Dupilumab Treatment Research Articles

Dupilumab treatment reduces total IgE levels in patients 6 months and older with moderate-to-severe atopic dermatitis

Dupilumab treatment reduces total IgE levels in patients 6 months and older with moderate-to-severe atopic dermatitis

Dupilumab-associated ocular surface disease in atopic dermatitis patients: clinical characteristics, ophthalmic treatment response, and conjunctival goblet cell analysis.

Dupilumab-associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment response, and to learn more about the effect of dupilumab on conjunctival goblet cells (GC). This prospective study included dupilumab-treated AD patients between February 2020 and June 2022 from the University Medical Centre Utrecht. Patients were examined by an ophthalmologist and a dermatologist before start (baseline), and after 4 and 28 weeks of dupilumab treatment. Ophthalmological examination was assessed by the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. DAOSD was defined as an increase in UTOPIA score of ≥3 points from baseline. To quantify conjunctival GCs and to investigate the percentage of Cytokeratin 19 (CK19)-CD45-Mucin 5AC (MUC5AC)+ cells, conjunctival impression cytology samples were analysed. Ocular surface disease (OSD) was present in 91.3% (n=63/69) patients at baseline. DAOSD was observed in 28.9% (n=20/69) patients, in whom GC numbers remained stable and the percentage of CK19-CD45-MUC5AC+ cells decreased at onset of DAOSD compared with baseline. After 28 weeks of dupilumab treatment, DAOSD was seen in 14.5% (n=10/69) patients. Of the 85.5% (n=59/69) patients without DAOSD or with controlled DAOSD at week 28, 40.7% (n=24/59) patients received anti-inflammatory ophthalmic drugs. OSD is common in moderate-to-severe AD patients before starting dupilumab. During treatment with dupilumab DAOSD severity improves with early ophthalmic treatment. The decrease in percentage of CK19-CD45-MUC5AC+ cells during dupilumab treatment suggests an impairment of the GC function due to dupilumab treatment.

Efficacy and Safety of Dupilumab in Prurigo Nodularis: A Real-World Study

Prurigo Nodularis (PN) is a chronic inflammatory skin disease characterized by severe itching accompanied by multiple nodules throughout the body. There is currently no effective drug-targeted treatment for PN. Dupilumab is a fully human monoclonal antibody which can suppress the Th2 inflammatory reaction. We aimed to assess the efficacy and safety of dupilumab in PN. There were 29 PN patients who received dupilumab treatment for four months. Serum total Immunoglobulin E (Ig E), eosinophil counts, Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS) were assessed on patients before and after treatment. And we count the vaccination of novel coronavirus pneumonia (COVID-19) in patients and the impact on skin diseases and treatment measures after vaccination. Plotting was performed using GraphPad Prism8, and statistical analysis was performed using PASW Statistics18. The eosinophil counts in patients higher decreased to normal, and the Ig E levels gradually decreased and tended to normal levels after receiving dupilumab injection. The average DLQI score at baseline was 23.93±0.66, and decreased to 11.66±0.55 (P<0.01) and 1.83±0.22 (P<0.01) at 1-month and 6-month follow-up of treatment, respectively. The average NRS score at baseline was 9.79±0.08, and decreased to 3.52±0.23 (P<0.01) and 0.31±0.15 (P<0.01) at the 1-month and 6-month follow-up of treatment, respectively. Our study shows that dupilumab has achieved good efficacy in PN with few adverse reactions and high safety. We can recommend that patients follow the advice of specialists to be vaccinated and under the condition of stable disease, separated from dupilumab treatment for one week.

Non-Infectious Uveitis Secondary to Dupilumab Treatment in Atopic Dermatitis Patients Shows a Pro-Inflammatory Molecular Profile

ABSTRACT Severe uveitis is a rare complication of interleukin-4 receptor alpha blocking by dupilumab in topic dermatitis (AD) patients. The aim of this study was to describe five moderate-to-severe AD patients who developed uveitis during dupilumab treatment and to compare the proteomic profile of aqueous humor (AqH) of dupilumab-associated uveitis (n=3/5 available samples) with non-infectious uveitis (n=27) and cataract controls (n=11). Included patients were treated at the University Medical Center Utrecht (the Netherlands). Active dupilumab-associated uveitis complicated by serous detachment, cystoid macular edema, or secondary glaucoma developed within a median of 6.0 months (interquartile range 2.3–16.5 months) after starting dupilumab. Uveitis resolved after discontinuation of dupilumab and/or treatment with local or systemic corticosteroids. Proteomic profiling of AqH revealed that the molecular profile of dupilumab-associated uveitis resembled that of non-infectious uveitis. In conclusion, dupilumab-associated uveitis is a severe adverse event of dupilumab therapy, requiring urgent referral to an ophthalmologist.

