Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Atopic dermatitis yardstick: Practical recommendations for an evolving therapeutic landscape.

The implementation of treatment guidelines for atopic dermatitis is challenging, in part because of different guidance documents being used by different groups of specialists and in part because the language of guidelines often reflects the evidence base rather than the practical "how to." The Atopic Dermatitis Yardstick is part of a series developed in response to the need to proactively address the loss of disease control for atopic illnesses at all levels of severity. It presents a comprehensive update on how to conduct a sustained step-up in therapy for the patient with inadequately controlled or poorly controlled atopic dermatitis. Patient profiles, based on current guidelines and the authors' combined clinical experience, provide a practical and clinically meaningful guide to aid physicians in helping their patients achieve the goal of clear to almost clear. The intent is not to replace guidelines but to complement their recommendations incorporating the latest research and therapies.

Biologic Therapy for Atopic Dermatitis: Moving Beyond the Practice Parameter and Guidelines.

Atopic dermatitis (AD), a common chronic pruritic inflammatory skin disease, impacts the quality of life of patients and caregivers and has become a global health problem. It is increasingly recognized as a disease not only of children but also of adults who may have a persistent or relapsing course from childhood or who develop new-onset adult disease. Besides well-established atopic comorbidities, associations with a number of nonatopic comorbidities have been reported. AD is characterized by both immune dysregulation and epidermal barrier dysfunction. The findings that nonlesional skin in AD has both terminal keratinocyte differentiation defects and immune abnormalities as well as multiple markers of immune and inflammatory activation in the circulation point to the systemic nature of the disease and have important translational implications. Although AD is predominantly associated with type 2 immune responses, activation of other cytokine pathways including TH1, TH22, and TH17/IL-23 has been reported, suggesting potential therapeutic targets and provide a rationale for treatment with novel biologics. Dupilumab, a fully human mAb targeting the IL-4 Rα subunit, blocks signaling of both IL-4 and IL-13 and is the first biologic to be approved for the treatment of moderate-to-severe AD in adult patients. Other biologics in current trials for AD are targeting the IL-31 receptor, IL-13, and the common p40 subunit of IL-12/IL-23.

Wet wrap therapy in children with moderate to severe atopic dermatitis in a multidisciplinary treatment program.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic, relapsing inflammatory skin disease of children and is a global public health problem. National and international AD guidelines address AD care in a stepwise fashion. Wet wrap therapy (WWT) is a therapeutic intervention for moderate-to-severe AD. OBJECTIVE: This cohort study evaluated the effectiveness of WWT as part of a multidisciplinary AD treatment program to improve disease severity. Patients treated in this unique outpatient program had moderate-to-severe AD and had multiple therapies that failed. METHODS: An observational cohort study was completed. The primary outcome was improvement in AD severity as measured by SCORAD (Scoring Atopic Dermatitis). Demographics; clinical management of AD, including use of antibiotics and systemic treatments; and WWT methodology were comprehensively described. RESULTS: Seventy-two children with a mean ± SD age of 4.6 ± 3.12 years were included. By using a paired t test, the SCORAD at admission and at discharge showed significant differences in mean ± SD values, of 49.68 ± 17.72 versus 14.83 ± 7.45, respectively (t, 18.93; df, 71; P < .001). None of these patients required systemic immunosuppressive therapy during the treatment program. By using a previously published parent-administered outcomes tool, patients were shown to maintain clinical improvement of their AD 1 month after discharge. CONCLUSION: To our knowledge, this study is the largest to date of WWT for pediatric patients with moderate-to-severe AD by using a validated outcomes tool. None of the patients required systemic immunosuppressive therapy, and only 31% were treated with an oral antibiotic. This study demonstrated the benefit of incorporating WWT as an acute intervention in a supervised multidisciplinary AD treatment program with lasting benefit 1 month after discontinuing this intervention.

Investigational and unproven therapies in atopic dermatitis.

Atopic dermatitis can be a challenging disease to treat, often having a chronic or relapsing course. For patients with moderate to severe disease, it can result in significant morbidity and affect quality of life of patients or families. Current treatment can be associated with side effects or patient and caregiver concerns about use. Recent advances in the understanding of barrier defects and innate and adaptive immune systemic abnormalities in atopic dermatitis have provided potential new targets for therapeutic intervention. These advances include antimicrobial peptides, antistaphylococcal toxin strategies, Th2 cytokine inhibitors, and modulation of pruritus at the neuromediator level.

