Abrocitinib effect on patient-reported outcomes in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study.

BACKGROUND: Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at Weeks 12 and 16 in phase 3 studies, with a manageable safety profile. Patient-reported outcomes with long-term abrocitinib treatment were not reported. OBJECTIVE: To evaluate patient-reported outcomes with long-term abrocitinib treatment in patients with moderate-to-severe AD. METHODS: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis includes patients from the phase 3 trials JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) who completed the full treatment period of placebo or abrocitinib (200 or 100 mg once daily) and subsequently entered JADE EXTEND and were randomised to receive once-daily abrocitinib 200 or 100 mg. Patient-reported endpoints to Week 48 included the proportion of patients who achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (no effect of AD on quality of life [QoL]) and a ≥4-point improvement in Patient-Oriented Eczema Measure (POEM) score (clinically meaningful improvement). Data cut-off: April 22, 2020. RESULTS: Baseline DLQI mean scores were 15.4 and 15.3 in the abrocitinib 200- and 100-mg groups, respectively, which corresponded to a 'very large effect' on QoL; at Week 48, mean DLQI scores were lower with abrocitinib 200 mg (4.6; 'small effect' on QoL) and abrocitinib 100 mg (5.9; 'moderate effect' on QoL). Baseline POEM mean scores were 20.4 and 20.5 in the abrocitinib 200- and 100-mg groups, respectively; at Week 48, mean POEM scores were 8.2 and 11.0. Week 48 patient-reported responses with abrocitinib 200 mg and abrocitinib 100 mg were 44% and 34% for DLQI 0/1, and 90% and 77% for a ≥4-point reduction in POEM score. CONCLUSION: In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful improvement in patient-reported symptoms of AD, including QoL.

Patient perspectives of atopic dermatitis: comparative analysis of terminology in social media and scientific literature, identified by a systematic literature review.

Atopic dermatitis (AD) is a chronic skin disease that significantly impacts patient quality of life (QoL). It is unknown whether patients and physicians have the same interpretation of AD burden. Unmet needs and AD disease burden were evaluated by comparing terminology used in social media with terminology used in scientific literature. AD terminology in social media was identified using the NetBase platform, and natural language processing was performed. Topics and words driving negative sentiment were evaluated overall and in relation to specific symptoms. The systematic review of scientific literature identified publications that included AD and QoL terms was identified from PubMed. Term analysis of titles and abstracts was conducted via natural language processing. The occurrence of topics and co-occurrence of words associated with QoL terms were evaluated. More than 3 million social media mentions (2018-2020) and 1519 scientific publications (2000-2020) were evaluated. There were more negative than positive social media mentions, and flare and pain were common symptoms driving negative sentiment. Face and hands were major drivers of negative sentiment in relation to AD symptoms in social media. Sleep and pain were often mentioned together. In scientific literature, pruritus and depression were the most frequently occurring symptoms. Similarly, pruritus was the most common AD symptom co-occurring with QoL terms in the assessed scientific literature. Social media analyses provide a unique view into the patient experience of AD. Symptoms driving negative sentiment in social media appear to be discordantly represented in scientific literature. Incorporating patient perspectives may improve disease understanding and management.

High threshold efficacy responses in moderate-to-severe atopic dermatitis are associated with additional quality of life benefits: pooled analyses of abrocitinib monotherapy studies in adults and adolescents.

BACKGROUND: Once-daily abrocitinib treatment provided meaningful improvements in signs and symptoms of moderate-to-severe atopic dermatitis (AD) in randomized controlled studies. OBJECTIVE: To evaluate proportions of patients with responses meeting higher threshold efficacy responses than commonly used efficacy end points and to determine if these responses were associated with quality-of-life (QoL) benefits. METHODS: Data from a phase 2b (NCT02780167) and two phase 3 studies (NCT03349060/JADE MONO-1; NCT03575871/JADE MONO-2) in adult and adolescent patients (N = 942) with moderate-to-severe AD receiving once-daily abrocitinib 200 mg, abrocitinib 100 mg or placebo were pooled. Commonly used (Eczema Area and Severity Index [EASI]-75 and ≥4-point improvement in Pruritus Numerical Rating Scale [PP-NRS4]) and higher threshold efficacy end points (EASI-90 to

Impact of oral abrocitinib on signs, symptoms and quality of life among adolescents with moderate-to-severe atopic dermatitis: an analysis of patient-reported outcomes.