A real-world observational study of dupilumab treatment in adult patients with prurigo nodularis

BackgroundPrurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options. ObjectiveTo assess the efficacy and safety of dupilumab in adult patients with PN refractory to traditional therapies. MethodsThis ongoing, real-life study examined dupilumab treatment in 8 adult patients diagnosed with PN for at least 6 months. The included patients were prescribed 300 mg dupilumab biweekly for at least 16 weeks. Efficacy was the primary outcome by means of multiple standardized scale measurements while safety was also reported. ResultsPN patients treated with dupilumab showed notable clinical improvement. After 16 weeks of dupilumab treatment, the mean Investigator Global Assessment (IGA) score reduced from 3.75 to 1.50. Patients mean Numerical Rating Scale Itch Intensity (NRSI), Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS) ratings reduced from 8.625, 15.13, and 14.50 to 1.563, 4.625, and 1.000 respectively. The majority of the patients (87.5%) reported dupilumab as effective while no adverse events have been reported. Study limitationsThis study was limited to a small cohort of adult PN patients and a short-time observation period. ConclusionsDupilumab is effective and tolerable in adult PN patients with significant improvement in skin lesions, itching, and quality of life.

Dupilumab Inhibits Vascular Leakage of Blood Proteins Into Atopic Dermatitis Skin

Atopic dermatitis (AD) skin lesions are associated with oozing, bleeding, and erythema. This suggests AD is associated with vascular changes. Dupilumab is an antibody to the alpha-subunit of interleukin (IL) 4 receptor that demonstrates strong efficacy in the treatment of AD. IL-4 is known to reduce the permeability barrier function of vascular endothelium. To examine the effects of dupilumab on vascular barrier function in AD skin. Using proteomic analysis, we evaluated the plasma protein composition in skin tapes of lesional and non-lesional skin of adults and adolescents with moderate-to-severe AD over the course of a 16-week treatment with dupilumab and compared those to matched healthy subjects. At baseline, 115 plasma proteins were detected in AD skin and globally increased (1.5-fold or greater) compared to healthy skin. Functionally, these proteins included immunoglobulins, proteins involved in the coagulation process, enzymes, protease inhibitors, transport proteins, acute-phase proteins, complement proteins, and other pleiotropic proteins. Noteworthy, fibrinogens, fibronectin, and heme-binding proteins haptoglobin and hemopexin were among the top proteins originating from plasma and were increased in AD lesional versus healthy skin at baseline (p<0.0001). Dupilumab treatment resulted in significantly reduced levels of plasma proteins in AD skin (p<0.0001), with the majority dropping to levels seen in healthy skin or no longer detectable at week 16. Inhibition of IL-4/IL-13 action by dupilumab significantly reduces the efflux of plasma proteins into AD skin. Several of these proteins, such as fibrinogens and fibronectin, are known to enhance Staphylococcus aureuscolonization and are associated with AD skin severity.

Abrocitinib in the Treatment of Moderate-to-Severe Atopic Dermatitis Refractory to Dupilumab Treatment: An Analysis of JADE-EXTEND, a Phase 3 Long-Term Extension Study

Abrocitinib in the Treatment of Moderate-to-Severe Atopic Dermatitis Refractory to Dupilumab Treatment: An Analysis of JADE-EXTEND, a Phase 3 Long-Term Extension Study

Dupilumab-associated cutaneous adverse events among adult patients with atopic dermatitis: A retrospective study.