Successful strategies in atopic dermatitis management.

Successful strategies for managing atopic dermatitis require an accurate diagnosis, identification and elimination of exacerbating factors including irritants and allergens, adequate hydration of the skin, control of pruritus and infections, and appropriate use of topical anti-inflammatory and other medications. Proper patient education increases the chances of successful therapy.

Patient-reported outcomes from a multicenter, randomized, vehicle-controlled clinical study of MAS063DP (Atopiclair) in the management of mild-to-moderate atopic dermatitis in adults.

BACKGROUND: MAS063DP (Atopiclair) is a topical cream approved for symptomatic relief in the treatment of atopic and contact dermatitis. METHODS: This was a multicenter, randomized, double-blind, vehicle-controlled study in adults with mild-moderate atopic dermatitis. Patients were given MAS063DP or vehicle (2:1) three times per day to areas affected by atopic dermatitis for up to 50 days. A patient global assessment change from baseline was determined at days 8, 22, 36, and 50. Patient total body pruritus (visual analog scale) and patient opinion on treatment acceptability were also assessed. RESULTS: A total of 218 patients (active: n = 145, vehicle: n = 73) were enrolled. At Day 22, 77% of patients on MAS063DP had a patient global assessment of good improvement or better versus 21% on vehicle (p<0.0001, chi-squared test). Similarly, more patients had improvement in itch over their total body on MAS063DP than on vehicle (p<0.0001). CONCLUSION: MAS063DP treatment results in patient-perceived improvements in mild-moderate atopic dermatitis.

MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter, randomized, vehicle-controlled study.

OBJECTIVE: To examine the efficacy and safety of MAS063DP (Atopiclair) cream in the management of mild to moderate atopic dermatitis in infants and children. STUDY DESIGN: One hundred forty-two patients aged 6 months to 12 years were administered MAS063DP (n = 72) or vehicle (n = 70) cream 3 times per day to affected areas and sites prone to develop atopic dermatitis. The primary endpoint for efficacy was the Investigator's Global Assessment at day 22. Secondary endpoints included Investigator's Global Assessment at other time-points, patient's/caregiver's assessment of pruritus, onset, duration of itch relief, Eczema Area and Severity Index, subject's/caregiver's assessment of global response, and need for rescue medication in the event of an atopic dermatitis flare. RESULTS: MAS063DP cream was statistically more effective (P < .0001) than vehicle cream for the primary endpoint and all secondary endpoints. Treatment discontinuation as a result of an adverse event occurred in 9.9% of patients using MAS063DP cream and 16% of patients using vehicle cream. CONCLUSION: MAS063DP cream is effective and safe as monotherapy for the treatment of symptoms of mild to moderate atopic dermatitis in infants and children.

A multicenter, randomized, vehicle-controlled clinical study to examine the efficacy and safety of MAS063DP (Atopiclair) in the management of mild to moderate atopic dermatitis in adults.

BACKGROUND: MAS063DP cream has received marketing authorization in the US and the European Union for symptom relief of atopic dermatitis (eczema) and contact dermatitis. DESIGN: A multicenter, randomized, vehicle-controlled, phase IV study was completed in the US. METHODS: 218 patients aged 18 to 84 years joined this 50-day study. Patients self-administered MAS063DP cream (N=145) or vehicle cream (N=73) 3 times per day to affected areas and those areas prone to be affected. The primary endpoint for efficacy was the change in EASI at Day 22 of treatment, comparing the 2 treatment groups. Secondary outcomes included EASI scores at other time points, IGA, pruritus (100mm VAS), % BSA, and the need for rescue medication. RESULTS: MAS063DP was statistically (p<.0001) more effective than vehicle in all outcomes at all time points. The incidence of rash was 2.1% in the MAS063DP group versus 5.5% in the vehicle group. Only 2 patients discontinued MAS063DP due to an adverse event. CONCLUSION: MAS063DP cream was confirmed to be a safe and effective treatment for mild to moderate atopic dermatitis in adults.