BACKGROUND: A significant improvement in clinical signs was demonstrated with abrocitinib relative to placebo in adolescents with moderate-to-severe atopic dermatitis (AD) in three phase 3, randomized, double-blinded, placebo-controlled studies (JADE TEEN [ClinicalTrials.gov, NCT03796676], JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]). OBJECTIVES: To evaluate the impact of abrocitinib on patient-reported signs/symptoms, including sleep loss and quality of life among adolescents with moderate-to-severe AD. METHODS: JADE TEEN, JADE MONO-1 and JADE MONO-2 were conducted in the Asia-Pacific region, Europe and North America and included patients aged 12-17 years with moderate-to-severe AD and inadequate response to ≥ 4 consecutive weeks of topical medication or treatment with systemic therapy for AD. Patients were randomly assigned (1 : 1 : 1, JADE TEEN; 2 : 2 : 1, JADE MONO-1/-2) to receive once-daily oral abrocitinib (200 or 100 mg) or placebo for 12 weeks in combination with topical therapy (JADE TEEN) or as monotherapy (JADE MONO-1/-2). Data from adolescent patients in JADE MONO-1/-2 were pooled for these analyses. RESULTS: At week 12, more adolescents treated with abrocitinib (200 or 100 mg) vs. placebo achieved a ≥ 4-point improvement from baseline in the Patient-Oriented Eczema Measure in JADE TEEN (83.9% and 77.0% vs. 60.2%) and JADE MONO-1/-2 (83.0% and 69.4% vs. 43.5%) and a ≥ 6-point improvement from baseline in the Children's Dermatology Life Quality Index in JADE TEEN (73.8% and 67.5% vs. 56.5%) and JADE MONO-1/-2 (70.0% and 57.1% vs. 19.0%). Significant improvements in SCORing Atopic Dermatitis Visual Analog Scale for sleep loss scores were demonstrated with abrocitinib vs. placebo at weeks 2-12 in JADE TEEN and JADE MONO-1/-2. CONCLUSIONS: Patient-reported signs/symptoms, including reduction of sleep loss and quality of life, were substantially improved with abrocitinib monotherapy or combination therapy relative to placebo in adolescents with moderate-to-severe AD.

Patient-reported outcomes from the JADE COMPARE randomized phase 3 study of abrocitinib in adults with moderate-to-severe atopic dermatitis.

BACKGROUND: In JADE COMPARE, abrocitinib improved severity of atopic dermatitis (AD) and demonstrated rapid itch relief. OBJECTIVES: We examined clinically meaningful improvements in selected patient-reported outcomes (PROs). METHODS: JADE COMPARE was a multicentre, phase 3 randomized, double-blind, placebo-controlled trial. Adults with moderate-to-severe AD were randomized 2:2:2:1 to receive 16 weeks of oral abrocitinib 200 or 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo, with background topical therapy. PROs included Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Night Time Itch Scale (NTIS), Pruritus and Symptoms Assessment for Atopic Dermatitis, Patient Global Assessment, SCORing Atopic Dermatitis, and Hospital Anxiety and Depression Scale. RESULTS: At week 16, the proportion of patients achieving POEM scores <3 was 21.3% and 11.7% for 200 and 100 mg abrocitinib, 12.4% for dupilumab, and 4.8% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.04). Proportion achieving ≥4-point improvement from baseline in NTIS severity was 64.3% and 52.4% for 200 and 100 mg abrocitinib, 54.0% for dupilumab, and 34.4% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.007). Proportion achieving ≥4-point improvement from baseline in DLQI was 85.0% and 74.4% for 200 and 100 mg abrocitinib, 83.4% for dupilumab, and 59.7% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.005). CONCLUSION: Significant improvements in PROs were demonstrated with both abrocitinib doses vs. placebo, and abrocitinib 200 mg provided numerically greater effects compared with dupilumab in patients with moderate-to-severe AD.

Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis.

Given the lack of head-to-head studies of systemic therapies in moderate-to-severe atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision-making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short-term (12-16 weeks) efficacy (Investigator's Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient-reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti-inflammatory therapy). RCTs were analysed in fixed-effects and random-effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI-50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI-75 and EASI-90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI-50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment-emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45-2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35-2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short-term RCTs.

Prior myocardial infarction and presence of upper gastrointestinal conditions among patients with venous thromboembolism: prevalence, associated comorbidities and burden.

WHAT IS KNOWN AND OBJECTIVES: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious, life-threatening condition that often complicates treatment of individuals who are already ill and increases in risk with age. The comorbidity burden of VTE can complicate treatment; therefore, treatment should be influenced by the presence of comorbidities (Kearon 2012). The prevalence of common conditions in the VTE population is, therefore, an important subject of research. Prevalence of two common comorbid burdens, prior myocardial infarction (MI) and upper gastrointestinal (GI) conditions, was studied among survey respondents who reported DVT or PE. METHODS: Responses to the 2010 wave of the National Health and Wellness Survey (NHWS), a self-administered, internet-based questionnaire from a nationwide, demographically representative sample of adults, were evaluated. RESULTS AND DISCUSSION: Among the 814 participants reporting a history of VTE, 9·7% (n = 60) of the DVT subpopulation and 13·2% (n = 39) of the PE subpopulation also reported prior MI. In respondents with prior MI, cardiovascular, urological, and pain comorbidities were each reported as additional comorbidities by at least two thirds of respondents in both the PE and DVT subpopulations, with cardiovascular and urological conditions reported significantly (P < 0·05) more often than among respondents with no prior MI. Among the respondents reporting VTE, 48·9% (n = 302) of the subpopulation reporting DVT and 52·2% (n = 154) of those reporting PE also reported upper GI comorbidities. Cardiovascular and pain conditions in the respondents reporting upper GI comorbidities were each reported by more than three quarters of VTE patients in both the DVT and PE subpopulations and were significantly more common (P < 0·05) than among their counterparts without upper GI comorbidities. WHAT IS NEW AND CONCLUSION: The results of the NHWS indicate that VTE patients who have either of two common comorbid burdens, prior MI and concomitant upper GI conditions, also showed high levels of additional, concurrent comorbidities and generally poor health status. Clinicians must be aware of the total comorbidity profile of their patients who have experienced VTE in order to best manage them and prescribe appropriate therapy.