Dupilumab, a monoclonal antibody inhibiting interleukin (IL) 4 and IL-13, is approved for the treatment of moderate to severe atopic dermatitis (AD) in children aged ≥6 years, adolescents, and adults. Both clinical trials and real-life data demonstrate its efficacy and safety. However, some cutaneous adverse events (cAEs) have been observed during real-world experiences. The authors' aim was to analyze the spectrum of cAEs in patients receiving dupilumab for the treatment of AD in a real-world setting. A retrospective review of electronic medical records was conducted for 916 patients (475 males and 541 females; mean age, 50.23 ± 19.66 years [range, 18-91 years]) who had received dupilumab for a minimum of 1month for the treatment of AD from December 2018 to November 2022 at the Department of Dermatology of University Federico II of Naples (Italy). The mean duration of dupilumab treatment was 27.31 ± 21.26 months. A total of 148 of 916 (16.15%) (90 males; mean age, 50.91 ± 15.34 years) patients reported other cAEs apart of AD flare; namely, facial redness (82 of 916; 8.95%), psoriasis (39 of 916; 4.25%), alopecia areata (11 of 916; 1.2%), skin peeling (11 of 916; 1.2%), parapsoriasis (three of 916; 0.32%), and vitiligo (two of 916; 0.21%). Thirty-one of 916 (3.38%) patients discontinued dupilumab because of cAEs (18 of 916; 1.96%) for facial redness, 10 of 916 (1.09%) for psoriasis, and three of 916 (0.32%) for parapsoriasis. In our population, most of the cAEs were mild and did not require discontinuation of dupilumab. These findings would enable dermatologists understand the cutaneous side effects of dupilumab better, resulting in improved treatment plan decisions in clinical practice.

Barrier Factors of Adherence to Dupilumab Self-Injection for Severe Allergic Disease: A Non-Interventional Open-Label Study.

The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection. This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12. We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to "inconvenience/forgetfulness" between the good and poor adherence groups. The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.

Efficacy of Dupilumab in Children 6 Months to 11 Years Old With Atopic Dermatitis: A Retrospective Real-World Study in China.

Background: Atopic dermatitis (AD) is a common skin disease that affects patients' quality of life, especially in the pediatric population. Dupilumab has shown good efficacy and safety in the treatment of AD in adolescents and adults, but the real data on younger children using dupilumab are scarce. Objectives: We investigated the doses, efficacy, and safety of dupilumab in children with moderate-to-severe AD aged ≥6 months to 11 years. Methods: This single-center retrospective cohort analysis included dupilumab-treated patients with severe AD under 12 years of age. Primary endpoints included the proportion of Validated Investigator Global Assessment (vIGA) 0/1 achieved and the percentage change from baseline in eczema area and severity index (EASI) and SCORing Atopic Dermatitis (SCORAD) at week 24 (W24). Secondary endpoints were mean change in pruritus numerical rating score (P-NRS) and body surface area (BSA) after W24 of treatment, description of adverse events, and Children's Dermatology Life Quality Index (CDLQI) improvement from baseline in endpoints. Results: Fifty-seven patients were included (mean age 7.2 ± 3.0 years). The primary endpoint (vIGA = 0/1) was achieved by 51 of 57 (89.5%) patients at W24. Significant improvements in EASI, SCORAD, P-NRS, and CDLQI scores were observed from baseline to W24 with dupilumab treatment and remained until W40. In different age groups, the endpoint vIGA achieved 0/1: 95.2% (20/21) of younger children and 88.9% (32/36) of older children. No serious adverse drug reactions were reported. Conclusions: This study aimed to describe the safety and efficacy of dupilumab in pediatric patients and examined differences of efficacy with various doses. The outcomes are comparable with those of existing clinical trials. Phase III Clinical Trial: NCT03346434.

Serum biomarker-based endotypes of atopic dermatitis in China and prediction for efficacy of dupilumab.

Atopic dermatitis (AD) is a highly heterogeneous disease clinically and biologically. Serum biomarkers have been utilized for endotype identification and have the potential to be predictors for treatment. To explore the serum biomarker-based endotypes of Chinese patients with AD and to identify biomarkers for prediction of the efficacy of dupilumab. Sera from 125 patients with moderate-to-severe AD and 60 normal controls (NC) were analysed for 24 cytokines/chemokines using the magnetic Luminex assay. After the patients received 16 weeks of dupilumab treatment, the efficacy was evaluated, and blood eosinophils, serum immunoglobulin (Ig) E and biomarkers were measured. Chinese patients with moderate-to-severe AD were characterized by T-helper (Th)2-dominant serum biomarkers that were mixed with differentially increased Th1-, Th17- and Th22-type cytokines/chemokines, and it was mainly Th2-type serum biomarkers that were positively correlated with disease severity and eosinophil counts. Adult (but not adolescent or elderly) patients with AD showed a consistent and more significant increase of biomarkers across different types of inflammation. The patients were grouped into two clusters by unsupervised k-means analysis, which were differentially associated with inflammation. Treatment with dupilumab decreased the levels of most cytokines/chemokines analysed. While there was no difference between the two clusters in the efficacy of dupilumab, baseline levels of CD25/soluble interleukin (sIL)-2Rα, IL-31 and IL-36β were identified as predictive factors associated with the efficacy. Our study revealed two inflammation-related endotypes of Chinese patients with AD based on serum biomarkers. High levels of CD25/sIL-2Rα, IL-31 and IL-36β might predict good efficacy of dupilumab treatment.

