Atopic dermatitis and ocular surface disorders: a United States claims-based cross-sectional study

Abstract

Background

To estimate the prevalence of ocular surface disorders (OSDs) by atopic dermatitis (AD) status and evaluate healthcare resource utilization (HRU) among patients with AD.

Methods

Patients (all ages) enrolled in the Optum Clinformatics^® database were included in this two-part, retrospective, observational, cross-sectional study using administrative claims data. For objective 1, patients with/without AD who had continuous enrollment from July 1, 2018, through December 31, 2019, were included; for objective 2, patients with AD who had ≥ 18 months of continuous enrollment any time during April 1, 2016, through December 31, 2018. OSD prevalence was compared between patients with an AD diagnosis vs. those without. HRU was assessed among patients with AD and continuous enrollment for 6 months before and 12 months after AD diagnosis.

Results

A total of 79,761 patients with AD and 11,313,523 without AD were included in objective 1. By AD status, OSD prevalence was higher among patients with vs. those without AD (16.9% vs. 9.5%); by age, it was highest among children aged ≤ 5 years (11.4%). The most common OSD was conjunctivitis (8.7% vs. 3.1% by AD status). Among 325,979 patients with AD in objective 2, there was a mean ± standard deviation of 0.87 ± 3.44 OSD-related claims during a 1-year period. Among those with a ≥ 1 OSD-related claim, the mean number of claims was 4.46 ± 7.05. Patients with vs. those without an OSD during the 6 months before their AD diagnosis had higher all-cause HRU during the following year, mainly pharmacy claims (30.5 ± 41.45 vs. 21.23 ± 32.66) and outpatient visits (32.41 ± 34.50 vs. 21.36 ± 28.59).

Conclusions

In this US claims database study, the proportion of patients with ≥ 1 OSD-related claim was 1.8 times higher among patients with vs. without AD, with considerable OSD-related HRU. The highest rates of OSD were seen in children aged ≤ 5 years.

Supplementary information

The online version contains supplementary material available at 10.1186/s12886-026-04766-0.

Introduction

Various ocular diseases have been associated with atopic dermatitis (AD), including eyelid dermatitis, blepharitis, allergic conjunctivitis, keratoconjunctivitis, keratoconus, and ocular infections [1, 2]. More severe AD has been linked to an increased risk of conjunctivitis [3, 4], blepharitis, hordeolum [3], keratitis, keratoconus [4], and more severe ocular surface disorders (OSDs) [5].

Although the link between AD and OSDs has been well reported in clinical studies, there is paucity of data relating to real-world experience such as healthcare resource utilization (HRU) [6]. The objectives of the current study were, therefore, to: (1) estimate the prevalence of OSDs and related complications among patients with AD vs. those without in 2019 in a real-world setting in the US and (2) evaluate HRU among patients with AD, both related to OSDs and all-cause HRU according to OSD status.

Methods

Study design and data source

This retrospective, observational, cross-sectional study used administrative claims data from the Optum Clinformatics^® database, which provides a comprehensive, single-payer view of data on demographics, diagnoses (International Classification of Diseases, 10th revision, Clinical Modification [ICD-10-CM] codes), and procedures (Current Procedural Terminology 4 revenue codes) performed during outpatient visits or inpatient stays and outpatient prescription records (National Drug Codes). It comprises the commercial health plan and Medicare Advantage data of a geographically diverse population, spanning all 50 States, and is representative of the entire insured US population. Overall, the database includes approximately 15–18 million annual covered lives for a total of around 63 million unique individuals over a 10-year period (January 1, 2007 to March 31, 2018).

Study dates

For the estimation of OSD prevalence (objective 1), the only inclusion criterion was continuous enrollment throughout the 18-month study period (July 1, 2018 to December 31, 2019). The date of OSD diagnosis was the date of first OSD diagnosis during 2019. The annual OSD prevalence was then assessed from January 1 to December 31, 2019 (Fig. 1a). AD status was assessed only over 6 months in total as follows: during the 6 months up to (including) the date of OSD diagnosis (for those with an OSD diagnosis) or baseline (July 1 to December 31, 2018) for those without an OSD diagnosis). Due to the study being conducted prior to availability of validation data for AD diagnosis, patients were categorized as having AD if they had ≥ 1 record with an ICD-10-CM diagnosis code for AD in any position and in any setting or an ICD-10-CM diagnosis code for contact dermatitis or unspecified dermatitis plus ≥ 2 non-diagnostic records of ICD-10-CM diagnoses of allergic rhinitis, asthma, or food allergies ≥ 30 days apart and within ±30 days of the contact/unspecified dermatitis claim [7–9], with diagnosis codes in any position and in any setting.

