This is a summary of the original article “The safety data of dupilumab for the treatment of moderate-to-severe atopic dermatitis in infants, children, adolescents, and adults”. Atopic dermatitis (AD) is an inflammatory disease affecting the skin of people of all ages. Dupilumab is a drug used to treat infants, children, adolescents, and adults who have moderate-to-severe AD. Since patients with AD often require continuous, long-term treatment, it is important to understand the short- and long-term treatment risks. This summary provides a plain-language overview of the original article, which evaluated the side effects reported by patients who received dupilumab or placebo (inactive treatment) for up to 5 years in 8 clinical trials. Side effect rates were similar between dupilumab and placebo in short-term studies in all age groups. There was no increase in the number of reported side effects with long-term versus short-term treatment. Injection-site reactions, colds, and conjunctivitis side effects were more common in dupilumab versus placebo. One adult patient treated with dupilumab developed a delayed allergic reaction. Blood and urine tests indicated no need for laboratory testing during treatment. The study confirms that the overall safety of dupilumab over 8 clinical trials was consistent with previously presented safety data.

BACKGROUND:Numeric measures of atopic dermatitis (AD) disease severity are translated into severity bands to describe disease burden. Severity bands for clinician-reported outcomes (ClinROs), such as SCORing Atopic Dermatitis (SCORAD) and the Eczema Area and Severity Index (EASI), and patient-reported outcomes (PROs), such as the Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM) and SCORAD Sleep Loss and Pruritus Visual Analog Scales (VAS), are clinically meaningful tools for physicians and patients. OBJECTIVES:To develop severity bands for AD measures using a large data set from global, randomized, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD. METHODS:Disease severity data from 2822 adults and approximately 30,000 visits (excluding first visit) from five clinical trials were pooled. ClinROs and PROs were anchored to 5-level Investigator's Global Assessment and Patient Global Assessment of Disease Status questionnaires, respectively, based on correlation strength. Means (via spline regression), frequencies, medians and modes were used to select thresholds for five severity categories for each outcome measure. Goodness-of-fit and concordance were calculated using R2 and weighted κ-coefficients. RESULTS:All measures demonstrated high goodness-of-fit, and most demonstrated high concordance with the respective anchors (R2: 0.981-0.999; quadratic weighted κ-coefficients: 0.207-0.831). PROs showed reasonable agreement with previously published bands, while ClinROs displayed severity strata that differed from previously published bands. For the first time, severity bands for SCORAD Sleep Loss VAS were assessed. CONCLUSIONS:This severity bands analysis of ClinROs and PROs using a substantial, global, clinical trial data set of adults with moderate-to-severe AD, which included utilizing frequency crossover and spline regression as novel methodologies, may aid in the interpretation of AD disease severity and stratification in adult clinical trial settings. In agreement with other diseases, quality of life moderately correlates with clinical measures of severity. Further validation will provide additional insight for clinical practice applications.

As atopic dermatitis signs and symptoms wax and wane, assessing severity scores over time best captures sustained response to treatment. We report that the majority of pediatric patients (6 months to 17 years) had sustained improvements in skin lesions (Eczema Area and Severity Index ≤ 7), itch (SCORING Atopic Dermatitis pruritus Visual Analog Scale [SCORAD Pruritus VAS < 4]), and sleep loss (SCORAD sleep loss VAS < 4) over one year of treatment with dupilumab.

Background: Since dupilumab approval for moderate-to-severe atopic dermatitis (AD) in 2017, facial rash reports appeared in literature.Objective: To report facial rash treatment-emergent adverse events (TEAEs) incidence in dupilumab clinical trials for moderate-to-severe AD.Methods: Data were pooled from 14 randomized, placebo-controlled dupilumab clinical trials in pediatric (6-17 years) and adult (≥18 years) patients and were searched for facial rash TEAEs occurring during study treatment period, focusing on Medical Dictionary for Regulatory Activities (MedDRA) Lowest Level Terms (LLTs).Results: Pooled dataset included 1349 placebo-treated and 2615 dupilumab-treated patients. Facial rash incidence was low but slightly higher in dupilumab (dupilumab: 25 [1.0%]; placebo: 9 [0.7%] patients). The following LLT rates were numerically higher in dupilumab than placebo-treated patients: Erythema facial (7 [0.3%, 0.8 number of events (nE)/100 patient-years (PY)] vs 1 [<0.1%, 0.1 nE/100PY]); Redness facial (2 [<0.1%, 0.2 nE/100PY] vs 0); and rash on face (5 [0.2%, 0.4 nE/100PY] vs 1 [<0.1%, 0.1 nE/100PY]). Most cases were mild-to-moderate and recovered/resolved during study period; none led to treatment discontinuation.Conclusions: Facial rash analysis focused on MedDRA LLTs in dupilumab clinical trials for moderate-to-severe AD showed a small increase in dupilumab-treated patients compared with placebo. Most were mild-to-moderate and not treatment-limiting.

