Rapid response to dupilumab treatment in children with moderate-to-severe atopic dermatitis: A case series.
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SUBMITTER: Votto M
PROVIDER: S-EPMC9306756 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8776905 | biostudies-literature
Project description:Background: Atopic dermatitis (AD) is a chronic inflammatory condition causing itching skin, with a significant psychosocial impact on patients and relatives. AD affects 15 to 30% of children and 2 to 10% of adults. AD significantly affects patients' quality of life (QoL) given the chronicity and symptoms of the disease. Most AD patients have reported that the disease affects daily life, resulting in limited social contact and a strong impact on sexual health (SH), especially in moderate-severe cases. Materials and methods: We performed a prospective study from 1 May 2020 to 1 May 2022; the aim of the study was to evaluate the impact of moderate to severe AD on sexual desire, seduction, and partner relationships, and describe how it varies following dupilumab therapy. We used the Sexual Desire Inventory-2 (SDI-2), a validated instrument consisting of 14 items; moreover, we used a second questionnaire with eight items, an unvalidated instrument created specifically for this study, to obtain the assessment of the influence of AD on the body image, sexuality, and self-perception of those affected. Results and Conclusions: The impact of AD on sexual desire assessed using SDI-2 showed a significant improvement in both sexes during dupilumab treatment from the baseline to W4 and W16. Similar results were obtained with our questionnaire.
| S-EPMC9782472 | biostudies-literature
Project description:BackgroundModerate-to-severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side-effects. Dupilumab was recently approved for treatment of adolescent AD.ObjectivesA multicentre, prospective, real-world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate-to-severe AD was conducted. The main AD clinical phenotypes were also examined.MethodsData of adolescents with moderate-to-severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes.ResultsOne hundred and thirty-nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait-like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS-CoV-2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty-eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event.ConclusionsDupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID-19 pandemic era.
| S-EPMC9542087 | biostudies-literature
Project description:BackgroundThe patho-mechanism of ocular surface disease (OSD) in dupilumab-treated atopic dermatitis (AD) patients remains unclear. The aim of this study is to measure dupilumab levels in tear fluid and serum, and relate these findings to the severity of OSD during dupilumab treatment in AD patients.MethodsThis prospective study included dupilumab-treated moderate-to-severe AD patients who were seen by a dermatologist and an ophthalmologist before the start of dupilumab (baseline), and after 4 and 28 weeks of dupilumab treatment. Dupilumab levels in tear fluid and serum were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Additionally, a pilot study was conducted to measure dupilumab on conjunctival epithelial cells using flow cytometry and LC-MS/MS.ResultsAt baseline, 89.6% (n = 43/48) of the patients had OSD, with 50.0% having moderate-to-severe OSD. After 28 weeks of dupilumab treatment, the median dupilumab tear fluid levels were 0.55 mg/L (IQR 0.35-1.31) and 0.29 mg/L (IQR 0.16-0.60) in patients with moderate-to-severe OSD and patients with no or mild OSD, respectively (p = 0.02). Dupilumab levels could be detected on conjunctival epithelial cells of 5 AD patients treated with dupilumab for 4 weeks.ConclusionPatients with moderate-to-severe OSD had higher dupilumab tear fluid levels compared to patients with no or mild OSD, indicating that dupilumab reaches the ocular surface. Dupilumab was also detected in conjunctival cell suspensions and was found to directly bind CD45-conjunctival epithelial cells. This suggests that AD-induced changes of the conjunctival epithelium may play a role in the development of OSD as well as increased local drug availability.
| S-EPMC9842774 | biostudies-literature
Project description:We report 10 cases of conjunctivitis in atopic dermatitis (AD) patients treated with dupilumab from November 2017 to November 2018 in our institution, who were referred to the ophthalmology department for diagnosis and management of conjunctivitis. We also describe ocular surface findings in these patients before the first injection of dupilumab. During the first 6 months post initiation of dupilumab, incidence of conjunctivitis was 27% (5/18) in patients treated from November 2017 to April 2018 who had not had ocular examination previously. This rate dropped to 12% (3/25) after systematic ophthalmological referral before initiation of dupilumab. Patients who developed conjunctivitis had mean SCORAD score (Scoring Atopic Dermatitis) of 60.4 ± 20 (35-88) and mean EASI score (Eczema Area and Severity Index) of 37 ± 17 (14.6-56). Mean age was 36 years (20-51). Most patients had a long history of AD (> 10 years). Mean delay of ocular surface inflammation was 3.5 months, ranging from 1 to 8 months. One patient had to discontinue dupilumab because of severe follicular conjunctivitis. We observed two clinical patterns of ocular surface diseases: a mild non-specific conjunctivitis with dry eyes, which improved with warm compresses and artificial tears without any recurrence; and a severe dupilumab-induced follicular conjunctivitis without keratitis, which required specific ophthalmological management.
