Treatment Of Severe Atopic Dermatitis Research Articles

Re‐engagement, quality of life, and burden of treatment in adults on dupilumab for severe atopic dermatitis—A mixed methods study

AbstractBackgroundTargeted biologic therapies have revolutionised the treatment of severe atopic dermatitis (AD).ObjectivesTo assess effects of dupilumab on patient re‐engagement, quality of life (QOL), and burden of treatment (BOT) in severe AD.MethodsAdults on dupilumab for AD completed questionnaires on QOL, BOT, and provided qualitative reflections, with a subset interviewed to explore experience of leaving and re‐engaging with dermatology. Prior treatments, adverse events, and clinical severity scoring were evaluated. Statements and interviews were qualitatively reviewed.ResultsOf 41 patients; median age was 34 years, 68% were male; and 93% (n = 38) had trialled ≥1 immunomodulatory therapies before dupilumab. Median dermatology life quality index was 21 (range 9–30, SD ± 5.1) pre‐dupilumab, and 2 (range 0–11, SD ± 3.4) post‐dupilumab. Median eczema area and severity index was 31.4 (range 10–46.4, SD ± 11.8) pre‐dupilumab, and 6.4 (range 0.4–13.2, SD ± 3.6) on dupilumab. Burden of treatment scores on dupilumab were low (median 0–3/10) across all domains. Themes identified pre‐dupilumab included sleep disturbance, low self‐esteem, social isolation, disempowerment, frustration with ineffective treatments, and high financial costs. Benefits included confidence reacquisition, enhanced sleep, liberation from time‐consuming ‘messy’ topical regimes, improved relationships, and reclaimed autonomy. Side effects included red/itchy eyes (37%, n = 13) and facial dermatitis (20%, n = 7).Twelve patients had deeper interviews. Regarding disengagement with dermatology, themes included ineffectiveness and toxicity of older treatments, attendance futility, dermatologist fatigue, and ‘fizzling out’. Regarding re‐engagement with dermatology, themes included social media influence, novelty, exasperation with QOL, and life‐changing improvements seen with dupilumab.ConclusionsThe emergence of novel effective treatments for AD has significant implications for dermatology workforce and financial planning.

Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review.

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials.

Cost-Effectiveness Analysis of Abrocitinib Compared with Other Systemic Treatments for Severe Atopic Dermatitis in Spain.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, painful, and dry skin. Despite the great number of available therapies, economic evaluations are still needed to provide evidence on their cost efficiency. This research aimed to evaluate the cost effectiveness of the Janus kinase (JAK) inhibitor abrocitinib (200mg) compared with dupilumab (300mg), tralokinumab (300mg), baricitinib (2 and 4mg), and upadacitinib (15 and 30mg) for the treatment of patients with severe AD from the Spanish National Health System (NHS) perspective. A hybrid model consisting of a decision tree linked to a Markov model was developed to estimate costs, quality-adjusted life-years (QALYs), total years in response and incremental cost-per-QALY gained (willingness-to-pay [WTP] threshold: €25,000/QALY). Adults with severe AD entered the decision tree and response (75% reduction in baseline Eczema Area and Severity Index score, EASI-75) was considered at 16 and 52 weeks. After this time, patients entered the Markov model (remainder of the 10-year time horizon), which consisted of three health states: maintenance with active therapy, subsequent treatment, or death. All costs were presented in 2022 euros (€). Additionally, cost per number-needed-to-treat (NNT) was calculated for abrocitinib and dupilumab based on a head-to-head post-hoc analysis. Abrocitinib 200mg was dominant (i.e., lower incremental costs and higher incremental benefit) compared with all studied alternatives (dupilumab 300mg, tralokinumab 300mg, baricitinib 2 and 4mg, upadacitinib 15 and 30mg) with a QALYs gain of 0.49, 0.60, 0.64, 0.43, 0.45, and 0.08, respectively, and per-person costs savings of €22,097, €24,140, €14,825, €7,116, €12,805, and €45,189, respectively. Considering the WTP threshold, abrocitinib was dominant or cost effective compared with all alternatives for most simulations. Additionally, abrocitinib was dominant compared with all alternatives when evaluating the cost effectiveness over a 5-year time horizon. NNT showed that abrocitinib was dominant versus dupilumab. The results of the study show that abrocitinib is a cost-effective therapy compared with other JAK inhibitors and biological therapies from the Spanish NHS perspective.

