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https://www.readbyqxmd.com/read/28926467/a-systematic-review-and-meta-analysis-of-efficacy-and-safety-of-novel-interleukin-inhibitors-in-the-management-of-psoriatic-arthritis
#1
Jawad Bilal, Irbaz Bin Riaz, Muhammad Umar Kamal, Mazen Elyan, Dominick Sudano, Muhammad Asim Khan
OBJECTIVE: The aim of this study was to systemically review the efficacy and safety of inhibitors of interleukin 6 (IL-6): clazakizumab, IL-12/23: ustekinumab, and IL-17A: secukinumab, brodalumab, and ixekizumab in psoriatic arthritis (PsA). METHODS: The literature search was conducted using MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science. We included randomized controlled trials that assessed the efficacy of IL inhibitors and reported American College of Rheumatology 20 response at 24 weeks...
September 19, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#2
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28917383/efficacy-and-safety-of-ixekizumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis-results-through-108%C3%A2-weeks-of-a-randomized-controlled-phase-3-clinical-trial-uncover-3
#3
Andrew Blauvelt, Melinda Gooderham, Lars Iversen, Susan Ball, Lu Zhang, Noah O Agada, Kristian Reich
BACKGROUND: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A, is efficacious in treating moderate-to-severe plaque psoriasis through 60 weeks. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab through 108 weeks of treatment in UNCOVER-3. METHODS: Patients (N = 1346) were randomized 2:2:2:1 to 80 mg ixekizumab every 2 or 4 weeks, 50 mg etanercept twice weekly, or placebo. At week 12, patients switched to ixekizumab every 4 weeks during a long-term extension (LTE) period...
September 13, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28903122/impact-of-ixekizumab-treatment-on-depressive-symptoms-and-systemic-inflammation-in-patients-with-moderate-to-severe-psoriasis-an-integrated-analysis-of-three-phase-3-clinical-studies
#4
Christopher E M Griffiths, Maurizio Fava, Andrew H Miller, James Russell, Susan G Ball, Wen Xu, Nayan Acharya, Mark Hyman Rapaport
BACKGROUND: Depression is a common comorbidity in psoriasis, and both conditions are associated with systemic inflammation. The efficacy of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, was evaluated in patients with moderate-to-severe plaque psoriasis (psoriasis) and depressive symptoms that were at least moderately severe. METHODS: Data were integrated from 3 randomized, double-blind, controlled phase 3 trials. At baseline and week 12, depressive symptoms and inflammation were assessed by the 16-item Quick Inventory of Depressive Symptomology - Self-Report (QIDS-SR16) and by a high-sensitivity assay of serum C-reactive protein (hsCRP), respectively...
September 14, 2017: Psychotherapy and Psychosomatics
https://www.readbyqxmd.com/read/28895664/the-severe-and-acute-complications-of-the-biologics-in-psoriasis
#5
Elias Oussedik, Nupur U Patel, Devin R Cash, Angela S Gupta, Steven R Feldman
Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold-standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha (TNF-alpha) inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 inhibitors (secukinumab and ixekizumab)...
September 12, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28894754/natural-modulators-of-endosomal-toll-like-receptor-mediated-psoriatic-skin-inflammation
#6
REVIEW
Chao-Yang Lai, Yu-Wen Su, Kuo-I Lin, Li-Chung Hsu, Tsung-Hsien Chuang
Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28887948/psoriasis-pathogenesis-and-the-development-of-novel-targeted-immune-therapies
#7
REVIEW
Jason E Hawkes, Tom C Chan, James G Krueger
Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, autoantigens, and multiple environmental factors. Over the last 2 decades, research has unequivocally shown that psoriasis represents a bona fide T cell-mediated disease primarily driven by pathogenic T cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/type 17 T-cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition...
