An emerging epidemic of allergic contact dermatitis due to phytonadione epoxide (oxidised vitamin K1).

BACKGROUND: Reports of allergic contact dermatitis (ACD) to phytonadione epoxide (PE) in cosmetics suggest that PE is as powerful a sensitiser as its parent compound phytonadione. OBJECTIVE: To evaluate a case series of ACD to PE in Spain. METHODS: We reviewed the records of 20 patients with ACD to cosmetics containing PE diagnosed across Spain between January 2019 and June 2023. RESULTS: All 20 patients developed patch test (PT) or repeated open application test (ROAT) reactions to cosmetics containing PE. All involved women with eyelid eczema. PT or ROAT with PE preparations were positive in 17/20 (85%). PE at 1%, 5%, 10% and 20% in pet. was patch-tested in 8/17, 14/17, 11/17 and 8/17 patients; being positive in 6/8 (75%), 13/14 (92.85%), 11/11 (100%) and 8/8 (100%), respectively. CONCLUSION: Regulators should, not only ban the specific dangerous cosmetic ingredients, but also consider to ban or keep under close surveillance those closely related products or derivatives that might potentially cause similar harmful effects. PTs with PE are suggested to be performed at a 5% concentration in pet. Higher concentrations (10% pet.) should be tested whenever PTs with 5% pet. PE are negative.

Information and consensus document for the diagnostic and therapeutic management of pruritus associated with chronic kidney disease in patients on haemodialysis in Spain.

Chronic kidney disease-associated pruritus (CKD-aP) is one of the most common and disabling comorbidities in patients with advanced CKD. In addition, it is associated with an increased risk of mortality, poorer quality of life, sleep disorders, mental health disorders, and increased use of health care resources. The clinical presentation of CKD-aP is very heterogeneous, making it difficult to diagnose and treat. Currently, there are no national guidelines on the management of CKD-aP. The aim of this document is to provide national consensus recommendations for the diagnostic and therapeutic management of CKD-aP. The document was prepared in three phases: a diagnostic and therapeutic management algorithm was proposed by a small group of nephrology specialists; the proposal was validated by a larger group of nephrologists; and a second validation by a multidisciplinary group that also included dermatology specialists. The diagnostic and therapeutic management algorithm attempts to cover the current need of a lack of specific guidelines for the adequate management of CKD-aP. At the same time, it introduces the use of difelikefalin, the first and only drug specifically approved for CKD-aP, with a good safety and efficacy profile.

Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials.

BACKGROUND: Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema. METHODS: Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101. FINDINGS: Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis. INTERPRETATION: Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids. FUNDING: LEO Pharma.

A re-assessment of the value of markers of corticosteroid contact allergy in the Spanish baseline series: Clobetasol propionate in the spotlight.

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Italian S3-Guideline on the treatment of Atopic Eczema - First Update, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.

Polysensitization in the Spanish Contact Dermatitis Registry (REIDAC): A 2019-2022 prospective study with cluster and network analysis.

BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.

Sensitization to textile dyes in Spain: Epidemiological situation (2019-2022).

BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.

2-Hydroxyethyl methacrylate (2-HEMA) sensitization, a global epidemic at its peak in Spain?

BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.

Assessment of potential predictive factors of dupilumab response in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab has shown to be an effective and safe treatment for patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVE: To evaluate the predictive factors of response (PRF) in patients with moderate-to-severe AD treated with dupilumab. METHODS: Observational, retrospective and multicentre study conducted on adult patients diagnosed with moderate-to-severe AD treated with dupilumab, with a post-treatment follow-up of at least 16 weeks. The primary endpoints were EASI-75 and the IGA scale at week 52. RESULTS: A total of 198 patients were included in the analysis. Mean age was 38 ± 15.1 years and 116 (58.6%) were men. The most prevalent AD-predominant phenotypes were flexural eczema (45.3%), head-and-neck eczema (18.2%) and erythroderma (17.7%). At week 52, 140 (86.4%) patients achieved EASI-75 and 119 (93.0%) achieved an improvement in ≥2 points from baseline in IGA score. Women were 3.6 times more likely to achieve EASI-75 response than men (Odds ratio: 3.58; p = 0.020). While increased body mass index significantly reduced the probability of obtaining an improvement of ≥2 points in the IGA scale at week 52 (odds ratio: 0.88; p = 0.049). CONCLUSIONS: Dupilumab was an effective treatment in patients with moderate-to-severe AD. Additionally, sex and body mass index were significantly associated with achieving EASI-75 and an improvement of ≥2 points in the IGA scale, respectively, at week 52.

Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis.

BACKGROUND: Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis. METHODS: In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points. RESULTS: A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%). CONCLUSIONS: Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.).

Pathogenic mechanisms underlying itch in atopic dermatitis: the emerging role of neuroimmune interactions.

Itch is a frequent dermatological sensation that can occur in a variety of skin conditions, including atopic dermatitis, inflammatory disorders characterised by eczematous lesions and chronic itch. The pathogenic mechanisms that lead to itch in atopic dermatitis are not fully understood. The current knowledge of its aetiology highlights the complex interplay among multiple pathogenic factors such as epidermal barrier dysfunction, immune dysregulation, and its interaction with the nervous system. Furthermore, a relationship between itch intensity and certain factors such as stress, sleep disturbance, and pollutant exposure has often been shown in patients with itch. This article reviews the current advances in the processes behind itch signalling from the skin to the nervous system, focusing on atopic dermatitis pathophysiology. Studies investigating the underlying pathogenic mechanisms of atopic dermatitis have shown that itch management at the nervous system level may be sufficient to reduce itch sensation and improve skin lesions.

Pruritus and Pain Constitute the Main Negative Impact of Atopic Dermatitis From the Patient's Perspective: A Systematic Review.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense itching and highly visible signs, representing a great burden to the patient. Despite its straightforward diagnosis, AD severity and burden can be underestimated in routine clinical practice. This review aims to determine the impact of AD on patients' lives, establish which domains of life are most affected, and identify symptom drivers of AD burden. A systematic literature review was conducted in Pubmed/Medline, Web of Science, and Scopus following Cochrane and PRISMA recommendations. Observational studies published in English or Spanish between January 1, 2018, and August 31, 2022, evaluating the impact of AD and its symptoms from the patient's perspective, were included. Reviewed studies were assessed for quality following the STrengthening the Reporting of OBservational studies in Epidemiology Checklist. A total of 28 observational studies evaluating the impact of AD and its symptoms from the patient's perspective were included in the review. All domains of the AD patient's life were found to be greatly affected, including health-related quality of life (HRQoL), emotional health, sleep disorders, work impairment, health care resource utilization, cognitive function, and development of comorbidities. The more severe the disease, the greater the impact, worsening in patients with moderate and severe AD. Pruritus and pain are reported to be the disease symptoms with the greatest impact. In conclusion, AD impacts several domains of patients' lives, especially HRQoL and mental health. Pruritus and pain are identified as the main drivers of AD impact, suggesting that optimal symptom control may reduce the burden and improve disease management.

Treatment of severe atopic dermatitis with tralokinumab in clinical practice: short-term effectiveness and safety results.

BACKGROUND: Tralokinumab was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) and is the first selective interleukin (IL)-13 inhibitor that specifically neutralizes IL-13 with high affinity. OBJECTIVES: To determine the real-life short-term effectiveness and safety of tralokinumab treatment in patients with moderate-to-severe AD. METHODS: A multicentre retrospective study was conducted including adult patients with moderate-to-severe AD who started tralokinumab treatment from 1 April to 30 June 2022 in 16 Spanish hospitals. Demographic and disease characteristics, severity and quality of life scales were collected at the baseline visit and at weeks 4 and 16. RESULTS: Eighty-five patients were included. Twenty-seven patients (32%) were non-naive to advanced therapy (biological or Janus kinase inhibitors inhibitors). All included patients had severe disease with baseline Eczema Area and Severity Index (EASI) scores of 25.4 (SD 8.1), Dermatology Life Quality Index (DLQI) 15.8 (5.4) and peak pruritus numerical rating scale (PP-NRS) 8.1 (1.8) and 65% had an Investigator's Global Assessment (IGA) of 4. At week 16, there was improvement on all scales. The mean EASI decreased to 7.5 (SD 6.9, 70% improvement), SCORing Atopic Dermatitis improved 64% and PP-NRS, 57%. Also, 82%, 58% and 21% of the patients achieved EASI 50, 75 and 90, respectively. The percentage of EASI 75 responders was significantly higher among the naive vs. non-naive groups (67% vs. 41%). The safety profile was acceptable. CONCLUSIONS: Patients, with a long history of disease and prior multidrug failure, showed a good response to tralokinumab, confirming clinical trial results.

Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials.

BACKGROUND: Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. OBJECTIVES: To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). METHODS: Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. RESULTS: After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. CONCLUSIONS: After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients.

Background: The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized. Methods: The response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients. Results: HDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient's pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset. Conclusion: IgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.