Alopecia areata (AA) may negatively impact patient quality of life (QoL), disease perception, and work productivity. AA severity is not solely based on scalp hair loss; individuals with AA can experience psychosocial burdens, including emotional symptoms and activity limitations (ES/AL). Our objective was to identify discrete AA severity profiles and evaluate the association with patient-reported outcomes (PROs). Dermatologist and patient surveys from the Alopecia Areata Disease Specific Programme in France, Germany, Italy, Spain, and the United Kingdom were analyzed. PRO instruments included the Alopecia Areata Patient Priority Outcomes (AAPPO), Work Productivity Activity Index-AA, Skindex-16AA, Patient Satisfaction with Hair Growth (P-Sat), and Hospital Anxiety and Depression Scale (HADS). Latent class analysis identified distinct classes using the AAPPO hair loss, ES, and AL response options. A 5-class model was selected. Each class exhibited distinct profiles based on patient-reported hair loss and ES/AL burden: (1) very mild hair loss, very mild ES/AL (n=175); (2) mild hair loss, mild ES/AL (n=165); (3) moderate hair loss, very severe ES/AL (n=111); (4) severe hair loss, moderate ES/AL (n=52); and (5) very severe hair loss, severe ES/AL (n=33). Class 3 reported significantly more overall work impairment [β=16.3 (95% CI, 7.8-24.7)] than class 1. Overall Skindex-16AA scores were highest for class 3 [β=38.7 (95% CI, 33.3-44.2)]. Class 3 reported significantly more HADS anxiety [β=6.0 (95% CI, 4.9-7.0)] and depression [β=5.7 (95% CI, 4.6-6.9)] than class 1. Across all P-Sat domains, class 5 reported the least satisfaction with therapy. Generally, patients with more severe patient-reported hair loss and ES/AL had decreased QoL and satisfaction with care and greater work productivity impairment. Although class 3 had moderate patient-reported hair loss, patients experienced the most severe ES/AL burden, suggesting that AA impacts well-being and daily activities in patients with less extensive hair loss.

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat chronic kidney disease (CKD)-related anemia. This interim analysis presents findings from postmarketing surveillance (PMS) conducted in Japan, assessing the safety and effectiveness of vadadustat in real-world clinical practice. This ongoing 2-year observational, multicenter, prospective surveillance collected data from November 2020 to June 2024 to assess adverse drug reactions (ADRs) and hemoglobin (Hb) levels in patients with CKD-related anemia. ADRs of special interest included malignant tumors, thromboembolism, hepatic impairment, hypertension, cardiovascular events excluding thromboembolism, retinal hemorrhage-related ADRs, and the progression of autosomal dominant polycystic kidney disease. This interim analysis included 2263 patients enrolled from 420 sites across Japan, with 2191 and 2142 patients analyzed for safety and effectiveness, respectively. The safety analysis population comprised 1429 patients with non-dialysis-dependent (NDD)-CKD, 174 with peritoneal dialysis-dependent (PD)-CKD, and 588 with hemodialysis-dependent (HD)-CKD. The median treatment duration was 365.0days overall (365.0days for NDD-CKD and PD-CKD, and 189.0days for HD-CKD). Treatment with vadadustat was discontinued in approximately half of the patients in each CKD group during the observation period. ADRs and serious ADRs were observed in 14.79% and 6.30% of the patients, respectively. The most common ADRs were nausea (1.19%) and diarrhea (1.14%). ADRs of special interest occurring in more than 1% of patients were malignant tumors (1.14%) and thromboembolism (1.05%). The mean changes in Hb levels from baseline to 12months in patients who switched from erythropoiesis-stimulating agents (ESAs) to vadadustat and in those without prior ESA use were as follows: 0.30g/dL and 1.12g/dL for patients with NDD-CKD; 0.30g/dL and 0.34g/dL for PD-CKD; and 0.18g/dL and 0.90g/dL for HD-CKD, respectively. Across all CKD subgroups, mean Hb levels increased after treatment with vadadustat in patients with baseline Hb levels < 10g/dL. In this interim analysis, we identified no new safety concerns beyond those outlined in the Japanese package insert for vadadustat, which is based on the results from pivotal clinical trials. The ongoing PMS will continue to offer valuable insights into the safety and effectiveness of vadadustat in real-world clinical practice. UMIN000042349.

