Perception and Experience of Biologic Therapy in Atopic Dermatitis: A Qualitative Focus Group Study of Physicians and Patients in Europe and Canada

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterised by recurrent eczematous plaques and intense pruritus [1, 2]. AD commonly starts in childhood, affecting one-fifth of children [2]; recent estimates suggest global adult prevalence rates of persistent or adult-onset disease are 2.1–4.9% [3]. AD is associated with an increased risk of other atopic and allergic conditions, and mental health disorders such as anxiety and depression [1, 2]. AD pathophysiology is multifactorial, with genetic predisposition, epidermal barrier dysfunction and immune system dysregulation among the major components leading to barrier impairment, sensitisation and inflammation [4]. Patients with AD experience painful itching flares and sleep disturbances, and endure the psychosocial effects of embarrassment, reduced self-esteem, isolation and stigmatisation from having a visible disease [1, 2]. The burden of disease has substantial impact on quality of life (QoL), daily activities, and on social, academic and occupational life of patients and their families [5‐7].

Guidelines recommend initial therapy focused on skin hydration with emollients, avoidance strategies, flare management with topical anti-inflammatories and ultraviolet (UV) therapy [8]. Topical corticosteroids and topical calcineurin inhibitors continue to be the most widely used therapies [8]. For refractory cases, there are systemic immunosuppressive therapies [9]. More recently, novel targeted therapies (e.g. biologics and Janus kinase inhibitors) have been approved or are in clinical development [4, 10, 11].

The Biologics in Atopic Dermatitis: Experiences & Learnings (BADEL) project aims to improve the real-life understanding of how, where and when biologics can play a role in the treatment of AD from the perspective of healthcare professionals (HCPs) and patients. This study, conducted in 2020, used focus group meetings to assess the following: the extent to which currently available biologics are addressing the needs of HCPs and patients with AD, and which needs remain unmet; the extent to which these biologics control AD; and the main experiences of prescribing HCPs and patients with AD treated with biologics. At the time of the focus group meetings, the fully human monoclonal antibody dupilumab was the only novel therapy approved for the treatment of moderate-to-severe AD. Dupilumab targets the interleukin-4 receptor alpha subunit, thus down-regulating the type 2 inflammatory response [12]. Dupilumab has proven to be a safe drug in all ages, including adolescents from the age of 12 years and elderly patients. In May 2020, dupilumab was approved by the US Food and Drug Administration in children from 6 to 11 years with weight-based dosing [13‐17]. The recent expansion of available targeted therapies has radically changed the treatment landscape since the focus group meetings were held.

The following outcomes are the qualitative responses obtained from engaging directly with focus group participants.

This qualitative interview study provided personal accounts of experiences of patients living with AD and HCPs managing them. Patients considered that their QoL, in terms of their mental, emotional and physical wellbeing, had improved to near ‘normality’ with biologic therapy because of reduced symptoms, better sleep and ability to carry out activities. However, biologics could be partially effective, have side effects, were costly and elicited fear about their long-term impact. Physicians expressed satisfaction in dosing frequency, reduced patient monitoring and visits, efficacy and side effect profile. However, concerns were raised regarding discontinuation rates because of tolerability issues and partial efficacy. Our findings add to the growing body of real-world literature on the AD experience and its management, and reflect discussions in a recent interview with a patient with AD and her consulting physician [18].

Patients with AD face a long treatment journey, starting early in life and causing considerable psychosocial and physical burden. The significant negative impact of AD is consistent with other qualitative studies of AD [19‐21]. Pruritus is responsible for much of the patients’ disease burden [22], such as sleep disturbance [23], and lesions are associated with continual pain [24]. Thus, principal issues raised were the unrelenting itch–scratch cycle, pain, altered sleep patterns and symptom visibility.

The considerable effect of AD on psychosocial wellbeing is evidenced by its impact on interpersonal relationships, which leads to loneliness, depression, shame, poor self-image and stigmatisation [19, 20, 25]. Patients wish for better acceptance and understanding of AD in general [20]. AD limited patients’ daily activities such as washing (painful) and physical activities (worsened itch) [19]. Some patients also report difficulties or missing days at work, which can lead to impaired performance and lack of funding to cover treatment costs, respectively [19, 20].

