A Qualitative Tool to Guide in the Interpretation of the Numerical Rating Scale for Pruritus Intensity in Patients with Atopic Dermatitis.

Atopic dermatitis is a cutaneous inflammatory disease characterized by intense pruritus, which is often underestimated despite its direct impact on patients' health-related quality of life and the high burden it poses. The authors' goal was to design a qualitative tool to guide patients and healthcare professionals in their assessment and interpretation of pruritus intensity using a numerical rating scale. The draft of this tool, henceforth "guideline", was developed based on a systematic literature review and focus groups comprising patients and a scientific committee. This draft was validated with an independent group of patients and the final version was designed following their feedback. According to the results of the systematic review, pruritus impacts 6 health-related quality of life domains: sleep quality; emotional status; overall health-related quality of life; physical function; social/sexual activity; productivity, particularly affecting sleep quality and the emotional domain. Patients considered that physical function was the most strongly affected domain, followed by sleep quality and emotional well-being, establishing that a minimum pruritus intensity of 4 and 7 points impacts moderately and severely, respectively, on the different domains of patients' health- related quality of life. The guideline may help patients and healthcare professionals to interpret and assess pruritus intensity using a numerical rating scale and to understand the impact of pruritus on patients' health-related quality of life.

Pruritus in primary biliary cholangitis is under-recorded in patient medical records.

OBJECTIVE: Cholestatic pruritus in primary biliary cholangitis (PBC) reduces patients' health-related quality of life (HRQoL). Despite this, existing research suggests that pruritus is under-recorded in patients' health records. This study assessed the extent to which pruritus was recorded in medical records of patients with PBC as compared with patient-reported pruritus, and whether patients reporting mild itch were less likely to have pruritus recorded. We also evaluated clinico-demographic characteristics and HRQoL of patients with medical record-documented and patient-reported pruritus. DESIGN: This cross-sectional study used clinical information abstracted from medical records, together with patient-reported (PBC-40) data from patients with PBC in the USA enrolled in the PicnicHealth cohort. Medical record-documented pruritus was classified as 'recent' (at, or within 12 months prior to, enrolment) or 'ever' (at, or any point prior to, enrolment). Patient-reported pruritus (4-week recall) was assessed using the first PBC-40 questionnaire completed on/after enrolment; pruritus severity was classified by itch domain score (any severity: ≥1; clinically significant itch: ≥7). Patient clinico-demographic characteristics and PBC-40 domain scores were described in patients with medical record-documented and patient-reported pruritus; overlap between groups was evaluated. Descriptive statistics were reported. RESULTS: Pruritus of any severity was self-reported by 200/225 (88.9%) patients enrolled; however, only 88/225 (39.1%) had recent medical record-documented pruritus. Clinically significant pruritus was self-reported by 120/225 (53.3%) patients; of these, 64/120 (53.3%) had recent medical record-documented pruritus. Patients reporting clinically significant pruritus appeared to have higher mean scores across PBC-40 domains (indicating reduced HRQoL), versus patients with no/mild patient-reported pruritus or medical-record documented pruritus. CONCLUSION: Compared with patient-reported measures, pruritus in PBC is under-recorded in medical records and is associated with lower HRQoL. Research based only on medical records underestimates the true burden of pruritus, meaning physicians may be unaware of the extent and impact of pruritus, leading to potential undertreatment.

Janus kinase inhibitors in atopic dermatitis: an umbrella review of meta-analyses.

Background: Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent. Methods: Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE). Results: Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]). Conclusion: Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).

Lazertinib as a frontline treatment in patients with EGFR-mutated advanced non-small cell lung cancer: Long-term follow-up results from LASER201.

OBJECTIVE: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS). RESULTS: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively. CONCLUSION: This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported.

[Approved therapies and their effects on the main symptoms of urticaria : When symptom control of itchy wheals is not adequate-does updosing help?] / Zugelassene Therapien und ihre Wirkung auf die Leitsymptome der Urtikaria : Hilfreiche Therapieoptionen, wenn juckende Quaddeln nicht weichen ­ Viel hilft viel?

