Treatment Of Severe Atopic Dermatitis Research Articles

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.

Drug survival of systemic immunosuppressive treatments for atopic dermatitis in a long-term pediatric cohort.

Background: Systemic immunosuppressive treatments are central in the treatment of severe atopic dermatitis (AD). Yet, comparative data are sparse on the performance of such immunosuppressive treatments in pediatric cohorts with severe AD.Objective: This study aimed to examine the drug survival of systemic immunosuppressive treatments in a cohort of children with severe AD.Methods: A retrospective pediatric cohort was identified using diagnosis and treatment codes registered in medical charts. In total, 135 cases were identified; of these, 36 were excluded. All information was obtained through examination of clinical records. Drug survival was analyzed with Kaplan–Meier plots, and a log-rank test was used to test for differences in drug survival.Results: First-line treatment was primarily methotrexate (MTX; n = 63) and azathioprine (AZA; n = 32). For MTX, the drug survival rates were 69%, 50%, and 18% after 1, 2, and 4 years, respectively, with a median drug survival time of 1.58 years. For AZA, these rates were 63%, 53%, and 21%, respectively, with a median drug survival time of 1.14 years. There was no significant difference in drug survival between the treatments. The main reason for discontinuation was adverse effects (MTX: 25%; AZA: 41%). Despite this, a majority of patients experienced a good effect at the moment of discontinuation or data-lock (MTX: 60%; AZA: 53%), and treatment effect assessed as improvement in sleep quality was highly significant (p = .001). Second-line treatments included MTX (n = 12), AZA (n = 7), and cyclosporine (n = 5). These showed a median drug survival time of 1.8, 0.2, and 0.885 years, respectively.Conclusion: MTX and AZA were the dominant first-line treatments prescribed and were safe and equally valuable treatment options for severe childhood AD with similar drug survival outcomes. MTX was the most used second-line treatment.

Treatment of severe atopic dermatitis and eosinophilic esophagitis with dupilumab in a 14-year-old boy with autosomal dominant hyper-IgE syndrome

Autosomal dominant hyper-IgE syndrome (AD-HIES), also known as Job syndrome and Buckley syndrome, is characterized by elevated IgE levels, eosinophilia, recurrent cutaneous and internal organ abscesses, pneumonia leading to pneumatoceles, mucocutaneous candidiasis, characteristic facies, delayed shedding of primary teeth, bone fractures due to minor trauma, joint hypermobility, and scoliosis.1 In addition, allergic disorders such as atopic dermatitis (AD), food allergy, and eosinophilic esophagitis (EoE)2 may be associated with AD-HIES.

Dupilumab elicits a favorable response in type-2 inflammatory comorbidities of severe atopic dermatitis

BackgroundThis case is the first report describing rapid, successful treatment of severe atopic dermatitis (AD) and comorbid type-2 inflammatory diseases in the same patient, with dupilumab treatment, with no side-effects.Case presentationWe report on effects of dupilumab in a patient with severe AD, a long-standing history of a mild, perennial allergic rhino-conjunctivitis, moderate asthma and chronic rhinosinusitis with nasal polyps (CRSwNP).ConclusionsPatients suffering from AD, asthma, allergic rhinitis and CRSwNP may be eligible for dupilumab single treatment that is possibly advantageous also from the pharmaco-economic standpoint.

Uses of Antidepressant as Adjunct Treatment of Very Severe Atopic Dermatitis

This is a case of severe atopic dermatitis in a young married male age 37 years. This patient was very anxious and frustrated. The patient was using all the standard treatments for severe atopic dermatitis for e.g azathioprine, cyclosporine, tab deltacortril, applying emollients with clobetasol in it but he was not getting better. By chance the patient's family dragged him to visit a psychiatrist and the patient was advised to start venlafaxine and within 15 days the patient started getting better miraculously. Atopic Dermatitis is a very frustrating disease and patients face severe depression and bouts of severe itching exacerbated by exposure to dust, stress, sweating, changing and wearing clothes, etc. The use of antidepressants is not common practice in treating atopic dermatitis. Most general practitioners and dermatologists don't pay attention to how much a patient is suffering not only physically but also mentally and because of this, they don't suggest antidepressants. The role of antidepressants as an anti-inflammatory is still needed to be educated among physicians. This is a vicious cycle. The stress causes the exacerbation of this disease in which patients start itching all over the body and because of itching, lesions all over the body start getting infected as during itching staphylococcus aureus which resides under the nail enter in the lesion and cause infection and because of infection patients have a fever, lethargy, and weakness. The use of antidepressants is a game-changer in the management of atopic eczema.

