Advancements in the treatment of atopic dermatitis – the possibility of using JAK inhibitors and biologic drugs

Atopic dermatitis (AD) is a chronically recurring inflammatory skin disease characterized by itching and recurrent dermatitis/eczema, with a significant impact on the patient’s quality of life. Although the exact cause of atopic dermatitis is not fully understood, it is known to be a combination of genetic, environmental, and immunological factors. AD is often associated with other conditions such as allergic asthma, allergic rhinoconjunctivitis, and food allergies. Complications of AD include increased frequency of various infections, eye diseases, growth delay (or slowed growth) in children, and more. The treatment of the disease depends on the severity of the clinical presentation and symptoms, and therapeutic options have significantly advanced in recent years due to new insights into the disease. Treatment should be tailored to each patient, with the goal of reducing symptoms, including skin itching, restoring the impaired skin barrier, preventing exacerbations, complications, and associated diseases, thus improving the patient’s quality of life. In achieving these goals, biologic drugs and JAK inhibitors have shown great efficacy, particularly in severe forms of the disease.

Biological therapy such as dupilumab blocks specific extracellular signaling molecules, is highly selective, and specifically targets key cytokines, or signaling molecules (such as IL-4 and IL-13) that can activate immune cells and cause inflammation and other AD symptoms in patients. While these drugs can be effective in treating AD, they do not target the full spectrum of cytokines and signaling pathways involved in the disease, so some patients may not achieve the desired therapeutic goals. The safety profile of biological therapy is generally better than standard immunosuppressive therapy, although patients on biological therapy may experience certain transient side effects.

In addition to biological therapy (which blocks individual extracellular signaling molecules), there are also drugs that act within the cell, called JAK inhibitors. JAK inhibitors work by blocking the activity of JAK enzymes involved in the signaling pathway of many cytokines, including interleukins. Consequently, JAK inhibitors have the potential to block the activity of multiple cytokines involved in the inflammation process of AD, which has a positive effect on treatment. This broad-spectrum activity makes JAK inhibitors quite effective in treating AD, as it is a complex disease involving various cytokines and inflammatory pathways. Several drugs that inhibit JAK enzyme activity have been developed and have previously shown great success in treating autoimmune diseases such as various forms of arthritis and ulcerative colitis, for which they have been in use for some time.

Previous experiences with JAK inhibitors in patients with AD have shown rapid action and high effectiveness, with itch reduction within a week, and some studies have demonstrated faster and greater efficacy compared to biological therapy.

These therapeutic options and the new innovative therapy provide hope for faster, safer, and more effective treatment of AD for different patient groups. It is important to note that the effectiveness of these drugs may vary from person to person, and there may be individual factors that make one type of medication more effective and tolerable for a particular patient. Therefore, an individualized approach to each patient is crucial.

Overall, both treatment options using these two groups of drugs represent the current maximum achievements in the treatment of atopic dermatitis.

Prof. Liborija Lugović Mihić, MD, PhD, specialist in dermatovenerology

 

Figure based on articles:

Lugović-Mihić L, Meštrović-Štefekov J, Potočnjak I, et al. Atopic dermatitis: disease features, therapeutic options, and a multidisciplinary approach. Life 2023. (in press);

Eichenfield LF, Stripling S, Fung S, et al. Recent developments and advances in atopic dermatitis: a focus on epidemiology, pathophysiology, and treatment in the pediatric setting. Paediatr Drugs. 2022.

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