Atopic dermatitis: Key drivers in making treatment decisions

Atopic dermatitis (AD) is a chronic relapsing skin disease that requires long-term control. At the 25th World Congress of Dermatology (WCD) in Singapore, Professor Sonja Ständer, professor of dermatology and neurodermatology at the University Hospital Münster, Germany, and Professor Zuotao Zhao, dermatologist from the First Hospital, Peking University, Beijing, China, shared clinical approaches to managing patients with moderate-to-severe AD. The session was chaired by Professor Johannes Ring, director, Department of Dermatology and Allergy, Biederstein at the Technical University of Munich, Germany. Among the key topics discussed were the multifactorial nature of AD, its primary symptoms, and the various therapeutic options for itch relief.

A global problem with a huge impact
Despite new effective systemic therapies for AD, a significant proportion of patients continue to have uncontrolled disease. Moreover, flares occur in >80 percent of patients with AD. [J Eur Acad Dermatol Venereol 2022;36:1409-1431; Dermatol Ther (Heidelb) 2021;11:475-486; Am J Clin Dermatol 2019;20:565-569; Ann Allergy Asthma Immunol 2019;123:381-388.e2]

“AD is a global problem with significant societal, economic, and personal impact. It is a disease that affects quality of life (QoL). Often, it is not taken seriously enough, and patients suffer tremendously,” said Ring.

The pathophysiology of AD has three dimensions: Barrier, allergy, and psychoneurogenic inflammation. “The third dimension manifests as itch, which is one of the major symptoms of AD. Almost every AD patient suffers from itch,” Ring shared.

Many dermatologists consider itch as the ‘primary lesion’ in AD, and ~95 percent of patients reported itch as the most important symptom when evaluating treatment response. [Eur Acad Dermatol Venereol 2021;35:780; Acta Derm Venereol 2017;97:86-90]

Relieving itch improves quality of life
Itch is the most common and bothersome symptom of AD regardless of overall severity, said Ständer. “Itch is a key driver for treatment-seeking behaviour. Monitoring of itch is very important – it is more important than the lesions.”

“We usually assume that itch intensity and severity is as severe as the eczema, but this is not true,” she clarified. In a 2022 survey, most participants reported moderate-to-severe itch – yet they only had mild-to-moderate AD. “Even in mild AD, there can be very severe itching,” she said. Itch caused them sleep disruptions, and some had concomitant skin pain. Two in three patients experienced itch even without a visible rash. Actually, reduction of itch ranked first in the list of treatment goals, with improvement in appearance only coming in third, Ständer emphasized (Figure 1).

Importantly, itch leads to the desire to scratch (Figure 2). “We cannot neglect the effects of scratching because it damages the barrier and attracts inflammatory cells, which release interleukins that drive inflammation. We should also not neglect the stress that patients perceive, as this can worsen the itch and scratching,” said Ständer.

“Eczema control is important, but the top priority of patients is to get rid of the itch as it drives the QoL improvement,” she continued.

In patients treated with the Janus kinase (JAK) inhibitor abrocitinib 200 mg who achieved no itch or near resolution of itch in the Peak Pruritus Numeric Rating Scale (PP-NRS 0/1), 90 percent reported that AD had ‘no effect’ on their QoL. [J Eur Acad Dermatol Venereol 2022;36:1308-1317]

In a post hoc analysis of JADE COMPARE, early itch relief with abrocitinib (ie, achievement of ≥4-point improvement from baseline in PP-NRS [PP-NRS 4] by week 2) was also tied to better QoL by week 12. [Am J Clin Dermatol 2023;24;97-107]

Skin clearance equally important
While itch relief is a primary treatment goal, there are cases wherein skin clearance takes precedence. This applies to AD patients whose skin lesions are more bothersome than the pruritus – these are lesions developing in areas that heavily affect a patient’s appearance and, subsequently, self-esteem.

“We have to consider that the impact of AD is multifactorial, and that includes an indirect impact of symptoms on QoL and mental health,” said Zhao.

Rapid response to treatment and improvement of signs, disease control, and treatment safety are just as important, he added.

“Treatment success in one outcome measure such as pruritus does not necessarily confer success in others,” he said. “Skin lesion control and QoL improvement are as important as the pruritus control.”

“It is important to provide relief as soon as possible,” Zhao continued. Patients cannot wait a long time considering the embarrassment, anxiety, and QoL impairments triggered by the itch and skin lesions.

Pharmacological options for AD
Abrocitinib is a JAK1 selective inhibitor approved for the treatment of moderate-to-severe AD in adults. In JADE MONO-2, abrocitinib provided significant itch relief in patients with AD within 2 weeks of treatment. The mean percentage reductions in itch scores within a day of treatment were greater for both abrocitinib 200 and 100 mg than placebo. [JAMA Dermatol 2020;156:863-873]

Itch relief with abrocitinib was even faster when combined with topical corticosteroids (TCS). In JADE DARE, 11 percent of patients treated with abrocitinib 200 mg + TCS achieved a PP-NRS of 4 a day after the first dose. [Lancet 2022;400:273-282] On post hoc analysis, 17 percent of abrocitinib-TCS recipients achieved complete or almost complete itch relief as early as week 2. [3rd Annual RAD Virtual Conference, December 2021]

In JADE REGIMEN, most responders continuing abrocitinib did not flare. In those who experienced a flare requiring rescue therapy, abrocitinib plus topical therapy effectively recaptured a response. [J Am Acad Dermatol 2022;86:104-112]

Previous trials of upadacitinib, another JAK inhibitor, resulted in significant itch relief within a week of treatment. [Lancet 2021;397:2151-2168; Lancet 2021;397:2150]

Similarly, the biologic agent dupilumab delivered significant itch relief after 16 weeks in the SOLO 1 and 2 trials. [N Engl J Med 2016;375:2335-2348] A post hoc analysis of both studies showed a 25-percent reduction from baseline in daily PP-NRS at day 15 with the drug. [J Am Acad Dermatol 2020;82:1328-1336]

Takeaways
Itch is a major symptom in AD, but the disfigurement and the feeling of constantly being watched is also a significant part of the suffering, said Ring. “Management of AD involves action at multiple levels. There has been tremendous progress in the field that has paved the way for better disease management and enhanced understanding of the pathophysiology of AD,” he continued.

Systemic modulation with advanced biologics and JAK inhibitors offers new treatment opportunities for patients living with AD, Ring concluded.