scholarly journals Dupilumab in atopic dermatitis: rationale, latest evidence and place in therapy

2018 ◽  
Vol 9 (9) ◽  
pp. 159-170 ◽  
Author(s):  
Lieneke F.M. Ariëns ◽  
Daphne S. Bakker ◽  
Jorien van der Schaft ◽  
Floor M. Garritsen ◽  
Judith L. Thijs ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Treatment Guidelines ◽  
Human Monoclonal Antibody ◽  
Treatment Algorithm ◽  
Unmet Need ◽  
Current Treatment ◽  
Phase Iii ◽  
Treatment Standards ◽  
Inflammatory Skin Diseases

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The prevalence of AD is increasing and is currently estimated at 10–20% in adults worldwide. In the majority of patients, AD can be adequately controlled with topical treatment or ultraviolet light therapy, but there is a high unmet need for effective and safe therapeutics in patients with more severe or difficult to treat AD. During the past decade, new advances in the understanding of the underlying immune pathogenesis of AD have led to the development of new, more targeted therapies. Dupilumab, a fully human monoclonal antibody targeting the interleukin (IL)-4 receptor α, thereby blocking the IL-4 and IL-13 pathway, is one of the first biologics that has been developed for AD. Dupilumab has shown promising results in phase III trials and has recently been approved by the US Food and Drug Administration and the European Commission for the treatment of moderate to severe AD. With the approval of dupilumab, we are entering a new era of biological therapeutics in AD management. The place of dupilumab should be established in the current treatment standards. Based on current treatment guidelines and experts’ opinions in the management of AD, we have built a proposal for a treatment algorithm for systemic treatment of AD in European countries.

Reimbursement recommendations for cancer drugs supported by phase II evidence in Canada.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14133-e14133
Author(s):  
Regina Li ◽  
Helen Mai ◽  
Kaitlyn Chiasson ◽  
Maureen E. Trudeau ◽  
Kelvin K. Chan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Multivariable Analysis ◽  
Unmet Need ◽  
Current Treatment ◽  
Phase Iii ◽  
Treatment Standards ◽  
Exact Test ◽  
Phase Iii Study ◽  
Positive Recommendation

e14133 Background: Historically, pharmaceutical companies submitted phase III evidence for consideration of public reimbursement; however, phase II data is being more commonly used as primary evidence. Whether submissions with phase II data lead to similar rates of positive reimbursement recommendations as phase III data has not been comprehensively investigated. We compared frequency of reimbursement recommendations between phase II and phase III submissions for oncologic drugs and assessed for factors associated with a positive or conditional recommendation. Methods: We identified all submissions with phase II data from the CADTH pCODR’s expert review committee (pERC) recommendations from July 2011 to July 2019. We identified fourteen binary variables relating to clinical benefit, patient-based values, economic impact, and adoption feasibility. We used Fisher’s exact test to characterize associations between all variables and the final recommendation. We conducted multivariable analysis with logistic regression for three variables: feasibility of phase III study, hematologic indication, and unmet need. Results: We identified 139 submissions with a pERC final recommendation. Twenty-seven (19%) submissions were supported by phase II evidence, with 63% having a positive recommendation in comparison to 82% among submissions with phase III evidence. Clinical benefit (p < 0.001), gap in current treatment standards (p = 0.047), and patient alignment (p = 0.015) were associated with a positive recommendation, whereas the future feasibility of conducting a phase III study was associated with a negative recommendation (p = 0.040). No significant association was found between the recommendation and factors related to cost effectiveness or adoption feasibility. In multivariable analysis, only feasibility of a phase III study was significantly associated with a negative recommendation (p = 0.024, OR = 0.132). Conclusions: Oncologic submissions with phase II data were less likely to be recommended for public reimbursement than phase III studies. Positive or conditional recommendation was more likely if they demonstrated clinical benefit and aligned with patient values. pERC was less likely to recommend a submission with phase II if a phase III trial was either possible or already initiated.

scholarly journals Efficacy of Kampo Medicine in Treating Atopic Dermatitis: An Overview

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Tadamichi Shimizu
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Treatment Options ◽  
Current Treatment ◽  
Term Treatment ◽  
Kampo Medicine ◽  
Inflammatory Skin Diseases ◽  
Long Term Treatment ◽  
Inflammatory Skin

