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https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#1
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
https://www.readbyqxmd.com/read/28600810/infections-from-7-clinical-trials-of-ixekizumab-an-anti-interleukin-17a-monoclonal-antibody-in-patients-with-moderate-to-severe-psoriasis
#2
K A Papp, H Bachelez, A Blauvelt, K L Winthrop, R Romiti, M Ohtsuki, N Acharya, D K Braun, L Mallbris, F Zhao, W Xu, C D Walls, B Strober
BACKGROUND: Infections are associated with biologic therapies in psoriasis. OBJECTIVES: To summarise the incidence of infections in moderate-to-severe psoriasis patients treated with ixekizumab, an anti-interleukin (IL)-17A monoclonal antibody. METHODS: Infections are summarised from an integrated database of 7 controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (Weeks 0-12; UNCOVER-1, -2, and -3) and maintenance periods (Weeks 12-60; UNCOVER-1 and -2) as well as all ixekizumab-exposed patients pooled from all 7 trials...
June 10, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28581873/budget-impact-model-in-moderate-to-severe-psoriasis-vulgaris-assessing-effects-of-calcipotriene-and-betamethasone-dipropionate-foam-on-per-patient-standard-of-care-costs
#3
Carl V Asche, Minchul Kim, Steven R Feldman, Panagiotis Zografos, Minyi Lu
AIMS: To develop a budget impact model (BIM) for estimating the financial impact of formulary adoption and uptake of calcipotriene and betamethasone dipropionate (C/BD) foam (0.005%/0.064%) on the costs of biologics for treating moderate-to-severe psoriasis vulgaris in a hypothetical US healthcare plan with 1 million members. METHODS: This BIM incorporated epidemiologic data, market uptake assumptions, and drug utilization costs, simulating the treatment mix for patients who are candidates for biologics before (Scenario #1) and after (Scenario #2) the introduction of C/BD foam...
June 19, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28573743/impact-of-ixekizumab-treatment-on-skin-related-personal-relationship-difficulties-in-moderate-to-severe-psoriasis-patients-12-week-results-from-two-phase-3-trials
#4
L Guenther, R B Warren, J C Cather, H Sofen, Y Poulin, M Lebwohl, T Terui, A Potts Bleakman, B Zhu, R Burge, K Reich, P van de Kerkhof
BACKGROUND: Psoriasis symptoms may decrease quality of life for patients. Skin-related personal relationship difficulties in psoriasis patients are common, under-reported, and poorly understood. OBJECTIVE: To assess the effect of ixekizumab (IXE) treatment on skin-related personal relationship difficulties in patients with moderate-to-severe psoriasis. METHODS: Pooled data (N=2570) on skin-related relationship problems were obtained from two large phase 3 trials (UNCOVER-2 and UNCOVER-3) in patients with moderate-to-severe plaque psoriasis randomized to subcutaneous placebo (PBO, N=361), etanercept (ETN; 50 mg twice weekly, N=740), or 80 mg IXE as one injection every 4 (IXEQ4W, N=733) or 2 weeks (IXEQ2W, N=736) for 12 weeks, following a 160-mg initial dose...
June 2, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28551073/ixekizumab-for-the-treatment-of-patients-with-active-psoriatic-arthritis-and-an-inadequate-response-to-tumour-necrosis-factor-inhibitors-results-from-the-24-week-randomised-double-blind-placebo-controlled-period-of-the-spirit-p2-phase-3-trial
#5
Peter Nash, Bruce Kirkham, Masato Okada, Proton Rahman, Benard Combe, Gerd-Ruediger Burmester, David H Adams, Lisa Kerr, Chin Lee, Catherine L Shuler, Mark Genovese
BACKGROUND: Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. METHODS: In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America...
June 10, 2017: Lancet
https://www.readbyqxmd.com/read/28543445/psoriasis-in-those-planning-a-family-pregnant-or-breast-feeding-the-australasian-psoriasis-collaboration
#6
REVIEW
Marius Rademaker, Karen Agnew, Megan Andrews, Katherine Armour, Chris Baker, Peter Foley, John Frew, Kurt Gebauer, Monisha Gupta, Debra Kennedy, Gillian Marshman, John Sullivan
The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated...
May 23, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28542874/comparison-of-ixekizumab-with-ustekinumab-in-moderate-to-severe-psoriasis-24-week-results-from-ixora-s-a-phase-3-study
#7
K Reich, A Pinter, J P Lacour, C Ferrandiz, G Micali, L E French, M Lomaga, Y Dutronc, C Henneges, S Wilhelm, S Hartz, C Paul
BACKGROUND: The interleukin (IL)-23/IL-17 axis has been shown critical in the pathogenesis of psoriasis. OBJECTIVES: To present the primary endpoint (Week 12) and safety/efficacy data up to Week 24 from a head-to-head trial (IXORA-S) of the IL-17A inhibitor, ixekizumab (IXE), vs. the IL-12/23 inhibitor ustekinumab (UST). METHODS: Randomised patients received IXE (160-mg starting dose, then 80 mg every two weeks for 12 weeks, then 80 mg every four weeks, N=136) or UST (45 mg/90 mg weight-based dosing per label, N=166)...
