Abstract
Introduction/Background
Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. ...Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols.
Objectives
TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice.
Methods
TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients.
Results
Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation SD) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator’s Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness.
Conclusions
Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life.
What do a bionic supersoldier, space stations and religious fanaticism have in common? They are all vital elements of the plot in Halo, a series of first-person shooter games developed by Bungie and ...published by Microsoft Games. One of the interesting things about Halo is that the developers made use of quite a number of religious images and themes, especially from the Christian tradition. In modern Western society, science and religion are often portrayed as polar opposites, and Halo appears to reaffirm this narrative. Yet it might still be interesting to look at how exactly this animosity is portrayed, and to see whether there is more to it. This paper is an inquiry into the significance of religious imagery and themes in Halo, as well as an attempt to place the game in the broader context of the geopolitical situation of its time. In short, this article is going to be a case study of how the relationship between science and religion can be explored through the medium of video games. For an overview of the current debate on how science and religion relate to one another in academia, I am going to look at the works of American physicist and scholar of religion Ian Barbour, American paleontologist and historian of science Stephen Gould, and British ethologist and evolutionary biologist Richard Dawkins. To justify the academic study of videogames I will be drawing from the writings of Dutch cultural theologian Frank Bosman. The analysis itself will consist of a summary of the game’s main story, its portrayal of religion on the one hand and its depiction of science on the other, and its representation of how these two fields relate to one another. In the conclusion, finally, I will connect the dots between the different parts of the analysis and provide an answer to the main question.
Background We observed that basal cell carcinoma (BCC) on the ear demonstrates a more aggressive phenotype compared with other body sites. Objective We sought to determine if it is statistically ...significant that BCC on the ear is more aggressive. Methods We queried our 2009 database for all BCCs biopsied from the ear. Multiple data points, including tumor subtype and risk level, were analyzed for 100 BCCs on the ear and 100 BCCs on the cheek. Results BCC on the ear was diagnosed 471 times. Of the first 100 occurrences of BCC on the ear, 57% were high risk compared with 38% on the cheek (odds ratio 2.16, 95% confidence interval 1.23-3.81, P = .01). Men were more likely to have BCC on the ear: 79% male on the ear and 53% male on the cheek ( P < .001). However, BCC on the ear in women is also more likely to be aggressive (57%, 12 of 21). Limitations The data were retrieved from a single year at our institution, and there could potentially be regional bias given that the population of data is from a single institution. Many of the specimens we evaluate are reviewed in consultation and may thus represent a selection bias. Conclusion BCC on the ear presents as an aggressive phenotype in the majority of cases for both men and women, and it occurs much more frequently in men. Knowledge of this information can help guide physicians and ensure that these tumors are adequately biopsied and treated.
