▎ WuXi AppTec content team editor
Skin damage, itching is unbearable, people can't help but scratch hard, scratch all the time, can't sleep until dawn, and may also suffer from various accompanying diseases, such as allergic rhinitis, asthma and so on. These are likely to be related to a skin disease, atopic dermatitis.
Recently, two oral Janus kinase (JAK) inhibitors for the treatment of atopic dermatitis, uppatinib extended-release tablets and abucitinib tablets, were approved for marketing by the State Drug Administration of China (NMPA), respectively, providing new treatment options for patients with atopic dermatitis.
Image credit: 123RF
About atopic dermatitis
Atopic dermatitis (AD) is a common chronic, recurrent, inflammatory skin disease. Dry skin, chronic eczema-like lesions and marked itching are the most basic features of the disease and have a great impact on the patient's life, work and study. Because patients often have allergic rhinitis, asthma and other atopic diseases, it is considered a systemic disease.
Usually, the disease begins in infancy, with nearly 50% of all patients developing before the age of 1. In the past 10 years, the incidence of atopic dermatitis in people of different ages in China has been increasing.
Depending on the severity of the patient's condition, atopic dermatitis can be classified as mild, moderate, and severe. At the same time, according to the performance in different age groups, atopic dermatitis can be divided into four stages: infancy (born to 2 years), childhood (> 2-12 years), adolescent and adulthood (> 12-60 years old) and old age (>60 years).
At present, the etiology of atopic dermatitis is currently unknown. Scientists have analyzed that the onset of atopic dermatitis is closely related to genetic and environmental factors:
Family members such as parents with a history of allergic diseases are the strongest risk factors for this disease. Genetic factors mainly affect skin barrier function and immune balance. Patients with atopic dermatitis tend to have multiple immunological abnormalities, of which activation of helper T cells 2 (Th2) is an important feature, and there may be weakening or destruction of skin barrier function, such as a decrease or deletion of polyfilament protein in the epidermis.
Environmental factors include climate change, lifestyle changes, improper bathing, infectious agent and allergen stimulation, etc., which may cause abnormalities in the immune system and skin barrier through epigenetic modifications, and participate in the pathogenesis of atopic dermatitis.
Psychological factors, such as nervousness, anxiety, depression, etc., may also play a role in the onset of atopic dermatitis.
For the treatment of atopic dermatitis, the aim is to relieve or eliminate clinical symptoms, eliminate predisposing or exacerbating factors, reduce and prevent recurrence, reduce or alleviate comorbidities, improve the quality of life of the patient.
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About JAK inhibitors
In recent years, with the in-depth study of the pathogenesis of atopic dermatitis, small molecule targeted inhibitors represented by JAK inhibitors have gradually been used in clinical practice, which has promoted the change of the treatment mode of atopic dermatitis.
The JAK family is a class of non-receptor tyrosine kinases, including jak1, JAK2, JAK3, TYK2 four subtypes, which play an important role in the signaling cascade of a variety of type I and type II cytokine receptors, and the JAK-mediated signaling pathway is related to cell proliferation, differentiation, apoptosis, and inflammation.
Among them, JAK1 plays an important role in the pathophysiology of immune-mediated diseases, inhibition of JAK1 is believed to regulate a variety of cytokines involved in the pathophysiology of atopic dermatitis, including interleukin IL-4, IL-13, IL-31, IL-22 and thymic stromal lymphopoietin (TSLP).
About uppatinib extended-release tablets
Screenshot source: NMPA official website
Upadacitinib extended-release tablets (trade name: Rifford), a once-daily oral JAK1 inhibitor, were approved for "refractory, moderate to severe atopic dermatitis in adults and adolescents 12 years of age and older who do not respond poorly or are not suitable for other systemic therapies such as hormones or biologics).
Previously, uppatinib has obtained good efficacy and safety data in the Phase 3 registered study on atopic dermatitis.
The program evaluated more than 2500 patients spanning three studies (Measure Up 1, Measure Up 2, and AD Up), and about 52 percent had previously been treated for systemic atopic dermatitis.
The findings showed that both uppatinib monotherapy and combination therapy with topical corticosteroids met all primary and secondary endpoints at week 16. Some patients in the treatment group achieved higher lesion clearance compared to the placebo group.
