Advances in our understanding of the pathogenesis of atopic dermatitis (AD) have led to the development of new therapeutic strategies targeting, for the first time in the history of this disease, key elements in the pathogenic pathway. Current treatments vary in their nature and mechanisms of action. Most of the available safety and efficacy data for new treatments are from clinical trials, whose findings led to the authorization of drugs such as dupilumab, baricitinib, upadacitinib, tralokinumab, and abrocitinib.1

While clinical trials are necessary, they are insufficient for determining the true effectiveness and safety of new treatments. There are several reasons for this. First, clinical trials usually study select groups of patients, excluding those with certain comorbidities and a higher risk of toxicity.2 Second, they have limited sample sizes and hence only detect the most common adverse events (AEs). Less common events (those with a frequency of less than 1:1000) are generally only detected in real-life clinical practice.

Registries are a useful source of data for pharmacovigilance purposes and evaluating long-term data on a broad set of patients, many of whom have comorbidities and are on other treatments. The Healthy Skin Foundation of the Spanish Academy of Dermatology and Venereology (AEDV) has created several registries, including BIOBADADERM (the Spanish Registry of Systemic Treatments in Psoriasis), which was launched by the AEDV Psoriasis Group in 20073 and has become an international reference point for information on psoriasis in real-world clinical settings.4,5

The Spanish Atopic Dermatitis Registry, BIOBADATOP, was started in 2020, with the inclusion of the first patients. BIOBADATOP is an initiative of the AEDV established in collaboration with 2 of the academy's working groups: the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) and the Spanish Pediatric Dermatology Group (GEDP). The registry was designed in tune with the European TREatment of severe Atopic eczema (TREAT) survey, an international enterprise aimed at standardizing the collection of observational data for patients receiving systemic treatment for AD.6

The BIOBADATOP registry is designed to collect high-quality, standardized data on the safety, effectiveness, and impact on quality of life of systemic AD treatments used in Spanish hospitals. This information can then be integrated with other national or international registries.

The main aims of the BIOBADATOP project are to:

• 1.

  describe the short-term and long-term safety of systemic treatments for AD (including phototherapy) for pharmacovigilance purposes

• 2.

  describe the short-term and long-term effectiveness of systemic treatments for AD (including phototherapy) to inform decision-making and guideline development

The secondary aims are to:

• 1.

  describe the short- and long-term safety of topical treatments for AD

• 2.

  describe the effectiveness of different models of AD care, including patient education

• 3.

  describe comorbidities associated with AD

In this article, we describe the methodology used to create the BIOBADATOP registry and report on its initial findings.

The first 2 patients were enrolled in BIOBADATOP in March 2020. This report describes entries recorded up to November 2022. At the time of analysis, 13 hospitals were contributing to the registry.

Main Baseline Characteristics

As of November 2022, BIOBADATOP contained data on 258 patients (139 [54.3%] males). Mean (SD) age on enrolment was 32.6 (16.2) years. Mean follow-up was 9 months.

The main comorbidities are shown in Table 3. The most common conditions were asthma (50.4%) and allergic rhinoconjunctivitis (56.5%). Just 17% of patients had an atopic eye disease. Other notable comorbidities were anxiety (21.8%), chronic respiratory disease (17.7%), and depression (10.5%).

Table 3.

Atopic and Nonatopic Comorbidities in Enrolled Patients.

	No.	%
Atopic comorbidities
Personal history of cancer
Asthma	124	50.4
Allergic rhinoconjunctivitis	135	56.5
Atopic eye disease	40	17.0
Personal history of atopy
First-degree relative with atopic dermatitis	76	37.8
First-degree relative with asthma	52	26.9
First-degree relative with allergic rhinoconjunctivitis	44	23.7
First-degree relative with atopic eye disease	11	5.9
Nonatopic comorbidities
Anxiety	50	21.8
Depression	24	10.5
Myocardial infarction	1	0.4
Heart failure	0	0
Peripheral artery disease	4	1.7
Cerebrovascular disease	0	0
Dementia	0	0
Chronic respiratory disease	42	17.7
Connective tissue disease	0	0
Gastroduodenal ulcer	0	0
Mild chronic liver disease	0	0
Moderate/severe chronic liver disease	3	1.3
Diabetes	7	3
Diabetes with target-organ damage	0	0
Hemiparesis	0	0
Moderate/severe chronic kidney failure	1	0.4
Solid tumor or neoplasm	2	0.8
Solid tumor or neoplasm with metastasis	2	0.8
Leukemia	0	0
Lymphoma	3	1.3
Defined AIDS	0	0

The most common clinical presentations were dermatitis involving extensor surfaces (93.3%), the face and eyelids (84.6%), and the hands (67.1%). There was also genital involvement (31.6%), erythroderma (covering>70% of the body surface area) (17.2%), palmoplantar eczema (12.1%), nummular eczema (12.6%), and prurigo nodularis (≥5 palpable nodules) (11.6%).