May 19, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28521565/interleukin-17-inhibition-role-in-psoriasis-and-inflammatory-bowel-disease
#8
Megan Hohenberger, Leah A Cardwell, Elias Oussedik, Steven R Feldman
INTRODUCTION: Interleukin 17 (IL-17) antagonism provides a highly effective approach for treating psoriasis. Exacerbations of inflammatory bowel disease have been reported in anti-IL-17 psoriasis trials. AIM: To characterize the relationship between IL-17 inhibition and inflammatory bowel disease. METHODS: A review of English-language articles was performed. Search terms included IL-17, psoriasis, inflammatory bowel disease, secukinumab, ixekizumab and brodalumab...
May 31, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28513835/british-association-of-dermatologists-guidelines-for-biologic-therapy-for-psoriasis-2017
#9
C H Smith, Z K Jabbar-Lopez, Z Z Yiu, T Bale, A D Burden, L C Coates, M Cruickshank, T Hadoke, E MacMahon, R Murphy, C Nelson-Piercy, C M Owen, R Parslew, E Peleva, E Pottinger, E J Samarasekera, J Stoddart, C Strudwicke, V Venning, R B Warren, L S Exton, M F Mohd Mustapa
The overall aim of the guideline is to provide evidence-based recommendations on the use of biologic therapies (adalimumab, etanercept, infliximab, ixekizumab, secukinumab and ustekinumab) in adults, children and young people for the treatment of psoriasis; consideration is given to the specific needs of people with psoriasis and psoriatic arthritis. Biologic therapies have now been in use for over 10 years, and with accrued patient-years exposure and clinical experience, many areas that were covered in previous versions of the guideline are now part of the Summary of Product Characteristics (SPC) and/or routine care so that specific recommendations are redundant (see Toolkit A: Summary of licensed indications and posology for biologic therapy, in Supporting information 2)...
May 17, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28461763/emerging-targeted-therapies-for-plaque-psoriasis-impact-of-ixekizumab
#10
REVIEW
Tiana Kazemi, Benjamin Farahnik, John Koo, Kourosh Beroukhim
BACKGROUND: Recent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17) in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA)-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis. METHODS: We reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28461199/new-structural-formats-of-therapeutic-antibodies-for-rheumatology
#11
Christophe Dumet, Jérémy Pottier, Valérie Gouilleux, Hervé Watier
Pharmaceutical companies strive continuously to develop better medications in order to remain competitive. In the arena of monoclonal antibodies and related biologics (fusion proteins containing an IgG Fc fragment), the thrust is not only toward identifying new targets, but also toward developing new molecular formats. Here, new-generation antibodies used to treat rheumatic diseases are discussed, with emphasis on relations linking structure to pharmacological effects and on the improvements expected from the new formats...
April 28, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28457908/quantitative-evaluation-of-biologic-therapy-options-for-psoriasis-a-systematic-review-and-network-meta-analysis
#12
Zarif K Jabbar-Lopez, Zenas Z N Yiu, Victoria Ward, Lesley S Exton, M Firouz Mohd Mustapa, Eleanor Samarasekera, A David Burden, Ruth Murphy, Caroline M Owen, Richard Parslew, Vanessa Venning, Richard B Warren, Catherine H Smith
Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomised controlled trials (RCTs) makes choosing between them difficult for patients, clinicians and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase and Cochrane for RCTs of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics to one another, methotrexate or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment...
April 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28444889/invasive-fungal-infections-in-paediatric-patients-treated-with-macromolecular-immunomodulators-other-than-tumour-necrosis-alpha-inhibitors
#13
REVIEW
Ioannis Kyriakidis, Athanasios Tragiannidis, Ilse Zündorf, Andreas H Groll
An expanding list of immunomodulatory or immunosuppressive monoclonal antibodies (mAbs) and biologic therapeutics is currently entering clinical practice, particularly in the areas of oncology, transplantation and autoimmune disorders. These agents are directed against molecules or cells involved in inflammation and immunity and may therefore be associated with serious and opportunistic infections. The purpose of this review was to critically analyse the literature on invasive fungal infections (IFIs) occurring in association with mAbs and fusion proteins other than tumour necrosis alpha (TNF-α) inhibitors, including therapeutics modulating T-cell-mediated pathologies (muromonab, abatacept, belatacept, ipilimumab, basiliximab, daclizumab), inducing lymphopenia (alemtuzumab), depleting CD20+ B cells (rituximab) and interfering with various targets (anakinra, natalizumab, blodalumab, ixekizumab and others) with a focus on children, and to provide a framework of evaluating the risk for IFIs in this population...
