Atopic Dermatitis Research Articles

Practical Recommendations on Laboratory Monitoring in Patients with Atopic Dermatitis on Oral JAK Inhibitors.

Oral Janus kinase inhibitors (JAKi), a class of advanced targeted systemic therapy, have demonstrated efficacy and safety in the treatment of moderate-to-severe atopic dermatitis (AD). Like other small molecules, oral JAKi have the potential for off-target effects including laboratory-related adverse events (AEs). Product labels for oral JAKi recommend an initial laboratory assessment and follow-up 4-12weeks later to monitor for potential changes, based on evidence from clinical trials across therapeutic indications for oral JAKi, which may not reflect a population of moderate-to-severe AD patients typically seen in routine clinical practice. To address this gap, a panel of eight dermatologists with clinical and research experience with oral JAKi for the management of AD conducted a targeted review of the literature focused on key laboratory-related AEs associated with oral JAKi in the moderate-to-severe AD population. Based on the synthesis of evidence and informed opinion, a set of best practice statements related to fundamental standards of care and consensus recommendations on laboratory monitoring were suggested, and level of agreement was ascertained using a Likert scale from 0 to 100. There was a high level of agreement on three of the four suggested recommendations related to assessment and monitoring of key laboratory parameters and to dose reduction or switching in response to laboratory changes; there was a lower level of agreement related to the frequency of ongoing laboratory monitoring. Appropriate patient selection and laboratory assessment is an important strategy to mitigate the potential risks associated with oral JAKi when treating AD.

Factors Associated with Dupilumab Response in Atopic Dermatitis: A Systematic Review and Meta-Analysis

BackgroundDupilumab was approved for treating moderate-to-severe atopic dermatitis (AD). However, a notable subset of patients remains unresponsive and factors associated with dupilumab response are still limited. ObjectiveTo systematically review and establish factors related to dupilumab response in AD. MethodsWe searched electronic databases, including PubMed/MEDLINE, Embase, Ovid and the Cochrane Center of Controlled Trials, from inception to March 2023. The primary outcome was factors linked to dupilumab response in AD. The odds ratio (OR) and 95% confidence interval (CI) related to a 75% reduction at 12-16 weeks in Eczema Area and Severity Index (EASI) score were synthesized using random-effects meta-analysis. ResultsOf 21 studies involving 5,575 AD patients, 3 were post hoc analyses of phase 3 dupilumab studies, 12 were retrospective, and 6 were prospective studies. Factors associated with favorable responses to dupilumab, defined by the percentage of patients achieving EASI75 at 12-16 weeks, included female with the OR (95% CI) of 2.16 (1.38, 3.38), younger age 2.81 (1.64, 4.81), absence of allergic rhinitis 2.64 (1.07, 6.50), lower body mass index 1.97 (1.18, 3.30), and lower blood eosinophil count 6.47 (3.36, 12.48), with very low certainty of evidence. Age of onset, baseline EASI score, total IgE level, and serum lactate dehydrogenase level were unrelated to dupilumab response. ConclusionFemale, younger age, absence of allergic rhinitis, lower BMI, and lower blood eosinophil count were associated with favorable response to dupilumab in patients with AD. These factors should be taken into account when considering dupilumab therapy in clinical practice.

Efficacy of a Multi-lamellar Emulsion Containing a Synthetic Sphingosine Kinase 1 Activator and Pseudoceramide in Patients with Atopic Dermatitis: A Randomized Controlled Trial.

