Real-world response to dupilumab in patients with atopic dermatitis: a retrospective review of 100 patients

Dupilumab is a monoclonal antibody approved by the National Institute for Health and Care Excellence for the treatment of moderate-to-severe atopic dermatitis (AD) in 2018. It is indicated for patients who have not responded to at least one systemic medication or in whom these are contraindicated or not tolerated. Response criteria to allow continued treatment include at least a 50% reduction of Eczema Area and Severity Score (EASI) and/or at least a 4-point reduction in the Dermatology Life Quality Index (DLQI) score. Phase III clinical trials of dupilumab in AD reported a 75% reduction in EASI (EASI 75) of 51% in SOLO1 and 44% in SOLO2. Real clinic responses may differ from trials so we performed a retrospective review of 100 patients between June and August 2020 who had received dupilumab (44% female, 56% male;mean age 41 years). Fifty-eight per cent had a recorded diagnosis of asthma and 39% had a recorded diagnosis of allergic rhinitis. Seventy-six per cent of patients had received previous phototherapy. Ninety-seven per cent of patients received at least one systemic medication prior to commencing dupilumab. Thirty per cent (n = 29) received one, 33% (n = 32) received two, 33% (n = 32) received three and 4% (n = 4) received four prior to starting dupilumab. The most common were methotrexate (61%), followed by ciclosporin (22%) azathioprine (16%) and alitretinoin (1%). EASI scores were documented at baseline. The target time for EASI response assessment was 16 weeks, but we included outcome data recorded between 8 and 16 weeks, using the score nearest to 16 weeks where multiple scores were available. Seventy-five patients had response data recorded, 18 had stopped dupilumab and seven had missing data. Outcomes were 50% reduction in EASI [EASI 50;84% (n = 62)], EASI 75 [61% (n = 45)] and a 90% reduction in EASI [EASI 90;35% (n = 26)]. Mean (SE) EASI score pretreatment was 22 2 (1 2);at 16 weeks it was 5 8 (0 9). Sixty-five per cent of patients had a documented DLQI score at 8 and/or 16 weeks. Mean (SE) DLQI scores were 17 5 (0 7) predupilumab, 5 5 (1 1) at 8 weeks and 3 7 (0 8) at 16 weeks. Mean reduction was 13 8 (1 0). Eighty-six per cent (n = 56) had a reduction of four or more. Fifty-nine per cent of patients had Patient-Oriented Eczema Measure scores recorded. Mean (SE) values were 22 5 (0 5) predupilumab, 6 2 (1 2) at 8 weeks and 7 1 (1 1) at 16 weeks. Mean reduction was 15 4 (1 0). Compared with prospective clinical trials, real-world data have the limitations of missing data and slight scoring date variations, including the impact of the COVID-19 pandemic on missed appointments. Sixteen-week outcome data are not available for patients who withdrew from treatment. However, for the 75 patients with outcome data the proportion achieving EASI 75 and a 4-point reduction in DLQI is encouraging and similar to data from phase III trials.

SkinTracker: A novel smartphone app enabling remote clinical research in dermatology

A highly visual practice, dermatology as a field has significant potential to use emerging technology such as mobile applications for research and patient-centered mapping of the disease process. The UCSF team is working to create SkinTracker, a mobile application for patients with skin disease to remotely participate in clinical trials and research studies. The initial iteration of the application focuses on atopic dermatitis. The application includes an enrollment and consent module, validated surveys including the Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) for itch, link to a wearable device that collects biometric data, a voice diary, and a patient-directed photography module to facilitate physician evaluation of disease. Also included is the ability to report medication use, adverse events, and the ability to chat with the study team. The patient information is available to the research team on a secure online website, where researchers can assess patient photographs to perform Eczema Area and Severity Index (EASI) scoring, note important patient observations from the voice diary, and view quantitative data from both patient surveys and health measures like physical activity, sleep, and environmental factors. We believe this application and website will facilitate patient interest and participation in research, continue research despite in-person restrictions placed during the COVID-19 pandemic, and allow enrollment of more diverse patients for clinical studies who would otherwise be less likely to participate in research due to time or financial constraints.