Fig. 1.

Study designs for a the estimation of OSD prevalence and b the evaluation of HRU among patients with AD. ^aAD was assessed during the 6-month baseline (July 1 to December 31, 2018) among patients without an OSD diagnosis. AD atopic dermatitis, HRU healthcare resource utilization, OSD ocular surface disorders

For the evaluation of HRU among patients with AD (objective 2), a longer study period was used (October 1, 2015 to December 31, 2019; Fig. 1b). The index date was defined as the date of first AD diagnosis during the patient identification period (April 1, 2016 to December 31, 2018), and patients needed to have continuous enrollment for at least 18 months during this period. Baseline was the 6 months before (excluding) the index date, and HRU was assessed during 12 months from (including) the index date.

Inclusion criteria

Inclusion criteria were:

1. a diagnosis of AD (as defined in the previous paragraph) during the identification period

2. continuous enrollment throughout the baseline and follow-up periods. All ICD-10-CM codes are listed (Table S1).

Study outcomes

Objective 1

Epidemiological outcomes were the prevalence of:

1. overall OSDs (dry eye syndrome, conjunctivitis, other disorders of the conjunctiva [including pinguecula], keratitis, or other inflammation of the eyelid [including blepharitis])

2. select individual OSDs (conjunctivitis, other chronic allergic conjunctivitis, and unspecified keratoconjunctivitis)

3. severe OSDs (an OSD claim within the inpatient, emergency room, or urgent-care setting)

4. OSD-related complications (≥ 1 claim associated with a diagnosis of ≥ 1 of the following complications within ± 30 days of an OSD claim: keratitis, adherent leukoma, unspecified corneal scarring and opacity, central corneal opacity, other corneal scars and opacities, peripheral opacity of cornea, keratoconus, and other specified disorders of cornea, unspecified eye disorders) during 2019, by AD history status. All OSDs and related complications were identified using ICD-10-CM diagnosis codes (Table S1), in any position and – except for severe OSDs – in any setting.

The development of the definitions and classification of OSDs was based on the literature available at time of study and validated by two authors (PA and EKA) based on medical experience. OSD prevalence is reported for the total population by age (≤ 5, 6–11, 12–17, and ≥ 18 years) and AD history status (yes vs. no).

Objective 2

HRU outcomes included:

1. percentage of patients with AD with ≥ 1 OSD-related claim (overall and by age)

2. mean ± standard deviation (SD) number of OSD-related claims

   (total [overall and by age] and by visit type [primary care, outpatient, specialist {including ophthalmologist, allergist, dermatologist}, urgent care, emergency room, or inpatient] or pharmacy claim) per patient and per patient with ≥1 OSD-related claim

3. mean ± SD all-cause claims per patient with AD vs. those without an OSD during the 6-month baseline. OSD duration was defined as the number of days between the first OSD-related medical or pharmacy claim and the date of the last OSD-related medical claim or last day of a supplied OSD-related pharmacy claim in the same episode. Claims were considered part of the same OSD episode if there was a gap ≤ 60 days between claims.

Statistical methods

All analyses are descriptive and were performed using summary statistics for categorical and continuous data. Patients with missing data were assigned to unknown categories; means were calculated among patients with non-missing data.

The prevalence of the various OSD outcomes was calculated as the number of patients with an OSD outcome during 2019 divided by the total population with continuous enrollment from July 1, 2018, to December 31, 2019.

Mean ± SD numbers of OSD-related claims per patient with AD and per patient with AD with ≥ 1 OSD-related claim are reported. Mean ± SD numbers of all-cause claims per patient with AD are reported by OSD status during baseline. All statistical analyses were performed using the Aetion Evidence Platform version r4.6.20200724_2027.