September 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28881462/impact-of-ixekizumab-on-facial-psoriasis-and-related-quality-of-life-measures-in-moderate-to-severe-psoriasis-patients-12-week-results-from-2-phase-iii-trials
#8
C Paul, L Guenther, H Torii, H Sofen, R Burge, C Y Lin, A Potts Bleakman, L Mallbris, Y Poulin
BACKGROUND: Facial psoriasis was reported in 17-68% of patients with psoriasis and shown to have a negative impact on patients' personal and health-related quality of life (HRQoL). OBJECTIVES: Explore the association of facial psoriasis with patients' HRQoL and assess the relationship between ixekizumab (IXE) and improvement in facial psoriasis and changes in HRQoL. METHODS: This work reports the combined results of 2 phase III multicenter, randomized, double-blind, placebo-controlled, active-comparator trials in patients with moderate-to-severe psoriasis...
September 7, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28825875/monoclonal-antibodies-inhibiting-il-12-23-and-17-for-the-treatment-of-psoriasis
#9
Caleb Jeon, Sahil Sekhon, Di Yan, Ladan Afifi, Mio Nakamura, Tina Bhutani
Psoriasis is a chronic, inflammatory, immune-mediated skin condition that affects 3 to 4% of the adult U.S. population, characterized by well-demarcated, erythematous plaques with silver scale. Psoriasis is associated with many comorbidities including cardiometabolic disease and can have a negative impact on quality of life. The current armamentarium of psoriasis treatment includes topical therapies, phototherapy, oral immunosuppressive therapies, and biologic agents. Over the past two decades, there has been rapid development of novel biologic therapies for the treatment of moderate-to-severe plaque psoriasis...
August 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28792259/improvements-in-psoriasis-within-different-body-regions-vary-over-time-following-treatment-with-ixekizumab
#10
Andrew Blauvelt, Talia M Muram, Kyoungah See, Craig H Mallinckrodt, Jeffrey J Crowley, Peter van de Kerkhof
BACKGROUND: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A. OBJECTIVE: Examine the efficacy of ixekizumab in clearing psoriasis within different body regions. METHODS: Data from 3 placebo- (PBO) or PBO- and etanercept (ETN)-controlled trials were integrated. Patients with moderate-to-severe psoriasis were randomized to 12 weeks of PBO (UNCOVER-1, -2, -3, N = 792; UNCOVER-2, -3, N = 361), 50 mg ETN twice weekly (N = 740), or 80 mg ixekizumab every 2 (IXE Q2W; N = 1169; N = 736) or 4 weeks (IXE Q4W; N = 1165; N = 733) after a 160-mg starting dose...
August 9, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28791896/biologics-that-inhibit-the-th17-pathway-and-related-cytokines-to-treat-inflammatory-disorders
#11
Anna Balato, Emanuele Scala, Nicola Balato, Giuseppina Caiazzo, Roberta Di Caprio, Giuseppe Monfrecola, Annunziata Raimondo, Serena Lembo, Fabio Ayala
Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors. Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target...
August 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#12
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28760056/cost-per-additional-responder-for-ixekizumab-and-other-fda-approved-biologics-in-moderate-to-severe-plaque-psoriasis
#13
Sarah Al Sawah, Shonda A Foster, Russel Burge, David Amato, Alexander Schacht, Baojin Zhu, Susanne Hartz, Craig Leonardi
BACKGROUND: Evidence of the cost-efficacy of ixekizumab for the treatment of moderate-to-severe plaque psoriasis (PsO) in the United States (US) is limited. OBJECTIVE: To estimate the number needed to treat (NNT) and monthly cost of achieving one additional Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responder for ixekizumab and other Food and Drug Administration (FDA)-approved biologics in PsO. METHODS: A network meta-analysis estimated the probability of achieving PASI 75, 90, or 100 response during induction for each biologic...
August 1, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28755058/novel-biologic-agents-targeting-interleukin-23-and-interleukin-17-for-moderate-to-severe-psoriasis
#14
REVIEW
Zeyu Chen, Yu Gong, Yuling Shi
Psoriasis is a common, chronic inflammatory skin disease and cannot be cured. The treatment of moderate-to-severe plaque psoriasis has been revolutionized with the development of biologic agents for nearly 20 years. Current studies show that interleukin-23 and interleukin-17 play remarkable roles in the pathogenesis of psoriasis. Interleukin-23 can sustain the differentiation and maintenance of T helper-17 lineage. Interleukin-17 can recruit and stimulate many cells, which play important parts in psoriasis through interacting with the interleukin-17 receptor...