Atopic dermatitis (AD) is a common inflammatory skin disease with recurring episodes of itching and a chronic relapsing course. Current treatment options for AD include topical agents, such as topical corticosteroids and oral antiallergic drugs. Providing effective long-term treatment is sometimes difficult due to the chronic, relapsing nature of AD; therefore, there is a need to identify better therapeutic options with minimal side effects that are well tolerated over the variable course of the disease. Traditional herbal medicine, also known as Kampo medicine in Japan, has a long history and plays a role in the prevention and treatment of various diseases, including AD. Some Kampo medicines are useful for treating inflammatory skin diseases, and there has been increased interest in using Kampo medicine to develop new therapeutic agents for AD. Standard Kampo formulas for AD are effective in removing the symptoms of “Netsu Sho,” “Ketsu-Kyo,” “Ki-Kyo,” and “O-Ketsu.” This paper discusses the efficacy of Kampo medicines in treating AD. Knowledge of the mechanisms of action of Kampo medicines will result in greater choices of pharmacotherapeutic agents for AD.

scholarly journals Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

2021 ◽  
Vol 22 (4) ◽  
pp. 1553
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Jungmin Jeon ◽  
Yun Hoo Park ◽  
Tae-Cheol Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Immune Responses ◽  
Chromatin Remodeling ◽  
Skin Diseases ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Interleukin 4 ◽  
Inflammatory Skin Diseases ◽  
Immune Disorder

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

scholarly journals Itch in Atopic Dermatitis – What Is New?

2021 ◽  
Vol 8 ◽  
Author(s):  
Franz J. Legat
Keyword(s):  
Atopic Dermatitis ◽  
Intracellular Signaling ◽  
Sleep Disturbances ◽  
Skin Diseases ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Inflammatory Skin Diseases ◽  
New Era ◽  
Short And Long Term ◽  
Chronic Pruritus

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

scholarly journals Resources-Stratified Guidelines for Classical Hodgkin Lymphoma

2020 ◽  
Vol 17 (5) ◽  
pp. 1783 ◽  
Author(s):  
Allan Relecom ◽  
Massimo Federico ◽  
Joseph M. Connors ◽  
Bertrand Coiffier ◽  
Irene Biasoli ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Patient Survival ◽  
Treatment Guidelines ◽  
Haematological Malignancy ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Treatment Standards ◽  
Hodgkin Lymphoma Patient ◽  
Resource Levels ◽  
Global Initiative

Hodgkin lymphoma is a haematological malignancy predominantly affecting young adults. Hodgkin lymphoma is a highly curable disease by current treatment standards. Latest treatment guidelines for Hodgkin lymphoma however imply access to diagnostic and treatment modalities that may not be available in settings with restricted healthcare resources. Considerable discrepancies in Hodgkin lymphoma patient survival exist, with poorer outcomes reported in resources-constrained settings. Resources-stratified guidelines for diagnosis, staging and treatment of Hodgkin lymphoma were derived in an effort to optimize patient outcome provided a given setting of available resources. These guidelines were derived based on the framework of the Breast Health Global Initiative stratifying resource levels in basic, core, advanced and maximal categories.

CA184-104: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) with paclitaxel/carboplatin (PC) versus placebo with PC in patients (pts) with stage IV/recurrent non-small cell lung cancer (NSCLC) of squamous histology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7611-TPS7611 ◽  
Author(s):  
Martin Reck ◽  
Haolan Lu ◽  
Greta Gribkoff ◽  
Sabine Maier ◽  
Rachel McGovern ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Human Monoclonal Antibody ◽  
Specific Treatment ◽  
Stage Iv ◽  
Study Drug ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Response Patterns ◽  
Double Blind ◽  
Immune Therapies

TPS7611 Background: Years of research in advanced NSCLC have not improved outcomes for the squamous subtype beyond those of standard platinum doublets. Evidence of responses to immune therapies in NSCLC of squamous cell histology supports investigation in this subtype. Ipi, a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi improved overall survival (OS) in advanced melanoma, with side effects managed using product-specific treatment guidelines; immune-related response criteria (irRC) were derived from WHO criteria to better capture response patterns observed with Ipi. A randomized Phase 2 study of Ipi/PC in Stage IV NSCLC pts showed significant improvement in progression-free survival (PFS), as measured by mWHO or irRC, with a trend toward improved OS, over chemotherapy alone in pts receiving phased Ipi/PC (Ipi started after 2 cycles of PC). Phased Ipi/PC appeared to show efficacy in tumors of squamous histology. Addition of Ipi did not exacerbate PC toxicity, and immune-related adverse events were managed using protocol-specific guidelines. A Phase 3 trial (ClinicalTrials.gov identifier NCT01285609) is examining whether phased Ipi/PC will prolong OS in chemotherapy-naïve pts with squamous NSCLC. Methods: Stage IV/recurrent squamous NSCLC with ECOG 0-1 will be included; pts with CNS metastases or history of autoimmune disease will be excluded. Pts are randomized to receive 2 cycles of PC (175 mg/m2 and AUC=6, respectively; IV), followed by 4 cycles of study drug (Ipi in Arm A, placebo in Arm B; IV) with 4 additional cycles of PC (total 6 cycles). Pts without progressive disease (PD) after induction receive maintenance therapy with blinded study drug Q12W until PD per mWHO. The study will randomize 920 pts 1:1 between arms. The primary endpoint of this study is OS; secondary endpoints include OS among pts who receive blinded therapy, PFS and best overall response rate.