Results

Patient population

Estimations of OSD prevalence (objective 1) were performed in study population 1 (n = 11 393 284, of which 79 761 with AD and 11 313 523 without AD); and estimation of HRU among patients with AD (objective 2) was performed in study population 2 (n = 325 979 patients with AD), as shown in Fig. 2. The objective 1 population had a mean ± SD age of 50.0 ± 24.1 years, 52.2% were female, and 0.7% had AD (Table 1). The objective 2 population (patients with AD) had a mean ± SD age of 39.9 ± 28.5 years and 56.9% were female (Table 1).

Fig. 2.

Patient populations for the estimation of a OSD prevalence and b the evaluation of HRU among patients with AD. ^aAD status was assessed during the 6 months up to (and including) the date of OSD diagnosis (for those with an OSD diagnosis) or baseline (for those without an OSD diagnosis). ^b ≥ 1 record with an ICD-10-CM diagnosis code for AD in any position and in any setting or an ICD-10-CM diagnosis code for contact dermatitis or unspecified dermatitis plus ≥ 2 non-diagnostic records of ICD-10-CM diagnoses of allergic rhinitis, asthma, or food allergies ≥ 30 days apart and within ±30 days of the contact/unspecified dermatitis claim, with diagnosis codes in any position and in any setting. AD atopic dermatitis, HRU healthcare resource utilization, ICD-10-CM International Classification of Diseases, 10th revision, OSD ocular surface disorders

Table 1.

Baseline demographics and baseline characteristics

	Cohort for the estimation of OSD prevalence (n = 11 393 284)	Cohort for the evaluation of HRU among patients with AD (n = 325 979)
Agea (years), mean ± SD	50.0 ± 24.1	39.9 ± 28.5
Sex, n (%)
Female	5 945 745 (52.2)	185 398 (56.9)
Male	5 447 059 (47.8)	140 568 (43.1)
Other/unknown	480 (< 0.1)	13 (< 0.1)
Race, n (%)
Caucasian	6 672 901 (58.6)	197 172 (60.5)
Hispanic	1 246 368 (10.9)	34 233 (10.5)
African American	929 979 (8.2)	29 350 (9.0)
Asian	514 866 (4.5)	23 540 (7.2)
Missing	2 029 170 (17.8)	41 684 (12.8)
AD,bn (%)	79 761 (0.7)	325 979 (100)
OSD,cn (%)	1 083 216 (9.5)	34 767 (10.7)
CCI,d mean ± SD	0.15 ± 0.54	0.15 ± 0.55

AD atopic dermatitis, CCI Charlson Comorbidity Index, HRU healthcare resource utilization, OSD ocular surface disorder, SD standard deviation

^aCohort for the estimation of OSD prevalence: January 1, 2019; cohort for the evaluation of HRU among patients with AD: at AD diagnosis

^bCohort for the estimation of OSD prevalence: during 6 months pre-OSD or July to December 2018 (if no OSD); cohort for the evaluation of HRU among patients with AD: from April 2016 to December 2018

^cCohort for the estimation of OSD prevalence: OSD or OSD-related complications during July to December 2018; cohort for the evaluation of HRU among patients with AD: OSD during 6 months pre-AD

^dCohort for the estimation of OSD prevalence: during April 2016 to December 2018; cohort for the evaluation of HRU among patients with AD: during 6 months pre-AD

Prevalence of OSDs – Objective 1

The overall prevalence of OSDs was 9.5% (Table 2). It was highest among children aged ≤ 5 years (11.4%), lower among older children (5.3% aged 6–11 years), and lowest in children aged 12–17 years (4.0%), increasing again among patients aged ≥ 18 years (10.1%).

Table 2.

Prevalence of OSDs by age group

	n	Prevalence (%)
Full population	11 393 284	9.5
≤ 5 years	410 820	11.4
6–11 years	522 366	5.3
12–17 years	580 976	4.0
≥ 18 years	9 787 772	10.1

OSD, ocular surface disorder

Patients with AD had a higher prevalence of OSDs than patients without AD (16.9% vs. 9.5%; Fig. 3). Those with AD also had a higher prevalence of conjunctivitis (8.7% vs. 3.1%), chronic allergic conjunctivitis (2.4% vs. 0.6%), unspecified keratoconjunctivitis (0.03% vs. 0.02%), severe OSDs (0.6% vs. 0.3%), and OSD-related complications (2.6% vs. 1.9%) (Fig. 3).