Longitudinal skin tape strip global proteomic assessment reveals normalization of epidermal development in atopic dermatitis patients treated with dupilumab

Atopic dermatitis (AD) is characterized by epidermal dysfunction and interleukin (IL)-4/IL-13-predominant inflammation. Dupilumab, a monoclonal antibody that targets IL-4Rα, has demonstrated clinical efficacy/safety in AD. The skin barrier proteomic changes in AD patients with dupilumab treatment are not established.

Dupilumab for Atopic Dermatitis-From Clinical Trials to Molecular and Cellular Mechanisms.

Dupilumab is a monoclonal antibody that represents the first approved targeted biological therapy for adults, adolescents, and children older than 6 years with moderate-to-severe atopic dermatitis (AD). Dupilumab binds the shared chain of the interleukin-4 and interleukin-13 receptor blocking the downstream signaling of these cytokines. The clinical improvements induced by dupilumab were associated with remission of the dysregulated immune mechanisms linked with AD. Dupilumab reversed the epidermal barrier defects and improved the global molecular signature of AD. This review seeks to provide an overview on the development of dupilumab as the first target-specific biological treatment for AD, with a description of the clinical trials that have been performed in different age groups, their outcomes, and reported adverse effects. Novel aspects of dupilumab treatment, as well as the current knowledge on the molecular and cellular mechanisms underlying the treatment of AD with dupilumab, are summarized and discussed.

Successful response to upadacitinib in the treatment of atopic dermatitis lesions involving sensitive and visible areas resistant to dupilumab treatment.

Beneficial effects of upadacitinib in the treatment of atopic dermatitis (AD) in patients who were unresponsive to dupilumab therapy have been described. In this study AD lesions resistant to dupilumab and localized in sensitive and visible areas showed a marked improvement with upadacitinib therapy.

Dupilumab Treatment Reduces Total IgE Levels in Patients 6 Months and Older with Moderate-to-Severe Atopic Dermatitis

Dupilumab Treatment Reduces Total IgE Levels in Patients 6 Months and Older with Moderate-to-Severe Atopic Dermatitis

Dupilumab treatment for atopic dermatitis is associated with decreased utilization of psychostimulants for attention deficit hyperactivity disorder: A retrospective cohort study

Dupilumab treatment for atopic dermatitis is associated with decreased utilization of psychostimulants for attention deficit hyperactivity disorder: A retrospective cohort study

Tralokinumab treatment for patients with moderate-to-severe atopic dermatitis in daily practice.

Evidence about tralokinumab treatment for moderate-to-severe atopic dermatitis (AD) in daily practice is limited. To report the first evidence, to our knowledge, from daily practice of treatment with tralokinumab in patients with AD. In this observational prospective study, patients with AD who received tralokinumab treatment in the context of routine care at the Erasmus Medical Centre were included between November 2021 and February 2022. This included 28 patients who had previously been treated with dupilumab, and 14 patients who had been treated with a Janus kinase inhibitor (JAKi). The Investigator's Global Assessment (IGA; 0-4) and the numeric rating scale peak pruritus during the past 7 days (NRS itch 7d: 0-10), adverse events and reasons for discontinuation were analysed. A good clinical response was defined as any decrease in IGA and NRS itch 7d and if a patient was satisfied with the treatment and wished to continue with therapy. In total, 37 patients were treated with tralokinumab. Twenty-two (59%) patients showed a good response to tralokinumab treatment. Fifteen (41%) patients discontinued treatment because of inadequate AD control or adverse events. Treatment-related adverse events were mild in most patients. Half of the patients where treatment with dupilumab had failed had a good clinical response to tralokinumab. Tralokinumab was found to be effective in most patients in this cohort with difficult-to-treat, severe AD from daily practice. Interestingly, tralokinumab was also found to be effective in 50% of patients who had previously experienced insufficient response or adverse events with dupilumab treatment.