Atopic Eczema: Pathophysiological Findings as the Beginning of a New Era of Therapeutic Options.

Atopic eczema (AE) is a chronic inflammatory disease hallmarked by intense pruritus and eczematous lesions. It depicts one of the most common skin diseases affecting a major part of children and several percentages of adults.Both pathogenesis and pathophysiology are based on complex orchestrated interactions of skin barrier defects, immunological changes, the environment, and an abundance of other contributing factors. Frequently, AE displays the starting point for other allergic diseases such as allergic asthma and rhinoconjunctivitis. Additionally, the risk of developing food allergy is increased. Furthermore, the disease is accompanied by a susceptibility to bacterial, fungal, and viral infections. The development of new therapies received great impetus by an ample research of the pathophysiological mechanisms, leading to a new era in the treatment of severe atopic eczema due to targeted treatments, e.g. the IL-4R alpha specific monoclonal antibody dupilumab.This article provides an overview of the causative and pathophysiological characteristics, the clinical and diagnostic aspects as well as current and future therapeutical possibilities focusing allergic aspects contributing to the course of the disease.

M561 DUPILUMAB FOR TREATMENT OF SEVERE ATOPIC DERMATITIS IN CHILDREN UNDER 6 YEARS

Dupilumab is a monoclonal antibody against the interleukin (IL)-4 receptor alpha subunit of the IL-4 and IL-13 receptor. It is approved for the treatment of severe atopic dermatitis (AD) above six years of age. We present a patient with severe AD under six years of age inadequately controlled by other therapies who noticed substantial improvement with Dupilumab.

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.
 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.
 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.
 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<€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.
 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.

Painless thyroiditis in a dupilumab-treated patient.

SummaryDupilumab an inhibitor of the interleukin (IL)-4R-alpha subunit is used for the treatment of allergic diseases. The patient was a 49-year-old man who received dupilumab for the treatment of severe atopic dermatitis. He presented hyperthyroidism with elevated thyroglobulin and anti-thyroid antibody negativity at 4 months after the initiation of therapy. On scintigraphy, the thyroid radioiodine uptake was low. Ultrasonography showed a diffuse hypoechoic area in the thyroid gland. A pathological study revealed lymphocytic infiltration. The administration of dupilumab was continued because of his atopic dermatitis that showed an excellent response. The patient`s hyperthyroidism changed to hypothyroidism 3 weeks later. Six months later his thyroid function normalized without any treatment. We herein describe the case of a patient with atopic dermatitis who developed painless thyroiditis under treatment with dupilumab. To the best of our knowledge, this is the first report of this event in the literature.Learning points:Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has been shown to be effective in the treatment atopic dermatitis and asthma with eosinophilia.Painless thyroiditis is characterized by transient hyperthyroidism and hypothyroidism and recovery without anti-thyroid treatment.This is the first report of painless thyroiditis as an adverse effect of dupilumab, although conjunctivitis and nasopharyngitis are the main adverse effects of dupilumab.

Single-use IgE-selective immunoadsorber column for the treatment of severe atopic dermatitis.

BackgroundAtopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with unmet therapeutic need in a critical cohort of recalcitrant cases. Immunoadsorption (IA) aims at an immunomodulatory depletion of pathogenic serum mediators and has recently revealed promising clinical results for the treatment of AD.ObjectiveTo determine efficacy, sustainability, safety, and clinical impact of IgE selective IA in AD using a single‐use IgE immunoadsorber column.MethodsThis open‐label pilot study comprised five patients (mean SCORAD 67.9 ± 11.4, range 52.2‐81.9; mean serum IgE level 5904 ± 5945 U/mL, range 1000‐15 600 IU/mL) who underwent IgE‐selective IA. Three patients continued prior therapy with systemic immunosuppressive drugs during IA as an add‐on therapeutic approach. All patients received three courses of IA. The first course consisted of three consecutive daily treatments followed by two sequences with two consecutive applications. All courses were performed on a monthly regimen.ResultsIA proved efficacy in selectively depleting serum IgE levels in all participants (mean reduction by cycle of 81% ± 12%, range 64%‐93%). It further led to a clinically relevant and sustained improvement of AD with a maximum decline in SCORAD and EASI scores by up to 35% and 52%, respectively, compared to baseline. Scores persisted below baseline for at least 12 weeks beyond the last IA. The intervention was also well tolerated with no severe adverse events during a total of 35 procedures.ConclusionData of this preliminary trial indicates clinical efficacy, feasibility, safety as well as tolerability of IgE‐selective IA in AD.