Fig. 3.

Prevalence of OSDs and OSD complications by AD history status. AD atopic dermatitis, OSD ocular surface disorders

OSD-related HRU among patients with AD – Objective 2

Overall, 57 150 of 325 979 (17.5%) patients with AD had ≥ 1 OSD-related claim, which varied by age as shown in Fig. 4.

Fig. 4.

Patients with ≥ 1 OSD-related claim, in the full population and by age group among patients with AD. AD atopic dermatitis, OSD ocular surface disorders

Among all patients with AD, the most common OSD-related claims were pharmacy (0.21 ± 0.94), allergist (0.16 ± 1.88), outpatient (0.13 ± 0.64), and ophthalmologist (0.09 ± 0.50). Overall, < 0.01% of patients had an OSD-related inpatient stay, with a mean ± SD duration of 11.72 ± 13.83 days. Among patients with AD and ≥ 1 OSD-related claim, the mean ± SD number of OSD-related claims was 4.46 ± 7.05. during 1 year. The mean ± SD OSD duration among those with ≥ 1 OSD-related claim was 23.03 ± 49.5 days.

All-cause HRU among patients with AD – Objective 2

Among patients with AD, those with an OSD during baseline had a higher mean number of all-cause claims during 1-year follow-up than those without an OSD during baseline, mainly pharmacy claims (30.5 ± 41.45 vs. 21.23 ± 32.66) and outpatient visits (32.41 ± 34.50 vs. 21.36 ± 28.59). (Table S2).

Discussion

With the aims of reporting OSD occurrence independently of therapy use, the key findings of this administrative claim database study are that (1) the proportion of patients with OSD during baseline was 1.8 times higher among patients with vs. without AD during baseline (16.9% vs. 9.5%) and (2) 17.5% of patients with AD had ≥ 1 OSD-related claim. The similarity between OSD prevalence (16.9%, objective 1) and patients with ≥ 1 OSD-related claim (17.5%, objective 2) adds credence to the results. The rate of OSDs was highest among children aged ≤ 5 years.

Clinical studies have reported higher or much higher prevalence of OSDs among patients with AD. For example, 23.8% of 80 patients with AD (mainly mild or moderate) had OSDs (allergic conjunctivitis, blepharitis, keratoconjunctivitis, dry eye syndrome) and 25.0% had other ocular manifestations (ocular hypertension, cataract, epiblepharon) when examined by an ophthalmologist in a study in a dermatology referral center in Malaysia [10]. In another study, 38.6% of 740 adults with moderate or severe AD reported ≥ 1 eye disorder diagnosis (dry eye, perennial allergic conjunctivitis, atopic keratoconjunctivitis, herpes simplex virus infection of the eye, rosacea of the eye, keratoconus) in the past year when specifically asked about this before starting a dupilumab trial [11]. Lastly, as many as 90% of 70 adults with moderate or severe AD in a study in The Netherlands had signs of OSDs (conjunctivitis, blepharitis, meibomian gland dysfunction, limbal vascularization, punctate corneal lesions, limbitis) when examined by an ophthalmologist before starting dupilumab treatment [5]. These two studies [5, 11] potentially reported higher OSD prevalence than the current study because they included a wider range of OSD diagnoses than the current study; they only included patients with moderate or severe AD (and the risk of OSDs increases with AD severity [3, 4]); and they were clinical studies designed to specifically look for eye conditions in patients with AD rather than claims-based analyses.

Conjunctivitis prevalence in the current study was 2.8-fold higher among patients with AD vs. those without (8.7% vs. 3.1%), which is very similar to results from a Japanese claims database analysis that compared patients with AD vs. matched controls (8.9% vs. 4.1%) [12]. A Danish registry study reported a lower baseline prevalence (3.3% vs. 1.1% in the past 5 years), lower follow-up incidence rates (1.7 vs. 0.7 per 1,000 person-years), and lower adjusted hazard ratios for new-onset conjunctivitis (1.48 [mild AD] and 1.95 [severe AD]) [4]. A questionnaire-based survey of Danish adults with AD showed that 12.7% had current conjunctivitis (slightly higher than the current study), while the lifetime prevalence of conjunctivitis was 66.6% [3]. Adjusted odds ratios ranged from 2.19 to 7.24 with increasing AD severity for current conjunctivitis, and from 1.48 to 2.17 for lifetime conjunctivitis [3]. Similarly, a cross-sectional study from the US reported that adults with vs. those without AD had a 4.38-fold higher risk of conjunctivitis [13]. Lastly, a meta-analysis by Ravn et al. [14] reported a much higher prevalence of conjunctivitis (31.7% vs. 13.3% among patients with vs. without AD), with a similar increase in risk as found in the current study (odds ratio: 2.78). Among patients with moderate-to-severe AD, the prevalence of conjunctivitis was even higher (39.6%) [14].