EE239 How to Consider Caregiver Health-Related Quality of Life in a Cost-Effectiveness Analysis? An Illustration with Dupilumab for the Treatment of Severe Atopic Dermatitis in Infants in France

EE239 How to Consider Caregiver Health-Related Quality of Life in a Cost-Effectiveness Analysis? An Illustration with Dupilumab for the Treatment of Severe Atopic Dermatitis in Infants in France

ATOPIC DERMATITIS: CURRENT STATE OF THE PROBLEM IN UKRAINE AND THE WORLD

Introduction. Social and environmental disasters in recent years have induced an increase in morbidity, which poses a threat to the health and life of the population not only in Ukraine but also in the world. Among the most common skin diseases is atopic dermatitis (AD), a chronic recurrent disease characterized by skin inflammation, disruption of the epidermal barrier, and, as a result, a decrease in the skin's ability to retain moisture. Today general practitioners are usually the first to encounter this pathology, and they must assess self level of competence in a particular case and provide the necessary medical care or justify a referral to a dermatologist.
 The aim. To carry out an analytical review of domestic and foreign literature on the problem of atopic dermatitis (AD), methods of diagnosis and personalized approach to the treatment of this disease and to substantiate further directions of necessary scientific research to improve appropriate medical care.
 Materials and methods. A search, synthesis and analysis of world and national scientific publications on a personalized approach to the diagnosis and treatment of atopic dermatitis were conducted. A systematic approach, bibliosemantic method and method of structural and logical analysis were applied.
 Results and discussion. AD occurs with a frequency of up to 20% among children and up to 10% among adults in European countries. In Ukraine, as of 2020, the prevalence of AD among the pediatric population ranges from 9.0 to 28.5%.
 The study of the complex pathogenesis of the disease, where genetic factors, immune dysregulation and epidermal barrier disorders play a key role, has allowed scientists to identify endotypes and phenotypes of AD, which has become an important step in the development of personalized therapy for patients with AD. It was biological drugs (blockers of IL-4 and IL-13 and JK-inhibitors) that made a breakthrough in the treatment of severe AD. Another promising direction in the treatment of AD is the use of probiotics, as it is known that in patients with AD there is a decrease in the number of commensal bacterial skin flora and colonization of the skin with S. aureus.
 Conclusions. Thus, the incidence of atopic dermatitis, which is characterized by a complex etiopathogenesis, is increasing every year in the population of Ukraine and the world. The medical and social significance of AD opens up new challenges for the search for new approaches to the management of patients with AD. In recent years, biologic therapies have been actively introduced into medical practice, opening up new opportunities for personalized management of patients with severe forms of AD. As for the treatment of mild and moderate forms of AD, the issue is still relevant, given the problem of corticophobia in society. That is why at this stage, attention to the treatment and prevention approach should be more focused, and treatment methods with high efficacy and low side effect profile should be a priority. The literature review revealed that the problem remains relevant, despite the large number of studies on the etiology, pathogenesis and treatment of AD, which substantiates promising areas for the development and application of methods of modern effective personalized treatment of AD.

Efficacy and Safety of Dupilumab for the Treatment of Severe Atopic Dermatitis in Clinical Practice: A Single Center Experience

BackgroundDupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. ObjectiveExplore our experience with dupilumab for AD in clinical practice at a tertiary care center. Material and methodUnicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. ResultsFifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. ConclusionOur findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.

Canalicular obstruction associated with dupilumab.

