Severe Adult Atopic Dermatitis Research Articles

Tapinarof Cream 1% Once Daily: Significant Efficacy in the Treatment of Moderate to Severe Atopic Dermatitis in Adults and Children Down to 2 Years of Age in the Pivotal Phase 3 ADORING Trials

Tapinarof Cream 1% Once Daily: Significant Efficacy in the Treatment of Moderate to Severe Atopic Dermatitis in Adults and Children Down to 2 Years of Age in the Pivotal Phase 3 ADORING Trials

LC and LC-MS/MS Studies for Identification and Characterisation of Related Substances and Degradation Products of Abrocitinib

In the pharmaceutical industry, Related Substances (RCs), impurities or Degradation Products (DPs) are associated with the Active Pharmaceutical Ingredient (API) in the final drug product. These compounds must be within permissible limits for safe therapeutic use for consumers. Hence there is a need to quantify these compounds using an appropriate analytical method. No method is reported in the literature for quantification of these compounds in abrocitinib which is a medical drug prescribed to treat severe atopic dermatitis in adults. This study includes the optimisation of stability indicating the HPLC method for resolution and subsequent quantification of abrocitinib RCs and structural characterisation of stressinduced DPs of abrocitinib. The method was optimised by varying mobile phase solvents, pH, flow rate and wavelength of the detector. The finalised conditions were validated and applied for the resolution and evaluation of stress-induced DPs. The stress was induced in abrocitinib pure drug HCl (0.1M), NaOH (0.1M), hydrogen peroxide (3%), 80°C in an air oven and 254nm in a UV chamber. The generated DPs were structurally characterised with the LCMS experiment. Abrocitinib and DPs along with known RCs were resolved on ACE Ultra Core Super C18 250mm column using 0.9mL/min gradient flow of methanol (Solvent A), acetonitrile and buffer (Solvent B). The resolved compounds were detected through a UV detector at 295nm and a mass detector at NMR positive mode. The method identifies 5.85min, 3.13min, 6.60min and 4.38min respectively for abrocitinib, related compounds 1 to 3 respectively with acceptable system suitability. A very high correlate (< 0.999) linear graph was achieved within 5 to 30 μg/mL concentration level for abrocitinib and 0.05 to 0.3μg/ mL for related compounds. Three DPs with molecular mass and formula of C10H13N5 (203.2 g/mol), C11H14N4 (202.2 g/mol) and C13H19N5O2S (309.3 g/mol) in acid-induced stress study and two DPs of C12H21N5O2S (299.3 g/mol) and C11H19N5O2S (285.3 g/mol) in peroxide-induced stress study and one DP of C10H14N4 (190.2 g/mol) in base induced stress study were successfully characterised. The method proposed in this study can effectively resolve unknown degradation products, and known related compounds along with abrocitinib and is hence applicable for quality control analysis of abrocitinib.

Matching-adjusted Indirect Comparison (MAIC) of Tralokinumab Versus Dupilumab for the Treatment of Moderate to Severe Adult Atopic Dermatitis

Matching-adjusted Indirect Comparison (MAIC) of Tralokinumab Versus Dupilumab for the Treatment of Moderate to Severe Adult Atopic Dermatitis