CA184-240: A single-arm, open-label phase II study of vemurafenib followed by ipilimumab in patients with BRAF V600-mutated advanced melanoma (AM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS9103-TPS9103
Author(s):  
F. Stephen Hodi ◽  
Asim Amin ◽  
Yvonne M. Saenger ◽  
Gregory K. Pennock ◽  
Troy H. Guthrie ◽  
...  
Keyword(s):  
Disease Progression ◽  
Treatment Guidelines ◽  
Cytotoxic T Lymphocyte ◽  
Human Monoclonal Antibody ◽  
Resistance Mechanisms ◽  
Braf V600e ◽  
Phase Iii ◽  
Open Label ◽  
Ecog Ps ◽  
Unacceptable Toxicity

TPS9103 Background: Ipilimumab (Ipi), a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte antigen-4 expressed on T cells, and vemurafenib (Vem), a small molecule inhibitor of BRAF V600-mutated kinase, are both approved treatments for AM. Ipi has shown improved overall survival (OS) in two randomized phase III trials of patients with previously treated (3 mg/kg monotherapy) and previously untreated (10 mg/kg plus dacarbazine) AM. Vem has shown improved OS in a randomized phase III trial of patients that harbor the BRAF V600E mutation. The most common drug-related adverse events (AEs) with Ipi monotherapy were immune-related GI tract and skin toxicities, which were generally manageable using treatment guidelines. The most common AEs with Vem were arthralgia, rash, and fatigue. Vem can induce rapid and substantial responses, and resistance mechanisms are a focus of current investigation. This study will evaluate the safety of Vem lead-in followed by Ipi (prior to resistance) in patients with BRAF V600-mutated AM. Methods: An estimated 45 patients will be enrolled. Eligible patients include those ≥18 years old with previously untreated AM, a BRAF V600 mutation, and an ECOG PS of 0 or 1. Major exclusion criteria are primary ocular melanoma, active brain metastases, and autoimmune disease. Patients will initially receive Vem for 6 weeks (960 mg twice daily). After a washout period of 3-10 days (per protocol), patients will be initiated on Ipi at 10 mg/kg (every 3 wk for 4 doses, then once every 12 wk beginning at week 24, until disease progression or unacceptable toxicity). Vem will be restarted at the time of disease progression on Ipi (no minimum time to restart) or unacceptable toxicity on Ipi (restart minimum of 1 mo after the last dose of Ipi). Vem will be restarted at the last dose level tolerated at the end of the lead-in phase. Patients will be followed every 12 weeks for toxicity and/or disease progression, and subsequently will be followed every 12 weeks for survival. The objectives of this study are to estimate the incidence of grade 3-4 drug-related AEs. Exploratory objectives include the evaluation of efficacy (OS). Clinical trial information: NCT01673854.

scholarly journals Relationship between Skin Microbiota and Skin Biophysical Parameters in Inflammatory Skin Disease: A Systematic Review

2021 ◽  
Vol 7 (1) ◽  
pp. 1-6
Author(s):  
Paola Perugini ◽  
Keyword(s):  
Systematic Review ◽  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Bacterial Flora ◽  
Skin Microbiota ◽  
Biophysical Parameters ◽  
Microbial Composition ◽  
Inflammatory Skin Diseases ◽  
Starting Point ◽  
Inflammatory Skin

Many recent studies highlight the importance of skin microbiota for skin health. Alterations in the balance of bacterial flora cause the development of inflammatory skin diseases such as acne, atopic dermatitis, or psoriasis. This systematic review aims to investigate the relationship, in these skin diseases, between skin microbiota and skin biophysical parameters, such as pH, Transepidermal Water Loss (TEWL), Hydration (HI) and sebum levels. Google Scholar, Medline via Pubmed, and Web of Science were considered as scientific database to search studies about this topic. Research about acne and psoriasis did not produce any results. For this reason, in this review, only articles concerning atopic dermatitis were discussed. Therefore, a possible correlation between skin barrier functionality and microbial composition was also investigated. So, this could be a starting point for the diagnosis of atopic dermatitis or, more generally, for all inflammatory skin diseases.

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