What is new in the treatment of atopic dermatitis and how are comorbidities affecting it?
Allergic rhinitis, conjunctivitis, bronchial asthma, or autoimmune diseases like alopecia, vitiligo, celiac disease, and idiopathic inflammatory bowel diseases – these are comorbidities that often trouble patients with atopic dermatitis (AD). Modern systemic treatments bring new hope to these patients. "The primary benefit of targeted treatment, especially for severe AD, is the mitigation or elimination of chronic inflammation and persistent itching, significantly improving the quality of life for patients," says Chief Physician MUDr. Miroslav Nečas, Ph.D., from the 1st Department of Dermatovenereology of MU and St. Anne's University Hospital in Brno.
What allergic and autoimmune comorbidities are most commonly associated with atopic dermatitis?
It includes allergic rhinitis, conjunctivitis, and bronchial asthma. Literature states that approximately two-thirds of patients with AD suffer from one of these comorbidities. Interestingly, in young children, AD generally develops first (in the vast majority within the first year of life) and is followed by the development of asthma, rhinitis, or conjunctivitis. This process is known as the atopic march.
Among autoimmune comorbidities, the most frequent are alopecia areata and vitiligo, but it can also include idiopathic inflammatory bowel diseases or celiac disease.
What role do comorbidities play in choosing the appropriate systemic treatment?
Quite a significant one. For example, in a patient with bronchial asthma, we might prefer the biologic dupilumab, whereas for comorbidities like alopecia areata or vitiligo, we might lean towards small molecules – Janus kinase inhibitors. This is related to the mechanisms of action of these treatments and sometimes also to the already approved indications of these treatments for specific comorbidities.
With atopic patients, you also encounter non-allergic comorbidities. Which ones should be considered when choosing therapy?
Especially ocular, neuropsychiatric, and cardiovascular comorbidities.
What is new in the management of AD, and what benefits does it bring to patients?
The basic general principle is stepwise therapy according to the severity of the disease: for milder forms of atopic dermatitis, topical treatments suffice, while medium to severe forms require systemic treatment or phototherapy.
The foundation for all forms is basic care for the damaged skin barrier using various emollients, hydrants, or oil baths. It is also important to identify or test for possible triggers of the disease and try to eliminate or avoid them – which is not always easy.
The main novelties in the treatment of especially severe AD are targeted treatments – biologics (currently approved drugs include dupilumab and tralokinumab) and so-called small molecules (approved are baricitinib, abrocitinib, and upadacitinib). The key benefit of these modern therapies is the mitigation or elimination of chronic inflammation and persistent itching, significantly improving the quality of life for patients.
What is the advantage of dupilumab compared to other systemic treatments?
Dupilumab blocks the action of two cytokines that play a crucial role in the pathogenesis of atopic dermatitis: interleukin-4 and interleukin-13. Its main advantage is its high efficacy and safety.
What are the main recommendations regarding the use of dupilumab in systemic treatment?
This treatment is intended for patients with a severe form of AD after the failure of at least one conventional modality, excluding systemic corticosteroids, or for patients who cannot receive conventional systemic therapy due to intolerance or contraindications.
The drug is administered in the form of subcutaneous injections every 2 weeks, and in the vast majority of cases, the patient can manage it themselves. Success is evaluated at 16 and 24 weeks after starting therapy and then every 24 weeks.
Are there groups of patients for whom dupilumab is contraindicated, or should be used with caution?
Contraindication is only an allergy to the active substance or excipients, which is extremely rare in practice.
Data on the administration of dupilumab to pregnant women is limited. It can be used during pregnancy only if the potential benefit outweighs the possible risk to the fetus. It is not known whether this substance is excreted in human milk and whether it is systemically absorbed after oral administration. In any case, it is always necessary to decide whether to stop breastfeeding or treatment.
In patients with mild to moderate renal or hepatic impairment, or in elderly or obese patients, no dose adjustments are needed. For patients with severe ocular comorbidities (keratoconus, severe atopic keratoconjunctivitis, or blepharitis), it is necessary to consult an ophthalmologist before starting treatment. This consultation is also required if ocular issues worsen during treatment – a known possible side effect of dupilumab.
Is there any relationship between dupilumab treatment and cardiovascular safety?
Dupilumab does not pose any risk in terms of cardiovascular safety; on the contrary, by mitigating systemic inflammation within atopic dermatitis, it can reduce this risk. On the other hand, it has been found that AD is not an independent risk factor for the development of cardiovascular diseases. A riskier lifestyle plays a larger role, including smoking, alcohol abuse, obesity, and a sedentary lifestyle.
What are the current expectations regarding the future development in the treatment of AD?
More targeted treatments will certainly be added, both in the group of biologics and small molecules, as well as antihistamines or medications affecting pruritus. Gene therapy for atopic dermatitis is more likely to be part of a distant future given the complexity of the disease.
MUDr. Andrea Skálová
Editorial team of proLékaře.cz
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