Societal costs and health related quality of life in adult atopic dermatitis

BackgroundCost-of-illness studies are widely used for healthcare decision-making in chronic conditions. Our aim was to assess the cost-of-illness of adult atopic dermatitis (AD) from the societal perspective in Hungary.MethodsWe conducted a multicentre, cross-sectional questionnaire survey between February 2018 and January 2021. Data was collected from consecutive AD patients aged ≥ 18 years and their physicians at dermatology departments in Hungary. We calculated direct and indirect costs, including costs for treatments, outpatient visits, hospital admissions, informal care, travel costs and productivity loss. To assess indirect costs, the Work Productivity and Activity Impairment (WPAI) questionnaire was used to collect data, and costs were estimated with the human capital approach. Generalized linear model was used to analyse predictors of total, direct and indirect costs.ResultsAltogether 218 patients completed the survey (57.8% female) with an average age of 31.3 (SD = 11.7). Patients’ average Dermatology Life Quality Index (DLQI) score was 13.5 (SD = 8.5). According to Eczema Area and Severity Index (EASI) score, 2.3% (n = 5), 21.2% (n = 46), 54.4% (n = 118) and 22.1% (n = 48) had clear, mild, moderate, and severe AD, respectively. We found that the average total, direct medical, direct non-medical and indirect annual costs per patients were €4,331, €1,136, €747, and €2450, respectively, with absenteeism and presenteeism being the main cost drivers, accounting for 24% and 29% of the total cost of AD. A one-year longer disease duration led to, on average, 1.6%, and 4.2% increase in total and direct non-medical costs, respectively. Patients with worse health-related quality of life (higher DLQI score) had significantly higher total, direct medical, direct non-medical costs, and indirect costs.ConclusionsOur results indicate a substantial economic burden of AD from a societal perspective, mainly driven by productivity losses.

AtopyReg®: the prospective Italian patient registry for moderate to severe atopic dermatitis in adults by SIDeMaST.

AtopyReg®: the prospective Italian patient registry for moderate to severe atopic dermatitis in adults by SIDeMaST.

083 Characterization of IL-13 producing cells in moderate to severe adult atopic dermatitis patient’s skin

083 Characterization of IL-13 producing cells in moderate to severe adult atopic dermatitis patient’s skin

A review of adherence to nice criteria for initiation and continuation of treatment of dupilumab in atopic dermatitis

Abstract Introduction Atopic dermatitis is a chronic, recurrently flaring, generalised skin condition that can be life-limiting, debilitating and isolating. A typical treatment pathway involves emollients and topical corticosteroids (first line), topical calcineurin inhibitors (second line), phototherapy (third line) and systemic immunosuppressant therapies (fourth line. Dupilumab is recommended by NICE1 as an option for treating moderate to severe atopic dermatitis in adults, only if the disease has not responded to at least one other systemic therapy, such as ciclosporin, methotrexate, azathioprine and mycophenolate mofetil, or these are contraindicated or not tolerated, and the company provides dupilumab according to the commercial arrangement. Dupilumab should be stopped at 16 weeks if the atopic dermatitis has not responded adequately i.e. at least a 50% reduction in the Eczema Area and Severity Index score (EASI, ranges from 0 to 72, with higher scores indicating greater severity) from when treatment started and at least a 4-point reduction in the Dermatology Life Quality Index (DLQI) from when treatment started. Aim To ascertain whether dupilumab (a payments by results excluded drug, commissioned by integrated care systems) was used in a teaching district general hospital according to the stated criteria within the NICE technology appraisal. Methods Patients prescribed and supplied with dupilumab for more than 16 weeks were identified and Dermatology letters were scrutinised by a pharmacy team member. Ethical review was not required as this was a service evaluation. Results Eighty-eight patients had received dupilumab and the records of 30 (mean age 44, range 18-73, 18 male) were reviewed. Most entries were from when NICE first approved dupilumab, though some were chosen from late 2021/early 2022. All but one had been on at least one prior systemic therapy. This one patient was admitted urgently with severe dermatitis and so was referred for dupilumab as it is quicker acting than immunosuppressant therapy and no need to wait for blood tests. One patient did not have a starting EASI score (under a tertiary hospital). Twenty-nine of the 30 patients experienced both the required 50% or more reduction in EASI score at the review meeting and the at least a 4-point reduction in DLQI. The one patient who did not respond had treatment ceased. At approximately week 16, for all patients the ASI score changed from a mean of 29.7 (range 3-66.7) to 3.6 (range 0-27.9), and DLQI from a mean of 18.9 (range 7-30) to 4.4 (range 0-28). Discussion/Conclusion This study found that all but one of 30 patients had been on prior systemic therapy, and all but one patient met the NICE criteria at the review period (treatment then ceased). This was a sample of approximately one-third of the patients who had received dupilumab. Acknowledging that the dupilumab NHS price is about £16,000 per patient per year, these reassuring results of NICE compliance have been shared with Dermatology. We recognise the limitations of a single centre, very small-scale study. We do not report prolonged follow up of patients in relation to any improvement in their atopic dermatitis other than what we observed documented in Dermatology letters at commencement and review of treatment.