The prevalence of allergic conjunctivitis in the current study was 4.1-fold higher among patients with vs. those without AD (2.4% vs. 0.59%). Another US administrative claims study reported lower incidence rates of allergic conjunctivitis (3.9 vs. 3.0 per 1,000 person-years among patients with vs. without AD; adjusted relative risk: 1.50) [6]. However, as many as 18.8% of 80 patients with AD had allergic conjunctivitis in a study in Malaysia when examined by an ophthalmologist [10]. The above-mentioned US cross-sectional study reported that adults with vs. those without AD had an 8.03-fold higher risk of allergic conjunctivitis [13]. Finally, the Ravn et al. meta-analysis [14] reported much higher prevalence of allergic conjunctivitis (31.8% vs. 16.9% among patients with vs. without AD).

Ravn et al. [14] reported a bidirectional association between AD and conjunctivitis. However, a recent bidirectional two-sample Mendelian randomization study reported that genetically predicted AD was linked to significantly higher risks of conjunctivitis, allergic conjunctivitis, and chronic conjunctivitis (odds ratio: 1.48, 1.53, and 1.76, respectively), but there were no significant associations in the reverse direction [15].

In the current study, only 0.03% of patients with AD had unspecified keratoconjunctivitis, which is considerably lower than in other studies. For example, the study by Gan et al. [10] performed in Malaysia reported that 1.3% of 80 patients with AD had keratoconjunctivitis identified by an ophthalmologist. Also, the meta-analysis by Ravn et al. [14] reported an 8.8% prevalence of atopic keratoconjunctivitis among patients with AD. Lastly, 12.2% of 740 adults with moderate or severe AD reported having an atopic keratoconjunctivitis diagnosis in the previous year [11]. However, these differences could be related to the nature of the studies (claims data vs. clinical) and the definitions used.

Overall, the prevalence of various OSDs varies widely by study, depending on multiple factors, including study design, location, OSD definitions, and AD severity. The latter is important, because the risk of various OSDs (e.g., conjunctivitis, blepharitis, and keratitis) increases with AD severity [3, 4], as does the use of ocular anti-inflammatories and anti-infectives [4]. The severity of OSDs also increases with AD severity [5]. However, our results and those of previous studies clearly show that patients with AD are at greater risk of OSD. Given that patients with AD have an increased risk of various ocular comorbidities – including OSDs – it is important that: (1) dermatologists proactively inquire about ocular symptoms and inform patients with AD that they are at increased risk of ocular manifestations and (2) ophthalmologists are involved in the treatment of patients with AD and OSDs, as necessary [2, 16].

Regarding HRU among patients with AD in the current study, there was an average of 0.87 OSD-related claims per patient with AD during 1 year. Among the 17.5% of AD patients with ≥ 1 OSD-related claim, there was an average of 4.46 OSD-related claims during 1 year, highlighting the financial burden of OSDs among patients with AD. The most common OSD-related claims were for pharmacy claims and allergist, outpatient, and ophthalmologist visits. To our knowledge, the only other study to report OSD-related HRU among patients with AD was a 2005 US claims data analysis [6]. Suh et al. [6] reported that mean costs among patients with AD who developed allergic conjunctivitis increased by $99 (from $238 for AD in the year before to $337 for AD and allergic conjunctivitis in the year after) because of prescription drugs and outpatient visit costs ($54 and $45, respectively).

The Optum database is representative of the commercially insured US population and includes > 85 million patients of various ages, sexes, and ethnicities. Therefore, these data permit generalizable prevalence estimates of OSDs within the larger US population with health insurance, and the results of the care management and HRU analyses are expected to be generalizable to real-world US patients with AD and OSDs.