Patients with atopic dermatitis(AD) have impaired barrier function, which decreases skin hydration, weakens their defense against microorganisms, and culminates in increased inflammatory responses. Here, we conducted a clinical trial to evaluate the efficacy of a multi-lamellar emulsion (MLE) containing the pseudoceramide PC-9S and a synthetic sphingosine kinase 1 (SPHK1) activator, Defensamide™, in improving mild-to-moderate atopic dermatitis. Forty patients aged ≥ 2years were randomized into a combined-therapy group treated with the MLE containing PC-9S and Defensamide™ plus a topical corticosteroid and a topical-corticosteroid-only group. Assessments based on therapeutic methods included the Eczema Area and Severity Index (EASI), the Investigator Global Assessment (IGA), transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin dryness, a visual analogue scale (VAS) of itchiness, a VAS of sleep disturbance, patientsatisfaction, and the Dermatology Life Quality Index (DLQI). Thirty-eight patients completed this study. In the combined-therapy group, significant improvements in clinical and instrumental measures such as EASI scores, skin hydration, and skin dryness were noted at 4weeks compared to baseline, but such improvements were not noted in the topical corticosteroid-only group. Subjective assessments of itching and sleep disturbance and DLQI scores also showed significant improvements in the combined-therapy group. Combined therapy with the MLE containing Defensamide™ and PC-9S and with topical corticosteroid demonstrated superior clinical outcomes compared with topical corticosteroid monotherapy. Our findings underscore the potential of MLE-containing formulations as effective adjunctive therapies for AD, offering both objective and subjective symptomatic relief and enhancing patients' quality of life.

Causal effects of lipid-lowering drugs on inflammatory skin diseases: Evidence from drug target Mendelian randomisation.

Clinical research has revealed that inflammatory skin diseases are associated with dyslipidaemia. Modulating lipids is also a rising potential treatment option. However, there is heterogeneity in the existing evidence and a lack of large-scale clinical trials. Observational research is prone to bias, making it difficult to determine causality. This study aimed to evaluate the causal association between lipid-lowering drugs and inflammatory skin diseases. A drug target Mendelian randomisation (MR) analysis was conducted. Genetic targets of lipid-lowering drugs, including proprotein convertase subtilis kexin 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitor, were screened. Common inflammatory skin diseases, including psoriasis, allergic urticaria, rosacea, atopic dermatitis, systemic sclerosis and seborrhoeic dermatitis, were considered as outcomes. Gene-predicted inhibition of PCSK9 was causally associated with a decreased risk of psoriasis (ORIVW [95%CI] = 0.600 [0.474-0.761], p = 2.48 × 10-5) and atopic dermatitis (ORIVW [95%CI] = 0.781 [0.633-0.964], p = 2.17 × 10-2). Gene-predicted inhibition of HMGCR decreased the risk of seborrhoeic dermatitis (ORIVW [95%CI] = 0.407 [0.168-0.984], p = 4.61 × 10-2) but increased the risk of allergic urticaria (ORIVW [95%CI] = 3.421 [1.374-8.520], p = 8.24 × 10-3) and rosacea (ORIVW [95%CI] = 3.132 [1.260-7.786], p = 1.40 × 10-2). Among all causal associations, only PCSK9 inhibition demonstrated a robust causal effect on psoriasis after a more rigorous Bonferroni test (p < 4.17 × 10-3, which is 0.05/12). Modulating lipids via PCSK9 inhibition may offer potential therapeutic targets for psoriasis and atopic dermatitis. Given the potential cutaneous side effects associated with HMGCR inhibitors, PCSK9 inhibitors could be considered viable alternatives in lipid-lowering medication.

The effect of dupilumab on caregiver- and patient-reported outcomes in young children with moderate-to-severe atopic dermatitis: Results from a placebo-controlled, phase 3 study

