Peak Pruritus Numerical Rating Scale Research Articles

417 Dupilumab Significantly Improves Sleep Disturbance in Adults with Moderate-to-Severe Atopic Dermatitis: Results of the DUPISTAD study

DUPISTAD (NCT04033367) evaluated the impact of dupilumab on sleep. Adults with moderate-to-severe AD (EASI ≥12, Pruritus numerical rating scale (NRS) ≥ 3 and sleep NRS ≥5) were randomized 2:1 to dupilumab 300mg every 2 weeks (q2w) or placebo for 12 weeks (W12); both groups were permitted concomitant topical corticosteroids. The primary efficacy endpoint was sleep quality percentage change from baseline to W12, assessed by 11-point sleep NRS. Secondary endpoints included percent change in peak pruritus NRS, change in SCORing AD (SCORAD), SCORAD sleep visual analog scale (VAS), EASI and the Patient-Reported Outcomes Measurement Information System sleep-impairment SF8a score (PROMIS-T).

Benvitimod for the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Benvitimod is a topical drug that has recently been approved for mild to moderate psoriasis and atopic dermatitis. The drug has just completed phase 3 trials for psoriasis, which calls for a systematic update of current evidence on the efficacy and safety of this drug. We searched MEDLINE (PubMed), EMBASE, Science Direct, International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials, and Google Scholar for all available randomized controlled trials concerning the topic. We included six randomized controlled trials evaluating the efficacy of benvitimod 1.0% with a total of 1925 patients. Our meta-analysis demonstrated that more patients in the benvitimod group achieved physician global assessment score of 0 or 1 (RR 6.53, 95% CI 4.39-9.71), psoriasis area and severity index (PASI) 75 (RR 4.34, 95% CI 2.96-6.36), PASI 90 (RR 8.83, 95% CI 5.22-14.95) and body surface area reduction (MD -3.85, 95% CI -4.83, -2.88) than placebo at week 12. Patient-reported outcomes were also analyzed, yielding a significant benefit in the benvitimod group for peak pruritus numerical rating scale (PP-NRS) score (MD -1.20, 95% CI -1.98, -0.42), ≥4-point decrease in PP-NRS score (RR 1.58, 95% CI, 1.24-2.03) and dermatology life quality index score (MD -2.54, 95% CI -4.00, -1.07). There was a significantly higher incidence of adverse events in the benvitimod group compared to placebo (RR 1.98, 95% CI 1.73-2.27), while the risk was found to be non-significant for serious adverse events. Benvitimod is an effective treatment of psoriasis as compared to a placebo. However, more large-scale, high-quality trials are needed to comment on the safety of this drug.

Exploratory analyses of biomarkers in blood and stratum corneum in patients with atopic dermatitis.

Background:The pathogenesis of atopic dermatitis (AD) involves various mediators, including cytokines and chemokines, which are produced by immune cells, such as dendritic cells and lymphocytes, and non-immune cells, such as epidermal cells. Several mediators, including thymus and activation-regulated chemokine (TARC), are used as biomarkers for AD severity and activity. However, additional local and systemic biomarkers of AD are required.Methods:This study will include 10 male patients with AD and 5 healthy adult males (age range: 20–80 years). The Eczema Area and Severity Index will be used to objectively evaluate the clinical findings. In addition, the severity of eruptions will be assessed on a 5-point scale by scoring symptoms (erythema, edema/papules, oozing/crusting, excoriation, lichenification, and xerosis), and the total intensity will be calculated by adding the symptom scores together. Subjective symptoms will be assessed using a peak pruritus numerical rating scale. Laboratory tests, including measurements of peripheral eosinophil count and serum total immunoglobulin E, TARC, and lactate dehydrogenase levels, will be performed. Using blood samples and extracts of stratum corneum samples obtained by tape stripping, we will conduct an exploratory analysis of protein expression using an antibody array to identify mediators whose levels are significantly altered in patients with AD. After 4 to 8 weeks, blood samples and stratum corneum samples will be collected again from AD patients. Moreover, we will examine whether the candidate proteins can be quantified using enzyme-linked immunosorbent assays.Discussion:This is an important study exploring potential local and systemic biomarkers of AD. The results of this study will be clinically meaningful for the discovery of new biomarkers for diagnosing and assessing the severity of AD.

Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis is Efficacious Regardless of Age of Disease Onset: a Post Hoc Analysis of Two Phase 3 Clinical Trials.

Adults with atopic dermatitis (AD) commonly report adult-onset disease. AD is associated with different genetics, lesion morphology and distribution, and symptoms by age of onset. Yet little is known about possible differences in treatment efficacy between adults with adult-onset or childhood-onset AD. We evaluated the efficacy of dupilumab by age of AD onset in adults with moderate-to-severe AD, using pooled data from the LIBERTY AD SOLO 1 and 2 studies (NCT02277743, NCT02277769). Results were stratified based on self-reported age of AD onset, divided into four age subgroups: 0-4, 5-9, 10-19, and over 20years. This analysis included 460 patients treated with placebo and 457 treated with dupilumab 300mg every 2weeks (q2w), with a mean patient age of 38years. Most patients (53.2%) reported AD onset at 0-4years, with 14% at 5-9years, 13.4% at 10-19years, and 18.5% at 20years or older. Dupilumab significantly improved AD signs and symptoms over 16weeks compared with placebo, regardless of age of onset. Dupilumab treatment resulted in a significantly greater proportion of patients achieving Eczema Area and Severity Index (EASI)-50, EASI-75, and EASI-90 (50%, 75%, and 90% improvement from baseline EASI, respectively), and clear or almost clear skin (Investigator's Global Assessment score 0 or 1) across all age-of-onset subgroups compared with placebo. In addition, EASI improvements were significant across all anatomical regions in all subgroups. Weekly average peak pruritus Numerical Rating Scale and Dermatology Life Quality Index also improved consistently and significantly with dupilumab versus placebo, regardless of age of onset. Despite possible differences in presentation and progression of AD linked to age of onset, dupilumab showed similar significant and sustained improvements in AD signs, symptoms, and quality of life in adults compared with placebo, over 16weeks of treatment. LIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769. Infographic available for this article.

Magnitude and Time Course of Response to Abrocitinib for Moderate-to-Severe Atopic Dermatitis

Emerging treatments for moderate-to-severe atopic dermatitis (AD) may provide greater and faster improvement in AD signs and symptoms than current therapies. To examine JADE COMPARE (NCT03720470) data using stringent efficacy end points. Adults with moderate-to-severe AD were randomly assigned 2:2:2:1 to receive oral abrocitinib 200 or 100 mg once daily, subcutaneous dupilumab 300 mg every 2 weeks (600-mg loading dose), or placebo, with medicated topical therapy for 16 weeks. Stringent response thresholds were applied for Eczema Area and Severity Index (EASI), Investigator's Global Assessment, Dermatology Life Quality Index, Peak Pruritus Numerical Rating Scale, and Night Time Itch Scale severity. At week 16, 48.9%, 38.0%, and 38.8% of the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, achieved greater than or equal to 90% improvement from baseline in EASI versus 11.3% placebo; 14.9%, 12.6%, and 6.5% achieved Investigator's Global Assessment 0 (clear) versus 4.8% placebo; 29.7%, 21.6%, and 24.0% achieved Dermatology Life Quality Index 0/1 (no/minimal impact on quality of life) versus 10.6% placebo; and 57.1%, 44.5%, and 46.1% achieved Night Time Itch Scale severity 0/1 (no/minimal night-time itch) versus 31.9% placebo. Kaplan-Meier median time to greater than or equal to 90% improvement from baseline in EASI was 59, 113, and 114 days in the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, and was not evaluable for placebo; median time to Peak Pruritus Numerical Rating Scale 0/1 (no/very minimal itch) was 86 and 116 days for abrocitinib 200-mg and dupilumab groups, respectively, and was not evaluable for abrocitinib 100-mg and placebo groups. A greater proportion of patients treated with abrocitinib than placebo had almost complete control of AD signs and symptoms.