BACKGROUND:Lichenification, common in moderate to severe atopic dermatitis (AD) at any age, is often difficult to treat. This analysis assessed dupilumab vs placebo in AD lichenification by age and race-defined groups. METHODS:This post hoc analysis included pooled data from five clinical trials of dupilumab (NCT03054428, NCT03345914, NCT02277743, NCT02277769, NCT02395133), including 1,997 patients aged 6 to 88 years of all races with moderate to severe AD. RESULTS:Placebo/dupilumab randomized groups analyzed by age (n=1,535) included 123/244 children, 85/166 adolescents, and 460/457 adults; groups analyzed by self-reported racial background (n=1,902) included 132/234 Asian, 74/112 Black/African American, and 427/923 White patients. Dupilumab treatment resulted in nominally significant reductions vs placebo in Global Individual Signs Score lichenification from week 1 (adults/adolescents) or week 2 (children) through week 16. Lichenification measured by SCORing Atopic Dermatitis and Eczema Area and Severity Index improved similarly. By week 16, dupilumab significantly improved lichenification, with nominal significance vs placebo across all racial groups. CONCLUSION:Dupilumab treatment resulted in rapid and sustained improvement in lichenification across anatomic regions in all ages. Lichenification improved to a similar extent across racial groups. J Drugs Dermatol. 2025;24(2):167-173. doi:10.36849/JDD.8585R1.

Dupilumab and lebrikizumab have demonstrated efficacy in atopic dermatitis (AD) clinical trials; however, no direct comparisons exist. Efficacy outcome achievement (dupilumab and lebrikizumab with topical corticosteroids [TCS]) at 16 weeks and efficacy outcomes maintenance (dupilumab and lebrikizumab monotherapy without TCS) at 52 weeks were assessed using a placebo-adjusted Bucher indirect treatment comparison (ITC). Week 16 data were sourced from LIBERTY AD CHRONOS (dupilumab, n = 106; placebo, n = 315) and ADhere (lebrikizumab, n = 145; placebo, n = 66) trials. Week 52 data were sourced from SOLO-CONTINUE (dupilumab, n = 80; placebo, n = 39) and ADvocate 1 and 2 (lebrikizumab, n = 231; placebo, n = 60) trials, including patients who had achieved ≥ 75 Dupilumab and lebrikizumab are two drugs used to treat patients with moderate-to-severe atopic dermatitis (AD), a long-lasting condition that makes the skin dry, red, and itchy, affecting patients' everyday life. Both drugs work by blocking proteins that cause inflammation in the body, but differently: dupilumab blocks two proteins (interleukin-4 and interleukin-13) by targeting their receptor, while lebrikizumab blocks one protein (interleukin-13) directly. Several studies compared each drug with a placebo (inactive drug) with/without prescription skin creams (topical corticosteroids), but no studies have compared them with each other. We wanted to understand which drug might be more effective in treating AD, both short term and long term. We compared data from studies where each drug was tested against a placebo group, allowing us to indirectly compare the two drugs using a scientific method: "placebo-adjusted indirect treatment comparison". Two 16-week studies were used to understand the short-term effects when patients used dupilumab or lebrikizumab with prescription skin creams. For long-term effects, we used data from studies that included patients who got better at week 16 with either dupilumab or lebrikizumab, continued treatment up to week 52, and did not use prescription skin creams. Our results showed that in the short-term studies, patients treated with dupilumab had a better chance of improving how itchy their skin felt, the number of skin sores, and overall well-being, compared with those treated with lebrikizumab. In addition, patients who got better with dupilumab were more likely to maintain these improvements over 1 year compared with patients treated with lebrikizumab.

