Biologic treatment for atopic dermatitis: new therapies changing the treatment landscape

Written by Dr Emma Porter, Dermatology Registrar, South Infirmary Victoria University Hospital

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, affecting up to 25% of the paediatric population and up to 7% of adults. The pathophysiology is characterised by epidermal barrier dysfunction and Th2 cytokine mediated inflammation. Moderate to severe AD can significantly affect both the physical and psychological wellbeing of patients, and is associated with anxiety, depression, and sleep disorders. When severe and/or when topical management is ineffective in achieving disease control, until recently practice has been limited to introduction of phototherapy or conventional immunosuppressive therapy. Traditionally used immunosuppressant agents for AD can include ciclosporin, methotrexate, azathioprine and mycophenolate mofetil. Beyond the impact of disease itself on quality of life, there is significant burden associated with treatments - the need for regular topical regimes, financial implications, frequent hospital or clinic visits, potential for side effects and monitoring all play a role in patients’ quality of life.

In recent years, the availability of biologic agents for atopic dermatitis has changed the treatment landscape for those with severe disease. Dupilumab, a monoclonal antibody blocking interleukin 4 and interleukin 13 via their shared IL-4α subunit, has demonstrated clinical efficacy and safety in treating moderate-to-severe atopic dermatitis. This was approved by the Food and Drug Administration (FDA) in 2017, by the European Medicines Agency (EMA) in 2019, and was first approved for reimbursement by the HSE in 2021 for the treatment of moderate-to-severe AD in those who have failed systemic treatment or for whom it is contraindicated. Tralokinumab, targeting interleukin 13, is another recent addition, with clinical efficacy and tolerability demonstrated in clinical trials. In Ireland, biologic medications for moderate to severe AD may only be prescribed by consultant dermatologists who have agreed to the terms of the relevant access protocol, and require the submission of detailed applications to the HSE Medicines Management Programme for consideration of reimbursement. Clinical trials of dupilumab have shown significant improvement in AD signs and symptoms, including itch, sleep disturbances, anxiety, and depression. Phase III clinical trials demonstrated that dupilumab-treated patients experienced significant improvement in symptoms and quality of life measures. Patients reported significant improvements in pruritus, sleep disturbance, anxiety, and depression compared to placebo-treated patients. Long-term open-label studies have also confirmed the effectiveness, safety, and tolerability of dupilumab up to four years. In a study published in the British Journal of Dermatology, patients treated with dupilumab reported significant improvements in quality of life and mental health measures. The study found that patients experienced significant reductions in anxiety, depression, and sleep disturbance, which corresponded to their clinical response to dupilumab treatment. A Danish study found excellent long-term efficacy with 2-year drug survival at 86%, though importantly highlighted the prevalence of conjunctivitis in 25% of patients, and difficulty treating head-andneck atopic dermatitis as well as facial erythema secondary to dupilumab treatment.

Oral janus kinase (JAK) inhibitors such as upadacitinib and abrocitinib are other recent additions to treatment options for moderate-to-severe AD in adults who are candidates for systemic therapy. Upadacitinib, a novel selective JAK1 inhibitor, was approved by the FDA in 2022 and EMA in 2021. Like dupilumab, upadacitinib is licensed for patients with severe AD who failed to respond or are intolerant of conventional systemic treatment and has demonstrated efficacy in improvement of AD severity as well as itch. A head to head trial comparing efficacy and safety of dupilumab and upadacitinib found that improvement with upadacitinib was greater and more rapid in onset, though with increased incidence of serious infection, viral infection including herpes zoster, eczema herpeticum, and laboratory-related adverse events. Conjunctivitis and injection-site reactions were more frequent in those receiving dupilumab.

While these studies have shown promising clinical findings, there is still more to be explored regarding the long-term psychological effects of treatment with monoclonal antibodies and JAK inhibitors on patients with AD. An international qualitative study evaluated both patient and healthcare provider perspectives on treatment with dupilumab, finding that patients describe dramatic improvements in quality of life, though increased choice and flexibility is sought particularly for a significant minority who experience ocular side effects that may prompt treatment cessation A recent Italian study evaluated the psychological outcomes for patients treated with dupilumab for up to 3 years. Excellent clinical improvements were observed, however there was variability in psychological outcomes irrespective of clinical response noted for certain patient subgroups. Patients who developed atopic dermatitis in childhood were more likely to subjectively report improved psychological outcomes, but younger patients (those under age 30) who developed atopic dermatitis after age 19, particularly females, were less likely to perceive improved psychological benefits even with positive clinical improvement of eczema. These findings support the fostering of a biopsychosocial approach for these patients. Further research is needed to better understand the impact of treatment with biologics and JAK inhibitors on psychological outcomes and to identify factors that may influence treatment response.

As more therapies become available and longer-term studies further inform our practice, the treatment landscape for those with moderate and severe AD continues to evolve. As was experienced with emergence of biologics for psoriasis, the advent of these new therapies marks an exciting turning point for treatment of our patients with severe AD beyond the limits of conventional immunosuppression.

References available on request