33553 Real-world treatment patterns and outcomes up to 1 year among children aged

Background: We describe real-world treatment patterns in patients aged <12 years with moderate-to-severe AD, focusing on systemic treatments. Methods: PEDISTAD (NCT03687359) is an ongoing, international, noninterventional registry in patients aged <12 years with moderate-to-severe AD inadequately controlled with topical therapies. Treatment was per investigator discretion. In this interim analysis (data cutoff 30 July 2020), we report baseline data for all patients, and changes in the following outcomes (from therapy start [TS] to last observation [LO]) for patients receiving systemic treatments of interest (dupilumab, cyclosporine, or methotrexate): Eczema Area and Severity Index (EASI), AD-affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM), Children’s Dermatology Life Quality Index (CDLQI; 4–<12 years), and current-day peak pruritus numerical rating scale (PP-NRS). No formal statistical testing was performed. Results: At baseline, 77.2% (565/732) of patients were receiving nonsystemic AD therapies (topical corticosteroids: 69.9%); 23.1% were receiving systemic therapies, including: dupilumab: 2.6% [n = 19]; cyclosporine: 8.1% [n = 59]; and methotrexate: 9.0% [n = 66]. The median duration of patient follow-up was 8.7 months. Physician-reported outcomes (change in mean ± SD) improved from TS to LO: EASI (dupilumab [n = 31], cyclosporine [n = 80], methotrexate [n = 69]: -13.8 ± 15.4, -4.6 ± 12.2, -6.2 ± 12.8) and % BSA (-18.4 ± 25.0, -13.6 ± 22.3, -14.6 ± 18.8). Change in patient/caregiver-reported outcomes were: POEM (-7.6 ± 8.5, -2.1 ± 11.1, -4.3 ± 11.2), CDLQI (-7.2 ± 7.8, 0.3 ± 5.5, -2.9 ± 6.8) and PP-NRS (-2.6 ± 2.3, 0.7 ± 3.0, 0.6 ± 2.5). Time-to-discontinuation (mean ± SD, months) was: dupilumab (8.6 ± 6.4); cyclosporine (5.2 ± 4.1); methotrexate (7.0 ± 4.7). Conclusions: The most common treatment at baseline for children aged <12 years with moderate-to-severe AD was topical corticosteroids. Dupilumab was associated with greater improvements in clinical assessments/patient-reported outcomes vs other systemic therapies.

34358 Long-term efficacy of dupilumab in adults with moderate-to-severe atopic dermatitis (AD): Results from an open-label extension (OLE) trial up to 4 years

Background: AD is a chronic systemic inflammatory disease often requiring long-term management. Here, we present long-term efficacy of dupilumab up to 4 years in adult patients with moderate-to-severe AD. Methods: The OLE (NCT01949311), with an initial duration of 3 years, enrolled adults with moderate-to-severe AD who participated in a dupilumab parent study. Protocol amendments extended the maximum treatment duration to 5 years. Following protocol amendments in 2017 and 2018, 114 and 272 patients re-entered the trial; 103 and 207 patients had a treatment interruption of >8 weeks between Weeks 148 and 164. Patients were treated with 300 mg dupilumab weekly. In 2019, patients transitioned to 300 mg every 2 weeks to align with approved dosage. Concomitant topical anti-inflammatory treatments were permitted. Data shown are for the overall study population (N = 2677). Results: 2207/1065/557/362/352 patients completed up to 52/100/148/172/204 weeks of treatment. 240 patients had treatment duration >204 weeks. Most withdrawals (59.5%) were due to dupilumab approval; 8.4%/4.3% withdrew due to adverse events/lack of efficacy. At Week 204, 95%/91%/76% of patients achieved 50%/75%/90% reductions in Eczema Area and Severity Index from parent study baseline (PSBL). 78.7%/70.8% of patients achieved ≥3/≥4-point reduction in the Peak Pruritus Numerical Rating Scale score from PSBL at Week 204. Treatment-emergent adverse events were reported in 2273 (84.9%) patients, with 99 (3.7%) permanently discontinuing treatment. Conclusions: Long-term dupilumab treatment showed sustained efficacy substantiated by improvement of AD signs and symptoms in patients with moderate-to-severe AD up to 204 weeks. Safety data were consistent with prior studies.