Burden of Moderate to Severe Atopic Dermatitis in Adults from France, Italy, and the UK: Patient-Reported Outcomes and Treatment Patterns

IntroductionModerate to severe atopic dermatitis (AD) is associated with a significant disease burden, impacting sleep, quality of life, and treatment needs. The aim of this study was to characterize disease burden and treatment patterns for adults with moderate to severe AD in three European countries: France, Italy, and the UK.MethodsThis retrospective analysis of adult patients with moderate to severe AD in Europe used medical records and physician/patient survey data collected in August 2019 to April 2020. Demographic and baseline disease characteristics, information on current comorbidities, disease flares, and current and previous treatments were collected by the physician. Patient-perceived burden was assessed using patient-reported outcome (PRO) questionnaires, which were completed on a voluntary basis and included the following instruments: Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), EuroQol five-dimensional (EQ-5D), and Work Productivity and Activity Impairment (WPAI). Disease severity was subjectively assessed by physicians and was based on their own definition of the terms mild, moderate, and severe. Data were analyzed descriptively.ResultsThe physician-reported sample included 912 patients with moderate to severe disease from France (n = 314), Italy (n = 309), and the UK (n = 289); approximately 30% of patients provided PRO data. Across these countries, 22–41% of patients reported current flares; mean POEM and DLQI scores were 10.6–13.1 and 9.5–11.1, respectively, indicating a high disease burden. However, systemic therapy use was low (e.g., conventional systemics were used by 18–24% of patients). Physician-assessed disease severity did not fully align with EASI scores, indicating that factors in addition to skin signs are impacting AD severity.ConclusionPatients with moderate to severe AD report significant disease burden, highlighting unmet treatment needs, particularly with respect to the underuse of systemic treatments despite AD being a systemic disease and the associated disease burden.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00777-z.

Abrocitinib for the treatment of atopic dermatitis

Abrocitinib (Cibinqo) is a new janus kinase inhibitor for the treatment of moderate to severe atopic dermatitis in adults and adolescents. This article reviews its properties and place in therapy.

Selective inhibition of JAK1 in treatment of atopic dermatitis: Prescription features and experience with upadacitinib

Therapy of moderate-to-severe atopic dermatitis (AD) is associated with a number of diffculties due to the propensity of the disease to a chronic relapsing course, the tendency to develop in childhood and young age. However, a new selective JAK1 inhibitor, which suppresses cytokineinduced inflammation in the skin, has been added to the arsenal of AD systemic therapy.Objective. To evaluate the effcacy, antipruritic activity, impact on quality of life, levels of anxiety and depression, and safety of upadacitinib treatment of moderate-to-severe AD in adult patients.Material and methods. The inclusion criteria were the presence of moderate-to-severe AD, age over 18 years, signed informed consent of the patient to participate in the study. Effcacy was assessed based on clinical indices. All patients received upadacitinib (RANVEK) 15 mg once daily with or without food, topical corticosteroids (if needed), and emollients.Results. The number of patients with an IGA score of 0 or 1 was 50%. The dynamics of the maximum intensity of pruritus according to NRS during 16 weeks of therapy was 56.4%. The proportion of patients with an improvement in the assessment of the maximum severity of itching according to NRS ≥3 points at week 16 relative to the baseline was 77.8%. The dynamics of the EASI index in percent was 65.3%, and the number of patients who achieved an EASI-50 response at week 16 was 83.3%, EASI-75 was 61.1%. The dynamics of the overall SCORAD index as a percentage of the initial value for 16 weeks was 76.9%. The DLQI decreased by 68.9%. The number of patients with HADS less than 7 points on a scale of both anxiety and depression was 88.9%.Conclusions. Thus, upadacitinib demonstrates high effcacy in terms of the effect on rashes and pruritus, favorably affects the quality of life and psychosomatic characteristics of patients, and has a favorable safety profle in the treatment of moderate and severe AD in adults.