July 28, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28744098/spotlight-on-brodalumab-in-the-treatment-of-moderate-to-severe-plaque-psoriasis-design-development-and-potential-place-in-therapy
#15
REVIEW
Michael Roman, Melvin W Chiu
Brodalumab is a novel fully human immunoglobulin G2 monoclonal antibody that antagonizes the interleukin (IL)-17 pathway by binding with high affinity to human IL-17RA. The role of IL-17A in the pathogenesis of psoriasis, as well as the remarkable effectiveness of IL-17 inhibitors in the treatment of moderate-to-severe plaque psoriasis, is well established. The mechanism of action of brodalumab is unique in that it inhibits the IL-17 receptor compared to the two other currently FDA-approved IL-17 inhibitors, secukinumab and ixekizumab, which inhibit the IL-17A molecule itself...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28677075/urticarial-reaction-to-ustekinumab-during-the-treatment-of-plaque-psoriasis-in-a-hepatitis-c-positive-patient
#16
Christopher H Chu, Charles Davis
A 62-year-old white woman with a history of hepatitis C and type 2 diabetes mellitus developed urticaria during treatment with ustekinumab for plaque psoriasis. The patient received two 45-mg ustekinumab injections in her first 2 months and then one 45-mg injection every 3 months for her psoriasis. After 10 months, she developed a round red rash on her skin diffusely on her body. She also complained of joint pain in her hands. Rheumatology became involved, and investigations revealed that her antinuclear antibody titer was negative, but her rheumatoid factor, erythrocyte sedimentation rate, and liver function enzymes were elevated...
December 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/28652702/spotlight-on-ixekizumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis-design-development-and-use-in-therapy
#17
REVIEW
Alessandro Giunta, Alessandra Ventura, Maria Sole Chimenti, Luca Bianchi, Maria Esposito
Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population, associated with discomfort and impaired quality of life. In recent years, the pathogenic cytokine network of psoriasis has been extensively studied leading to the development of new treatments that provide greater efficacy. Interleukin 17A (IL-17A) has been recognized as a crucial cytokine that mediates immunopathogenesis of psoriasis. Ixekizumab - indicated for the treatment of adults with moderate-to-severe plaque psoriasis - is a subcutaneously administered humanized monoclonal antibody that targets IL-17A...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28650001/brodalumab-the-first-anti-il-17-receptor-agent-for-psoriasis
#18
REVIEW
L Puig
Psoriasis is a chronic immune-mediated inflammatory skin disease in which the alteration of the interleukin-23 (IL-23)/IL-17 cytokine axis appears to be crucial from a pathogenetic perspective. This has been confirmed by the efficacy of monoclonal antibodies blocking IL-17A, such as secukinumab and ixekizumab. Brodalumab is a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that inhibits the biological activity of IL-17A, IL-17F and other IL-17 isoforms, and has been approved (210 mg s.c. at weeks 0, 1, 2 and every 2 weeks thereafter) for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma in Japan (Lumicef)...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28635026/efficacy-and-safety-of-ixekizumab-treatment-in-japanese-patients-with-moderate-to-severe-plaque-psoriasis-subgroup-analysis-of-a-placebo-controlled-phase-3-study-uncover-1
#19
Shinichi Imafuku, Hitoe Torisu-Itakura, Atsushi Nishikawa, Fangyi Zhao, Gregory S Cameron
The present study describes a subgroup analysis of 33 Japanese patients participating in UNCOVER-1, an international, placebo-controlled, phase 3 study of ixekizumab in patients with moderate-to-severe psoriasis. Patients were randomized to a placebo (n = 13) or ixekizumab 80 mg every 4 (IXEQ4W, n = 12) or 2 (IXEQ2W, n = 8) weeks, from week 0-12. At week 12, ixekizumab-treated patients with a static Physician Global Assessment score 0 or 1 (sPGA [0,1]; n = 16) were re-randomized to a placebo (n = 6), ixekizumab 80 mg every 12 (IXEQ12W, n = 5) or 4 (IXEQ4W, n = 5) weeks, from week 12-60...
June 21, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#20
REVIEW
Florian C Kurschus, Sonja Moos
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis...
June 15, 2017: Journal of Dermatological Science
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