Moderate-to-severe atopic dermatitis (AD) greatly impacts children/caregivers. Evaluate the impact of treatment with dupilumab on caregiver- and patient-reported AD symptoms and quality of life (QoL) in young children. In the LIBERTY AD PRESCHOOL (randomized, placebo-controlled) study, children aged 6months to 5years with moderate-to-severe AD received dupilumab or placebo plus low-potency topical corticosteroids for 16weeks. This posthoc analysis assessed the change from baseline to week 16 in caregiver-reported outcome measures of AD symptoms (eg, itch and sleep) and QoL of patients and their caregivers/families. Dupilumab (n=83) vs placebo (n=79) provided significant improvements in caregiver-reported AD symptoms and QoL. Significant improvements were seen as early as week 4 and sustained through the end of the study. Additionally, dupilumab vs placebo provided rapid and significant improvement in QoL measures for the patients' caregivers/families. Few patients aged <2years; significance only reported for prespecified endpoints; Infant's Dermatitis QoL Index severity strata adopted from Children's Dermatology Life Quality Index. Dupilumab improved AD symptoms and QoL in patients and their caregivers/families.

Childhood Obesity, Weight Change, and Pediatric Immune-Mediated Skin Diseases.

Whether childhood obesity or weight gain leads to the development of pediatric immune-mediated skin diseases remains unclear. We aimed to determine the associations between body mass index or body mass index changes and the development of 3 main immune-mediated skin diseases-alopecia areata, atopic dermatitis (AD), and psoriasis-by analyzing a longitudinal cohort of 2,161,900 Korean children from 2009 to 2020. The findings indicated that children who were obese had a higher risk of pediatric immune-mediated skin diseases than those with normal weight (P for trend < .01). An increase in body mass index was associated with a higher risk of AD, whereas a decrease in body mass index was correlated with a reduced risk of AD. Children who gained weight, transitioning from normal to overweight, exhibited a higher AD risk than those who maintained a normal weight (adjusted hazard ratio= 1.15, 95% confidence interval= 1.11-1.20). However, those who shifted from being overweight to achieving a normal weight (adjusted hazard ratio= 0.87, 95% confidence interval= 0.81-0.94) had a lower AD risk than children who were overweight who maintained their weight. In summary, early childhood obesity may increase the risk of pediatric immune-mediated skin diseases. Weight gain may increase AD risk, whereas weight loss may lower the risk.

Prospective Clinical Study: Full-Body Blue Irradiation in the Treatment of Atopic Dermatitis.

Ultraviolet-free (UV-free) blue light phototherapy has emerged as a promising option due to its reported efficacy and minimal adverse effects. This study aims to evaluate the effectiveness of full-body blue light irradiation in both adult and pediatric patients with atopic dermatitis (AD), assessing its impact on skin condition and mood regulation by investigating serum concentrations of serotonin and kynurenine pathway metabolites. 20 patients (age 9-45) with moderate and severe AD were included in the study. Treatment consisted of 10 irradiations with Full Body Blue device (453nm). Serum concentrations of serotonin, quinolinic acid, kynurenic acid, tryptophan, and kynurenine were measured before and after irradiations. After 10 sessions of full blue light therapy (453nm) statistically significant improvements were observed in Eczema Area Severity Index (EASI 13.16 vs. 8.65; p = 0.00016), SCORing Atopic Dermatitis (SCORAD 44.99 vs. 23.73; p < 0.00001), Visual Analogue Scale (VAS 6.53 vs. 3.95; p = 0.00251), 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001). Moreover, statistically significant decrease in Dermatology Life Quality Index (DLQI) was noted (14.37 vs. 7.42; p = 0.00351). Additionally, increase in the serum concentration of serotonin was observed after completing 10 irradiation sessions (median 139.77mg/ml vs. 274.92mg/ml; p < 0.00001). Blue light may be a promising and safe treatment in patients with AD. It might also positively influence mood. Further investigations are needed to confirm those findings. ClinicalTrials.gov identifier, NCT06516783.

Sleep and quality of life in adults with atopic dermatitis: cross sectional study.