Development of obesity management medications (OMMs) for use in children and adolescents calls for patient-reported outcome (PRO) measures to evaluate treatment efficacy. Existing weight-specific symptom and impact PROs are limited to age≥11years and may not fully capture treatment benefit of new OMMs. A targeted literature review was conducted to identify obesity symptom and impact outcomes and weight-specific PROs relevant to children and adolescents 6-17years of age. Concept elicitation (CE) interviews were conducted by telephone with children and adolescents, including parents of children 6-11years of age, to identify relevant weight-specific concepts. Key concepts relevant to three developmental age groups-6-7, 8-11, and 12-17years-informed the creation of a pediatric weight-specific PRO to assess key symptoms and impacts of obesity: the Pediatric Weight Questionnaire (PWQ). Cognitive interviews (CI) were conducted by telephone to assess the comprehension, relevance, and comprehensiveness of the PWQ across the three age groups. Eight domains were identified from the literature as relevant to pediatric obesity: physical symptoms, physical function, psychological health, emotional behavior/function, family and social relationships, school functioning, and health-related quality of life. No existing weight-specific PRO encompassing these domains was identified. Twenty CE interview participants (mean age 11.4years, 60% female, 50% Hispanic/Latino) confirmed that physical symptoms and physical, emotional, and social impacts were most relevant to their weight experience. The 23-item PWQ for adolescents 12-17years of age and the 17-item PWQ for children 8-11years of age are self-administered, while the 13-item PWQ for children 6-7years of age is interviewer-administered. The three versions of the PWQ were evaluated with 34 CI participants (mean age 12years, 64.7% female, 17.6% Hispanic/Latino), who found the PWQ easy to complete, relevant, and comprehensive. The PWQ provides a means of assessing the impact of obesity and benefits of treatment in children and adolescents 6-17years of age with obesity. Study findings support the content validity of this new measure for use in pediatric obesity clinical trials and observational research.

This study aimed to describe treatment patterns, frequency of comorbidities, and healthcare cost burden among patients with atopic dermatitis (AD) initiating systemic therapy (or re-initiating it after more than 12 months) versus matched controls without AD. Patients with AD initiating oral corticosteroids (OCS), immunosuppressants (SIS), or biologics between 1/1/2017 and 6/30/2022 (index=first treatment) were identified for analysis in the MarketScan claims databases. Patients were continuously enrolled 12 months before (baseline) and after index (follow-up). Direct and propensity score matching were used to adjust for baseline differences between cases and controls. Comorbidities and all-cause healthcare costs within service categories were compared between AD cases and matched controls during follow-up and treatment patterns were described for all patients with AD. A total of 20,503 patients with AD were identified. On index,12% initiated biologics, 86% OCS, and 2% SIS, and discontinuation rates were high during follow-up (SIS: 80%; biologics: 35%) The incidence of several comorbidities, including cardiovascular disease, atopic conditions, and mental health disorders, was higher in the AD cohort compared with matched controls (p<0.001). Patients with AD (vs. matched controls) also had significantly higher mean total all-cause healthcare costs (US$15,134 vs. $6832; p<0.001). Patients with AD who are initiating systemic treatment experience an increased risk of being newly diagnosed with several comorbidities and higher healthcare costs compared with matched controls, which places increased burden on patients and healthcare systems.

This trial evaluated long-term safety, tolerability, and maintenance of efficacy of adjunctive brivaracetam (BRV) in Japanese and Chinese patients aged ≥ 16years with focal-onset seizures (FOS). Interim analysis of data from EP0085 (NCT03250377), a long-term follow-up trial of adjunctive BRV 50-200mg/day in Japanese and Chinese patients. Post hoc analyses assessed efficacy for 12- and 24-month completers and BRV retention. At data cutoff (June 1, 2023), 207 patients had enrolled; of these, 157 (75.8%) were ongoing and 50 (24.2%) had discontinued. Overall, 137 patients were 12-month completers and 63 were 24-month completers. Mean age was 36.7years and 107 (51.7%) patients were female (100 [48.3%] male). Mean duration of epilepsy was 17.16years. At data cutoff, total duration of BRV exposure was 378.5 patient-years. Mean duration of BRV exposure was 667.8days (median 427.0days), with a median modal dose of 200.0mg/day (range 25.0-200.0mg/day). Kaplan-Meier-estimated BRV retention rates at 12, 24, and 36months were 85%, 76%, and 68%, respectively. Treatment-emergent adverse events (TEAEs) were reported by 184 (88.9%) patients, drug-related TEAEs by 60 (29.0%), serious TEAEs by 29 (14.0%), and 8 (3.9%) discontinued as a result of TEAEs. Median FOS frequency/28days decreased from 7.59 during baseline to 4.11 during the evaluation period. For the overall evaluation period, 12-month, and 24-month completers, median percentage reductions from baseline in FOS frequency/28days were 42.4%, 44.0%, and 38.9%, respectively, and 50% responder rates were 46.4%, 46.7%, and 38.1%. Based on this interim and post hoc analysis, long-term adjunctive BRV was well tolerated and efficacious in Japanese and Chinese patients with FOS. The efficacy response was maintained over time in those completing 12 and 24months of trial participation. Overall, 68% of patients remained on BRV treatment for 3years. ClinicalTrials.gov NCT03250377. Graphical abstract available for this article.