Systemic treatments received prior to inclusion in the BIOBADATOP registry are shown in Fig. 1. Twenty percent of patients had not been previously treated with a systemic agent. The most widely used previous systemic treatments were cyclosporine (> 50% of patients) and oral corticosteroids (49%), followed at quite a distance by methotrexate, at just over 20%.

Figure 1.

Systemic treatments initiated prior to enrolment in the BIOBADOTOP registry.

(0,14MB).

Phototherapy, mostly with narrowband UVB light, had been used in 44.3% of cases. The vast majority of patients (97.4%) had been treated with topical corticosteroids; 44.3% had received topical calcineurin inhibitors.

The AEDV BIOBADATOP registry was created to collect clinical-epidemiological, pharmacovigilance, and effectiveness data on patients with moderate to severe AD under treatment with conventional or novel systemic therapies at a turning point in the history of the treatment of this disease. In this first report, we describe the current situation captured by the registry and the main characteristics of the patients enrolled.

Most patients prescribed a systemic treatment for AD in our setting have severe disease, in terms of not just clinical manifestations but also itching severity and impact on quality of life. While these are key aspects that influence decisions by both physicians and patients, they are not part of the reimbursement criteria for new drugs. Despite the clinical heterogeneity of AD, almost all the patients in the BIOBADATOP registry had dermatitis affecting the extensor surfaces. In addition, many patients had lesions in locations that have a greater impact on everyday life and can be challenging to treat, such as the face, eyelids, genitals, and hands. A large percentage of patients had atopic comorbidities such as asthma. Other comorbidities, notably mood disorders, were also common.

Dupilumab was approved by the European Medicines Agency in September 2017. Authorization was subsequently granted for baricitinib, followed by tralokinumab and upadacitinib. Dupilumab is the most widely used systemic AD treatment used by the hospitals participating in the BIOBADATOP project. This is, at least in part, because it was approved earlier, meaning that clinicians are more familiar with its use, and there is a greater understanding of longer-term effects in real-world settings. Choice of drug, however, can also be influenced by other factors, such as access to authorization or first-line treatment policies in different health care regions.

Although the BIOBADATOP registry covers both pediatric and adult patients, the patients included were on average aged between 30 and 40. This is probably because most of the researchers that contribute to the registry are heads of units that mainly treat adults with moderate to severe AD. Pediatric units are less well represented. In addition, new systemic therapies for AD were approved later, and at different time points, for children.

This first report on the BIOBADATOP registry is limited by the short follow-up times, which precluded comparisons and an accurate measure of incidence rates. We were only able to describe frequencies, which do not reflect time of exposure to given drugs. Most of the AEs reported were associated with the most widely used drugs: dupilumab and cyclosporine. Despite this limitation, no serious AEs had been reported for any of the novel systemic treatments at the time of this analysis. There was 1 serious infection (mastoiditis), linked to cyclosporine. Other nonserious but relatively common AEs were headache, hypertrichosis, and gum bleeding.

Of all the novel systemic treatments used by Spanish hospitals in the BIOBADATOP registry, dupilumab was the medication with the most available data. The most common AEs were conjunctivitis and other AEs affecting the surface of the eye, such as blepharitis and xerophthalmia. There was just 1 case of facial erythema. These findings are consistent with recent real-world data on drug safety.10,11 Our findings did not reveal any new safety alerts.

The incidence of certain key AEs, such as cancer and other potentially serious AEs, is too low to be accurately captured in national registries, but this limitation can be overcome by combining data from different countries. BIOBADATOP is directly linked to the TREAT project and uses a standardized European protocol, similar to that followed by the United Kingdom, the Netherlands, Germany, and other European countries. Combining data from different registries should provide the necessary statistical power to calculate incidence rates for less common AEs. Germany (TREATgermany)12 and Denmark (SCRATCH)13 have both reported findings from their national registries, and the TREAT Registry Taskforce published a recent status update on the 8 databases in the network, including BIOBADATOP. The update covered 4702 patients enrolled up to May 2022.14

The treatment of AD is undergoing a major transformation.15 Until very recently, patients with disease refractory to topical treatment and/or phototherapy were largely treated with cyclosporine or off-label immunosuppressants, such as methotrexate and azathioprine. This is reflected in the data on previous treatments showing the use of at 1 conventional immunosuppressive treatment and a high use of corticosteroids. Although clinical trial data suggest that novel systemic therapies for AD have an adequate safety profile, their effects in the broader population must be studied.