Dupilumab is a novel treatment for severe atopic dermatitis and is associated with a range of ocular complications such as blepharoconjunctivitis, keratitis, cicatricial ectropion and punctal stenosis. We report 4 patients with canalicular obstruction in association with dupilumab therapy, and we describe their treatment and outcomes in each case. Canalicular obstruction was diagnosed by an oculoplastic consultant between 3years and 3months and 4years and 9months after the commencement of dupilumab therapy. Case 1 underwent nasolacrimal intubation, case 2 was treated conservatively, and case 4 underwent endonasal dacryocystorhinostomy and these patients' symptoms resolved. Unfortunately, in case 3 despite endonasal dacryocystorhinostomy with stenting they remained symptomatic. This case series adds to the growing number of ocular complications associated with dupilumab therapy, and there is yet an optimal treatment strategy to mitigate these complications. It is possible that simple conservative measures such as discontinuation of dupilumab and topical treatments with steroids can eventually lead to some form of recovery and recanalisation of the canalicular system. Early referral to an ophthalmologist prior to the development of canalicular obstruction to control the inflammatory ocular surface could reduce the risks of cicatricial sequelae from dupilumab, and temporary stenting of the canalicular system could be attempted as a method to keep the canalicular system patent, whilst the patient remained on treatment.

43142 Clinical features and real-world pharmacological treatment of severe Atopic Dermatitis in Colombia: data from an ongoing National Registry of Patients (RENDAC)

43142 Clinical features and real-world pharmacological treatment of severe Atopic Dermatitis in Colombia: data from an ongoing National Registry of Patients (RENDAC)

Dupilumab for the Treatment of Severe Atopic Dermatitis in an Immunosuppressed Transplant Patient.

Dupilumab for the Treatment of Severe Atopic Dermatitis in an Immunosuppressed Transplant Patient.

A real-world Australian experience of upadacitinib for the treatment of severe atopic dermatitis.

Upadacitinib is a selective Janus kinase-1 (JAK-1) inhibitor that has been shown in clinical trials to be effective for the treatment of moderate-to-severe atopic dermatitis (AD). This study aimed to evaluate the real-world experience of patients with AD treated with upadacitinib in a single-centre Australian cohort. Our study revealed a higher propensity for herpetic infections compared with previous randomised controlled trials (RCTs).

Treatment of severe atopic dermatitis with Tralokinumab in real clinical practice. Short-term effectiveness and safety results.

Tralokinumab was recently approved for the treatment of moderate to severe AD and is the first selective IL-13 inhibitor that specifically neutralizes IL-13 with high affinity. To determine the real-life short-term effectiveness and safety of Tralokinumab treatment in AD patients with moderate to severe AD. A multicentre retrospective study was conducted including adult patients with moderate to severe AD who initiated 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. Eighty-five patients were included. Twenty-seven patients (31.8%) were non-naïve to advanced therapy (biological or JAK inhibitors). All included patients had severe disease with baseline EASI scores of 25.4 ± 8.1, DLQI 15.8 ± 5.4 and PP-NRS 8.1 ± 1.8. Sixty-five percent of the patients had an IGA of 4. At week 16, all scales improved significantly. The mean EASI decreased to 7.5 ± 6.9 (70.4% improvement), SCORAD improved 64.1% and PP-NRS, 57.1%. Also, 82.4%, 57.6% and 21.2% of the patients achieved EASI 50, 75 and 90, respectively. The percentage of EASI75 responders was significantly higher among naïve versus non-naïve patients (67.2% vs 40.7%). The safety profile was quite acceptable. Patients, with a long history of disease and prior multidrug failure, showed a good response to Tralokinumab, confirming clinical trial results.

Dupilumab for treatment of severe atopic dermatitis accompanied by lichenoid amyloidosis in adults: Two case reports

Lichenoid amyloidosis (LA) is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules, usually on the lower leg, back, forearm, or thigh. LA may be associated with several skin diseases, including atopic dermatitis (AD). The treatment of LA is considered to be difficult. However, as there is some overlap in the etiopathogenesis of LA and AD, AD treatment may also be effective for LA. Case 1: A 70-year-old man was diagnosed with severe AD with LA based on large dark erythema and papules on the trunk and buttocks and dense hemispherical millet-shaped papules with pruritus on the extensor side of the lower limbs. He had a long history of the disease (8 years), with repeated and polymorphic skin lesions. Given the poor efficacy of traditional treatments, this patient was recommended to receive dupilumab treatment. At the initial stage, 300 mg was injected subcutaneously every 2 wk. After 28 wk, the drug interval was extended to 1 mo due to the pandemic. Follow-up observations revealed that the patient reached an Eczema Area Severity Index of 90 (skin lesions improved by 90% compared with the baseline) by the end of the study. Moreover, Investigator's Global Assessment score was 1, and scoring atopic dermatitis index and numeric rating scale improved by 97.7% and 87.5% compared with the baseline, respectively, with LA skin lesions having largely subsided. Case 2: A 30-year-old woman was diagnosed with severe AD with LA, due to dense and substantial papules on the dorsal hands similar to changes in cutaneous amyloidosis, and erythema and papules scattered on limbs and trunk with pruritus, present for 25 years. After 16 wk of dupilumab treatment, she stopped, and skin lesions completely subsided, without recurrence since the last follow-up. Dupilumab shows rational efficacy and safety in the treatment of severe AD with LA, in addition to benefits in the quality of life of the patients.