Being passed from one physician to another, receiving different diagnoses and trying various treatments is not uncommon for patients with AD [19]. Patients and carers have expressed dissatisfaction with the ‘trial and error’ approach to treatment [21, 26]. Patients have voiced frustration and helplessness with ineffective treatments, worry over poor AD understanding and awareness [19], and lack of new effective drugs to treat their disease [20].

In this study, the vast majority of patients using biologics experienced good relief from their AD symptoms for the first time in their lives, finding it to be ‘life changing’. The most prevalent side effects were eye-related while other side effects may have been a consequence of previous treatments, such as bruising from long-term corticosteroid use and itching following their withdrawal. Evidence of long-term clinical efficacy and safety of dupilumab in patients with AD has been established in real-world clinical practice [27‐29]. A real-world study found disease severity was improved in 86% of patients, 30% had complete skin clearance [28], and 29% of adverse events were ophthalmic [27]. We found that patients with AD receiving biologics made trade-offs between the treatments’ benefits and living with any of a variety of side effects, continuing treatment because (at the time of the study) there was no equally effective alternative.

Key challenges in AD management included preventing flares and stabilising the disease, overcoming fear of systemic/ biologic therapies, patient education and an effective therapy that is safe for long-term use. Under-utilisation of systemic and biologics for inflammatory conditions is reported despite their efficacy and tolerability compared with corticosteroids [30‐32]. A real-world study found that at 1 year, dupilumab persistence was 77%, suggesting patients with AD were overall satisfied with treatment; 79% of those who discontinued dupilumab reinitiated therapy within 4 months [33]. Many issues are due to poor adherence to treatment [9, 34]. Risk perception among patients with inflammatory conditions appears to affect their fear of biologics, although they report willingness to accept risks for therapies offering significant therapeutic benefit [31]. Patient education interventions can help patients to better understand their disease, adhere to treatment and may assist in alleviating their concerns [9].

Effective treatment with a biologic was considered to be often delayed through lack of knowledge and expertise among GP/HCPs and that with education, patients may be escalated to biologic treatment sooner. This is recognised, with more patients now receiving the appropriate guidance from HCPs to benefit from these treatments [24].

We also found HCPs see patients less frequently when they are treated with biologics, because of the benefits of fewer blood level tests and less frequent monitoring. However, safety concerns over conjunctivitis mean that without adequate monitoring and care patients may prematurely discontinue therapy [24].

Biologics are considered to represent a breakthrough in AD management because of the improvement seen in clinical outcomes and quality of life of their patients [24]. However, while dupilumab (the only biologic available for AD at the time of this study) presents an advancement in AD therapy, there remains an unmet need for an effective agent for those patients for whom dupilumab is contraindicated or has low efficacy or adverse effects. AD management also needs to be generally improved because few patients with moderate-to-severe AD receive the best treatment for their condition [24, 30].

A strength of our study is that we included patients and HCPs from several countries and therefore the perspectives are appropriate to different populations. Qualitative research enabled an understanding of the scope, in-depth details and importance of the participant’s experiences [35]. Prompting elicited directional and more detailed responses.

A limitation is the inclusion of relatively few participants who may not be representative of a population. Patient selection by HCPs may have meant inclusion of more severely affected patients, and we cannot be sure that the patients’ contributions were not influenced by underlying comorbidities. Additionally, interviews were conducted in different languages, leading to possible translation or cultural bias.

This qualitative study collected the individual experiences of patients with AD and HCPs with an AD speciality. Many patients had suffered from AD for a considerable number of years, it negatively impacting on all aspects of life. Patients had seen many dermatologists and been prescribed a variety of therapies without long-term success. From our study, it is evident that biologics can provide the degree of symptom improvement to provide many patients with AD a near normal QoL. Patients who have long-standing disease or a recent diagnosis should be informed that there are effective treatments and be offered the opportunity to benefit from all available novel therapies. Education and good patient-HCP communication will enable patients to manage their disease and treatment expectations. Patients and HCPs alike eagerly await alternative biologic and other treatment options to enable more choice and flexibility.