Background.Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that causes sleep disturbances and worsens quality of life.However, few studies have been conducted on sleep in adults with atopic dermatitis. This study aimed to evaluate sleep and quality of life in adults with AD. Methods. A cross-sectional study was conducted with 36 adults diagnosed with AD and 21 healthy volunteers (controls), who completed questionnaires on sleep, itching, and quality of life. Disease severity was estimated using SCORing Atopic Dermatitis (SCORAD). All participants wore actigraphy watches for one week to objectively assess sleep quality. Results. Adults with AD slept worse than controls as measured by self-report (Global Pittsburgh Sleep Quality Index, mean ± SD, 9.33 ± 3.59 vs 5.00 ± 2.30, p < 0.001) and by actigraphy (sleep efficiency, SE), mean ± SD, 74.48 ± 11.63 vs 85.6 ± 6.53, p < 0.001). Actigraphy showed that adults with AD slept, on average, almost one hour less (p = 0.010), stayed awake during sleep for almost 44 minutes more (p < 0.001), and woke up 25% more than the controls (p = 0.047). In the AD group, SE and total sleep time were significantly inversely correlated with SCORAD (rs = -0.601, p < 0.001 and rs = -0.604, p < 0.001, respectively), but no significant correlation was found between itch and SE. A decreased quality of life was observed in adults with AD (DLQI, mean ± SD, 8.75 ± 6.7). Conclusions. Adults with AD slept worse than the controls and had a diminished quality of life. Actigraphy is a useful tool to objectively measure sleep quality in adults with AD especially those with moderate to severe disease.

Early-pregnancy BMI, maternal gestational weight gain, and asthma and allergic diseases in children.

Association of early pregnancy body mass index (BMI) and maternal gestational weight gain (GWG), and asthma and allergic disease in children is unclear. We analyzed data from 3176 mother-child pairs in a prospective birth cohort study. Maternal anthropometric measurements in the first and last antenatal clinic visits were obtained through post-delivery questionnaires to calculate early pregnancy BMI and maternal GWG. Asthma and allergic diseases in children by the age of 5 years was assessed using a validated questionnaire. Furthermore, serum samples were analyzed for IgE antibodies to eight allergens. We applied Cox proportional hazards and logistic regression analyses to estimate the association of early pregnancy BMI and maternal GWG (as continuous variables and categorized into quarters), and asthma, atopic eczema, atopic sensitization, and allergic rhinitis in children. Neither early pregnancy BMI nor maternal GWG was associated with asthma and allergic disease in children when analyzed as continuous variables. However, compared to the first quarter of GWG (a rate <0.32 kg/week), mothers in the third quarter (rate 0.42-0.52 kg/week) had children with significantly higher odds of developing atopic eczema (adjusted OR 1.49, 95% CI [1.13-1.96]) by 5 years of age. Association of early pregnancy BMI and maternal GWG, and asthma and allergic disease in children, is inconsistent. High maternal GWG may be associated with increased odds of atopic eczema.

Environmental and behavioral mitigation strategies for patients with atopic dermatitis

Although numerous medications have recently been approved for the treatment of atopic dermatitis (AD), the current treatment guidelines often lack information on non-pharmacologic approaches to disease management. In contrast, patients and caregivers frequently express strong interest in environmental and behavioral mitigation strategies. Herein, we summarize the evidence-base for these interventions with a focus on the role of specific chemicals in driving AD. We outline avoidance strategies for the various routes of exposure such as air pollution, water contamination, or inclusion in home goods, skin care products, and cleansers. Evidence for and against dietary modification and emollient use as primary prevention are discussed. To remember these interventions we propose a mnemonic, HELPSS AD: Home decor, Emollients, Laundering, Probiotics, Soaks, Social support, Air quality, and Diet. Each of these categories presents nuanced molecular differences that must be considered. For example, probiotic responses vary by the specific species while home products and pollution must be analyzed by the specific toxins. Although the interventions discussed lack the level of evidence required for inclusion into formal guidelines, awareness of these approaches may offer aid to, and build trust with, patients and caregivers.

Preclinical Development of SHR-1819, a Potent Humanized IL-4Rα Antibody for Treating Type 2 Inflammatory Diseases.