Real-Life Effectiveness and Safety of Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Single-Center 16-Week Study.

The treatment of severe atopic dermatitis (AD) includes cyclosporine and recently approved biologics and small molecules. Among these, upadacitinib is a selective inhibitor of Janus kinase 1, approved for the treatment of severe AD in adolescents/adults. Upadacitinib has shown efficacy and safety in several phase 3 clinical trials, but data on real-life patients are still lacking. We conducted a retrospective real-life observational study to evaluate the effectiveness and safety of upadacitinib up to week 16 in a cohort of both bio-naïve and bio-experienced patients. This study was carried out by analyzing the AD database records of an Italian referral hospital. Thirty-eight patients were included in this study, and 35 completed 16weeks of treatment. At week 16, out of 35 patients, the percentages of Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90 and EASI 100 responses were 94.29, 91.43, 74.29, and 60%, respectively. A decrease of at least 4 points from baseline of itch-NRS was reported by 94.74 and 91.43% of patients at weeks 8 and 16. Regarding the safety of upadacitinib, 26.32% of patients experienced at least one adverse event (AE), and a total of 13 AEs were recorded, including blood test abnormalities and papulopustular acne. None of our patients interrupted the drug because of an AE. We observed higher rates of EASI75/EASI90/EASI100 responses at week 16, compared with data from clinical trials. The safety profile of upadacitinib was favorable, as no AEs leading to discontinuation were experienced by our patients up to week 16.

EE13 Cost-Utility Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Children and Adolescents in Portugal

Atopic dermatitis (AD) is a chronic, systemic, type-2 inflammatory disease caused by an increased production/signaling of IL-4/IL-13 associated with long-term negative effects and variable disease course. Dupilumab is the first-in-class targeted therapy (anti-IL4/IL-13) approved and reimbursed in Portugal for the treatment of children/adolescent with AD. We aimed to evaluate cost-utility of dupilumab versus best supportive care (BSC) in children/adolescents (6-17 years) with severe AD candidates for systemic therapy in Portugal.

Systemic treatment for severe atopic dermatitis in children: a case series.

Atopic dermatitis (AD) is children's most frequent chronic inflammatory skin disease. In most patients, this condition is controlled with topical treatments; however, some patients with severe AD do not respond to these treatments, requiring systemic therapy. There is insufficient information about the ideal dose, time of use, clinical response, and safety of systemic therapy in children with severe AD. This study described the clinical characteristics of patients with severe AD who required systemic treatment, drugs used, their clinical course, adverse effects, and associated complications. We conducted a retrospective review of the records of pediatric patients with severe AD treated in the Dermatology Clinic, Instituto Nacional de Pediatría (2000 to 2018), who required systemic treatment for more than 3 months. We included 21 patients. The mean age at disease onset was 3.31 years. The drugs used were methotrexate (57.1%), thalidomide (38%), prednisone (42.8%), azathioprine (19%), mycophenolate mofetil (9.5%), cyclosporine (4.7%), and systemic steroids as bridging therapy (42.8%). Adverse effects were mild and were observed in two patients (9.5%) treated with methotrexate and mycophenolate mofetil. Methotrexate was the most frequently used drug in > 50% of the patients, and most patients attained remission. Cyclosporine, azathioprine, and mycophenolate mofetil were also effective. Side effects were mild and infrequent. Comparative studies of systemic treatments for severe AD in the pediatric population are necessary.