In addition to being approved for the treatment of atopic dermatitis, uppatinib extended-release tablets are approved by NMPA for the treatment of adult patients with moderate to severe rheumatoid arthritis and active psoriatic arthritis.
Abucitinib tablets
Image source: Screenshot of NMPA's official website
Abucitinib tablets (trade name: hippico), also a once-daily orally JAK1 inhibitor, were approved for "adult patients with refractory, moderate to severe atopic dermatitis who do not respond well or are not suitable for other systemic therapies such as hormones or biologics".
Previously, abucitinib tablets have obtained positive results in several phase 3 clinical trials in patients with moderate to severe atopic dermatitis, which have shown statistically significant improvements in skin symptom clearance, disease severity, and more rapid improvement of pruritus symptoms in patients compared with placebo.
In a randomized, double-blind, placebo-controlled Phase 3 clinical study called JADE MONO-1, 43.8% and 23.7% of patients achieved or nearly completely disappeared skin symptoms compared with the placebo group after 12 weeks of treatment (investigator overall score [IGA] score 0/1), compared with the placebo group, respectively (investigator overall score [IGA] score 0/1), compared with 7.9% in the placebo group.
Moreover, in the treatment group, 62.7% and 39.7% of patients, respectively, had eczema area and severity index changes by at least 75% from baseline (ECZE area and severity index score [EASI] 75), compared with only 11.8% in the placebo group, meeting the primary efficacy endpoint of the trial.
About basic treatment
In the case of atopic dermatitis, in addition to drug therapy, basic therapy is an essential therapeutic component.
Basic treatment consists mainly of proper bathing, restoring and maintaining skin barrier function, improving the environment, food intervention and avoidance of exposure to allergens.
Reasonable bathing
A reasonable bath can not only remove the dirty scab on the surface of the skin, but also reduce the number of Staphylococcus aureus colonization on the surface of the skin.
It is recommended that the bath water temperature be 32 ° C -37 ° C, and the bath time is 5-10 min. It is recommended to use a low-sensitivity, non-irritating cleanser whose pH is preferably close to the normal epidermal pH (about 6). Bathing frequency is appropriate once a day or every other day.
Restores and maintains skin barrier function
Topical moisturizers not only prevent moisture loss, but also repair damaged skin barriers and reduce the stimulation of exogenous adverse factors, thereby reducing the number and severity of disease attacks.
Patients are advised to choose their own moisturizing agent, use it multiple times in sufficient quantities, and should be used immediately after bathing. In winter, lipid-rich emollients can be used depending on the dryness of the skin. A weekly dose of at least 100 g is recommended for children and 250 g per week for adults.
Improve the environment
Avoid all kinds of mechanical and chemical stimuli, such as scratching, rubbing, wool fabrics, acids, bleach and other irritations, timely remove sweat irritation to the skin; avoid alcohol and spicy food; avoid over-drying and high temperature and other stimuli, suitable living temperature is 18 °C-22 °C; control the environment of allergens, such as dust mites, animal dander, pollen, etc.
Image credit: 123RF
Food interventions
According to studies, common food allergens in children under 5 years of age are milk, eggs, wheat, peanuts and soybeans; common food allergens in children over 5 years of age are nuts, shellfish and fish; food allergies in adolescents and adults are rare, and some people have pollen-related food allergies, such as birch pollen-related foods such as apples, celery, carrots and hazelnuts.
If the causal relationship between food and rash is clear, it is recommended to avoid these foods for 4 to 6 weeks, observe the improvement of the rash, if the patient has no previous history of severe allergic reactions, and if necessary, perform a food provocation test. Blind avoidance is not recommended unless a causal relationship between food and rash is clear, and excessive avoidance can lead to malnutrition.
Avoid contact with allergens
Allergic contact allergies are common in patients with atopic dermatitis, with an incidence of about 6% to 60%, and common contact allergens are nickel, neomycin, fragrance, formaldehyde, preservatives, lanolin and rubber. Patients with atopic dermatitis are advised to avoid contact with these allergens as much as possible.
Image credit: 123RF
We expect that with the approval of uppatinib extended-release tablets and abucitinib tablets, more treatment options will be available for patients with atopic dermatitis." At the same time, it is also hoped that patients can resolve or significantly improve their symptoms and enjoy a normal life in regular and good treatment, as well as disease management.