Atopic dermatitis (AD) significantly affects quality of life in patients of all ages and requires long-term treatment. Dupilumab is approved for uncontrolled moderate-to-severe AD in patients aged ≥ 6 months and in other type 2 inflammatory diseases. Data from placebo-controlled, randomized clinical trials (RCTs) and long-term open-label extensions (OLEs) enable comprehensive assessment of dupilumab’s safety profile for up to 5 years. To integrate short- and long-term dupilumab safety data in patients with moderate-to-severe AD. We describe safety from eight phase 3 trials with > 7000 patient-years of dupilumab use: five 16-week RCTs in children (6 months–11 years, with concomitant topical corticosteroids [TCS]) and adolescents and adults (≥ 12 years, without TCS); one 52-week RCT in adults (with TCS); and two OLEs in children and adolescents (6–11- and 12–18-year cohorts, ± TCS, duration ≤ 1 year) and adults (± TCS, duration ≤ 5 years). The proportion of patients experiencing ≥ 1 treatment-emergent adverse event (TEAE) in RCTs was lower with dupilumab versus placebo in children/infants and was similar with dupilumab versus placebo in adults/adolescents. Exposure-adjusted incidence rates with longer-term treatment in OLEs were similar to the RCTs. Most TEAEs reported in RCT and OLE studies were mild to moderate and not related to study drug (per investigators). Fewer patients in the dupilumab versus placebo treatment arms experienced serious TEAEs (16-week RCTs: infants/children 0.8 Atopic dermatitis is a chronic skin disease that affects people of all ages. Since patients with atopic dermatitis require continuous, life-long treatment, doctors and patients must understand the risks and benefits of treatment options before choosing one medication over another. This study reviews the safety of the drug dupilumab, which is used to treat infants, children, adolescents, and adults who have moderate-to-severe atopic dermatitis that is not well controlled with topical corticosteroids. We looked at side effects and safety data from more than 4000 patients who received either dupilumab or placebo treatment for up to 5 years in eight clinical trials. This study is the largest safety analysis of dupilumab to date. We found that children 6 months to 11 years receiving dupilumab had fewer side effects than patients in the placebo group. Adolescents and adults (12 years and older) taking dupilumab and placebo had similar rates of side effects. Serious side effects were more frequent in the placebo than in the dupilumab group in all age groups. Most side effects in patients who received dupilumab were mild or moderate, were not caused by dupilumab, and did not stop patients from taking dupilumab. The most common side effects that occurred more frequently in dupilumab-treated patients were pain or swelling around the injection location, common colds, and conjunctivitis. In conclusion, the safety of dupilumab in over 3000 patients in this study is consistent with the known dupilumab safety profile for infants, children, adolescents, and adults.

10.1093/ndt/gfae202 Video Abstract Watch the video abstract of this contribution https://academic.oup.com/ckj/pages/author_videos gfae202Media1 6363227785112

Atopic dermatitis (AD) is the most common inflammatory skin disease in children. Children with severe AD have a multidimensional disease burden characterized by skin lesions, itching, frequent infections, sleep deprivation, and a high rate of comorbidities. These impact the mental health and overall quality of life of not only the children but also of their parents and caregivers. There are few effective available treatment options for young children with severe AD that are suitable for long-term use. Due to their adverse effects, practice guidelines consider systemic agents inappropriate for this age group, although they are still used off-label in extreme cases. The biologic dupilumab has recently been approved for children aged 6-11 years with severe (EU) and moderate-to-severe (USA) AD, offering hope to this population of patients with a high unmet clinical need. The purpose of this review is to describe the unmet needs of AD patients aged 6-11 years prior to dupilumab approval and to summarize existing clinical data supporting dupilumab's safety and efficacy in these children.

Background: Previous reports show that dupilumab treatment reduces IgE levels in patients with moderate-to-severe atopic dermatitis (AD). This analysis reports the impact of dupilumab-induced reduction in total IgE levels on flare probability in patients with moderate-to-severe AD.

Abstract Introduction/Background As symptoms of atopic dermatitis (AD) can wax and wane over time, disease control is better represented by consistency of response over a long treatment duration rather than at a single time point. Objective To evaluate the proportion of pediatric patients achieving and maintaining mild or no itch (defined by a SCORing Atopic Dermatitis (SCORAD) itch visual analog scale (VAS; 0-10 over last 3 days) score of lower than 4) across 5 visits during a 52-week open label extension trial of dupilumab. Methods Patients who previously participated in 16-week trials and were aged 0.5–5 years (LIBERTY AD PRESCHOOL; NCT03346434), 6–11 years (LIBERTY AD PEDs; NCT03345914), and 12–17 years (LIBERTY AD ADOL; NCT03054428), were subsequently enrolled in the phase 3, open-label extension trial, LIBERTY AD PED-OLE (NCT02612454). Patients were treated with 300 mg q4w or 200/300 mg q2w (body weight <60 or ≥60 kg, respectively). In this analysis, patients with a SCORAD itch VAS score of greater than 4 at OLE baseline, were assessed for the maintenance of SCORAD itch VAS lower than 4, at 5 timepoints: Weeks 4, 16, 28, 40, and 52. Results In 763 patients, 400 patients with a SCORAD itch VAS score of greater than 4 were assessed. Mild or no itch was achieved in at least 4 of 5 timepoints in most patients aged 0.5–5 years (55/110; 50%), 6–11 years (76/148; 51%), and 12–17 years (73/142; 51%). Across these age groups, over 65% maintained this response for at least 3 of 5 timepoints. Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions Most pediatric patients achieved improvement in itch, maintained during 1 year of treatment with dupilumab. Results were consistent for infants/preschoolers, children, and adolescents.