Abrocitinib efficacy and safety in moderate-to-severe atopic dermatitis by race, ethnicity, and Fitzpatrick skin type.

BACKGROUND: Response to abrocitinib treatment for moderate-to-severe atopic dermatitis (AD) has not been evaluated across racial and ethnic subpopulations. OBJECTIVE: To assess the efficacy and safety of abrocitinib on the basis of patient race, ethnicity, and Fitzpatrick skin type (FST). METHODS: Data were pooled post hoc from patients treated with abrocitinib 200 mg, 100 mg, or placebo in 3 monotherapy trials (NCT02780167, NCT03349060, and NCT03575871). Race and ethnicity were self-reported; FST was determined by study investigators. Evaluations through Week 12 include the following: (1) Investigator's Global Assessment of clear or almost-clear skin; (2) greater than or equal to 75% improvement in Eczema Area and Severity Index or SCORing AD; (3) a greater-than-or-equal-to 4-point improvement in Peak Pruritus Numerical Rating Scale score; (4) least squares mean changes in Dermatology Life Quality Index and Patient-Oriented Eczema Measure scores; and (5) treatment-emergent adverse events. RESULTS: The sample comprised 628 White, 204 Asian, and 83 Black patients; 37 were Hispanic or Latino; 624 had FST I to III and 320 had FST IV to VI. Treatment with either abrocitinib dose was associated with greater proportions of patients achieving Investigator's Global Assessment of clear or almost-clear skin, ≥ 75% improvement in Eczema Area and Severity Index, ≥ 75% improvement in SCORing AD, and a ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale, or greater score changes from baseline in Dermatology Life Quality Index and Patient-Oriented Eczema Measure vs placebo regardless of race, ethnicity, or FST. Dose-response was most prominent in White patients. In Black patients, the effects of the 2 doses were similar. Treatment-emergent adverse events were more common in White and Black than in Asian patients. CONCLUSION: Abrocitinib was more efficacious than placebo across the racial and ethnic groups and ranges of phototypes analyzed. Studies with increased representation of populations of color are warranted to elucidate potential variations in response across diverse populations. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02780167 (phase 2b), NCT03349060 (phase 3 MONO-1), and NCT03575871 (phase 3 MONO-2).

Early Itch Response with Abrocitinib Is Associated with Later Efficacy Outcomes in Patients with Moderate-to-Severe Atopic Dermatitis: Subgroup Analysis of the Randomized Phase III JADE COMPARE Trial.

BACKGROUND: Abrocitinib, an oral Janus kinase 1 inhibitor, provided significant itch relief by week 2 in patients with moderate-to-severe atopic dermatitis (AD) in the phase III JADE COMPARE trial. OBJECTIVES: This post-hoc analysis of JADE COMPARE aimed to further characterize itch response and determined whether early itch relief could predict subsequent improvements in AD severity. METHODS: JADE COMPARE was a randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (aged ≥ 18 years) with moderate-to-severe AD were randomly assigned to receive oral abrocitinib 200 mg or 100 mg once daily, subcutaneous dupilumab 300 mg every other week (after a 600-mg loading dose), or placebo, plus medicated topical therapy for 16 weeks. Assessments were ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) from days 2 to 15, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA) response, and Dermatology Life Quality Index (DLQI) scores at week 12. Association between week 2 PP-NRS4 and efficacy at week 12 was evaluated by chi-squared tests. The predictive value of early response for later efficacy was assessed by area under the receiver operating characteristic curve. RESULTS: As early as day 4 after treatment, a significantly greater proportion of patients achieved PP-NRS4 response with abrocitinib 200 mg (18.6%) versus dupilumab (5.6%; p < 0.001) and placebo (6.0%; p < 0.003). A similar trend was observed with abrocitinib at the 100-mg dose, with significantly greater PP-NRS4 response rates versus placebo as early as day 9. With both doses of abrocitinib, week 12 IGA 0/1, EASI-75, EASI-90, and DLQI 0/1 response rates were greater in week 2 PP-NRS4 responders than nonresponders; no differences were observed between week 2 PP-NRS4 responders and nonresponders in the dupilumab and placebo groups. Early improvement in PP-NRS at week 2 was associated with skin clearance at week 12 in abrocitinib-treated patients. CONCLUSIONS: Abrocitinib resulted in rapid relief from itch in patients with moderate-to-severe AD, with significant improvement in itch as early as day 4 after treatment with abrocitinib 200 mg compared with dupilumab and placebo. Abrocitinib-induced itch relief by week 2 was associated with subsequent improvements at week 12. [Video abstract available.] TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03720470. Early itch response with abrocitinib is associated with later efficacy outcomes in patients withmoderate-to-severe atopic dermatitis: subgroup analysis of the randomized phase III JADE COMPARE trial (MP4 335,375kb).

Atopic dermatitis (AD), also called atopic eczema, is a skin disease that affects people throughout their lives. About 10% of adults worldwide have AD. Itch is the most bothersome symptom reported by people with AD and scratching this itch can damage the skin, resulting in painful sores. It is unknown if relief from itch can influence other symptoms of AD. We analyzed data from the JADE COMPARE study, which included 837 people who received treatment with abrocitinib, dupilumab or placebo. We studied how fast itch relief occurred after people received these treatments. We also wanted to study if rapid itch relief was associated with improvement in other signs of AD later on with continued treatment. We found that as early as 4 days after treatment, abrocitinib 200 mg provided significant relief from itch compared with dupilumab or placebo. People who had rapid itch relief within 2 weeks of treatment with abrocitinib were more likely to have clear or almost clear skin and improved quality of life after 12 weeks of continued treatment with abrocitinib. Rapid itch relief did not appear to increase the likelihood of clear skin at week 12 in people who received dupilumab. Larger studies are needed to confirm this result. This study provides important evidence for physicians as they analyze itch relief and determine treatment options for people with AD.

COVID-19 in Spain: age, Interleukin-6, C Reactive Protein and lymphocytes as key clues from a multicentre retrospective study

BackgroundSARS-CoV-2 infection has widely spread to the hugest public health challenge to date, COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. Spanish case-fatality rate is 11.94%, far higher to those reported in Asia or by other European countries. A multicenter retrospective study was performed of demographic, clinical, laboratory and immunological features of 574 Spanish COVID-19 hospitalized patients and their outcomes. The use of use of renin-angiotensin system blockers was also analyzed as a risk factor. ResultsIn this study, 27.7% of cases presented a mild curse, 42% a moderate one and for 30.3% of cases, the course was severe. Ages ranged from 18 to 98 (average 63.2). Fifty eight percent (58.9%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19 and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of renin-angiotensin system blockers was associated with moderate or mild disease courses. ConclusionsAge and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for immune system effectors severity-related hampering. Adaptive immunity would go exhausted and a huge ineffective and almost deleterious innate response would account for COVID-19 severity. Renin-angiotensin system blockers treatment in hypertensive patients has a protective effect as regarding COVID-19 severity.