Lebrikizumab, a high-affinity IgG4 monoclonal antibody that selectively inhibits interleukin-13 with high binding affinity and slow dissociation rate, prevents the formation of the ...interleukin-4Rα/interleukin-13Rα1 heterodimer receptor signaling complex. Here we report the impact of lebrikizumab on responses to two non-live vaccines in adult patients with moderate-to-severe atopic dermatitis (AD).INTRODUCTIONLebrikizumab, a high-affinity IgG4 monoclonal antibody that selectively inhibits interleukin-13 with high binding affinity and slow dissociation rate, prevents the formation of the interleukin-4Rα/interleukin-13Rα1 heterodimer receptor signaling complex. Here we report the impact of lebrikizumab on responses to two non-live vaccines in adult patients with moderate-to-severe atopic dermatitis (AD).ADopt-VA (NCT04626297) was a double-blind, placebo-controlled, parallel-group, 16-week, phase 3 randomized study to assess the impact of lebrikizumab treatment on non-live vaccine immune responses, and efficacy and safety of lebrikizumab compared with placebo. Eligible patients included adults from 18 to 55 years of age with moderate-to-severe chronic AD who were randomly assigned 1:1 to lebrikizumab 250 mg every 2 weeks or placebo and stratified according to disease severity. The primary endpoints were the development of a booster response to tetanus toxoid and a positive antibody response to meningococcal conjugate vaccine (MCV), 4 weeks after administration of the corresponding vaccine.METHODSADopt-VA (NCT04626297) was a double-blind, placebo-controlled, parallel-group, 16-week, phase 3 randomized study to assess the impact of lebrikizumab treatment on non-live vaccine immune responses, and efficacy and safety of lebrikizumab compared with placebo. Eligible patients included adults from 18 to 55 years of age with moderate-to-severe chronic AD who were randomly assigned 1:1 to lebrikizumab 250 mg every 2 weeks or placebo and stratified according to disease severity. The primary endpoints were the development of a booster response to tetanus toxoid and a positive antibody response to meningococcal conjugate vaccine (MCV), 4 weeks after administration of the corresponding vaccine.At week 16, 73.6% of patients in the lebrikizumab group (n = 78/106) achieved Tdap booster response compared with 73.4% of patients in the placebo group (n = 58/79). MCV vaccine response was observed in 86.9% of patients in the lebrikizumab group (n = 86/99) and 75.0% of patients in the placebo group (n = 60/80). At week 16, IGA 0,1 with ≥ 2-point improvement from baseline was achieved by 40.6% (n = 51/125) of patients treated with lebrikizumab and 18.9% (n = 23/122) of patients who received placebo (p < 0.001). There was a higher proportion of patients achieving EASI 75 at week 16 in the lebrikizumab-treated patients (58.0%, n = 72/125) compared with placebo (32.7%, n = 40/122, p < 0.001).RESULTSAt week 16, 73.6% of patients in the lebrikizumab group (n = 78/106) achieved Tdap booster response compared with 73.4% of patients in the placebo group (n = 58/79). MCV vaccine response was observed in 86.9% of patients in the lebrikizumab group (n = 86/99) and 75.0% of patients in the placebo group (n = 60/80). At week 16, IGA 0,1 with ≥ 2-point improvement from baseline was achieved by 40.6% (n = 51/125) of patients treated with lebrikizumab and 18.9% (n = 23/122) of patients who received placebo (p < 0.001). There was a higher proportion of patients achieving EASI 75 at week 16 in the lebrikizumab-treated patients (58.0%, n = 72/125) compared with placebo (32.7%, n = 40/122, p < 0.001).Treatment with lebrikizumab did not impact response to non-live vaccines Tdap and MCV in this study. Lebrikizumab treatment had a significant degree of efficacy compared to placebo across multiple endpoints.CONCLUSIONSTreatment with lebrikizumab did not impact response to non-live vaccines Tdap and MCV in this study. Lebrikizumab treatment had a significant degree of efficacy compared to placebo across multiple endpoints.ClinicalTrials.gov identifier NCT04626297.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT04626297.
Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not.
To develop an algorithm by integrating the 31-gene ...expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence i31-ROR) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions.
Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold.
Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death.
Multicenter, retrospective study.
Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone.