298 Sleep improvement with dupilumab in adults with moderate-to-severe atopic dermatitis: Results of the DUPISTAD study

Background: Patients with atopic dermatitis (AD) often report sleep disturbance due to nighttime itching and scratching, leading to daytime fatigue and impaired quality of life. The DUPISTAD phase 4 randomized double-blinded placebo-controlled study (NCT04033367) evaluated the impact of dupilumab treatment on sleep in adults with moderate-to-severe AD. Methods: Adult patients with an Eczema Area and Severity Index (EASI) ≥ 12, Peak Pruritus Numerical Rating Scale (NRS) ≥ 3 and sleep NRS ≤ 5 were randomized 2:1 to dupilumab 300 mg every 2 weeks (q2w) or placebo for 12 weeks (W12); both treatment groups were permitted to apply concomitant topical corticosteroids as needed.

Chronic Pruritus in Atopic Patients Treated with Dupilumab: Real Life Response and Related Parameters in 354 Patients.

Chronic pruritus is a major symptom of atopic dermatitis (AD). Its etiopathogenesis is complex, and an understanding of the driving factors of its pathogenesis allows for the development of new molecule-targeted therapies. Dupilumab, targeting and blocking interleukin-4 (IL-4) and interleukin-13 (IL-13) molecules, has shown great efficacy in treating AD symptoms such chronic itching. We performed a retrospective observational study to evaluate possible chronic-itch-related characteristics and parameters in 356 AD patients who received dupilumab. The objective of the study was to evaluate the factors associated with the level of pruritus reported by patients at each of the 1575 detections in the form of the peak pruritus numerical rating scale (NRSpp) and sleep disturbance numerical rating scale (NRSsd). We focused on: the eczema area and severity index (EASI), dermatology life quality index (DLQI), patient-oriented eczema measure (POEMS), eosinophilia, L-lactate dehydrogenase (LDH), immunoglobulin E (IgE) and the time from the start of dupilumab therapy. NRSpp fell from 8.6 (sd 1.7) at baseline to 1.7 (sd 2.3) at 36 months and NRSsd from 7 (sd 3) to 0. Regarding the parameters that correlate with NRSpp, all the parameters analysed were significantly correlated except for eosinophils (p = 0.136). In the multivariate analysis, both considering and not considering treatment duration, the parameters were correlated (p < 0.001); EASI, DLQI, POEM, and LDH significantly correlated with NRSpp (p < 0.001 for each, except for LDH p = 0.003); while IgE tot lost significance (p = 0.337). Similar results were obtained for the parameters correlating with NRSsd. Our results confirm the efficacy of dupilumab on pruritus. The use of questionnaires such as DLQI and POEM is advisable in clinical practice and is adequate for assessing the impact of itching on AD. The low correlation of IgE and eosinophils, the ambiguity of LDH levels with the level of pruritus, and a poor clinical validity and unclear correlation with disease severity suggest a progressive abandonment of monitoring of these values.

Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a randomised, double-blind, multicentre phase 3 trial

Phase 3 trials have assessed efficacy of abrocitinib versus placebo in moderate-to-severe atopic dermatitis, a common immunoinflammatory skin disease. This study assessed the efficacy and safety of abrocitinib versus dupilumab. This randomised, double-blind, double-dummy, active-controlled, parallel-treatment, phase 3 trial enrolled adults with moderate-to-severe atopic dermatitis who requir=ed systemic therapy or had inadequate response to topical medications. Participants were enrolled from 151 sites, located in Australia, Bulgaria, Canada, Chile, Finland, Germany, Hungary, Italy, Latvia, Poland, Slovakia, South Korea, Spain, Taiwan, and the USA. These participants were then randomly assigned (1:1) with block randomisation to receive oral abrocitinib (200 mg per day) or subcutaneous dupilumab (300 mg every 2 weeks) for 26 weeks. Participants were required to apply topical corticosteroids (medium or low potency), topical calcineurin inhibitors, or a topical phosphodiesterase 4 inhibitor to active lesion areas. Primary endpoints were response based on achieving a 4 point or higher improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 2 and a 90% or better improvement in Eczema Area and Severity Index (EASI-90) at week 4. Family-wise type 1 error was controlled via a sequential multiple-testing procedure (two sided, α=0·05). Randomly assigned participants who received at least one dose of study intervention were included in the efficacy and safety analysis sets. This trial was completed on July 13, 2021 (NCT04345367). Between June 11, 2020, and Dec 16, 2020, 940 patients were screened and 727 were enrolled (362 in the abrocitinib group and 365 in the dupilumab group). Compared with dupilumab, a larger proportion of patients treated with abrocitinib reached the primary outcomes, PP-NRS4 at week 2 (172 [48%] of 357, 95% CI 43·0-53·4 vs 93 [26%] of 364, 21·1-30·0; difference 22·6%, 15·8-29·5; p<0·0001), and EASI-90 at week 4 (101 [29%] of 354, 23·8-33·2 vs 53 [15%] of 364, 10·9-18·2; difference 14·1%, 8·2-20·0; p<0·0001). Treatment-emergent adverse events were reported by 268 (74%) of 362 patients treated with abrocitinib and by 239 (65%) of 365 patients treated with dupilumab. Two non-treatment-related deaths occurred in the abrocitinib group. Abrocitinib 200 mg per day was more efficacious than dupilumab in adults with moderate-to-severe atopic dermatitis on background topical therapy in inducing early reductions of itch and atopic dermatitis disease signs. Both treatments were well tolerated over 26 weeks. Pfizer.

Atopic keratoconjunctivitis alleviated with dupilumab

Dupilumab (Dupixent) is a first-in-class biological that was initially approved for the treatment of atopic dermatitis (AD), but has since had its approval expanded for the treatment of other atopic disorders, including asthma and uncontrolled chronic rhinosinusitis with nasal polyps. Dupilumab is a fully human monoclonal antibody that inhibits both interleukin-4 (IL-4) and IL-13, consequently intercepting the Th2 mediated inflammatory pathway that directs major atopic etiologies. Dupilumab has demonstrated statistically and clinically substantial results in mitigating symptoms of AD as demonstrated in SCORing AD (SCORAD), Peak Pruritus Numerical Rating Scale, and Quality of Life Index for AD (QoLIAD) indices.

Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND)

Abrocitinib efficacy by prior dupilumab response status in patients with moderate-to-severe atopic dermatitis has not previously been assessed in phase 3 studies. Examine efficacy and safety of abrocitinib among patients who received prior dupilumab. Patients with moderate-to-severe atopic dermatitis received abrocitinib 200mg or 100mg once daily in JADE EXTEND (phase 3 extension) after dupilumab in double-blind, placebo-controlled phase 3 JADE COMPARE. Among prior dupilumab responders, ≥75% improvement in Eczema Area and Severity Index was achieved in 93.5% and 90.2% of patients who received 12weeks of abrocitinib 200mg and 100mg, respectively; ≥4-point improvement in Peak Pruritus Numerical Rating Scale was achieved in 89.7% and 81.6%, respectively. Among prior dupilumab nonresponders, ≥75% improvement inEczema Area and Severity Index was achieved with abrocitinib 200mg and 100mg in 80.0% and 67.7% and ≥4-point improvement inPeak Pruritus Numerical Rating Scale in 77.3% and 37.8%, respectively. Most common adverse events among abrocitinib-treated patients were nasopharyngitis, nausea, acne, and headache. Conjunctivitis occurred less frequently with abrocitinib in comparison to prior dupilumab. Short-term, 12-week analysis; no placebo arm. Efficacy and safety profile of abrocitinib in JADE EXTEND supports the role of abrocitinib as a treatment for patients with moderate-to-severe atopic dermatitis, regardless of prior dupilumab response status.