Baricitinib: A Review in Moderate to Severe Atopic Dermatitis.

Baricitinib (Olumiant®) is an oral small molecule inhibitor of Janus kinase (JAK)1 and JAK2, which have been implicated in the pathogenesis of atopic dermatitis (AD). In phase III studies in adults with moderate to severe AD who were inadequately controlled with topical corticosteroids (TCS) or systemic treatments (e.g. ciclosporin), or for whom these therapies were not advisable, baricitinib, alone or in combination with TCS, achieved significant and/or clinically relevant improvements in multiple measures of disease severity, pruritus, skin pain, sleep disturbance and health-related quality of life (HR-QOL) over 16 weeks. Benefit onset was rapid, with efficacy generally sustained over the longer term (treatment duration ≤ 68 weeks). In this patient population, the safety profile of baricitinib was consistent with that established in the moderate to severe rheumatoid arthritis (RA) population. Although further longer-term data would be beneficial, current evidence indicates that baricitinib, alone or in combination with TCS, provides an oral alternative to subcutaneous biologics for the treatment of moderate to severe AD in adults who are candidates for systemic therapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-022-00684-1.

New Drug for Atopic Dermatitis.

Tralokinumab-ldrm (Adbry) is now approved for the treatment of moderate to severe atopic dermatitis in adults whose disease has not been controlled by topical therapies.Nurses and NPs should teach patients how to administer the drug subcutaneously and that more than one injection is needed to fulfill the prescribed dose.

Effects of systemic therapies on pruritus in adults with atopic dermatitis: a systematic review and meta-analysis.

Pruritus is a hallmark of atopic dermatitis (AD), which affects disease severity and patient quality of life. In AD uncontrolled with first-line topical therapies or in moderate to severe AD, systemic therapies are used; however, there is a paucity of head-to-head trials comparing the effectiveness of these therapies. The aim of this study was to compare the effectiveness of systemic therapies in relieving pruritus in moderate to severe AD in adults, using a meta-analysis. The PubMed, EMBASE, Medline and CINAHL databases were searched from inception up to 31 May 2020 for randomized, placebo-controlled trials investigating the effectiveness of systemic therapies on pruritus with moderate to severe AD in patients aged ≥ 16 years. In total, 26 studies (n = 5190 participants) were identified. Compared with placebo, there was a large and statistically significant (P < 0.001 for all) reduction in pruritus [standard mean difference (SMD); 95% CI] with dupilumab every 2 weeks (-0.88; -1.13 to -0.63), dupilumab every 2 weeks plus topical corticosteroids (-0.77; -0.91 to -0.62), dupilumab once weekly (-0.99; -1.29 to -0.68), dupilumab once weekly plus topical corticosteroids (-0.70; -0.81 to -0.59). There was also a large and statistically significant reduction with ciclosporin (-1.30; -2.34 to -0.26; P = 0.01) and a large, although not statistically significant reduction with azathioprine (-0.85; -2.07 to 0.35). There was a small reduction with both mepolizumab (-0.27; -0.89 to 0.35) and interferon-γ (-0.31; -0.75 to 0.12). Of the investigational drugs, nemolizumab 2.0 mg/kg was the most effective (-8.13; -9.31 to -6.94). The majority of systemic therapies were superior to placebo in reducing pruritus. In particular, the dupilumab studies consistently showed large improvements in pruritus, while nemolizumab showed the strongest antipruritic effects. However, future head-to-head trials are required for conclusive evidence.

Selective reversible JAK1 inhibitor in the treatment of moderate and severe atopic dermatitis