O06: A randomized controlled trial assessing the effectiveness and safety of ciclosporin vs. methotrexate in the treatment of severe atopic eczema in children and young people: the TREatment of severe Atopic eczema Trial (TREAT)

O06: A randomized controlled trial assessing the effectiveness and safety of ciclosporin vs. methotrexate in the treatment of severe atopic eczema in children and young people: the TREatment of severe Atopic eczema Trial (TREAT)

Cost-Utility Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Children and Adolescents in Italy

BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a chronic, multifactorial, inflammatory condition characterized by a significant impact on patients’ quality of life. Dupilumab is reimbursed by the Italian Medicines Agency (AIFA) for the treatment of adolescent and adult patients with severe AD (according to AIFA registry criteria). Recently, dupilumab has been reimbursed in the treatment of children with severe AD. The objective of this analysis was to estimate the incremental cost-utility ratio (ICUR) of dupilumab compared to current supportive care (SC), for the treatment of severe AD in children (6-11 years) and adolescents (12-17 years) in Italy.MATERIALS AND METHODS: Cost-effectiveness analysis was conducted using a 1-year decision tree followed by a Markov model over a lifetime period. The base case analysis was performed on the overall population of the LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914) studies, adopting the National Health Service (NHS) perspective. The following costs were considered: acquisition of treatment, management of disease, adverse events and complications. The robustness of the model was tested through sensitivity analysis. In addition, a scenario analysis adopting the social perspective was performed.RESULTS: In the base case, over a lifetime, dupilumab was more effective than SC in both children and adolescents (+2.44 and +1.62 quality-adjusted life years—QALYs, respectively). The introduction of dupilumab generated an increase in treatment costs (+€ 64,800 and +€ 52,853 € for children and adolescents, respectively), partially offset by a decrease in the costs of disease management and complications. Incremental cost-utility ratios (ICURs) were € 21,189 per QALY gained, for children, and € 26,569 per QALY gained, for adolescents. In both cases, the ICUR was lower than the willingness to pay threshold considered in Italy (€ 50,000 per QALY gained). Both the deterministic and probabilistic sensitivity analysis confirmed the robustness of the base case results. Finally, the scenario analysis, adopting the social perspective, showed coherent results compared to the base case.DISCUSSION: Dupilumab is a cost-effective option for the treatment of children and adolescents with severe AD eligible for systemic treatment in Italy compared to SC, from both the NHS and social perspective, confirming the results obtained in the adult population.

POSA50 Cost-Effectiveness Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Adolescent and Children Patients in Italy

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory systemic condition. Recently, dupilumab has been reimbursed by Italian Medicines Agency (AIFA) for the treatment of adolescents (according to the AIFA registry criteria) and adults with severe AD. Furthermore, it has been authorized by European Medicines Agency in children with severe AD. The objective of this analysis was to estimate the incremental cost-effectiveness ratio (ICER) of dupilumab versus current supportive care (SC), for the treatment of severe AD in children (6-11 years) and adolescents (12-17 years) in Italy.

104-week safety and effectiveness of dupilumab in the treatment of severe atopic dermatitis. The experience of 5 reference dermatology units in Spain

104-week safety and effectiveness of dupilumab in the treatment of severe atopic dermatitis. The experience of 5 reference dermatology units in Spain

Optimization of approaches to the management of adult patients with severe atopic dermatitis: analysis of real clinical practice outcomes

Atopic dermatitis (AD) is a multifactorial genetically determined immune-mediated skin disease. It is difficult to treat and significantly affects patients quality of life. The development of an integrated approach focusing on atopic multimorbidity, implementation of validated control tools and distinction of clinical parameters specific for different phenotypes of severe forms of disease is especially relevant to patients resistant to standard therapy techniques. Dupilumab, a biologic, is approved for the treatment of the resistant group of patients with moderate to severe AD in the Russian Federation. Dupilumab inhibits the functions of two key cytokines of T2-mediated inflammation IL-4 and IL-13. The article presents personal experience of the authors concerning individual approach to the choice of therapy for the management of this cohort of patients in routine clinical practice. The disease aggravating criteria were determined, which are fundamental for the formation of individual patient portrait for the biologic (dupilumab) treatment for severe AD.