Dupilumab treatment in adult patients is efficacious regardless of age at atopic dermatitis onset

Introduction (contexte de la recherche) Adult-onset AD accounts for ∼25% of adult patients (pts) and is described to have clinical characteristics distinct from childhood-onset AD. To report dupilumab efficacy in adults with moderate-to-severe AD, stratified by age of AD onset. In LIBERTY AD SOLO 1 and 2 ( NCT02277743 , NCT02277769 ), 2 identically designed phase 3 trials, 1379 pts aged ≥ 18 years with moderate-to-severe AD received subcutaneous dupilumab 300 mg every 2 weeks (q2w) or weekly (qw), or placebo (PBO) qw, for 16 weeks. Least squares (LS) mean percent change (standard deviation [SD]) from baseline (BL) in Eczema Area and Severity Index (EASI) and weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) scores in pts who received dupilumab q2w ( n = 457) vs. PBO ( n = 460) by age of AD onset are reported. Age of AD onset was self-reported; P values compared to the corresponding PBO are nominal: ** P < 0.01, *** P < 0.001, **** P < 0.0001. In the dupilumab/PBO groups, mean age and duration of AD were 38.3/38.4 years and 27.9/28.8 years, respectively. BL distribution of age of AD onset ( n [%]) in the < 5 years, 5–9 years, 10–19 years and ≥ 20 years age groups was 239 (52.3)/249 (54.1), 61 (13.3)/67 (14.6), 63 (13.8)/60 (13.0) and 91 (19.9)/79 (17.2), respectively, for the dupilumab/PBO arms. Disease severity measured by mean EASI and mean weekly PP-NRS showed high consistency at baseline across age of onset groups. At week 16, statistically significant improvements in EASI and PP-NRS scores were observed in the dupilumab vs. PBO groups in all age of onset groups: EASI, −69.7**** vs. −32.0, −65.8*** vs. −37.5, −70.0**** vs. −35.0, −70.4**** vs. −38.7; PP-NRS, −48.3**** vs. −18.6, −46.0** vs. −25.3, −39.3** vs. −18.3, −46.0**** vs. −19.1. Dupilumab was generally well tolerated, with an acceptable safety profile. Dupilumab is efficacious in adults regardless of age at AD onset. Approximately 1 in 5 adults reported onset of AD in adulthood. Total EASI scores were comparable by age of onset, and dupilumab had similar efficacy on EASI and PP-NRS scores during 16 weeks of treatment.

Dupilumab provides long-term efficacy for up to 4 years in an open-label extension study of adults with moderate-to-severe atopic dermatitis