However, claims data are primarily collected for reimbursement purposes rather than research and are prone to incomplete or inaccurate coding of diagnoses, leading to potential misclassification and under- or over-reporting of baseline characteristics or outcomes of interest. There may, thus, have been missing data that impacted the study outcomes. In addition, it is possible that selection bias was introduced by requiring 18 months of continuous enrollment.

The algorithms that we used to identify AD and OSD diagnoses have not been formally validated, but they were reviewed by clinicians and epidemiologists for validity. Also, the AD inclusion criteria (≥ 1 AD diagnosis code or another dermatitis code + atopic comorbidities) may have led to the inclusion of some patients who could have been misdiagnosed with AD, and a population with largely mild AD, which could explain the lower OSD prevalence compared to previous studies. Future studies should utilize the newly validated algorithm for moderate-to-severe AD [17]. In addition, the short (6-month) AD assessment period for the estimation of OSD prevalence may have been too short to capture all patients with AD, and assessing AD status differently for patients with vs. without an OSD diagnosis could have impacted the results.

The prevalence of OSDs in the current study was likely underestimated. As noted above, some other studies included a wider range of OSD diagnoses, patients with more severe AD, and specifically looked for eye conditions. In addition, the Optum database does not capture optometry visits, so patients with milder eye conditions may have been missed. Also, some OSD diagnoses could have been missed if a patient attended a non-ocular specialist with multiple complaints. We also note that most OSD-related claims were not from ophthalmologists; hence, some diagnoses may not have been accurately classified, especially among children, for whom OSD diagnoses are more difficult [18].

Lastly, it is possible that reimbursable codes may have been used in preference to non-reimbursable codes. However, while OSD prevalences were likely underestimated, the ratios between patients with and without AD are likely representative.

Of note, we did not attempt to assign causality to AD. We also did not stratify for asthma or allergic rhinitis, which may also be associated with OSDs [19, 20]. Further, the 12-month follow-up period for HRU assessment is relatively short; hence future studies could follow patients with AD for longer periods of time.

Conclusions

In this US claims database study, 16.9% of patients with AD during baseline had OSDs, compared to only 9.5% of those without AD, although the true burden of OSDs may be even higher. By age, the prevalence of OSDs was highest among children aged ≤ 5 years. Given the high prevalence of OSDs among patients with AD, it is important to ensure appropriate ophthalmological assessment and treatment, as necessary, alongside AD management, especially among children.

Electronic supplementary material

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Abbreviations

AD

Atopic dermatitis

CCI

Charlson Comorbidity Index

HRU

Healthcare resource utilization

ICD-10-CM

International Classification of Disease, 10th revision, Clinical Modification

OSD

Ocular surface disorder

SD

Standard deviation

Author contributions

DS, RL, PA, and EKA contributed to study concept and design. RL and DS contributed to data collection. All authors interpreted the data, provided critical feedback on the manuscript, approved the final manuscript for submission, and were accountable for the accuracy and integrity of the manuscript.

Funding

This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

Data availability

Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in this manuscript. Individual anonymized participant data will be considered for sharing once the product and indication has been approved by major health authorities (e.g., FDA, EMA, PMDA, etc), if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification. Submit requests to (https://vivli.org/).

Declarations

Ethics approval and consent to participate

No human participants were included in this study. This was a review of de-identified administrative claims data. Informed consent was not obtained. Due to the nature of the study, Institutional Review Board/Ethics Committee approval was not required. No animal subjects were included in this study.

Consent for publication

Not applicable.

Competing interests

PA is a consultant for Regeneron Pharmaceuticals Inc.; and has received research grants from UTHSC (The University of Tennessee Health Science Center). EKA has no relevant disclosures. JFM is a consultant and/or investigator for AbbVie, Amgen, Biogen, Boehringer Ingelheim, BMS, Dermavant, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi, Sun Pharma, and UCB. JPT is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Eli Lilly, LEO Pharma, OM Pharma, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi, and UNION Therapeutics; is a speaker for AbbVie, Almirall, Eli Lilly, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi; has received research grants from Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi; and is a part-time employee of LEO Pharma, since May 1, 2023. AM and MA are employees and shareholders of Regeneron Pharmaceuticals Inc. RL and DS are employees of Sanofi and may hold stock and/or stock options.