Omalizumab as an adjuvant therapy for treating severe atopic dermatitis in children. A serie of cases.

Atopic dermatitis (AD) is a chronic skin disease that affects 5-20% of children. This disease compromises the quality of life. Omalizumab offers a promising role in the treatment of severe atopic dermatitis. To share our experience with the use of omalizumab for treating severe AD in children. A retrospective review of the cases of pediatric patients with severe atopic dermatitis who were treated with omalizumab as an adjuvant therapy in an outside allergy service. Patients under 18 who had been treated for at least 6 months were included. 19 patients were included. At the beginning of the study, all patients reported a compromise of life quality of 8/10 or more on a analogue scale. A majority of patients had previously received either systemic steroids or other immunosuppressive therapies without obtaining symptom control. At maximum treatment time, the obtained SCORAD scores revealed that the disease in 85.7% of the patients was mild/moderate while, in 14% of the patients, the disease was severe. The Children's Dermatological Life Quality Index (CDLQI) was consistent with the SCORAD scores. From the beginning of treatment to the last visit to the doctor's office, no patient required systemic steroid therapy. Omalizumab appears promising for treating severe atopic dermatitis in pediatric patients. That results shows that omalizubam improves the quality of life, also decreases the severity of the disease and the need for systemic steroid and immunosuppressive therapy, which decreases the side effects that are caused by these medications.

671 Discovery of LEO 39652 a novel PDE4 inhibitor for topical treatment of atopic dermatitis

Topical treatment of severe atopic dermatitis frequently requires application of drug to more than 30% of the body surface area of the patient. The atopic skin barrier is highly compromised and thus there is a risk that a large portion of the applied dose will reach the systemic circulation, leading to a significant systemic load of the applied compound. Previously we have described the discovery of LEO 29102, a “soft” PDE4 inhibitor designed to achieve high local skin concentrations but low systemic exposure upon topical application, due to a high systemic clearance driven by rapid liver metabolism.[1] In the end, the clinical development of this compound was however discontinued in part due to safety concerns related to the systemic exposure of the candidate drug. Here we wish to describe our effort to reduce even further the systemic compound exposure observed upon topical administration, an exercise with the aim of minimizing the risk of target-related, systemic side effects. The approach was to benefit from esterase-mediated compound degradation in compartments like the blood. Despite the fact that tissue distribution in humans is not fully characterized for all esterases, some differences in expression levels in for instance skin versus blood have been reported. Thus it was hypothesized that it should be possible to identify ester-containing compounds suitable for topical delivery. Compounds that should be sufficiently stable in skin to provide the desired pharmacological effect but at the same time they should be rapidly degraded both in blood and by the liver. Here we report the discovery of a novel series of PDE4 inhibitors and our efforts to optimize the in vitro pharmacokinetics of these using phenotypic screening models of skin and blood stability. Eventually LEO 39652 was selected as a clinical development candidate and a characterization of its metabolism, pharmacokinetic profile as well as the early clinical efficacy data obtained with this compound will be presented in this poster.[1] J. Med. Chem., 2014, 57 (14), 5893–5903

A Retrospective Study of Systemic Treatment of Severe Atopic Dermatitis With Azathioprine: Effectiveness and Tolerance in 11 Pediatric Patients

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease that typically affects children. Severe forms may have a profound effect on patients’ quality of life. Some forms are resistant to conventional treatment and require the use of systemic immunosuppressants such as azathioprine (AZA) to adequately manage the disease. ObjectiveTo evaluate the effectiveness and tolerance of AZA in children with severe AD. Patients and methodsWe performed a retrospective study of children with severe AD treated with AZA between January 2007 and May 2017. ResultsWe reviewed the cases of 11 patients (6 boys and 5 girls) with a mean age of 13 years (range, 8-18 years). The mean (SD) age at start of treatment was 10.9 (2.2) years (95% CI 8.6-13.1). The mean initial dosage of AZA was 1.8 (0.2) mg/kg/d. We evaluated treatment response after 4 weeks, 12 to 16 weeks, and 6 months. Mean treatment duration was 10.8 (5.7) months. Treatment had to be suspended in 2 patients because of adverse effects. Seven of the 9 remaining patients presented complete or almost complete clearance of the AD after 6 months of treatment. ConclusionIn our experience, AZA is well tolerated and may be considered as a treatment option in children with severe AD resistant to conventional treatment.

Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis.

Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical effect of dupilumab. Nine of 10 developed eye-complications, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an effective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with severe, long-lasting atopic dermatitis and/or previous eye disease.

The efficacy of wet wrap therapy in children with atopic dermatitis in a single center

Purpose: Wet wrap therapy is a well-known treatment for severe atopic dermatitis (AD). However, wet wrap therapy with usual ban dage was a troublesome and time-consuming process of application. The aim of this study was to evaluate the efficacy, safety and convenience of wet wrap therapy with new garments in children with moderate-to-severe AD. Methods: We compared 56 AD children treated with wet wrap therapy and 14 AD children treated with only conventional therapy. We retrospectively reviewed the clinical features, change of SCORing Atopic Dermatitis (SCORAD) index, adverse effects and par ent’s reports. Results: The initial mean SCORAD index was 60.3±15.3 points. No significant differences in sex, age, initial SCORAD index, total eo sinophil count, total IgE level, food allergen sensitization, inhalant allergen sensitization or associated allergic diseases were found between the wet wrap and conventional groups. The pharmacological and nonpharmacological interventions except wet wrap therapy were same in the 2 groups. Wet wrap therapy with garments or tubular bandage was easily done one time per day over night in 10.6±3.5 days by parents. Improvement in total SCORAD index, intensity, subjective symptoms and pruritus were signifi cantly higher in the wet wrap group than in the conventional group (36.2 vs. 26.9, 6.0 vs. 4.0, 9.9 vs. 7.4, and 4.8 vs. 3.6 points). No fol liculitis and serious adverse effects were reported. Conclusion: Wet wrap therapy with new garments could be easily done by parents. Wet wrap therapy may be effective and safe in controlling moderate-to-severe AD in children. (Allergy Asthma Respir Dis 2019;7:13-21)

SUBCUTANEOUS ALLERGEN IMMUNOTHERAPY IN THE TREATMENT OF ATOPIC DERMATITIS

Introduction Atopic dermatitis has a wide variety of therapies, including topical moisturizers, topical corticosteroids, and biologics. However, there is still a debate regarding the efficacy of allergen immunotherapy in the treatment of atopic dermatitis. We report atopic dermatitis treated successfully with allergen immunotherapy. Case Description A patient was referred to our practice for the treatment of severe atopic dermatitis. A 48-year old man presented with a history of severe atopic dermatitis since childhood. Previous therapies, including mid and high potency topical corticosteroids, as well as the calcineurin inhibitors, pimecrolimus and tacrolimus, were ineffective. He had also required multiple doses of systemic corticosteroids for exacerbations. Biologic therapy was not available. He had positive specific IgE and allergy skin testing to multiple inhaled allergens, including dust mite, weeds, trees, grasses, mold, cat, and dog. The IgE level was 10,000 IU/mL. His initial Scoring Atopic Dermatitis Index (SCORAD) was 79.4. He was started on subcutaneous allergen immunotherapy to these inhaled allergens, while his topical therapies remained the same. In one year, at maintenance therapy at 1:1 dilution (0.5 cc injections), patient reported significant benefit in symptoms, and SCORAD index decreased to 48.5. He did not require systemic systemic steroid therapy once he reached maintenance dose of immunotherapy. Discussion Subcutaneous allergen immunotherapy can be an effective therapy for atopic dermatitis. This therapy can be used in conjunction with other treatments, including topical ones. Larger studies are required to further evaluate this therapy in atopic dermatitis.

