Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated with Improved Quality of Life Outcomes in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. OBJECTIVES: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. METHODS: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. RESULTS: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. CONCLUSION: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies.

Effect of abrocitinib on skin biomarkers in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: This is the first report on the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the expression of skin biomarkers in patients with moderate-to-severe atopic dermatitis (AD). METHODS: JADE MOA (NCT03915496) was a double-blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. The primary endpoint was change from baseline in markers of inflammation (matrix metalloproteinase [MMP]-12), epidermal hyperplasia (keratin-16 [KRT16]), T-helper 2 (Th2) immune response (C-C motif chemokine ligand [CCL]17, CCL18, and CCL26), and Th22 immune response (S100 calcium binding protein A8, A9, and A12 [S100A8, S100A9, and S100A12]) in skin through 12 weeks. RESULTS: A total of 46 patients received abrocitinib 200 mg (n = 14), abrocitinib 100 mg (n = 16), or placebo (n = 16). Abrocitinib improved AD clinical signs and reduced itch. Gene expression of MMP-12, KRT16, S100A8, S100A9, and S100A12 was significantly decreased from baseline with abrocitinib 200 mg (at Weeks 2, 4, and 12) and abrocitinib 100 mg (at Weeks 4 and 12) in a dose-dependent manner. Abrocitinib 200 mg resulted in significant decreases from baseline in CCL17 expression at Week 12 and CCL18 expression at Weeks 2, 4, and 12; no significant decreases were observed for CCL26. CONCLUSIONS: Alongside improvements in clinical signs and symptoms of AD, 12 weeks of abrocitinib treatment resulted in downregulation of genes associated with inflammation, epidermal hyperplasia, and Th2 and Th22 immune responses in the skin of patients with moderate-to-severe AD.

Abrocitinib 100 mg Once Daily for Moderate-to-Severe Atopic Dermatitis: A Review of Efficacy and Safety, and Expert Opinion on Use in Clinical Practice.

Abrocitinib is a Janus kinase (JAK) 1-selective inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). Although specific dose recommendations for abrocitinib vary across regional product labels, abrocitinib 100 mg once daily is recommended as a starting and maintenance dose. This review summarizes the efficacy and safety of abrocitinib 100 mg once daily for patients with moderate-to-severe AD based on data from the pivotal phase 3 studies of the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) clinical program, JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE COMPARE (NCT03720470), JADE TEEN (NCT03796676), and JADE REGIMEN (NCT03627767). Preliminary long-term efficacy and safety data are also summarized from the long-term extension study JADE EXTEND (NCT03422822). Expert opinion on use of abrocitinib 100 mg once daily in clinical practice is provided. In addition to efficacy, the decision to use abrocitinib for the treatment of AD should allow for individual patient factors such as age, comorbidities, previous therapy, quality of life, and treatment tolerability, and involve shared decision-making between the patient and clinician.

Predictors of nonresponse to dupilumab in patients with atopic dermatitis: A machine learning analysis.

BACKGROUND: Many patients with atopic dermatitis (AD) have a suboptimal response to systemic therapy. OBJECTIVE: This study assessed predictors of nonresponse to dupilumab in patients with AD. METHODS: Data (April 2017 through June 2019) for patients aged 12 years and above with AD (International Classification of Diseases-9/10-Clinical Modification: 691.8/L20.x) who initiated dupilumab on or after April 1, 2017 (index date) were collected from an electronic health record and insurance claims database. Nonresponse indicators (dupilumab discontinuation, addition of another systemic therapy or phototherapy, addition of a high-potency topical corticosteroid, AD-related hospital visit, AD-related emergency department visit, incident skin infection) were predicted from available demographic and clinical variables using machine learning. RESULTS: Among 419 patients (mean age: 45 years), 145 (35%) experienced at least 1 indicator of nonresponse in the 6-month postindex period. In patients with at least 1 indicator, the most common was dupilumab discontinuation (47% [68/145]). Of note, this analysis could not capture nonmedical reasons for dupilumab discontinuation (eg, cost, access). The most common predictors of nonresponse were a claim for ibuprofen (in 69% of patients with a nonresponse indicator) and a Quan-Charlson Comorbidity Index value of 3 to 4 (59%). CONCLUSION: Systemic dupilumab therapy for AD can be associated with a relatively high prevalence of nonresponse indicators. Factors associated with these indicators-that is, predictors of nonresponse-may be used to optimize disease management.