Comparative study of efficacy and safety of cetrizine and bilastine in patients of chronic spontaneous urticaria: open label, randomised, parallel group study.

Urticaria or hives is a common skin condition that affects population with a lifetime prevalence of up to 22% and point prevalence of 1%. Chronic urticaria (CU) and Chronic idiopathic urticaria now known as Chronic spontaneous urticaria (CSU) is defined as daily or near-daily episodes of urticaria for more than 6 weeks ­[1].CSU is known to be the most common form of urticaria (66% to 93% of cases). The peak incidence of CSU is seen between 20 and 40 years of age and duration of the disease is usually several years but is likely to be longer in more severe cases.

Urticaria can be classified into spontaneous urticaria, physical urticaria and other urticaria types. Spontaneous urticaria is further divided into acute and chronic spontaneous urticaria (disease duration for less and more than 6 weeks, respectively). The physical and other urticaria types share the characteristic that symptoms are induced by different triggers, e.g. low temperature, heat, pressure or exercise. In contrast, in spontaneous urticaria, the lesions usually occur without an obvious stimulus [2]. CSU is characterized by pruritic wheal and flare-type skin reactions with or without angioedema that usually persist for <24 hour. In some patients, only angioedema is present [3]. In many cases of chronic urticaria, the disease may be regarded as idiopathic primarily as a result of an unknown or only infrequently identified etiology [4]. Patients with urticaria report impaired quality of life and has detrimental effect on patients sleep and affect their daily activities such as work/school performance [5]. It also has a large impact on society in terms of direct and indirect health care costs as well resulting in huge socioeconomic burden.

The pathogenesis of CSU is yet to be fully characterized. It is thought to be mediated by aberrant release of histamine and other inflammatory mediators from mast cells and basophils[1]. IgG autoantibody-mediated activation of high affinity Ig E receptors (Fc_RI) on basophils and dermal mast cells causes activated mast cells to release histamine and other mediators such as, eicosanoids, cytokines, and proteases; which are involved in the manifestation of urticaria and angio-edema. Dermal mast cell-derived histamine is generally associated with the development of the symptoms of pruritus, edema and erythema [4].

The mainstay of therapeutic options is aimed at symptomatic relief of urticaria by antagonizing the specific actions of H1-receptor-mediated histamine actions upon endothelial cells and on sensory nerves producing wheal and pruritus. The first-generation antihistamines have potent anticholinergic effects and sedative actions on central nervous system lasting longer than 12 h and therefore not preferred. The recommended first line treatment is second generation, non-sedating H1-antihistamines [6]. Newer second-generation antihistamines like cetirizine, loratadine, fexofenadine were extensively evaluated in the management of urticaria for safety and efficacy even up to four-fold elevation of the standard doses [1]. These newer drugs have the advantage of not impairing psychomotor performance (driving etc need not be contraindicated, produce no subjective effects, no sleepiness, do not potentiate alcohol or benzodiazepines.

Cetirizine is a well-known drug commonly used for the treatment of urticaria and is classified as a long acting second generation H1-antihistamine and has potent selective peripheral histamine H1 receptor antagonist activity [7].

Therapeutic efficacy of cetirizine has been evaluated in patients with seasonal allergic rhinitis, perennial allergic rhinitis, urticaria (especially CSU), atopic dermatitis, allergic asthma, allergic cough and local reactions to mosquito bite [8].

Bilastine is a novel second-generation H1-antihistamine approved for the symptomatic treatment of chronic spontaneous urticaria. It is a new piperidine molecule and belongs to the same chemical group as many new antihistamines (ebastine, fexofenadine). Bilastine has high specificity for H1 receptors. The affinity for the H1 receptor is 3 to 6 times higher than for cetirizine and fexofenadine [9]. Bilastine has a rapid onset of action (60 min) and a long duration (24 h) of effect. A study by Zuberbier T.et al confirms that a therapeutic dose of bilastine 20 mg is a novel effective and safe treatment option for the management of symptomatic patients with C U [4].

Bilastine is said to have a similar safety and tolerability profile to the other new H1 antihistamines, without anticholinergic effects, no significant effects on cognition or psychomotor performance (CNS), and no cardiovascular or electrocardiographic changes at the doses studied, even in case of drug interactions [9].

Bilastine received DCGI approval for CU and SAR in Feb 2019. Till date, there are very few studies in Indian population comparing the safety and efficacy of bilastine with second generation antihistaminic [9].

Hence the present study is planned to assess and compare the efficacy and safety of bilastine and cetirizine in patients of CSU.