to patients. A topical finasteride formulation has been developed to minimize systemic exposure by acting specifically on hair follicles. OBJECTIVES: To evaluate the efficacy and safety of topical finasteride compared with placebo, and to analyse systemic exposure and overall benefit compared with oral finasteride. METHODS: This randomized, double-blind, double dummy, parallel-group, 24-week study was conducted in adult male outpatients with AGA at 45 sites in Europe. Efficacy and safety were evaluated. Finasteride, testosterone and dihydrotestosterone (DHT) concentrations were measured. RESULTS: Of 458 randomized patients, 323 completed the study and 446 were evaluated for safety. Change from baseline in target area hair count (TAHC) at week 24 (primary efficacy endpoint) was significantly greater with topical finasteride than placebo (adjusted mean change 20.2 vs. 6.7 hairs; P < 0.001), and numerically similar between topical and oral finasteride. Statistically significant differences favouring topical finasteride over placebo were observed for change from baseline in TAHC at week 12 and investigator-assessed change from baseline in patient hair growth/loss at week 24. Incidence and type of adverse events, and cause of discontinuation, did not differ meaningfully between topical finasteride and placebo. No serious adverse events were treatment related. As maximum plasma finasteride concentrations were >100 times lower, and reduction from baseline in mean serum DHT concentration was lower (34.5 vs. 55.6%), with topical vs. oral finasteride, there is less likelihood of systemic adverse reactions of a sexual nature related to a decrease in DHT with topical finasteride. CONCLUSION: Topical finasteride significantly improves hair count compared to placebo and is well tolerated. Its effect is similar to that of oral finasteride, but with markedly lower systemic exposure and less impact on serum DHT concentrations.

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.

Patient satisfaction with injection devices: a randomized controlled study comparing two different etanercept delivery systems in moderate to severe psoriasis.

BACKGROUND: There is limited information regarding the acceptability of injection devices for biological agents. OBJECTIVES: The primary objective of the study was to investigate patients' perceptions on the acceptability of two devices delivering etanercept. The secondary objectives of the study were to explore whether patients' attributes are associated with preferences. METHODS: This was a multicentre, open-label, randomized, parallel-design study. Adult patients with psoriasis were randomized to receive etanercept 50 mg twice-weekly subcutaneously for 12 weeks, either as a pre-filled syringe or as a pre-filled pen. The primary outcome was the patient satisfaction at week 12 with the injection device, as measured on a 0-10-point Likert scale. The study was powered to demonstrate non-inferiority of a pen over a syringe for the primary endpoint. RESULTS: A total of 421 patients were randomized. Mean patient satisfaction at week 12 was 8.9 (±1.9) points in the pen group and 7.6 (±2.6) points in the syringe group. There was a statistically significant advantage for the pen compared with the syringe. Multiple correspondence analysis showed that very satisfied patients were the oldest and had had psoriasis for a longer duration, while less satisfied patients were the most anxious and depressed. PASI 75 response was achieved by 61% of patients in the pen group and 57% in the syringe group at week 12. CONCLUSIONS: This study showed higher patient satisfaction when injecting etanercept with a pen compared with a syringe. Factors associated with lower satisfaction are younger age, anxiety and depression.

Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe.

BACKGROUND: Imiquimod is an immune response modifier that acts through toll-like receptor 7 to induce cytokine production and a subsequent innate and adaptive cell-mediated immune response. Clinical studies have demonstrated clinical and histological clearance of superficial basal cell carcinoma (sBCC) after treatment with imiquimod 5% cream. OBJECTIVES: To evaluate the safety and clinical efficacy of imiquimod (Aldaratrade mark; 3M Pharmaceuticals, St Paul, MN, U.S.A.) 5% cream for the treatment of sBCC in a multicentre, randomized, parallel, vehicle-controlled, double-blind, phase III clinical study conducted at 26 centres in Europe. METHODS: Subjects who had at least one histologically confirmed sBCC tumour were randomized to apply imiquimod or vehicle cream to the target tumour once daily, seven times per week (7 x/week) for 6 weeks. The target tumour location was identified with an indelible ink mark before treatment initiation. The treated tumour site was clinically assessed for treatment response at 12 weeks post-treatment and was then excised for histological evaluation. Efficacy assessments included the composite response rates (proportion of subjects with clinical and histological clearance) and response rates solely based on histology (proportion of subjects with histological clearance). Safety assessments, which included adverse events and scoring of local skin reactions (LSRs), were carried out throughout the study. RESULTS: In total, 166 subjects were enrolled in this study. For the intent-to-treat dataset, there was a statistically significant difference between imiquimod and vehicle groups for both composite clearance rates (clinical and histological assessments) and histological clearance rates. Composite clearance was demonstrated in 77% and 6% of subjects treated with imiquimod and vehicle cream, respectively. Histological clearance was demonstrated in 80% and 6% of subjects treated with imiquimod and vehicle cream, respectively. The most frequently reported safety findings were investigator-assessed LSRs and spontaneous reports by subjects of application site reactions, which occurred more frequently in the imiquimod group than in the vehicle group. CONCLUSIONS: Imiquimod 5% cream administered 7 x/week for 6 weeks is a safe and effective treatment for sBCC when compared with vehicle cream.

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.