To document the decision-making criteria physicians use when selecting regimens for second- and third-line therapy for patients with relapsed and/or refractory multiple myeloma (RRMM) in Germany. Experienced multiple myeloma (MM) physicians extracted data from medical records from 30 June to 8 September 2023 for patients who initiated approved second- and third-line therapy for MM in 2021. Regimens, most important treatment goal, and key reasons for prescribing were reported in addition to patient characteristics. All data were summarised descriptively. MM physicians (33 hospital-based, 16 office-based) with a median of 17years of treatment experience extracted data from a total of 268 patient records (second-line, n=170; third-line, n=98). In second- and third-line, 17 and 16 different regimens were documented, respectively. The most utilized second-line regimens were: daratumumab (D), lenalidomide (R) and dexamethasone (d) (DRd 16.5%); carfilzomib (K), d and D (KdD 12.4%); Kd (11.2%); KRd; (10.0%); D, bortezomib (V) and d (DVd 9.4%); and V with cyclophosphamide (C) and d (VCd 7.1%). The main reasons for selecting the regimen were treatment effectiveness, patient characteristics/status, and relapse. Inducing deepest possible response and prolonging survival or symptom control were the most important treatment goals for triplet regimens. The main third-line regimens were: pomalidomide (P) and d (Pd 15.3%); DRd (13.3%); Rd (13.3%); elotuzumab (E) and Pd (EPd 12.2%); isatuximab (Isa) and Kd or KdD (10.2%); and ixazomib (I) and Rd (IRd 8.2%). The main reasons for selecting the regimens varied for third-line regimens but primarily focused on treatment effectiveness, patient characteristics/status, and prior therapy response or mechanism of action. The most important treatment goal was prolongation of survival. The results suggest that in the absence of a single standard of care for RRMM, prescribers made patient-centred choices of regimens with efficacy as the main goal of therapy.

Metformin, a well-established, first-line therapy for type2 diabetes mellitus, is still gaining interest for its potential applications beyond glycaemic control. In addition to its insulin-sensitising effects, metformin exhibits anti-inflammatory, antioxidant, anti-proliferative, and immunomodulatory properties, rendering it a promising candidate for various dermatological conditions. Emerging evidence suggests that metformin may play a beneficial role in inflammatory skin diseases, such as acne, hidradenitis suppurativa, acanthosis nigricans, rosacea and psoriasis. Furthermore, recent studies highlight its potential in promoting wound healing and modulating skin ageing. This narrative review summarises current knowledge of the mechanisms of action of metformin in dermatology and explores its potential as a novel therapeutic approach for skin disorders.

Therapeutic options for patients with advanced non-small cell lung cancer (NSCLC) after progression on immune checkpoint inhibitors (ICIs) remain a significant challenge. This analysis compared outcomes of anlotinib plus docetaxel versus docetaxel alone in this population using the pooled data from two prospective randomized trials (ALTER-L016; ALTER-L018). Adult patients with EGFR/ALK/ROS1 wild-type advanced NSCLC progressing on first-line ICIs were eligible. Patients were randomly assigned to anlotinib plus docetaxel or docetaxel alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Seventy-one patients were included in this pooled analysis (L016, n = 39; L018, n = 32), of whom, 40 received anlotinib plus docetaxel and 31 received docetaxel. The median follow-up of all patients was 27.0months. The median PFS was longer with anlotinib plus docetaxel than with docetaxel alone (5.4months [95% CI 5.0-9.3] vs. 2.3months [95% CI 1.4-2.9]; hazard ratio [HR], 0.34; 95% CI 0.18-0.63; P < 0.001). Both ORR (25.0% vs. 12.9%) and DCR (82.5% vs. 45.2%) were higher in the anlotinib plus docetaxel group than in the docetaxel group. Median OS was 16.2months (95% CI 8.3-21.3) with anlotinib plus docetaxel versus 13.7months (95% CI 4.6-22.3) with docetaxel (HR = 0.82; 95% CI 0.47-1.44; P = 0.488). Subsequent ICI therapy was associated with a longer OS. Grade 3 treatment-related adverse events occurred in 32.5% of patients receiving anlotinib plus docetaxel and 6.5% of patients receiving docetaxel. Anlotinib plus docetaxel improved PFS but not OS versus docetaxel in patients with advanced NSCLC progressing on ICIs. Larger standardized phase 3 trials are needed to verify these findings. ALTER-L016 (ClinicalTrials.gov identifier, NCT03726736). ALTER-L018 (ClinicalTrials.gov identifier, NCT03624309).