In recent decades, industrialized countries have recorded a steady increase in the incidence of atopic dermatitis (AD). The pathogenesis of AD is complex and diverse and includes hereditary determinism leading to a disruption of the skin barrier, as well as the Th2 immune response, which is supported by a wide range of pro-inflammatory mediators released by immunocompetent and epithelial cells, which play a key role in the activation and maintenance of inflammation in the skin. Progress in the treatment of immunoinflammatory diseases, including in the skin, has been achieved with the advent of a new class of targeted synthetic oral immunomodulatory drugs, Janus kinase inhibitors. Janus kinases are part of the JAK – STAT intracellular signaling system; STAT proteins are responsible for signaling more than 60 cytokines, hormones and growth factors that regulate key cellular processes. Currently, second generation JAK inhibitors have been developed, such as upadacitinib (trade name Rinvoq), which distinguish them from non-selective JAK inhibitors by their selectivity for certain JAK isoforms. In June 2021, the Ministry of Health of the Russian Federation approved the use of upadacitinib (UPA) for the indication “treatment of moderate to severe atopic dermatitis in adults and children aged 12 years and older who are indicated for treatment with systemic drugs”; the drug can be used in monotherapy or in combination with topical therapy in adults at a dose of 15 or 30 mg per day depending on the individual characteristics of the course, in adolescents weighing at least 40 kg – at a dose of 15 mg per day. Results from a Phase 3 clinical trial program involving more than 2500 patients worldwide in three global key studies: Measure Up 1, Measure Up 2 (UPA monotherapy at a dose of 15 mg or 30 mg per day) and AD Up (UPA in the same doses in combination with topical glucocorticosteroids (TGCS) demonstrated high efficacy and favorable benefit/risk profile of UPA both in monotherapy and in combination with TGCS in patients with moderate to severe AD.

Evaluation of adult patients with atopic dermatitis treated with dupilumab: A single-center real-life experience.

Adult atopic dermatitis (AD), especially adult-onset type appears to have different clinical manifestations. Dupilumab is an IL-4 receptor antagonist used in patients with moderate and severe atopic dermatitis, aged 12years and older and it works by inhibiting the IL-4 and IL-13signaling pathway. The purpose of our study is to retrospectively investigate the side effect profile and drug efficacy of thirteen adult patients who received dupilumab treatment and to evaluate the drug use status and the results during the COVID-19 pandemicour stuAdult atopic dermatitis (AD), especially adult-onset type appears to have different clinical manifestations. Dupilumab is an IL-4 receptor antagonist used in patients with moderate and severe atopic dermatitis, aged 12years and older and it works by inhibiting the IL-4 and IL-13signaling pathway. The purpose of our study is to retrospectively investigate the side effect profile and drug efficacy of thirteen adult patients who received dupilumab treatment and to evaluate the drug use status and the results during the COVID-19 pandemicAdult atopic dermatitis (AD), especially adult-onset type appears to have different clinical manifestations. Dupilumab is an IL-4 receptor antagonist used in patients with moderate and severe atopic dermatitis, aged 12years and older and it works by inhibiting the IL-4 and IL-13signaling pathway. The purpose of dy is to retrospectively investigate the side effect profile and drug efficacy of thirteen adult patients who received dupilumab treatment and to evaluate the drug use status and the results during the COVID-19 pandemicAdult atopic dermatitis (AD), especially adult-onset type appears to have different clinical manifestations. Dupilumab is an IL-4 receptor antagonist used in patients with moderate and severe atopic dermatitis, aged 12years and older and it works by inhibiting the IL-4 and IL-13signaling pathway. The purpose of our study is to retrospectively investigate the side effect profile and drug efficacy of thirteen adult patients who received dupilumab treatment and to evaluate the drug use status and the results during the COVID-19 pandemic. Thirteen patients with clinical and/or histopathological diagnoses of atopic dermatitis who received dupilumab treatment and were subsequently followed up in Bezmialem Vakif University dermatology outpatient clinic between April 2019 and October 2021 were included in our study.Patient files were reviewed, and patients were interviewed in-person or by phone to learn about the COVID-19 contagion.Descriptive statistical analysis was performed with Microsoft Excel, and the data obtained were calculated as mean and percentage. All of our patients responded to the treatment after one course of dupilumab injection and also CRP and LDH levels decreased. Conjunctivitis side effect was found at a slightly higher rate than in previous clinical studies. The treatment was continued during the COVID-19 pandemic in most patients. Meanwhile, four patients had COVID-19 infection, but one of them was not using dupixent at that time. We can conclude that dupilumab is an effective and safe therapy for patients with severe AD also in cases of severe infections.