342 A case series of live attenuated vaccine administration in dupilumab-treated children with atopic dermatitis

Abstract In patients with atopic dermatitis (AD), it is unknown whether suppression of dysregulated type 2 immune cytokines, interleukin-4 and interleukin-13, with dupilumab impacts the risk of viral infections following live attenuated vaccination. Current medical consensus and regulatory labelling recommend completing age-appropriate non-live vaccinations according to immunization guidelines at least 4 weeks prior to starting dupilumab and to avoid the use of live vaccines in patients treated with dupilumab. Phase 3 dupilumab AD clinical trial protocols prohibited the administration of live attenuated vaccines within 4 weeks before the baseline visit and during treatment. For patients in the LIBERTY AD PED open-label extension (OLE; NCT02612454) who required a live attenuated vaccine, the protocol specified that the study drug be discontinued for 12 weeks prior to planned administration and could be re-initiated 4 weeks after vaccine administration. However, one patient in the 16-week LIBERTY AD PRESCHOOL (NCT03346434, part B) study received a live attenuated vaccine with a ≤ 12 weeks gap between dupilumab administration and vaccination and eight patients in the LIBERTY AD PED-OLE received a live attenuated vaccine, four patients were vaccinated with a ≤ 12 weeks gap and four patients &amp;gt; 12 weeks after discontinuing dupilumab. To describe the clinical course of children with moderate-to-severe AD administered a live attenuated vaccine during the LIBERTY AD PRESCHOOL or LIBERTY AD PED-OLE study. Paediatric patients with moderate-to-severe AD who had previously participated in the phase 2 open-label, multicentre, sequential study LIBERTY AD PRESCHOOL (part A; 3 or 6 mg/kg dupilumab single dose) or the randomized, double-blind placebo-controlled phase 3 study LIBERTY AD PRESCHOOL (part B; 200 mg dupilumab every 4 weeks [q4w] if baseline weight 5 to &amp;lt;15 kg, or 300 mg q4w if 15 to &amp;lt;30 kg) were subsequently enrolled into the LIBERTY AD PED-OLE study (200 mg dupilumab q4w if baseline weight 5 to &amp;lt;15 kg, 300 mg q4w if 15 to &amp;lt;30 kg, or 200 mg q2w if 30 to &amp;lt;60 kg). This case series includes nine patients with severe AD at the parent study baseline (Investigator’s Global Assessment score = 4) and Peak Pruritus Numerical Rating Scale (range: 0–10) scores of 5.2 (n = 1), 8 (n = 2), 9 (n = 4) or 10 (n = 2), who were administered a live attenuated vaccine, with or without pause, during dupilumab treatment in the LIBERTY AD PRESCHOOL (part B; n = 1) or LIBERTY AD PED-OLE study (n = 8). Of the nine patients in this case series, eight were male. All were first diagnosed with AD between 0 and 6 months of age and age at enrolment varied from 8 to 56 months old. Dupilumab treatment duration up to the date of vaccination with live attenuated measles, mumps, rubella (MMR) and varicella vaccines (n = 5) or MMR vaccine only (n = 4) ranged from 85 to 840 days. No adverse events (AEs), including serious AEs, treatment-emergent infections and infestations, or serious infections were observed in the 4-week window post-vaccination. In this limited prospective case series of children with moderate-to-severe AD who also received the live attenuated MMR vaccine, with or without live attenuated varicella vaccine, no serious adverse events were observed within 4 weeks or after 4 weeks post-vaccination. Additional research is needed to assess the safety of live attenuated vaccines in patients on dupilumab treatment and to investigate whether dupilumab treatment impacts vaccine efficacy.

