Systemic Immunomodulatory Treatments for Atopic Dermatitis: Living Systematic Review and Network Meta-Analysis Update.

Importance: There are multiple approved systemic treatments for atopic dermatitis. Lebrikizumab is a newly licensed biologic medication that has been compared to placebo in clinical trials but not to other systemic treatments. Objective: To compare reported measures of efficacy and safety of lebrikizumab to other systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis. Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Latin American and Caribbean Health Science Information database, the Global Resource of Eczema Trials database, and trial registries were searched from inception through November 3, 2023. Study Selection: Randomized clinical trials evaluating 8 or more weeks of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis. Titles, abstracts, and full texts were screened in duplicate. Data Extraction and Synthesis: Data were abstracted in duplicate and random-effects bayesian network meta-analyses were performed. Minimal important differences were used to define important differences between medications. Certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). The updated analysis was completed from December 13, 2023, to February 20, 2024. Main Outcome Measures: Efficacy outcomes were the Eczema Area and Severity Index (EASI), the Patient Oriented Eczema Measure (POEM) Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS) and were compared using mean difference (MD) with 95% credible intervals (CrI). Safety outcomes were serious adverse events and withdrawal due to adverse events. Other outcomes included the proportion of participants with 50%, 75%, and 90% improvement in EASI (EASI-50, -75, -90) and the proportion with success on the Investigator Global Assessment compared using odds ratios with 95% CrI. Results: The study sample included 97 eligible trials, with a total of 24 679 patients. Lebrikizumab was associated with no important difference in change in EASI (MD, -2.0; 95% CrI, -4.5 to 0.3; moderate certainty), POEM (MD, -1.1; 95% CrI -2.5 to 0.2; moderate certainty), DLQI (MD, -0.2; 95% CrI -2.1 to 1.6; moderate certainty), or PP-NRS (MD, 0.1; 95% CrI -0.4, 0.6; high certainty) compared to dupilumab among adults with atopic dermatitis who were treated for up to 16 weeks. Dupilumab was associated with higher odds of efficacy in binary outcomes compared with lebrikizumab. The relative efficacy of other approved systemic medications was similar to that found by previous updates of this living study, with high-dose upadacitinib and abrocitinib demonstrating numerically highest relative efficacy. For safety outcomes, low event rates limited useful comparisons. Conclusions and Relevance: In this living systematic review and network meta-analysis, lebrikizumab was similarly effective to dupilumab for the short-term treatment of atopic dermatitis in adults. Clinicians and patients can use these comparative data to inform treatment decisions.

A comparison of family physician and dermatologist topical corticosteroid prescriptions: A population-based cross-sectional study.

BACKGROUND: Topical corticosteroids (TCS) are commonly prescribed to treat inflammatory skin diseases, and appropriate prescription is necessary for treatment success. OBJECTIVE: To quantify differences between TCS prescribed by dermatologists at consultation and family physicians for patients treated for any skin condition. METHODS: Using administrative health data in Ontario, we included all Ontario Drug Benefit recipients who filled at least one TCS prescription from a dermatologist at consultation and a family physician in the year prior between January 2014 and December 2019. We estimated mean differences and 95% confidence intervals in amount (in grams) and potency between the index dermatologist prescription and the highest and most recent family physician prescription amounts and potencies in the preceding year using linear mixed-effect models. RESULTS: A total of 69,335 persons were included. The mean dermatologist amount was 34% larger than the highest amount and 54% larger than the most recent amount prescribed by family physicians. There were small but statistically significant differences in potency using established 7-category and 4-category potency classification systems. CONCLUSIONS: Compared to family physicians, dermatologists prescribed substantially larger amounts and similarly potent TCS at consultation. Further research is needed to determine the effect of these differences on clinical outcomes.

Development of a Website for a Living Network Meta-analysis of Atopic Dermatitis Treatments Using a User-Centered Design: Multimethod Study.

BACKGROUND: A rapid expansion of systemic immunological treatment options for atopic dermatitis (AD) has created a need for clinically relevant and understandable comparative efficacy and safety information for patients and clinicians. Given the scarcity of head-to-head trials, network meta-analysis (NMA) is an alternative way to enable robust comparisons among treatment options; however, NMA results are often complex and difficult to directly implement in shared decision-making. OBJECTIVE: The aim of this study is to develop a website that effectively presents the results of a living systematic review and NMA on AD treatments to patient and clinician users. METHODS: We conducted a multimethod study using iterative feedback from adults with AD, adult caregivers of children with AD, dermatologists, and allergists within a user-centered design framework. We used questionnaires followed by workshops among patients and clinicians to develop and improve the website interface. Usability testing was done with a caregiver of a patient with eczema. RESULTS: Questionnaires were completed by 31 adults with AD or caregivers and 94 clinicians. Patients and caregivers felt it was very important to know about new treatments (20/31, 65%). Clinicians felt the lack of evidence-based comparisons between treatments was a barrier to care (55/93, 59%). "Avoiding dangerous side effects" was ranked as the most important priority for patients (weighted ranking 5.2/7, with higher ranking being more important), and "improving patients' overall symptoms" was the most important priority for clinicians (weighted ranking 5.0/6). A total of 4 patients and 7 clinicians participated in workshops; they appreciated visualizations of the NMA results and found the website valuable for comparing different treatments. The patients suggested changes to simplify the interface and clarify terminology related to comparative efficacy. The user in the usability testing found the website intuitive to navigate. CONCLUSIONS: We developed a website, "eczematherapies.com," with a user-centered design approach. Visualizations of NMA results enable users to compare treatments as part of their shared decision-making process.