Interim analysis results from a proof-ofconcept study for ASLAN004 in adult moderate to severe atopic dermatitis: A double blind, randomized, placebo-controlled study

Background: ASLAN004 is a fully human monoclonal antibody that binds to IL-13Ra1 with high affinity and inhibits IL-4 and IL-13 signaling via the Type 2 cytokine receptor, an important target in atopic dermatitis (AD). Objective: To evaluate the emerging safety, tolerability, and efficacy of ASLAN004 in a multipleascending dose escalation phase in patients with moderate to severe AD. Methods: Twenty-five adult patients with moderate to severe AD were recruited from the US, Australia and Singapore and randomized 3:1 in three cohorts to receive once weekly 200, 400 or 600mg of subcutaneous ASLAN004 or matching placebo over eight weeks, with a 12-week recovery period. An interim data readout was conducted after Cohorts 1-3 completed eight weeks of treatment to evaluate various clinical endpoints in a limited number of patients before conducting an expansion cohort (Cohort 4, results reported elsewhere). Endpoints in the interim analysis include change from baseline in Eczema Area Severity Index (EASI) score at week 8 and safety assessments including local tolerability and incidence of adverse events (AEs). [NCT04090229] Results: Three of 25 patients randomized into Cohorts 1-3 discontinued due to restrictions imposed in response to the COVID-19 pandemic. 18 of the remaining 22 patients in the planned interim data readout completed at least 29 days of dosing and assessment and were evaluable for efficacy. The mean ± SD (n=18) baseline scores were 32.5±11.8 for EASI and 44% had severe Investigator Global Assessment (IGA) scores. At Week 8, mean reductions in EASI from baseline were 50 percent, 74 percent and 76 percent for the 200mg (n=4), 400 mg (n=6) and 600 mg (n=3) ASLAN004 dose groups respectively, compared with 42 percent (n=5) for placebo. Mean reductions of peak pruritus from baseline to Week 8 were 34 percent, 48 percent and 39 percent for 200mg (n=4), 400mg (n=6) and 600mg (n=2) ASLAN004 dose groups respectively, compared with 16% for placebo (n=5). Other secondary endpoints were also improved for ASLAN004 compared with placebo (EASI-50, EASI- 75, results reported elsewhere). The proportion of patients with AEs and treatment-emergent adverse events (TEAEs) were similar across ASLAN004 treatment and placebo arms. There were no TEAEs leading to discontinuation in the ASLAN004 treatment groups. Conclusion: ASLAN004 was well tolerated, with 400mg and 600mg showing promising eicacy in adults with moderate to severe AD.

Portuguese immunoallergology clinical experience in patients with severe atopic dermatitis under dupilumab treatment