International guidelines for the treatment of chronic spontaneous urticaria support the updosing of second-generation antihistamines to four times of the approved dose when adequate symptom control cannot be achieved with the standard dosage. However, this recommendation is primarily based on expert opinions, and there is a lack of large, well-designed, double-blind clinical trials. Most the existing trials provide insufficient data, and due to the heterogeneity of the conducted trials on antihistamine effects (definition of control, design, quality, lack of an active comparator, no placebo arm, small sample size, outcomes) and their short duration, comparative analysis is challenging. However, it can be concluded that the use of modern second-generation antihistamines is both effective and safe based on the available data and our own long-term experiences in the specialized outpatient clinic of a university dermatology department, even though increased dosages (up to fourfold as per the current international guidelines) may be necessary for symptom control. Another therapeutic option for refractory symptoms in chronic spontaneous urticaria is subcutaneous administration of omalizumab at a dosage of 300 mg at 4­week intervals as a very safe and effective treatment.

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

Yeast-Derived Nucleotides Enhance Fibroblast Migration and Proliferation and Provide Clinical Benefits in Atopic Dermatitis.

Nucleotides, glycosaminoglycans, and omega-3 essential fatty acids (O3s) could be used for improving skin health, although their modes of action, alone or in combination, are not yet fully understood. To gain some insight into these mechanisms, we performed two in vitro tests and one in vivo pilot trial. The effects on human dermal fibroblast proliferation and migration were evaluated with the following compounds and combinations: 0.156 mg/mL O3s, 0.0017 mg/mL hyaluronic acid (HA), 0.0004 mg/mL dermatan sulfate (DS), 0.0818 mg/mL nucleotides, and [O3s + HA + DS] and [O3s + HA + DS + nucleotides] at the same concentrations. In both in vitro assays, adding nucleotides to [O3s + HA + DS] provided significant improvements. The resulting combination [O3s + HA + DS + nucleotides] was then tested in vivo in dogs with atopic dermatitis by oral administration of a supplement providing a daily amount of 40 mg/kg nucleotides, 0.9 mg/kg HA, 0.18 mg/kg DS, 53.4 mg/kg EPA, and 7.6 mg/kg DHA. After 30 days, the pruritus visual analog scale (pVAS) score was significantly reduced, and no adverse effects were observed. In conclusion, the combination of nucleotides plus glycosaminoglycans and O3s could serve as a useful therapeutic alternative in skin health applications.

Guselkumab in Patients with Scalp Psoriasis: A post hoc Analysis of the VOYAGE 2 Phase III Randomized Clinical Trial.

Scalp psoriasis affects approximately 80% of patients with psoriasis and can negatively impact their quality of life. This post hoc analysis of the VOYAGE 2 Phase III randomized clinical trial evaluated scalp response to guselkumab treatment and its association with skin response and patient-reported outcomes. The study included patients with moderate-to-severe plaque psoriasis and baseline scalp psoriasis who were initially randomized to receive guselkumab. Patients were divided into 3 groups based on their achievement of a Psoriasis Area and Severity Index 90 response at week 28: responder continuation, non-responder continuation and responder withdrawal. In all 3 groups, mean Psoriasis Area and Severity Index head and scalp-specific Investigator's Global Assessment scores improved through week 28. In the responder withdrawal group, these scores worsened after treatment withdrawal at week 28, but remained stable through week 48 in both continuation groups. Trends in Dermatology Life Quality Index and Psoriasis Symptoms and Signs Diary itch scores mirrored those of mean scalp-specific Investigator's Global Assessment scores through week 48. Within-subject correlations were 0.83 between scalp-specific Investigator's Global Assessment and Psoriasis Area and Severity Index head scores and 0.78 between scalp-specific Investigator's Global Assessment and Psoriasis Symptoms and Signs Diary itch scores. Through week 252, Psoriasis Area and Severity Index head scores remained stable in the responder continuation group, improved in the non-responder continuation group and rapidly improved by week 84 in the responder withdrawal group after retreatment.

AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients.

BACKGROUND AND HYPOTHESIS: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients. MATERIALS AND METHODS: The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured. RESULTS: The VAS score began to be lower in the AST-120 treatment group after the 5th visiting (p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone. CONCLUSION: This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.

Real-world experience of maralixibat in Alagille syndrome: Novel findings outside of clinical trials.

OBJECTIVE: Maralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients aged ≥3 months with Alagille syndrome (ALGS). Approval was based on reductions in pruritus from the pivotal ICONIC trial, information from two additional trials (ITCH and IMAGO), and long-term extension studies. Although participants in these trials met strict inclusion and exclusion criteria, patients have received maralixibat under broader circumstances as part of an expanded access program or commercially. The expanded access and postapproval settings inform a real-world understanding of effectiveness and safety. The objective was to report on the use of maralixibat in the real-world setting in eight patients who otherwise would not have met entrance criteria for the clinical trials, providing unique insights into its effectiveness in the management of ALGS. METHODS: We reviewed records of patients with ALGS who received maralixibat but would have been excluded from trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, administration of medication through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation. RESULTS: Maralixibat appeared to be effective with reductions in pruritus compared to baseline. Consistent with clinical trials, maralixibat was well tolerated without appreciable gastrointestinal complications. Liver enzyme elevations were observed but were interpreted as consistent with normal fluctuations observed in ALGS, with no increases in bilirubin. CONCLUSION: Maralixibat may be effective and well tolerated in patients with ALGS in broader clinical contexts than previously reported.

Dysregulation of the Skin-Liver Axis in Prurigo Nodularis: An Integrated Genomic, Transcriptomic, and Population-Based Analysis.

Pruritus has long been linked to hepatic dysfunction; however, there are limited data characterizing the association between liver disease and prurigo nodularis (PN), a chronic inflammatory skin disease featuring severe pruritis. We thus conducted a cross-sectional analysis of hepatic comorbidities in PN patients using TriNetX, a large global health research network. This analysis revealed that PN patients had a higher risk (p < 0.001) of developing liver cirrhosis, acute and subacute hepatic failure, inflammatory liver disease, chronic hepatitis, nonalcoholic steatohepatitis, portal hypertension, fatty liver, chronic passive congestion of the liver, and hepatocellular carcinoma compared with healthy controls. The cumulative incidence of liver disease was about three times higher in PN patients compared with healthy controls. These findings provided the basis for translational studies to investigate a genetic mechanism for this association. Cutaneous transcriptomic analysis performed on PN patients revealed the dysregulation of genes related to hepatic failure in lesional PN compared with both nonlesional PN and control skin. Similarly, gene set variation analysis (GSVA) revealed a significantly increased (p < 0.05) activation of liver metabolism, chronic hepatic failure, acute hepatic failure, cholestatic liver disease, polycystic liver disease, and hepatocellular carcinoma pathways in lesional PN compared with control skin. A subsequent genome-wide association study (GWAS) identified shared single-nucleotide polymorphisms (SNPs) in the genes AR, EDIL3, MACROD2, PCSK5, RUNX1T1, TENM4, and ZEB2 between PN and liver disease from the FinnGen cohort. Significant dysregulation of the skin-liver axis in PN patients may explain the increased incidence and severity of hepatic comorbidities and help identify future therapeutic targets for PN.

Impact of 1-year treatment with dupilumab on work productivity in Japanese patients with atopic dermatitis.