Interleukin (IL)-4 and IL-13 are critical pathogenic factors for type 2 inflammation-related allergic diseases, sharing the mutual receptor subunit IL-4Rα. However, it was ineffective for certain type 2 inflammation diseases by targeting IL-4, IL-13 ligand alone or both in clinical studies. The work presented herein aimed to evaluate the preclinical efficacy and pharmacokinetics profile of a novel monoclonal antibody against IL-4Rα, SHR-1819, as a promising therapy for type 2 inflammation diseases. SHR-1819 was generated through immunization by C57BL/6 mice with recombinant hIL-4Rα protein, followed by humanization and affinity maturation. Then, its binding properties with IL-4Rα were determined using surface plasmon resonance (SPR) and ELISA. In vitro inhibitory effects of SHR-1819 were assessed on hIL-4-/hIL-13-induced cell proliferation and signal transducer and activator of transcription 6 (STAT6) signaling activation. In vivo efficacy of SHR-1819 was evaluated in several type 2 inflammatory diseases models, including asthma, atopic dermatitis (AD), and allergic rhinitis (AR) by using hIL-4/hIL-4Rα transgenic mice. Furthermore, the pharmacokinetic (PK) profiles of SHR-1819 were characterized. SHR-1819 showed high binding affinity to human IL-4Rα and effectively blocked IL-4Rα at sub-nanomolar concentration. In vitro assays indicated that SHR-1819 significantly inhibited TF-1 cell proliferation and STAT6 activation induced by hIL-4/hIL-13. In the asthma model, SHR-1819 could reduce airway hyperresponsiveness, decrease serum IgE levels, and alleviated inflammatory lung cell infiltration. In the AD model, SHR-1819 could significantly alleviate inflammatory and skin symptoms. In the AR model, it could remarkably decrease the frequencies of nasal rubbing and sneezing, and inflammatory cell infiltration in nasal tissues. These in vivo efficacy studies demonstrated the therapeutic potential of SHR-1819 in preclinical disease models. Moreover, subcutaneous administration of SHR-1819 exhibited favorable bioavailability in mice. The results supported SHR-1819 as a promising preclinical candidate for the treatment of type 2 inflammatory diseases, including asthma, AD and AR.

Atopic Dermatitis (Eczema) Guidelines 2023: Highlights

Atopic Dermatitis (AD) is one of the most common chronic inflammatory skin disorders with a complex pathogenesis. AD is characterized by eczematous skin lesions, pruritus, and recurrent skin infections; with negative impact on patients (and caregivers) quality of life.The American Academy of Allergy, Asthma and Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force (JTF) Atopic Dermatitis Guideline Panel recently released updated AD guidelines. This guideline focuses on addressing clinical questions using trustworthy guideline development standards, including mitigating the potential influence of financial and non-financial conflicts of interest, and GRADE methodology. A multidisciplinary panel used systematic reviews and meta-analyses to inform specific recommendations addressing optimal use of (1) topical treatments, (2) dilute bleach bath, (3) dietary avoidance/elimination, (4) allergen immunotherapy and (5) systemic treatments. The comprehensive recommendations, emphasizing the third principle of evidence-based medicine - that evidence alone is never enough; that patient values and preferences must be carefully considered when determining optimal treatments for patients and populations - provide a framework to support clinicians in selecting an optimal treatment plan for each patient.This review provides an overview of the guideline and discusses how those recommendations relate to current practice.

