Meeting individual needs of patients with atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease with complex aetiology and presentation. Globally, AD incidence is heterogeneous – it is higher in Africa and Oceania and lower in India and northeastern and eastern Europe, said Prof Martin Steinhoff, director, Translational Research Institute, Hamad Medical Corporation in Doha, Qatar, who chaired a Pfizer-sponsored symposium during WCD 2023.

AD has a variable course, and its heterogeneous presentation adds complexity to how the disease is managed. The burden of AD is the highest among all skin diseases, added Steinhoff. It has mental health manifestations such as anxiety and depression, chronic itch, fatigue, skin pain, and sleep disturbance. AD may also co-exist with other comorbidities that could impact patients’ general health. “We need to assess every patient carefully and manage them optimally,” he pointed out.

Steinhoff is joined by renowned experts Dr Mahreen Ameen, consultant dermatologist, Royal Free London NHS Foundation Trust, London, UK, and Dr Chih-Ho Hong, dermatologist, Saint Paul Hospital in Vancouver, Canada. Together, they shared four global cases of AD, including treatment options for patients.

Case 1: Intolerant to traditional systemic therapy
A 32-year-old man has AD since childhood. He gets seasonal flares, with an intractable itch that has been disturbing his sleep. He’s been drinking 7–10 glasses of wine a week. BSA is 45%, with an EASI of 30, and PP-NRS is 9.*

He failed standard topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI). He received ciclosporin for 4 months but was discontinued due to mild renal impairment. He is reluctant to take oral steroids and has a negative perception of injections.

Taking all of these into account, what are his options for treatment?
“The patient is a candidate for long-term systemic therapy,” said Ameen. “Between a JAK inhibitor and biologics, the choice would be based on the appreciation of the risk of these drugs and the onset of actions. I would use methotrexate (MTX) only if there are no options available because MTX takes 10–12 weeks to work. Oral steroids can be used as a bridge therapy until the efficacy of MTX takes effect. I would also counsel the patient to reduce alcohol intake,” added Ameen.

Abrocitinib is an oral JAK1 inhibitor approved for patients with moderate-to-severe AD who have not responded to systemic medications. In the JADE-DARE study, abrocitinib was superior to dupilumab, a biologic drug, in reducing itch and clinical signs of AD. [Lancet 2022;400:273-282]

Case 2: Intermittent flares related to the environment
A man in his 40s, with mild-to-moderate AD as a child, experiences flares that have become progressively worse and are affecting his torso, back, and flexures of the arms and legs. BSA is 35%, with IGA** of 4. EASI score is 22, PP-NRS is 8, and DLQI*** is 22.

He works in a cargo ship for 3 months each time and comes home after. He was previously on TCS and TCI for mild disease. He has also been treated with increased potency TCS and pulses of ciclosporin for flares, but these were no longer working for him when he moved to Singapore.

Can AD treatment be flexible?
“There should be shared decision-making with the patient to ask what he feels is important,” said Hong. “An oral agent prior to getting off the ship would be a potential option if he wanted to be treated for flares. If he stops oral medications but is worried about relapsing, he can either continue with his oral treatment or consider an injectable agent.”

Ameen said during peaks of AD flaring, the patient can either take a biologic without breaks as this is not recommended or a JAK inhibitor so he can stop and start therapy as needed. “When a JAK inhibitor is stopped, there would be quick relapse. When restarted, the efficacy would be fast acting.”

“It’s good that we now have a therapy that we can start, stop, and restart safely,” said Steinhoff. In the phase III JADE REGIMEN study, induction treatment with abrocitinib 200 mg QD for 12 weeks was effective. Most responders who continued with abrocitinib did not flare. In those who flared, rescue treatment with abrocitinib plus topical therapy effectively recaptured response. [J Am Acad Dermatol 2022;86:104-112]

Case 3: Itch as a primary complaint
A 52-year-old woman with a long-standing AD experienced flares that have become severe and persistent as an adult. Her lesions were well-controlled on dupilumab, but chronic itch continues to disrupt her daily life. BSA is 5%, IGA is 1, EASI is 8, PP-NRS is 4, and DLQI is 20. She was pre-diabetic (HbA_1c 6.1 percent).

She previously had multiple courses of oral steroids. She’s been taking dupilumab with TCS and has achieved an EASI-90 response but is getting persistent itch even in areas with no visible lesions. She reported breakthrough symptoms 3-4 days prior to her next dupilumab dose.

She had completed family. The patient wanted a nonsteroidal option because her mother developed osteoporosis on oral steroids.

What are her options?
As the patient has been tolerating dupilumab well, the frequency may only need to be increased, said Ameen. “If it is not feasible, a JAK inhibitor would be a good choice. But as the patient’s EASI indicates treatment success, I may not be able to switch therapy,” added Hong.

Itch is the number one complaint of patients with AD. JAK inhibitors work well for itch reduction, said Steinhoff. In the JADE EXTEND trial, abrocitinib provided itch relief through week 96 regardless of patient age and prior dupilumab response. The study also showed that it is safe to transition from dupilumab to abrocitinib. [Br J Dermatol 2023;doi.org/10.1093/bjd/ljad162.043]

As the patient is prediabetic, she should be evaluated for risk factors, including clotting disorders, and cardiovascular and malignancy risks, added Ameen.

Case 4: Concerns about risk factors
A woman, 47 years of age, with mild-to-moderate AD as a child, has been experiencing increasingly frequent flares of lesions on her arms and legs. Sweating during exercise exacerbates her itch. Prior to dupilumab treatment, BSA was 30%, EASI was 20, IGA was 3, PP-NRS was 7, and DLQI was 20. Currently, EASI is 9, with moderate itch. She takes statin for hyperlipidaemia.

Previous treatments include multiple courses of ciclosporin and oral corticosteroids and different potencies of TCS and TCI. She tried an immunosuppressant but discontinued due to nausea. She has been on dupilumab for 18 months but is still having flares, requiring high-potency TCS, with mixed success.

She is a retired teacher, who quit smoking 3 years ago after she was diagnosed with hypertension and dyslipidaemia. She runs 5K races monthly but has stopped due to pruritus that gets worse with sweating. The patient wants to try a new therapy to control the disease but is concerned about side effects given her medical history.

How would you treat this patient?
Ameen said she would be concerned about putting the patient on a JAK inhibitor right away because of her comorbidities. “I would want her cardiac profile to improve before putting her on a JAK inhibitor.” Hong, however, said that for as long as the hypertension and dyslipidaemia are controlled and well managed, he would have no issues switching the patient to a JAK inhibitor.

“However, if the patient is >65 years, with untreated hypercholesterolaemia, cancer, or baseline hereditary thrombotic disease, or has multiple cardiovascular risk factors that are not being addressed, I would be cautious combining a JAK inhibitor with another immunosuppressant,” concluded Hong.