Introduction (contexte de la recherche) Patients with moderate-to-severe atopic dermatitis (AD) often have an inadequate response to topical therapies. We present long-term efficacy of dupilumab up to 4 years in adults with moderate-to-severe AD from an open-label extension (OLE) study (LIBERTY AD OLE, NCT01949311 ). Adults (≥ 18 years) with moderate-to-severe AD from any dupilumab parent study (phase 1–3) were enrolled into the long-term, multicenter, OLE with an initial duration of 3 years (extended up to 5 years in certain countries). Initially, patients received 300 mg dupilumab weekly; in 2019, patients transitioned to dupilumab 300 mg every 2 weeks (approved dose). Concomitant treatments for AD, including topical corticosteroid and topical calcineurin inhibitors, were permitted. Data shown are for the overall study population. Of 2677 patients enrolled in the OLE, 2207 completed treatment up to week 52, 1065 up to week 100, 557 up to week 148, 362 up to week 172, and 352 up to week 204. 240 patients had treatment duration > 204 weeks. Most withdrawals (810 [59.5%]) during the OLE study period were due to dupilumab approval and commercialization in the patients’ country of enrolment; 114 (8.4%) withdrew due to adverse events (AEs) and 58 (4.3%) due to lack of efficacy. At week 204, 91% of patients achieved a 75% reduction in Eczema Area and Severity Index (EASI) from parent study baseline (PSBL), 76% of patients achieved a 90% reduction in EASI from PSBL, and 70.8% of patients achieved a ≥ 4-point reduction in the Peak Pruritus Numerical Rating Scale score from PSBL. A total of 2273 (84.9%) patients reported treatment-emergent AEs, and 99 (3.7%) patients discontinued treatment permanently due to reported AEs. Dupilumab had an acceptable safety profile. Long-term dupilumab treatment showed sustained efficacy with durable and progressive improvements in AD signs and symptoms in adults with moderate-to-severe AD up to 204 weeks. Dupilumab was generally well tolerated with an acceptable safety profile.

Dupilumab Demonstrates Rapid Onset of Response Across Three Type 2 Inflammatory Diseases

Type 2 inflammatory diseases often coexist in patients. Dupilumab targets type 2 inflammation and has demonstrated treatment benefits in patients with atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP) with an acceptable safety profile. This post hoc analysis across five phase 3 studies in patients with moderate to severe AD or asthma, or severe CRSwNP, evaluated time of onset and duration of the treatment response. Patients received subcutaneous dupilumab 200/300 mg or placebo. Assessments included the Eczema Area and Severity Index, Peak Pruritus Numerical Rating Scale, and Dermatology Life Quality Index in AD; pre-bronchodilator FEV1, daily morning peak expiratory flow, and symptom scores in asthma; and University of Pennsylvania Smell Identification Test, daily nasal congestion, and loss of smell scores in CRSwNP. At week 2 after the initiation of dupilumab versus placebo, 67.8% versus 36.5% of AD patients achieved a clinically meaningful benefit (Eczema Area and Severity Index: 50% or greater improvement; Peak Pruritus Numerical Rating Scale: 3 point or greater improvement; or Dermatology Life Quality Index: 4 point or greater improvement) (P < .001). Moreover, 61.6% versus 39.9% of asthma patients achieved improvements in pre-bronchodilator FEV1 of 100 mL or greater and 48.8% versus 26.3% achieved 200 mL or greater improvement (both P < .001); 33.2% versus 5.6% of CRSwNP patients regained a sense of smell (P < .001). Treatment effects further improved or were sustained to the end of treatment. Clinically meaningful responses were achieved rapidly after the first dupilumab dose in AD, asthma, or CRSwNP and were sustained throughout treatment (see Video in this article's Online Repository at www.jaci-inpractice.org).

A 52\xa0weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety.