Cost-effectiveness analysis of dupilumab for the treatment of severe atopic dermatitis in adults in Italy

BackgroundAtopic dermatitis (AD) is a chronic, multifactorial, inflammatory skin disease with significant impact on patients’ quality of life.&#x0D; ObjectiveThe objective of this analysis was to estimate the incremental cost-effectiveness ratio (ICER) of dupilumab, administered every other week, vs supportive care (SC), in the Italian adult population with severe AD, for whom ciclosporin treatment is contraindicated, ineffective or not tolerated.&#x0D; MethodsSimulation of outcomes and costs was undertaken using a 1-year decision tree, followed by a 20-year time horizon Markov model. Clinical data were derived from a pooled analysis of two studies. Given the uncertainty on final National Health Service (NHS) cost of dupilumab in Italy (confidential discount might be applied) multiple cost-utility analyses were conducted using different price hypotheses, starting from dupilumab published ex-manufacturer price, and progressively reducing it up to 50%. Model robustness were tested using sensitivity analyses.&#x0D; ResultsIn the base-case, dupilumab was more effective than SC (+1.92 quality adjusted life years, QALYs). In Analysis A (NHS perspective), -8.0% discount on dupilumab ex-manufacturer price was required to achieve an ICER&lt;€50,000 QALY gained with dupilumab vs SC; in Analysis B (Societal perspective), dupilumab ICER vs SC was already below the acceptability threshold at its current published ex-manufacturer price. Both one-way deterministic and probabilistic sensitivity analyses confirmed robustness and reliability of base-case results.&#x0D; ConclusionsDupilumab is a cost-effective option for the treatment of patients with severe AD in Italy, compared with SC, when both NHS and societal economic consequences of AD treatment and management are considered.

Progression of cutaneous T-cell lymphoma after dupilumab: Case review of 7 patients

To the Editor: Dupilumab is a fully human monoclonal antibody that binds the interleukin (IL) 4 receptor-α subunit and inhibits signaling of IL-4 and IL-13. It was approved by the Food and Drug Administration for the treatment of moderate to severe atopic dermatitis in adults and adolescents, with efficacy in reducing pruritus.1 The 2 most common subtypes of cutaneous T-cell lymphoma are mycosis fungoides and Sézary syndrome. Mycosis fungoides, Sézary syndrome and atopic dermatitis are similarly driven by T-helper 2 cytokine profiles2 and may present with similar morphology (ie, erythema, lichenification, fissuring) with pruritus,3 disruption of the skin barrier, and impetiginization.

Prevalence of Severe Atopic Dermatitis in Adults and Children in a Health Area of Madrid, Spain.

Prevalence of Severe Atopic Dermatitis in Adults and Children in a Health Area of Madrid, Spain.

Prevalence of severe atopic dermatitis in adults and children in a health area of Madrid, Spain

Prevalence of severe atopic dermatitis in adults and children in a health area of Madrid, Spain

Novel systemic drugs in treatment of atopic dermatitis: results from phase II and phase III studies published in 2017/2018

The present review will give an update of recently published clinical studies on novel systemic treatment approaches in atopic dermatitis. Until 2017 immunosuppressive drugs such as cyclosporine had to be used in atopic dermatitis when the disease could not sufficiently be treated with topical drugs. Several new substances specifically targeting inflammation in atopic dermatitis are currently studied. In 2017, dupilumab was approved in the United States and in Europe for first-line biologic treatment of moderate to severe atopic dermatitis in adults. The antibody blocks a subunit of the interleukin (IL)-4 and IL-13 receptor, thus inhibiting effects of two key cytokines in type 2 polarized inflammation. In addition to the studies on dupilumab recent clinical investigations on the effects on anti-IL-13 (lebrikizumab, tralokinumab), anti-IL-31 receptor (nemolizumab), anti-IL-22 (fezakinumab), and on small molecules targeting the histamine-4-receptor (ZPL389) and the Janus kinase inhibitor baricitinib have been published as full papers in the last 2 years. A couple of promising novel therapeutical targets have recently been investigated and published in clinical trials on atopic dermatitis.