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BACKGROUND: Abrocitinib efficacy by prior dupilumab response status in patients with moderate-to-severe atopic dermatitis (AD) has not previously been assessed in phase 3 studies.OBJECTIVE: Examine efficacy and safety of abrocitinib among patients who received prior dupilumab.METHODS: Patients with moderate-to-severe AD received abrocitinib 200 mg or 100 mg once-daily in JADE EXTEND (phase 3 extension) after dupilumab in double-blind, placebo-controlled phase 3 JADE COMPARE.RESULTS: Among prior dupilumab responders, ≥75% improvement in Eczema Area and Severity Index (EASI-75) was achieved in 93.5% and 90.2% of patients who received 12 weeks of abrocitinib 200 mg and 100 mg, respectively; ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) was achieved in 89.7% and 81.6%, respectively. Among prior dupilumab nonresponders, EASI-75 was achieved with abrocitinib 200 mg and 100 mg in 80.0% and 67.7% and PP-NRS4 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.LIMITATIONS: Short-term, 12-week analysis; no placebo arm.CONCLUSION: Efficacy and safety profile of abrocitinib in JADE EXTEND supports the role of abrocitinib as a treatment for patients with moderate-to-severe AD, regardless of prior dupilumab response status.

Supplemental digital content is available in the text., Background Itch, the most bothersome symptom in atopic dermatitis, is largely mediated by pruritogenic cytokines via Janus kinase 1 signaling in cutaneous sensory neurons. Objectives The aims of the study were to assess the magnitude and rapidity of itch relief with the Janus kinase 1 selective inhibitor abrocitinib and to evaluate the extent to which the effect of abrocitinib on itch relief is independent of overall disease improvement. Methods Pooled data from 1 phase 2b (NCT02780167) and 2 phase 3 (NCT03349060, NCT03575871) double-blind, randomized, placebo-controlled monotherapy trials in moderate to severe atopic dermatitis (N = 942) were analyzed. Results Abrocitinib produced significant and clinically meaningful itch relief versus placebo from week 2 through week 12 (end of treatment) that was associated with marked sleep and quality-of-life improvements. Mean percentage reductions in itch scores 24 hours after the first dose were greater for both abrocitinib doses (200 and 100 mg) versus placebo. Itch improvement occurred regardless of baseline itch severity, sex, race, body mass index, or Investigator Global Assessment response, suggesting that abrocitinib-associated itch relief is at least partially independent of overall disease improvement. Conclusions Abrocitinib showed a rapid and profound antipruritic effect, partially independent of improvement in overall disease.

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.

Abrocitinib, a once-daily, oral Janus kinase 1 selective inhibitor, was shown to be an effective treatment for moderate-to-severe atopic dermatitis in phase 2 b/3 monotherapy trials. These analyses included data for Investigator’s Global Assessment responder (clear [0] or almost clear [1] with ≥2-grade improvement) and nonresponder patients with moderate-to-severe atopic dermatitis who received abrocitinib (200 mg or 100 mg) or placebo in three abrocitinib monotherapy trials (phase 2 b, NCT02780167; two phase 3, NCT03349060/JADE MONO-1 and NCT03575871/JADE MONO-2). Outcomes measuring skin clearance, itch, and quality of life were evaluated. Both nonresponders (n = 548) and responders (n = 260) treated with abrocitinib had rapid and clinically meaningful improvement in skin clearance, itch, and quality of life compared with placebo. Patients with moderate-to-severe atopic dermatitis treated with abrocitinib who did not achieve an Investigator’s Global Assessment 0/1 response at week 12 still experienced rapid, clinically meaningful improvements across several other validated measures of efficacy and quality of life. NCT02780167, NCT03349060, NCT03575871

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.

Efforts to increase patient comfort by minimizing pain and anxiety have been shown to improve clinical outcomes, reduce pain thresholds, decrease analgesic requirements and complication risk, strengthen the physician-patient relationship, and increase overall patient satisfaction. Patients also have a strong preference for patient-centered communication and educational discussion with physicians. In recent years, the increasing emphasis on patient experience scores as a metric for quality care has had significant implications for physician practice and has reinforced attempts to provide more patient-centered care. Though different pharmacologic agents and techniques have been extensively reviewed in the dermatologic literature, there have been few studies of non-pharmacologic strategies for improving patient-centered care. This evidence-based review describes alternative techniques that have been suggested for use in dermatologic surgery. Mechanoanesthesia, cold therapy, verbal and audiovisual distraction, music, optimal needle insertion methods, hypnosis and guided-imagery, perioperative communication, and educational strategies have been reported to improve the patient experience in dermatologic surgery. These interventions are often cost-effective and easy to implement, avoid medication side effects, and serve as adjunct approaches to enhance patient comfort. This review examines the corresponding evidence for these nonpharmacologic strategies to provide a clinical resource for the dermatologic surgeon seeking to optimize the patient experience.

The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC (n=150) enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations of both, HPV seropositivity and HPV DNA positivity with subsequent SCC. The five year cumulative incidence of subsequent SCC was 72%. Seropositivity to cutaneous HPV was not associated with the risk of subsequent SCC (HR = 0.83, 95% CI = 0.41–1.67). Any beta HPV infection in EB was associated with reduced risk (HR = 0.30, 95% CI = 0.11–0.78) of subsequent SCC among cases who were positive for beta HPV DNA in tumor tissue. Infection with beta HPV type 2 (HR = 0.32, 95% CI = 0.12–0.86) in EB was associated with reduced risk of subsequent SCC among HPV DNA positive SCCs. In conclusion, beta HPV infection was inversely associated with the risk of subsequent SCC.

PurposeDermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL.MethodsA comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments.ResultsThirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome 14 (HFS-14)).ConclusionsWhile there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

The majority of toxic epidermal necrolysis (TEN) cases are provoked by "high risk" medications (e.g. allopurinol, aromatic anticonvulsants, nevirapine, oxicam non-steroidal anti-inflammatory agents, and sulfonamides). TEN usually occurs 1 to 8 weeks after initial administration of the offending agent, but re-administration can evoke TEN within hours to days. Hydroxychloroquine has rarely been associated with TEN, with one case proving fatal. Herein, we report a case of hydroxychloroquine-induced fatal TEN complicated by angioinvasive Rhizopus. To our knowledge, this is the first case report of angioinvasive Rhizopus in a TEN patient. Initial misidentification of the offending agent causing TEN also serves as an important teaching point worth highlighting.

We investigated gap formation and gap replace- ment in the Knysna Forest. Most (70 %) trees died standing, most gaps were small (median gap size of 35 m2; Gap diam- eter/Canopy height ratio of 0.24) and were formed by a single dead individual. No large differences were found among the more common species in terms of the size of gaps they created when they died or in the size of gaps they colonised. This is probably because the more common species are shade tolerant and they established before the gaps were formed. Regenerat- ing individuals were almost never found on root mounds in pits or on logs. There were no indications of specific replacement pat- terns. In contrast, random replacement appears to be the domi- nant pattern for the more common species. Overall succes- sional patterns suggest that the forest is relatively stable. We conclude that the gaps/non-gaps paradigm is not as useful as a lottery paradigm for explaining gap dynamics in the Knysna Forest.