337 Dupilumab treatment is not associated with an increased overall risk of infections in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Abstract Patients with atopic dermatitis (AD) have an increased risk of infection, including skin infections. Previous studies in children aged 6–11 years and adolescents showed that dupilumab is not associated with an increased risk of overall infections and is associated with a lower incidence of skin infections compared with a placebo. This post-hoc analysis reports the impact of dupilumab treatment on infections, including skin infections, in children aged 6 months to 5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled trial (NCT03346434, part B), children aged 6 months to 5 years with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) were randomized 1 : 1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight was ≥5 to &amp;lt;15 kg, 300 mg if weight was ≥15 to &amp;lt;30 kg) or placebo with concomitant low-potency topical corticosteroids for 16 weeks. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) and systemic anti-infective medication use (nP/100PY) were used to compare treatment groups. 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). During the 16-week treatment period, total infections rates were numerically lower in the dupilumab-treated group (nP/100PY: 185.2) compared with the placebo-treated group (nP/100PY: 245.7). Fewer infections of skin-structure and soft tissues were reported in the dupilumab group (nP/100PY: 24.7) compared with the placebo group (nP/100PY: 40.2). Dupilumab-treated patients had significantly lower rates of non-herpetic skin infections (nP/100PY: 42.7) than placebo-treated patients (nP/100PY: 92.7; P &amp;lt; 0.05 vs. placebo). There was no significant difference in rates of herpetic skin infections between the dupilumab (nP/100PY: 20.0) and placebo groups (nP/100PY: 17.1; P = 0.817 vs. placebo). No helminthic infections were reported in either group. Systemic anti-infective medication use was significantly less frequent in the dupilumab group (nP/100PY: 104.7) compared with placebo (nP/100PY: 203.0; P &amp;lt; 0.05 vs. placebo). The overall safety of dupilumab was consistent with the known safety profile. Dupilumab treatment is associated with lower overall infections and significantly lower non-herpetic skin infections than placebo in children aged 6 months to 5 years with moderate-to-severe AD.

340 Dupilumab treatment of children with moderate-to-severe atopic dermatitis increases bone alkaline phosphatase, a marker of bone mineralization

Abstract Children with atopic dermatitis (AD) are at risk for low bone mineral density (BMD), which is associated with an increased prevalence of osteopenia, osteoporosis, and fracture risk.1,2 Factors such as restricted nutrition, vitamin D deficiency, poor sleep and corticosteroid use contribute to lower bone alkaline phosphatase (BALP) levels, a marker of bone mineralization, seen in children with moderate-to-severe AD compared with healthy children.3 A major determinant for the lifetime risk of fractures and osteoporosis is the magnitude of peak bone mass achieved during prepubescent years. Low BALP and BMD in children with moderate-to-severe AD could contribute to a higher prevalence of osteopenia and osteoporosis. The objective of this analysis is to report the impact of dupilumab treatment on markers of bone formation in children aged ≥ 6 to &amp;lt; 12 years with moderate-to-severe AD. The analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454). In LIBERTY AD PEDS, a double-blind, 16-week, phase 3 trial, children aged 6 to &amp;lt; 12 years were randomized 1 : 1 : 1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w for patients with baseline weight &amp;lt;30 kg, and 200 mg q2w for those with baseline weight ≥30 kg), or placebo; with concomitant medium-potency topical corticosteroids (TCS). After the initial 16-week trial, children aged 6 to &amp;lt;12 years were enrolled in the open-label extension study LIBERTY AD PED-OLE. Patients received dupilumab 300 mg q4w, which could be titrated up in case of inadequate clinical response at week 16 (200 mg q2w for patients with baseline weight &amp;lt;60 kg, and 300 mg q2w for those with baseline weight ≥60 kg); with concomitant medium-potency TCS. Bone biomarkers including BALP, procollagen type 1 N-terminal propeptide, C-terminal crosslinking telopeptide of type 1 collagen, osteocalcin, and insulin-like growth factor 1 were analysed at baseline, 8, 12, 16 and BALP only at 52 weeks. Dupilumab treatment led to a rapid and significant increase in geometric mean (standard error) levels of BALP in children with moderate-to-severe AD at 16 weeks compared with patients in the placebo group (77.7(1.02) μgL−1 vs. 65.0(1.04) μgL−1; P &amp;lt; 0.0001). As well as a rapid and significant increase in BALP levels in children from the placebo group once they joined the OLE trial. BALP levels increased over 52 weeks in all treated children, reaching a level of 78–84 μgL−1 which constitutes a significant improvement compared with baseline, and is comparable to healthy reference intervals. An increasing trend from baseline to 16 weeks of dupilumab treatment was observed for other biomarkers, however, there was a limited number of data points due to insufficient volumes of serum available for analysis. These placebo-controlled results show, for the first time, a rapid and significant increase in BALP, and a possible trend in other biomarkers, in children with AD during treatment with dupilumab. These results suggest increased bone mineralization during the treatment period.