Background: Dupilumab has been recently approved for treatment in patients with severe AD in Portugal-until now there is no published data regarding Portuguese experience in Allergy centers. Method: Cross sectional clinical and laboratory assessment of 33 patients (pts) with moderate to severe AD treated with dupilumab (dupi) for at least 16 weeks (W): prospective evaluation of severity scores (SCORAD-Scoring Atopic Dermatitis, EASI-Eczema Area and Severity Index, P-VAS-Pruritus Visual Analogic Scale), report of adverse events up to 52 weeks of treatment. SCORAD and EASI were assessed in 23 pts at W52, P-VAS in 21 pts at W52. Results: Of the 33 pts, 18 were female (55%) with a mean age (SD, range) of 35.3 years (13.2, 15-60). In 16 pts the age of onset was before 2 years old, mean (SD) disease duration 28.1 years (12);94% patients had a diffuse pattern of skin lesions;97% of pts had allergic rhinitis, 82% asthma, 52% conjunctivitis and 30% food allergy. Median total IgE at baseline was of 6313 U/ml (P25-P75: 2842-12491) with a 76% reduction at W52 in 16 pts. Median eosinophil count at baseline was 520 eosinophils/mm3 (P25-P75: 270-740). Before starting dupi 29 pts had been treated with cyclosporine. At the beginning, 15 pts were under oral corticosteroids, 14 under oral systemic immunosuppressive drugs (all pts but two stopped both until W12 of dupi) and 5 switched from omalizumab. At baseline, median SCORAD and EASI were 69.3 and 24.2 points. At W16, W36 and W52, median SCORAD was 27.4, 22.3 and 21.5, and median EASI 5.3, 4.1 and 2.1. At W16, the EASI-50, EASI-75 and EASI-90 were achieved by 91%, 61% and 18% pts, and at W52, by 87%, 70% and 52% pts. The mean percentage of SCORAD reduction at W16 and W52 was 55% and 73%;and of EASI was 76% and 82%. At W16 and W52, an improvement of ≥4 points in P-VAS was achieved by 77% and 95% pts. There was a mean reduction of P-VAS at W2, W4, W16 and W52 of 2.6;3.6;4.7 and 6.3 points, respectively. Conjunctivitis was reported in 10 (30%) pts, two of them with keratoconjunctivitis and blepharitis, without needing to interrupt treatment;two pts also had facial erythema. One patient had COVID, and dupilumab scheme treatment was maintained. Conclusion: The majority of AD patients had a significant and consistent improvement in all the severity scores, after one year of treatment with dupilumab. No relevant adverse events were reported.

Terrific improvement of refractory atopic dermatitis with benralizumab (anti-IL5 receptor) therapy

In 2012 a 25-year-old man presented to our outpatient clinic for severe atopic dermatitis (AD) and severe allergic eosinophilic asthma in polisensitivity (house dust mite, cat, gramineous plants, birch, milk protein and, in particular, Alternaria). His clinical history was also characterized by gastro-esophageal reflux disease and chronic rhinitis without polyposis, with septal deviation and turbinate hypertrophy, worthy of surgical intervention. History taking revealed egg and cow milk protein allergy and severe asthma since the first months of life, with frequent hospital admissions due to exacerbations. AD was severe and diffuse, involving especially face, neck, back and superior limbs, often complicated by impetigo. The esthetic, social and psychological impact led him to quit his job as a barman. At presentation, the Eczema Area and Severity Index (EASI) score was 72/72. Laboratory tests showed eosinophilic count ranging between 1.060 and 2.140/mm3, and high serum levels of total Immunoglobulin E (5.939 kUI/L). Tryptase levels were normal and autoantibody analysis was negative. Parasite stool examination was negative. Nasal swab tested positive for Staphylococcus aureus, which was treated with Sulfamethoxazole-Trimethoprim. Asthma Control Test was 15/25, pulmonary function tests (PFTs) showed mild obstruction (FEV1 4.43 L, 103%, FEV1/FVC 69%), with positive bronchodilator testing (FEV1 5.12 L, + 670 mL, + 16%). Firstly, he was treated with topical steroids and sometimes with oral corticosteroids, with poor response. Then, in July 2019, he initiated therapy with cyclosporine 3-5 mg/kg. Soon, the drug had to be discontinued due to adverse effects (gastrointestinal symptoms and infections). In November 2019, at the age of 32 years, he started therapy with monoclonal antibody anti-IL-5 receptor alpha (benralizumab 30 mg 1 subcutaneous vial every 4 weeks for the first three administrations and then every 8 weeks), with a terrific clinical improvement of AD since the first administrations and with benefit on asthma control (ACT after the first administration increased up to 25/25;PFTs could not be performed, due to SARS-CoV-2 pandemic). This therapy has always been well tolerated. The eosinophilic count decreased to 0/mm3 after the first administration. At the moment, after one year of therapy, AD is almost fully disappeared (EASI SCORE 4/72), despite being in free diet, and the quality of life of the patient has definitely improved.