Systemic Treatment for Severe Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory, relapsing disease of the skin, characterized by intense pruritus, maculopapular or vesicular erythematous lesions and scaling, sometimes accompanied by oozing, crusts and/or lichenification that has a negative impact on patients' quality of life. Prevalence is higher in children, around 15%, and approximately 5% in adults. Before introducing systemic therapy, it is mandatory to review patients' adherence to the correct use of topical treatments (corticosteroids, calcineurin inhibitors or cresoborole) and/or phototherapy. Ensure that environmental measures are being taken care of, irritant or proven allergic substances are not in use and even if the diagnostic is correct. If all is being done and topical treatment with corticosteroid, emollients and phototherapy have not been sufficient to achieve a good control in AD of adults or children patients, it is time to consider systemic agents. Up to now, most of systemic treatments were based on immunosuppressive therapies, being cyclosporine A, the usually first choice for moderate-to-severe AD. Recently, biologic drugs have been developed and approved for AD, as dupilumab, and a whole new group of drugs is giving much hope for patients to have a better control of the disease with less side effects.

Successful Treatment of Severe Atopic Dermatitis with Calcitriol and Paricalcitol in an 8-Year-Old Girl

Atopic dermatitis (AD) is a chronic inflammatory disease affecting children and adolescence. The traditional therapeutic options for AD, including emollients topically and immune modulatory agents systemically focusing on reducing skin inflammation and restoring the function of the epidermal barrier, are proven ineffective in many cases. Several studies have linked vitamin D supplementation with either a decreased risk to develop AD or a clinical improvement of the symptoms of AD patients. In this report, we present a girl with severe AD who under adequate supplementation with cholecalciferol was treated with calcitriol and subsequently with paricalcitol. She had significant improvement—almost healing of her skin lesions within 2 months, a result sustained for more than 3 years now. Because of hypercalciuria as a side effect from calcitriol therapy, treatment was continued with paricalcitol, a vitamin D analogue used in secondary hyperparathyroidism in chronic kidney disease. Calcitriol therapy may be considered as a safe and efficacious treatment option for patients with severe AD, particularly for those with refractory AD, under monitoring for possible side effects. Treatment with paricalcitol resolves hypercalciuria, is safe, and should be further investigated as an alternative treatment of atopic dermatitis and possibly other diseases of autoimmune origin.

A Systematic Scoping Literature Review of Publications Supporting Treatment Guidelines for Pediatric Atopic Dermatitis in Contrast to Clinical Practice Patterns.

IntroductionTreatment guidelines endorse a variety of strategies for atopic dermatitis (AD) which may vary from published data and clinical practice patterns. The objective of this review was to quantify the volume of available medical literature supporting pediatric AD treatments and compare these patterns to those recommended by published guidelines and/or clinical practice patterns.MethodsSearches of Embase (2005–2016) and abstracts from selected meetings (2014–2016) related to AD treatment in patients younger than 17 years of age yielded references that were assessed by study design, primary treatment, age groups, and AD severity.ResultsPublished literature partially supports clinical guidelines, with emollients and topical medications being the most investigated. There were disproportionately more publications for topical calcineurin inhibitors (TCI) compared with topical corticosteroids (TCS); however, the search interval may have biased the results toward treatments approved near the beginning of the time frame. In contrast, publications documenting clinical practice patterns reflect greater use of emollients and TCS (over TCI), as well as systemic corticosteroids. Data is relatively limited for long-term and combination treatment, treatment of severe AD, and patients younger than 2 years of age, and completely lacking for systemic corticosteroids.ConclusionThis scoping review demonstrates that available medical literature largely supports published guidelines for topical therapy; however, clinical practice patterns are less aligned. There is a lack of data for older, more frequently used generic treatments, including oral antihistamines, oral antibiotics, and systemic corticosteroids. Overall, literature is lacking for long-term treatment, treatment for patients younger than 2 years of age, and for systemic treatment for severe disease.FundingRegeneron Pharmaceuticals Inc.

A Retrospective Analysis of Real Life Medication Regimens for Adults with Atopic Dermatitis on Immunosuppressive Medication (Ramadil) In a Single Third Line Center in Belgium

Few Belgian data are available on the treatment of severe atopic dermatitis in adults. As in most other countries, only cyclosporine A is registered for the systemic treatment of atopic dermatitis. Although treatment periods are restricted, side effects may occur, and response failure is possible. Small trials with other immunosuppressive drugs (azathioprine, mofetylmycophenolate, and methotrexate) have indicated they may improve atopic dermatitis, although their effect is slower than with cyclosporine. In the future, treatment of atopic dermatitis may drastically change as the therapeutic effects of new biologicals are promising. This RAMADIL study, from a third line referral center in Belgium, was conducted in order to collect information about the way AD is treated in this pre-biological era.