Atopic dermatitis (AD) places a burden on work productivity. Recently, dupilumab was approved for AD, but its impact on work productivity in Japanese patients has not been reported. Furthermore, data on the effect of long-term treatment with dupilumab on work productivity are limited. We investigated the work productivity and activity in Japanese patients with moderate-to-severe AD, utilizing the Japanese version of the Work Productivity and Activity Impairment (WPAI-AD-Japan) questionnaire. Furthermore, we examined the impact of dupilumab on work productivity. Adult moderate-to-severe AD patients treated with dupilumab for more than 12 months from March 2020 to June 2022 who filled out the WPAI-AD-Japan questionnaire were included. Twenty-eight adult AD patients were analysed. Absenteeism was low (mean: 5.3%), but presenteeism, work productivity loss and activity impairment were high (36.8%, 39.7%, 48.9%, respectively). Significant positive correlations were observed between work productivity loss and visual analogue scale (VAS) score of pruritus and between activity impairment and dermatology life quality index (DLQI). Dupilumab treatment significantly reduced presenteeism, work productivity loss and activity impairment at both 6 and 12 months. The extent of their amelioration was numerically higher at 12 months than at 6 months. The reduction rates in presenteeism, work productivity loss and activity impairment were positively correlated with the reduction rates in DLQI and VAS score of pruritus at 12 months. Dupilumab improved work productivity in Japanese AD patients. Long-term remission of pruritus and improved quality of life are important for comprehensive improvement of work productivity.

Prospective Randomized Double-Blind Vehicle-Controlled Study of Topical Coconut and Sunflower Seed Oil-Derived Isosorbide Diesters on Atopic Dermatitis.

Background: Preliminary studies support the use of topical coconut and sunflower seed oil for atopic dermatitis (AD). However, standardized topical formulations of fatty acids from these sources have not been studied. Objective: This study investigates whether coconut oil- and sunflower seed oil-derived isosorbide diesters can be used in conjunction with colloidal oatmeal to improve itch, AD severity, and the need for topical steroids in adults. Methods: This was a single-center, 4-week, randomized, double-blind, and vehicle-controlled study conducted between 2021 and 2022. Thirty-two male and female adults with mild-to-moderate AD were enrolled and completed the study. Participants were randomized to receive either 0.1% colloidal oatmeal (vehicle) or isosorbide diesters (IDEAS, 4% isosorbide dicaprylate and 4% isosorbide disunflowerseedate) along with 0.1% colloidal oatmeal. The main outcomes of the study were changes in the visual analogue rating of itch and 75% improvement in the Eczema Area and Severity Index score (EASI 75) at 4 weeks. Other measures included the use of topical steroids and the relative abundance of skin Staphylococcus aureus. Results: Participants in the IDEAS group had a 65.6% improvement in itch compared with 43.8% in the vehicle group (P = 0.013). In total, 56.5% and 25% of the those in the IDEAS and vehicle groups, respectively, achieved EASI 75 at 4 weeks (P = 0.07). There was no difference in skin hydration or transepidermal water loss. The relative abundance of S. aureus was decreased in the IDEAS group at week 4 compared with no change in the vehicle group (P = 0.044). Topical corticosteroid use increased in the vehicle group compared with a decrease in the IDEAS group at week 1 (292.5% vs 24.8%; P value = 0.039) and week 2 (220% vs 46%; P value = 0.08). Conclusions: Topical application of emollients containing coconut oil- and sunflower seed oil-derived fatty esters may improve itch, reduce topical steroid use, and reduce the relative abundance of S. aureus in mild-to-moderate AD. CTR number: NCT04831892.

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

Assessing Itch Severity: Content Validity and Psychometric Properties of a Patient-Reported Pruritus Numeric Rating Scale in Atopic Dermatitis.