| S-EPMC6692787 | biostudies-literature
Project description:IntroductionIn a 52-week, phase 3 clinical trial (LIBERTY AD CHRONOS) in adult patients with moderate-to-severe atopic dermatitis (AD), dupilumab in combination with topical corticosteroids (TCS) resulted in a significant improvement in overall Eczema Area and Severity Index (EASI) compared with placebo plus TCS. In a post hoc analysis, dupilumab significantly improved the overall extent and severity of AD across four anatomic regions (head and neck, trunk, upper extremities, lower extremities) over 16 weeks. However, as AD severity and presentation may vary by body region, this analysis sought to determine whether there are regional variations in dupilumab efficacy.MethodsUsing data from the LIBERTY AD CHRONOS study, we performed a post hoc analysis of the mean percentage change in individual EASI signs (erythema, infiltration/papulation, excoriation, lichenification) from baseline through week 52 across four anatomic regions (head and neck, trunk, upper extremities, lower extremities).ResultsDupilumab plus TCS, compared with placebo plus TCS, significantly improved the severity of all individual AD signs to a similar extent across the four anatomic regions. Significant improvements in each sign were seen early, within the first 2-4 weeks of treatment, and were sustained through week 52 across all regions.ConclusionsIn adult patients with moderate-to-severe AD, treatment with dupilumab resulted in rapid and sustained improvement in the signs of AD across all anatomic regions.Trial registrationLIBERTY AD CHRONOS (NCT02260986).
| S-EPMC8776906 | biostudies-literature
Project description:This open-label drug-drug interaction study assessed whether blockade by dupilumab of interleukin (IL)-4 and IL-13 signaling affects the pharmacokinetics of drugs metabolized by cytochrome P450 (CYP450) enzymes. The pharmacokinetics of five CYP450 substrates given orally (midazolam, omeprazole, S-warfarin, caffeine, and metoprolol, metabolized by CYP3A, CYP2C19, CYP2C9, CYP1A2, and CYP2D6, respectively) were evaluated before and 28 days after initiation of dupilumab treatment (subcutaneous 300 mg weekly) in 14 patients with moderate-to-severe atopic dermatitis. Dupilumab had no clinically relevant effects on the pharmacokinetics of CYP450 substrates, provided substantial clinical benefit, and was generally well tolerated. Only one serious adverse event was reported, an episode of systemic inflammatory response syndrome that resolved after treatment was discontinued. In summary, blockade of IL-4/IL-13 signaling in patients with type 2 inflammation does not appear to significantly affect CYP450 enzyme activities; the use of dupilumab in atopic dermatitis patients is unlikely to influence the pharmacokinetics of CYP450 substrates.
| S-EPMC6282936 | biostudies-literature
Project description:ImportanceAtopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement.ObjectiveTo assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD.Design, setting, and participantsHeads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population.InterventionsPatients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week.Main outcomes and measuresThe primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug.ResultsOf 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 as early as week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib, whereas rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab.Conclusions and relevanceDuring 16 weeks of treatment, upadacitinib demonstrated superior efficacy vs dupilumab in patients with moderate-to-severe AD, with no new safety signals.Trial registrationClinicalTrials.gov Identifier: NCT03738397.
| S-EPMC8340015 | biostudies-literature
Project description:We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.
| S-EPMC8081439 | biostudies-literature
Project description:IntroductionDupilumab is a biologic therapy approved for treatment of moderate to severe atopic dermatitis (AD). Our objective was to assess the real-world effectiveness, safety and laboratory monitoring practices for dupilumab in a tertiary centre.MethodsA retrospective review of medical records of all patients receiving dupilumab between September 2017 and October 2019 was undertaken. Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) were collected at weeks 0, 12-16 and 26-30. Data on laboratory tests undertaken for dupilumab screening and monitoring were also collected.ResultsAt 12-16 weeks, 58.9% and 37.3% of patients achieved ≥ EASI 75 and ≥ EASI 90, respectively (n = 156). Ninety-four patients underwent further analysis at weeks 26-30 with those achieving ≥ EASI 75 increasing from 61.7% (12-16 weeks) to 75.31%, and EASI 90 increasing from 35.8% (12-16 weeks) to 49.8%. The most common side effects were eye symptoms occurring in 43.1% of patients, with 16.3% developing conjunctivitis. The mean treatment duration was 255 days, during which an average of three sets of blood tests were performed (n = 149). Of all laboratory abnormalities recorded, 24% started after initiation of dupilumab, and 93% were classified as 'mild'. Dupilumab was not documented as causative in any of the cases, nor was treatment stopped on account of laboratory abnormalities.ConclusionDupilumab provides an effective and safe treatment option for patients with AD. Clinical response continued to improve past 16 weeks in this real-world population. No laboratory abnormalities were felt to be secondary to dupilumab; screening and monitoring tests did not influence dupilumab prescribing.
| S-EPMC7859021 | biostudies-literature