Efficacy and Safety of Water-Free Lipid Formulation System Containing Calcipotriol Against Psoriasis Vulgaris

February 2023 | Volume 22 | Issue 2 | 197 | Copyright © February 2023


Published online December 6, 2022

Jan Holmback PhDa,b, Anders Carlsson PhDc, Puneet Rinwa PhDb

aDepartment of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden
bLipidor AB, Danderyd, Sweden
cMediGelium AB, Stockholm, Sweden

Abstract
Calcipotriol, a vitamin D analogue is widely used in the treatment of psoriasis. However, poor adherence to topical therapy has led to an ineffective use of the medication and built a barrier to the treatment's success. A water-free lipid-based formulation system has been developed to improve dosage and cosmetic properties along with patient compliance. This study was conducted to evaluate the efficacy and cutaneous safety of water-free lipid-based formulations containing calcipotriol (50 μg/g) as compared to their corresponding vehicles and marketed calcipotriol formulations in a psoriasis plaque test. In total, 24 subjects with chronic psoriasis vulgaris were enrolled in this single-center, randomized, vehicle, and comparator-controlled clinical trial and treated once daily over a 12-day period (10 applications). The anti-psoriatic effect was evaluated by sonographic measurement of psoriatic infiltrate and investigators' clinical efficacy assessments. The mean reduction in psoriatic infiltrate from baseline to day 12 (end of trial) with lipid-based calcipotriol formulations (-34% and -37%) was statistically significant (P<0.0001) when compared to their corresponding vehicles (6% and -4%) but not when compared with marketed calcipotriol solution and cream (-34% and -49% respectively). Mean total clinical assessment scores of these lipid-based calcipotriol formulations (1.7 each) were between those of the two comparators - greater than marketed calcipotriol solution (1.3) but lower than cream (2.0). Overall, nine mild non-serious treatment-emergent adverse effects related to all calcipotriol formulations were reported in four subjects, but all recovered at the follow-up visit. Therefore, novel lipid-based formulations of calcipotriol were clearly more efficacious than their corresponding vehicles and considered as safe therapy against psoriasis vulgaris.

J Drugs Dermatol
. 2023;22(2):197-202. doi:10.36849/JDD.7151

Citation: Holmbäck J, Carlsson A, Rinwa P. Efficacy and safety of water-free lipid formulation system containing calcipotriol against psoriasis vulgaris. J Drugs Dermatol. 2023;22(2):197-202. doi:10.36849/JDD.7151

INTRODUCTION

Psoriasis is a common chronic inflammatory skin disease which affects 2-3 % of the European population.1 Psoriasis vulgaris (chronic plaque psoriasis) is the most frequent form of psoriasis which is characterized by high degree of epidermal proliferation and damaged keratinocyte differentiation leading to thickened, scaly, and itchy skin plaques.2 Blood vessels in the affected skin areas get dilated and are infiltrated by inflammatory cells which further triggers the pathophysiological processes of psoriasis.3 Psoriatic infiltrate consists of variety of infiltrating cells that are distributed in the epidermis and upper dermis of the diseased skin and its analysis forms an important step in understanding the pathogenesis and therapeutics in psoriasis.4

Management of psoriasis includes regulation of epidermal proliferation and reduction of inflammatory reactions.5 There are several topical treatments available, including corticoids and vitamin-D derivates.6 Calcipotriol (vitamin D3-analogue) has been known to possess cutaneous safety and efficacy against psoriasis vulgaris in extensive, well-controlled clinical studies.7,8 Calcipotriol was well tolerated in these studies, with only mild adverse events which later diminished on continuation of the treatment. The monotherapy with calcipotriol cream was reported to be as efficient as the topical corticosteroid betamethasone.9 In recent years, treatment of topical agents under occlusive dressings has become a popular method of screening new drugs. A clinical study conducted on psoriasis vulgaris reported that the therapeutic response to calcipotriol increased with hydrocolloid occlusive dressing due to enhanced penetration.10 Relatively shorter study duration (2 weeks or less) used under occlusive treatment is known to provide a better insight into novel compounds and their formulations, offering quick decisions in early phase of clinical development.11,12 Shorter application duration also offers better standardization of protocol and a reduced cost of clinical trial.

Non-adherence to topical treatment has been identified as an important issue in the management of psoriasis and is likely to affect the treatment outcome.13 New formulation and drug delivery systems may help to improve compliance and can increase the choices for the patient to find a product with acceptable properties.14 An innovative dosage form, based on water-free lipid formulation system (AKVANO®, Lipidor AB, Danderyd, Sweden) for topical administration has been developed.15,16 The active ingredients are dissolved in a volatile