BACKGROUND: Pruritus, or itch, is a key symptom of atopic dermatitis (AD); as such, mitigating itch is an important outcome of AD treatment. This study explored the content validity and measurement properties of the Pruritus Numeric Rating Scale (Pruritus NRS), a novel single-item scale for assessing itch severity in clinical trials of AD treatments. METHODS: In this mixed-methods study, qualitative interviews were conducted with 21 people with moderate-to-severe AD (n = 15 adult, n = 6 adolescent) to develop a conceptual model of the patient experience in AD and explore the content validity of the Pruritus NRS. Data collected daily from adults with moderate-to-severe AD enrolled in a phase 2b study (NCT03443024) were used to assess the Pruritus NRS' psychometric performance, including reliability, construct validity, and responsiveness. Meaningful within-patient change (MWPC) thresholds were also determined using anchor-based methods. RESULTS: Qualitative findings highlighted the importance of itch in AD, including severity, persistence, frequency, and daily life interference. Patient debriefing of the Pruritus NRS indicated that the scale was relevant, appropriate, and interpreted as intended. Trial data supported overall good psychometric properties. MWPC was defined as a 3-point improvement in Pruritus NRS score, a finding supported by qualitative data. CONCLUSIONS: The Pruritus NRS provides a valid and reliable patient-reported measure of itching severity in patients with moderate-to-severe AD, and can detect change, indicating it is fit-for-purpose to evaluate the efficacy of AD treatments in this population. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03443024.

Comparison of the effect of topical triamcinolone 0.1% cream with sulfur 2.0% cream in the treatment of patients with hand eczema: A randomized controlled trial.

BACKGROUND: Hand eczema (HE) is a common and heterogeneous condition. It has a wide range of etiologies and clinical manifestations. In this study the efficacy of triamcinolone 0.1% cream and sulfur 2% creams was compared in treating patients with HE. METHODS: This randomized, triple-blind clinical trial was performed on 70 patients with HE (including 70 right and 70 left hands). In this study, two creams were used including triamcinolone 0.1% and sulfur 2.0%. Patients were treated with these creams twice a day (once in every 12 h) for 4 weeks. Follow-up was 4 weeks after treatment. Hand Eczema Severity Index (HECSI), itching, dryness, burning sensation, and erythema scores were collected three times during the study and compared between treatment regimens. RESULTS: Findings showed that both triamcinolone (0.1%) and sulfur (2.0%) creams could significantly reduce the scores of HECSI, itching, dryness, burning sensation, and erythema, and the therapeutic effects lasted for at least 4 weeks after cessation of topical treatment. CONCLUSION: Topical sulfur cream (2.0%) is as effective as triamcinolone (0.1%) cream in treatment of HE without any prominent adverse reactions.

Discovery of a Small Molecule Activator of Slack (Kcnt1) Potassium Channels That Significantly Reduces Scratching in Mouse Models of Histamine-Independent and Chronic Itch.

Various disorders are accompanied by histamine-independent itching, which is often resistant to the currently available therapies. Here, it is reported that the pharmacological activation of Slack (Kcnt1, KNa1.1), a potassium channel highly expressed in itch-sensitive sensory neurons, has therapeutic potential for the treatment of itching. Based on the Slack-activating antipsychotic drug, loxapine, a series of new derivatives with improved pharmacodynamic and pharmacokinetic profiles is designed that enables to validate Slack as a pharmacological target in vivo. One of these new Slack activators, compound 6, exhibits negligible dopamine D2 and D3 receptor binding, unlike loxapine. Notably, compound 6 displays potent on-target antipruritic activity in multiple mouse models of acute histamine-independent and chronic itch without motor side effects. These properties make compound 6 a lead molecule for the development of new antipruritic therapies targeting Slack.

A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis.

BACKGROUND: Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits. METHODS: In this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 [worst itch imaginable]) from baseline to month 6 among patients with a baseline score of at least 4 (indicating moderate-to-severe pruritus). RESULTS: Of the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy. A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001). Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001). Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, -3.2 vs. -1.7; least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5, P = 0.005). Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively. CONCLUSIONS: In this trial involving patients with primary biliary cholangitis, the percentage of patients who had a biochemical response and alkaline phosphatase normalization was significantly greater with seladelpar than with placebo. Seladelpar also significantly reduced pruritus among patients who had moderate-to-severe pruritus at baseline. The incidence and severity of adverse events were similar in the two groups. (Funded by CymaBay Therapeutics; RESPONSE ClinicalTrials.gov number, NCT04620733; EudraCT number, 2020-004348-27.).