The BIOBADATOP registry will generate useful data for pharmacovigilance purposes and for evaluating treatment effectiveness in real-world clinical settings, contributing to a greater understanding of moderate to severe AD and better management of this disease.

The BIOBADATOP project is led by the Healthy Skin Foundation of the Spanish Academy of Dermatology and Venereology (AEDV) and receives funding from the pharmaceutical companies Sanofi, AbbVie, Pfizer, and LEO Pharma. None of these companies had any involvement in study design or conduct; data collection, management, analysis, or interpretation; manuscript preparation, revision, or approval; or the decision to submit this manuscript for publication.

M. Munera-Campos has received fees for consultancy services, presentations, and other related activities from AbbVie, LEO Pharma, Janssen, Sanofi, and Galderma and has served as a principal or co-investigator on clinical trials sponsored by Lilly, LEO Pharma, Novartis, Janssen, Sanofi, Pfizer, AbbVie, Almirall, UCB, and Galderma. P. Chicharro has provided consultancy services for and participated in presentations and clinical trials organized by Janssen Pharmaceuticals, Almirall, Sanofi Genzyme, Lilly, AbbVie, Novartis, LEO Pharma, and Pfizer-Wyeth. A. González Quesada has provided consultancy services and participated in presentations and clinical trials for AbbVie, Pfizer, Novartis, Sanofi, Boeringher, Bristol-Meyer, LEO Pharma, and Jansen. Á. Flórez Menéndez has participated in clinical trials, given presentations, and provided consultancy services for AbbVie, Almirall, Amgen, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, and UCB Pharma. P. de la Cueva Dobao has served as a consultant and/or researcher and/or speaker for AbbVie, Almirall, BMS, Boehringer, Celgene, Janssen, LEO Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. A. M. Gimenez-Arnau has served as a medical advisor for Uriach Pharma/Neucor, Genentech, Novartis, FAES, GSK, Sanofi-Regeneron, Amgen, Thermo Fisher Scientific, Almirall, Celldex, and LEO Pharma. Y. Gilaberte-Calzada has served as a consultant for Isdin and Roche Posay, and Galderma, given presentations for Almirall, Sanofi, Avene, Rilastil, Lylly, Uriage, Novartis, and Cantabria Labs, and participated in research projects for Almirall, Sanofi, Pfizer, AbbVie, and LEO Pharma. M. Rodríguez Serna has served as a consultant for Sanofi, Pfizer, LEO Pharma, Novartis, and Abbie. M. Elosua-González has served as a researcher and/or speaker for AbbVie, Lilly, Galderma, LEO Pharma, Pfizer, UCB Pharma, and Sanofi Genzyme. E. del Alcázar has served as a speaker and/or principal or co-investigator on clinical trials for Amgen, Almirall, Janssen, Lilly, LEO Pharma, Novartis, UCB, and AbbVie. A. Batalla has participated in training activities and attended courses and conferences for AbbVie, Celgene, Faes Farma, Isdin, Janssen, LEO Pharma, Lethipharma, Lilly, Mylan, Novartis, Pierre Fabre, and Sanofi; served as a co-investigator on clinical trials sponsored by AbbVie, Celgene, LEO Pharma, Lilly, Novartis, Pfizer, and Sanofi; and provided consultancy services for AbbVie and Sanofi. H. Jin Suh Oh has received training fees and provided consultancy services and/or participated in clinical trials for AbbVie, Celgene, and Faes Farma. C. Mauleón Fernández has participated in clinical trials on atopic dermatitis for LEO Pharma and Sanofi. L. Curto Barredo has received speaker's and consultancy fees from Novartis, Sanofi, AbbVie, Lilly, LEO pharma, and Menarini and has worked as a principal and/or co-investigator in research projects/clinical trials for Sanofi, Amgen, Almirall, Lilly, LEO Pharma, Novartis, AbbVie, and Pfizer. G. Roustan Gullón has received consultancy and training fees from Sanofi, AbbVie, Lilly, Pfizer, and LEO Pharma. A. Rosell Díaz has received speaker's fees from Sanofi and LEO Pharma and worked as a co-investigator in studies for Sanofi and Pfizer. I. García-Doval has received financial support for attending conferences from AbbVie, MSD, Pfizer, and Sanofi. José Manuel Carrascosa has served as a principal/co-investigator and/or received speaker's fees, and/or served on expert or steering committees for AbbVie, Novartis, Janssen, Lilly, Sandoz, Amgen, Almirall, BMS, Boehringer Ingelheim, Biogen, UCB. The other authors declare no conflicts of interest.