BackgroundPatients with stage IB-IIA cutaneous melanoma (CM) account for approximately one quarter of all patients with melanoma, have 20–38% recurrence rates, and 6–12% melanoma-specific mortality ...rates by 10 years,1 2 but they are not eligible for adjuvant immunotherapy. By comparison, immunotherapy is approved for adjuvant treatment of patients with stage IIB CM. Molecular testing of stage IB-IIA patients with the 31-GEP test can identify patients who have a risk of recurrence similar to that seen for stage IIB patients and may benefit from immunotherapy. The 31-gene expression profile test (31-GEP) stratifies patients into low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of recurrence, metastasis, and death.MethodsPatients with stage IB-IIA (n=673) and IIB (n=174) CM from previously published prospective and retrospective studies (N=847) were analyzed by the 31-GEP.3–8 Five-year RFS and MSS risk stratification was assessed using Kaplan-Meier analysis with the log-rank test.ResultsThe 31-GEP stratified 5-year RFS among patients with stage IB-IIA CM (Class 1A=91.8% vs. Class 1B/2A=85.1% vs. Class 2B=64.2%, p<0.001) and those with stage IIB CM (Class 1A=75.0% vs. Class 1B/2A=78.4% vs. Class 2B=55.4%, p=0.02). The 31-GEP also significantly stratified 5-year MSS for those with stage IB-IIA CM (Class 1A=99.2% vs. Class 1B/2A=96.9% vs. Class 2B=87.6%, p<0.001) and those with stage IIB CM (Class 1A=100% vs. Class 1B/2A=94.9% vs. Class 2B=90.4%, p=0.02). Multivariable analysis with the 31-GEP (Class 1A, Class 1B/2A, and Class 2B) and AJCC stage (IB vs. IIA) found that, among stage IB-IIA patients, Class 1B/2A (HR=1.72, p=0.048), Class 2B (HR=3.33, p<0.001), and stage IIA (HR=1.84, p=0.006) were significant predictors of recurrence. Only the 31-GEP Class 2B result was a significant predictor of melanoma-specific mortality in multivariable analysis for patients with stage IB-IIA CM (HR=7.90, p<0.001).ConclusionsIn patients with stage IB-IIA CM, the 31-GEP identified those with a high risk of recurrent disease (64.2% 5-year RFS for Class 2B), which was like that of stage IIB CM (63.4% overall 5-year RFS), for whom adjuvant therapy is approved. The 31-GEP provided significant risk stratification for both recurrence and melanoma-specific mortality in patients with stage IB-IIA CM, a group that can have a nearly 40% recurrence rate but is not currently eligible for adjuvant immunotherapies. The 31-GEP provides personalized, independent risk stratification, which enhances adjuvant therapy selection in future clinical trials in this population.ReferencesGarbe C, Keim U, Amaral T, Berking C, Eigentler TK, Flatz L, et al. Prognosis of Patients With Primary Melanoma Stage I and II According to American Joint Committee on Cancer Version 8 Validated in Two Independent Cohorts: Implications for Adjuvant Treatment. JCO Internet. 2022 Jun 16 cited 2022 Jun 20; Available from: https://ascopubs.org/doi/pdf/10.1200/JCO.22.00202Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA: A cancer journal for clinicians. 2017 Nov;67(6):472–92.Podlipnik S, Carrera C, Boada A, Richarz NA, López-Estebaranz JL, Pinedo-Moraleda F, et al. Early outcome of a 31-gene expression profile test in 86 AJCC stage IB-II melanoma patients. A prospective multicentre cohort study. J Eur Acad Dermatol Venereol. 2019 May;33(5):857–62.Hsueh EC, DeBloom JR, Lee JH, Sussman JJ, Covington KR, Caruso HG, et al. Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma. JCO Precision Oncology. 2021 Nov 1;5(5):589–601.Greenhaw BN, Covington KR, Kurley SJ, Yeniay Y, Cao NA, Plasseraud KM, et al. Molecular risk prediction in cutaneous melanoma: a meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients. J Am Acad Dermatol. 2020 Mar;83(3):745–53.Gastman BR, Gerami P, Kurley SJ, Cook RW, Leachman S, Vetto JT. Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. J Am Acad Dermatol. 2019 Jan;80(1):149–157.e4.Jarell A, Skenderis B, Dillon LD, Dillon K, Martin B, Quick AP, et al. The 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma. Future Oncol. 2021 Dec;17(36):5023–31.Greenhaw BN, Zitelli JA, Brodland DG. Estimation of Prognosis in Invasive Cutaneous Melanoma: An Independent Study of the Accuracy of a Gene Expression Profile Test. Dermatol Surg. 2018 Dec;44(12):1494–500.Ethics ApprovalEach cohort included in the analysis received institutional review board approval at the affiliated institutional IRB.
PDF