Proxy endpoints — bridging clinical trials and real world data

Objective:Disease severity scores, or endpoints, are routinely measured during Randomized Controlled Trials (RCTs) to closely monitor the effect of treatment. In real-world clinical practice, although a larger set of patients is observed, the specific RCT endpoints are often not captured, which makes it hard to utilize real-world data (RWD) to evaluate drug efficacy in larger populations. Methods:To overcome this challenge, we developed an ensemble technique which learns proxy models of disease endpoints in RWD. Using a multi-stage learning framework applied to RCT data, we first identify features considered significant drivers of disease available within RWD. To create endpoint proxy models, we use Explainable Boosting Machines (EBMs) which allow for both end-user interpretability and modeling of non-linear relationships. Results:We demonstrate our approach on two diseases, rheumatoid arthritis (RA) and atopic dermatitis (AD). As we show, our combined feature selection and prediction method achieves good results for both disease areas, improving upon prior methods proposed for predictive disease severity scoring. Conclusion:Having disease severity over time for a patient is important to further disease understanding and management. Our results open the door to more use cases in the space of RA and AD such as treatment effect estimates or prognostic scoring on RWD. Our framework may be extended beyond RA and AD to other diseases where the severity score is not well measured in electronic health records.

Cost per responder analysis of abrocitinib versus dupilumab in moderate to severe atopic dermatitis.

The JADE COMPARE was a multicenter, phase 3 randomized, double-blind, placebo-controlled trial with the objective of comparing the 16-week efficacy and safety of oral abrocitinib 100 or 200 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo in adults with moderate-to-severe atopic dermatitis (AD). Pharmacoeconomic evaluation of these new drugs for AD is lacking. The objective of our study was to compare the cost per responder of abrocitinib versus dupilumab in patients with AD using the data from the JADE COMPARE trial. The cost per responder was calculated by multiplying the cost of treatment by the number needed to treat for each therapy, as obtained from the JADE COMPARE trial. The 12-week primary endpoint was the Investigator global assessment (IGA) 0/1 and eczema area and severity index improvement of at least 75% (EASI75) response rate. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16. The cost per responder model was based on the perspective of the Italian National Health System. Regarding the costs of drugs, ex-factory wholesale purchase prices were used, including the mandatory discounts according to the national legislation (5% discount, plus a further 5% reduction on the discount result). Abrocitinib 100 mg and 200 mg have flat price in Italy. The 12-week IGA 0/1 cost per responder was € 3955.77 and € 2984.94 for abrocitinib 100 mg and 200 mg, respectively, versus € 7467.96 for dupilumab; as for 12-week EASI75 the cost were € 2463.30 and € 2057.58 vs. € 4705.09, respectively. As far as the secondary end points, the costs per responder were always lower for abrocitinib 100 and 200 mg compared to dupilumab, including the PP-NRS (€ 3791.55 and € 2451.22, vs. € 6462.65), the IGA 0/1 at week 16 (€ 6931.05 and € 4854.15 vs. € 8787.85) and the EASI75 at week 16 (€ 3984.75 and € 3381.00 vs. € 5197.45). According to JADE COMPARE trial data, the costs per responder of abrocitinib were considerably lower than dupilumab. The results of the study are limited to the short time frame of JADE COMPARE trial.

Skin microbiome and causal relationships in three dermatological diseases: Evidence from Mendelian randomization and Bayesian weighting.

Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.

53880 Hybrid Concept Elicitation and Cognitive Debriefing Interviews with Patients with Atopic Dermatitis

53880 Hybrid Concept Elicitation and Cognitive Debriefing Interviews with Patients with Atopic Dermatitis

53111 Individual patient responses to IL-22RA1 inhibition in a Phase 2a monotherapy trial for moderate-to-severe atopic dermatitis

53111 Individual patient responses to IL-22RA1 inhibition in a Phase 2a monotherapy trial for moderate-to-severe atopic dermatitis

53143 Clinical measures of improvement in atopic dermatitis are correlated with reductions in relevant biomarkers in patients treated with lebrikizumab

53143 Clinical measures of improvement in atopic dermatitis are correlated with reductions in relevant biomarkers in patients treated with lebrikizumab

51738 Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database

51738 Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database

Correction to Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate‐to‐severe atopic dermatitis: Results from two terminated phase II trials

Correction to Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate‐to‐severe atopic dermatitis: Results from two terminated phase <scp>II</scp> trials