Anti-Interleukin Biologics for the treatment of the Atopic March Diseases

The atopic march refers to the natural history of allergic disorders as they develop from infancy to childhood. Classically, the atopic march begins with atopic dermatitis (AD), followed by food allergy, advancing to asthma, allergic rhinitis (AR), and finally to the fifth member eosinophilic esophagitis. The pathogenesis of the atopic march is complex, and involves genetic, immunological, and environmental factors. T helper type 2 (Th2) lymphocytes, and epithelial cells play a key role in the pathogenesis of the diseases in the atopic march. Th2 cells secrete cytokines, such as interleukin-5 (IL-5), IL-4, and IL-13, whereas, epithelial cell injury release alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Th2 cells and alarmin cytokines play an important role in the development of eczematous skin lesions, airway inflammation and remodeling, and oesophageal mucosal inflammation. Treatment of eosinophilic asthma and associated comorbid disorders is challenging, and requires a precision targeted approach with biologics. Dupilumab is a fully humanized IgG4 monoclonal antibody to the IL-4Rα, which mediates signaling to both IL-4 and IL-13, and blocks their immunopathological effects. Dupilumab is the only biologic that has been approved for the treatment of eosinophilic asthma, AD, and eosinophilic esophagitis. In patients with eosinophilic asthma treatment with dupilumab has been shown to improve asthma control, reduce exacerbations, and improve lung function. In patients with atopic dermatitis dupilumab has been demonstrated to improve the Eczema Area Severity Index (EASI) score, Investigator’s Global Assessment (IGA) response, SCORing Atopic Dermatitis (SCORAD) score, and the Peak Pruritus Numerical Rating (PNR) scale. Lebrikizumab and Tralokinumab (anti-IL-13) failed to show the expected results for the treatment of asthma, astoundingly, in several clinical trials they have been shown to significantly improvement EASI score, IGA response, SCORAD score, PNR scale, sleep architecture, and Dermatology Life Quality Index (DLQI). They have been granted First Tract Designation, and European Commission regulatory approval, respectively. Tezepelumab (anti-TSLP) is approved for the treatment of eosinophilic asthma, and has been shown to significantly reduce exacerbations, and improve asthma control, lung function, and HLQoL. However, tezepelumab did not meet the endpoints in phase II for the treatment of AD. Keywords: Atopic March; Atopic Dermatitis; Eosinophilic Asthma; Interleukin; Dupilumab; Tralokinumab

Efficacy of biologics and oral small molecules for atopic dermatitis: a systematic review and meta-analysis

Background As new targeted therapies continue to emerge for atopic dermatitis (AD), comparisons between agents are necessary to inform clinical decision-making. Objectives Assess the efficacy of biologics and oral small molecules on the clinical signs, symptoms, and quality of life in AD. Methods A systematic literature review identified phase II and III randomized clinical trials of biologics and oral small molecules in AD. Clinical benefit was assessed for three outcome measures: Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numerical Rating Scale (PP-NRS) by performing a meta-analysis using the inverse variance heterogeneity model ((IVhet)). Results The highest achievement of 75% reduction in EASI was seen with the higher dose of upadacitinib (30 mg) followed by abrocitinib and lebrikizumab, which outperformed dupilumab. Similarly, the highest proportion achieving at least a 4-point reduction of PP-NRS was seen with lebrikizumab followed by upadacitinib and abrocitinib which had greater reduction of itch than dupilumab. Abrocitinib had the greatest improvement in DLQI. Conclusions Upadacitinib, abrocitinib, and lebrikizumab had greater improvement of clinical signs, symptoms, and quality of life in AD compared to dupilumab and other targeted therapies.

Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis

Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD. To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD. The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion. Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy. Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored. This study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P < .05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P < .05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P < .01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs. This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile. ClinicalTrials.gov identifier: NCT03796676.

27603 Rapid itch relief with abrocitinib predicts later skin clearance: A post hoc analysis vs dupilumab and placebo in JADE COMPARE

Background: Rapid itch response is a desirable treatment goal for atopic dermatitis (AD). In JADE-COMPARE, more patients had clinically meaningful itch relief (≥4-point improvement in Peak Pruritus Numerical Rating Scale [PP-NRS4]) at week 2 with abrocitinib 200 mg (49.1%) vs dupilumab (26.4%) and placebo (13.8%) and with abrocitinib 100 mg (31.8%) vs placebo (all comparisons, P≤0.0002). We investigated itch response from days 2-15 and relationships between week 2 PP-NRS4 response and week 12 response of ≥90% improvement in Eczema Area and Severity Index (EASI-90).