Efficacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam Compared with Betamethasone 17-Valerate-Medicated Plaster for the Treatment of Psoriasis.

BACKGROUND: Fixed combination calcipotriol as hydrate (Cal) 50 µg/g plus betamethasone as dipropionate (BD) 0.5 mg/g aerosol foam is an alcohol-free treatment for psoriasis. Betamethasone 17-valerate 2.25 mg (BV)-medicated plasters are recommended for treating psoriasis plaques localized in difficult-to-treat (DTT; elbow, knee, anterior face of the tibia) areas. OBJECTIVE: The aim of this study was to compare the efficacy of Cal/BD foam with BV-medicated plaster in patients with plaque psoriasis. METHODS: In this phase IIa, randomized, single-center, investigator-blinded, 4-week study, both Cal/BD foam and BV-medicated plaster were applied once daily to six test sites (three for each treatment). The primary efficacy endpoint was absolute change in total clinical score (TCS; sum of erythema, scaling, and infiltration); secondary endpoints were changes from baseline in each individual clinical score, ultrasonographic changes (total skin and echo-poor band thickness), and safety; and post hoc analysis was change from baseline in TCS on DTT areas. RESULTS: Thirty-five patients were included. Least-squares mean change in TCS from baseline was significantly greater for Cal/BD foam (-5.8) than BV-medicated plaster (-3.7; difference -2.2; 95% confidence interval -2.6 to -1.8; p < 0.001); greater changes for Cal/BD foam were observed from day 8 for each clinical sign. Absolute total skin and echo-poor band thickness change was significantly greater for Cal/BD foam than for BV-medicated plaster (both p < 0.001). Post hoc analyses showed that Cal/BD foam was significantly more effective than BV-medicated plaster on DTT areas after 4 weeks (p < 0.001), and both treatments were well tolerated. CONCLUSION: Cal/BD foam demonstrated superior efficacy versus BV-medicated plasters, including on DTT areas, in patients with plaque psoriasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT02518048.

Effect of calcipotriene plus betamethasone dipropionate topical suspension on the hypothalamic-pituitary-adrenal axis and calcium homeostasis in subjects with extensive psoriasis vulgaris: an open, non-controlled, 8-week trial.

BACKGROUND: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate is effective and safe in the treatment of psoriasis on the body and scalp within the general psoriasis patient population. OBJECTIVE: To evaluate the systemic effects of once-daily use of two-compound topical suspension/gel on the hypothalamic-pituitary-adrenal (HPA) axis and calcium homeostasis in subjects with extensive psoriasis vulgaris. METHODS: An open-label, single-group, 8-week trial in 43 subjects with extensive psoriasis covering 15-30% of the body surface area. Blood and 24-hour urine samples were collected and a standard-dose adrenocorticotropic hormone (ACTH) stimulation test was performed at baseline, weeks 4 and 8. Primary endpoints were serum cortisol 30 minutes after ACTH injection (HPA axis response abnormal at serum cortisol ≤18 µg/dL) and changes from baseline in albumin-corrected serum calcium (sCa), 24-hour urinary calcium excretion (24hCa) and urine calcium:creatinine ratio (Ca:Crea). RESULTS: Two (4.7%) subjects showed signs of adrenal suppression based on the ACTH stimulation test results at week 4; both were withdrawn from treatment and had normal serum cortisol 30-minute values at follow-up 4 weeks later. None of the subjects who continued treatment to week 8 showed signs of adrenal suppression. There were no clinically relevant mean changes from baseline to weeks 4 and 8 in sCa, 24hCa or Ca:Crea and no subject had sCa above the reference range. CONCLUSION: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate may be applied once daily to extensive psoriasis vulgaris without generally causing adrenal suppression or disturbance of calcium homeostasis, consistent with previous findings. In a small number of patients with extensive psoriasis treated with large volumes of topical suspension, adrenal suppression may be observed. In the real-world setting, it is anticipated that systemic side-effects would occur in only a few cases within the general psoriasis patient population. ClinicalTrials.gov Identifier:

Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS).

INTRODUCTION: Trials comparing the use of full dose unfractionated heparin (UFH) or low molecular weight heparins (LMWHs) in very elderly patients with impaired renal function are lacking. IRIS aimed to assess whether LMWH is at least as safe as UFH in this population. MATERIALS AND METHODS: The study included renally impaired patients ≥70 years with acute symptomatic lower limb deep vein thrombosis (DVT). Patients were randomized to initial treatment with either tinzaparin 175 IU/kg once daily (n=269) or activated partial thromboplastin time-adjusted UFH twice daily (n=270). After acute management both groups received vitamin K antagonist to day 90. RESULTS: The trial was stopped prematurely due to a difference in mortality favoring the UFH group (11.5 vs. 6.3%; p=0.035). Rates of clinically relevant bleedings by day 90 were similar in the tinzaparin (11.9%) and UFH (11.9%) groups, as were rates of confirmed recurrent venous thromboembolism (VTE) (2.6 vs. 1.1%; p=0.34). As the mortality difference could not be explained by bleedings or recurrent VTE, a post-hoc analysis was performed. This identified six baseline characteristics significantly correlated with mortality, of which five were over-represented in the tinzaparin group. CONCLUSION: The IRIS study was a challenging study involving patients (mean age 83 years) usually excluded from clinical studies, but its early termination has left questions unanswered. The mortality difference observed with tinzaparin vs. UFH in elderly, renally-impaired patients with DVT cannot be explained on the basis of bleedings or recurrent VTE, and may reflect an imbalance of mortality risk factors at baseline.