Toluwalase Joseph MBChB III
Introduction
Atopic dermatitis (AD) (Figure 1), also referred to as atopic eczema, is a chronic skin condition that usually develops in the early stages of childhood and causes inflammation, irritation, and redness of the skin [1][3]. It is depicted by skin barrier dysfunction and pruritis (itching). It is a condition prevalent globally, with an estimated percentage of 15-20% of people within developed countries affected by it. However, over the past 10 years, there has been a slight increase in its occurrence among the masses [1][2]. Studies completed in Africa have shown a high prevalence of atopic dermatitis in children from countries like South Africa, Kenya, Nigeria, and Morocco, with rates ranging from 16.5% to 20.9% [1]. Similar findings have been observed in children from Eastern Asia. However, the occurrence of atopic dermatitis can still change depending on the geographic region as well as the population [1].
Figure 1: Atopic Dermatitis presentation[7]
Pathogenesis
Atopic dermatitis is a heterogeneous disorder, meaning that because of the complexity of the disorder, it cannot be limited to one cause [1]. Therefore, the pathogenesis of atopic dermatitis is not truly understood. However, scientists have associated several factors that contribute to AD’s development (See Figure 2). There are 2 factors more commonly documented in the patient’s genetic predispositions such as the loss-of-function mutation in filaggrin or an upregulation of interleukin-13 and interleukin-4, both resulting in the dysfunction of the skin’s barrier [1][2][3]. In filaggrin mutation, the patient presents with hyper linear palms and keratosis pilaris [1]. Other features include dysregulation of the immune system (acute food allergy, asthma, and hay fever), and skin microbiota dysbiosis (Staph A colonisation) [2][3].
Figure 2: Pathogenesis of Atopic Dermatitis[8]
Treatments: Moderate-Severe AD
Abrocitinib is an oral, Janus kinase 1 selective inhibitor (JAK1) just recently added to the family. The Janus kinase family is a group of cytoplasmic tyrosine kinases that bind cytokine receptors to intracellular chains to form functional signalling complexes. JAK2 forms homodimeric receptor complexes involved in haematopoiesis that result in side effects like neutropenia and anaemia [3][4]. Whilst JAK1 contains heterodimeric receptors, this down-streams the effects of TH2 cell differentiation and itch [3][4].
Dupilumab was the only drug that was used in the treatment of moderate-severe AD for adults until abrocitinib6. It is a human monoclonal immunoglobulin G4 antibody, that is administered through injections subcutaneously, impacting the willingness of patients to use it [4]. It binds to interleukin (IL)-4 receptor-α and IL-13 receptors therefore partially inhibiting Th2 inflammatory activity as well as induction of innate immune response genes [4][5].
Clinical Trial
According to the New England Journal of Medicine, two groups of patients (226 and 238 people) with atopic dermatitis that were unresponsive to topical agents or needed systemic therapy were randomly assigned to receive 200 mg or 100 mg of abrocitinib orally once daily, respectively. 243 patients received 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), and 131 patients received the placebo. Additionally, all patients, a total of 838, received topical therapy [5].
An IGA (Investigator’s global assessment), which is a system used by clinicians, and pharmaceutical developers to measure the severity of AD and evaluates whether a new psoriasis treatment meets the needs of the patient [5][7]. The IGA at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group [5].
During the trial, the administration of abrocitinib at either 200 mg or 100 mg per day showed significant reductions in symptoms of moderate-to-severe atopic dermatitis in comparison to placebo by weeks 12 and 16. At week 2, the 200-mg dose, but not the 100-mg dose, of abrocitinib showed greater superiority to dupilumab in terms of itch response. However, there were no significant differences observed between either abrocitinib dose or dupilumab for most other key secondary end-point comparisons by week 16 [5].
In addition to testing the efficacy of both dupilumab and abroctinib, the New England Journal of Medicine also notes the side effects that patients complained or presented with. It is stated that nausea occurs in 11.1% of patients that took 200 mg abrocitinib and 4.2% in the 100 mg group [5]. The PubMed Central substantiates the adverse effects of abroctinib, as their patients presented with side effects ranging from mild (headaches and dizziness) to severe, with more troubling effects presenting with the 200mg abrocitinib[4].
Conclusion
In conclusion, atopic dermatitis is a complex disorder, thus even with the advancement made in its treatment, the adverse effects of the disorder still overshadow the effectiveness of the drugs. We have only scratched the surface of atopic dermatitis, and until more research is done and more individuals take an interest in the topic, patients with Atopic dermatitis will keep wondering when the itch will finally stop.
Bibliography
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