April 26, 2017: Mycoses
https://www.readbyqxmd.com/read/28370467/the-effect-of-bodyweight-on-the-efficacy-and-safety-of-ixekizumab-results-from-an-integrated-database-of-three-randomised-controlled-phase-3-studies-of-patients-with-moderate-to-severe-plaque-psoriasis
#14
K Reich, L Puig, L Mallbris, L Zhang, O Osuntokun, C Leonardi
BACKGROUND: There is concern that increased bodyweight may impact efficacy of some therapies used to treat psoriasis. OBJECTIVE: To evaluate the effect of bodyweight on response to ixekizumab treatment in patients with moderate-to-severe psoriasis. METHODS: Patients were characterized under three bodyweight categories (<80 kg, 80 to <100 kg, ≥100 kg) in this preplanned subgroup analysis from an integrated database of three multicenter, randomised, double-blind, controlled Phase 3 clinical studies (UNCOVER-1, UNCOVER-2 and UNCOVER-3)...
April 1, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28352182/role-of-il-17-in-plaque-psoriasis-therapeutic-potential-of-ixekizumab
#15
REVIEW
Tessa L Hanley, Zenas Zn Yiu
Developments in the understanding of the immunopathogenesis of psoriasis have identified interleukin (IL)-17 as the key proinflammatory cytokine in the pathogenesis of plaque psoriasis, with the consequent development of drugs that target this cytokine or associated receptors. Ixekizumab is a subcutaneously administered humanized monoclonal antibody, which acts to neutralize IL-17A. This article reviews the role of IL-17 in the pathogenesis of psoriasis, the biological and pharmacokinetics of ixekizumab and the safety profile and the clinical efficacy of ixekizumab in Phase III clinical trials...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28342534/comparison-of-ixekizumab-with-etanercept-or-placebo-in-moderate-to-severe-psoriasis-subgroup-analysis-of-latin-american-patients-in-the-phase-3-randomized-uncover-3-study
#16
F Valenzuela, C de la Cruz Fernandez, R L Galimberti, S Gürbüz, M McKean-Matthews, L Goncalves, R Romiti
BACKGROUND AND OBJECTIVES: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. PATIENTS AND METHODS: Analysis included 102 Latin American patients randomized to receive placebo (n=14), etanercept 50mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80mg every 2 weeks (Q2W; n=29) or every 4 weeks (Q4W; n=29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W...
March 22, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/28322474/efficacy-of-ixekizumab-compared-to-etanercept-and-placebo-in-patients-with-moderate-to-severe-plaque-psoriasis-and-non-pustular-palmoplantar-involvement-results-from-three-phase-3-trials-uncover-1-2-and-3
#17
A Menter, R B Warren, R G Langley, J F Merola, L N Kerr, E B Dennehy, D Shrom, D Amato, Y Okubo, K Reich
BACKGROUND: Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. OBJECTIVE: To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis. METHODS: In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis (UNCOVER-1 (N=1296), UNCOVER-2 (N=1224), UNCOVER-3 (N=1346)) were randomised to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160 mg starting dose, or placebo through week 12...
March 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28319618/new-biologics-in-psoriasis-an-update-on-il-23-and-il-17-inhibitors
#18
Joanna Dong, Gary Goldenberg
As immune-related pathways involved in the pathogenesis of psoriasis are elucidated, new biologic treatments targeting these steps of the psoriatic immune cascade are developed. In this article, we review the literature on IL-23 and IL-17 inhibitors in the pipeline for use in moderate to severe psoriasis. Numerous pipeline biologic therapies, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab, are being investigated in phase 2 and 3 studies to establish the efficacy and safety of these new agents...
February 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28294430/rapid-improvements-in-health-related-quality-of-life-and-itch-with-ixekizumab-treatment-in-randomized-phase-3-trials-results-from-uncover-2-and-uncover-3
#19
C L Leonardi, A Blauvelt, H L Sofen, M Gooderham, M Augustin, R Burge, B Zhu, K Reich
BACKGROUND: Patients with moderate-to-severe psoriasis report impaired health-related quality of life (HRQoL). OBJECTIVE: To assess speed of onset of ixekizumab-induced clinically relevant improvement in HRQoL. METHODS: This post-hoc analysis used pooled data from patients randomized in UNCOVER-2 and UNCOVER-3, and treated with 80 mg ixekizumab every 2 weeks (IXEQ2W), 80 mg ixekizumab every 4 weeks (IXEQ4W), 50 mg etanercept (ETN) twice weekly, or placebo (PBO) for 12 weeks...
March 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28288981/nice-recommends-ixekizumab-for-persistent-severe-plaque-psoriasis
#20
Susan Mayor
No abstract text is available yet for this article.
March 12, 2017: BMJ: British Medical Journal
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