Spotlight on brodalumab in the treatment of plaque psoriasis: the evidence to date.
Ontology highlight
ABSTRACT:
SUBMITTER: Galluzzo M
PROVIDER: S-EPMC6503649 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Plaque psoriasis is an immune-mediated skin disease that affects roughly 3% of adults in the United States. Advances over the past 20 years in understanding the immune-mediated pathophysiology of psoriasis have led to the development of targeted biologic therapies for this condition. Currently, biologic medications approved for the treatment of plaque psoriasis include tumor necrosis factor ? inhibitors, interleukin (IL)-17 or IL-17 receptor inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors. Tildrakizumab-asmn is a monoclonal antibody that targets the p19 subunit of IL-23 and is approved for use in adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article reviews the current pharmacologic, efficacy, and safety data on tildrakizumab-asmn.
| S-EPMC6120577 | biostudies-literature
Project description:IntroductionPsoriasis is a common chronic, immune-mediated, inflammatory skin disease that in certain localization results difficult to treat. Psoriatic lesions in difficult-to-treat areas might be hardly managed as no standardized therapeutic approach and the application of topical treatments might have great limitations. Systemic agents, including biologic therapies, have been proven effective in treating this subgroup of patients. In particular, current evidence has shown beneficial effects with the use of brodalumab, a fully human IgG2 monoclonal antibody antagonizing the IL-17 receptor A subunit (IL-17RA).ObjectivesThe aim of this narrative review was to collect published data about efficacy and safety of brodalumab in the treatment of psoriasis occurring in difficult-to-treat areas.MethodsData on brodalumab effectiveness and safety deriving from both trials and real-world setting that had been published in the last 15 years were collected for this review, together with clinical findings issued during international meetings.ResultsIn phase 3 trials, brodalumab demonstrated to be effective in promoting a rapid response in scalp psoriasis as well as in generalized pustular psoriasis and erythrodermic psoriasis. Nail psoriasis demonstrated marked clinical improvement after treatment with brodalumab. Amelioration of palmoplantar psoriasis was also described in brodalumab-treated patients. Various retrospective real-world studies reported a complete clearance of psoriatic lesions in difficult-to-treat areas, including genitalia, through short-term brodalumab treatment.ConclusionsBrodalumab, combining rapid and sustained efficacy with a favorable safety profile, may be a valid therapeutic option for severe variants of psoriasis as well as for psoriasis localized in difficult-to-treat areas.
| S-EPMC10412049 | biostudies-literature
Project description:During the 28th Congress of the European Academy of Dermatology and Venereology (EADV) held in Madrid in October 2019, an industry hub was dedicated to the long-term management of psoriasis. Psoriasis is a systemic inflammatory disease primarily involving the skin that affects up to 4% of the European population, the majority of whom present with chronic plaque psoriasis. Topical therapies are well established in the first-line treatment of psoriatic plaque flares. Nevertheless, as psoriasis is a chronic disease, long-term control should be considered. The aim of the session was to provide expert opinion on the benefit of long-term maintenance therapy in chronic plaque psoriasis and introduce the concept of pro-active management to decrease the number of relapses and improve patient quality of life. The current guidelines and recommendations were reviewed, as well as the available data on published clinical trials. There is still an important role for topical therapy in psoriasis and current recommendations suggest a maintenance regimen for psoriasis. Adherence optimization and proactive management of relapse can be key factors for obtaining clinical outcomes in topical long-term therapy. Calcipotriol/betamethasone dipropionate foam is the only topical formulation with long-term data as a twice-weekly proactive treatment approach for up to 52 weeks for chronic plaque psoriasis.
| S-EPMC7397561 | biostudies-literature
Project description:The introduction of biological therapies into clinical practice has dramatically modified the natural history of chronic inflammatory diseases, such as rheumatoid arthritis (RA). RA is a systemic autoimmune disease that causes articular damage and has a great negative impact on patients' quality of life. Despite the wide spectrum of available biological treatments, ~30% of RA patients are still unresponsive, resulting in high disability and increased morbidity and mortality. In the last few decades, the scientific knowledge on RA pathogenesis vastly improved, leading to the identification of new proinflammatory molecules as potential therapeutic targets. Several in vitro and in vivo studies showed that granulocyte-macrophage colony-stimulating factor (GM-CSF), known to be a hematopoietic factor, is also one of the proinflammatory cytokines involved in macrophage activation, crucial for the pathogenic network of RA. Mavrilimumab, a human monoclonal antibody targeting the subunit α of GM-CSF receptor, was recently developed as a competitive antagonist of GM-CSF pathway and successfully adopted in human trials for mild to moderate RA. Mavrilimumab phase I and phase II studies reported an overall good efficacy and safety profile of the drug, and these encouraging results promoted the initiation of worldwide phase III studies. In particular, 158-week results of phase II trials did not show long-term lung toxicity, addressing the major concern about this target of pulmonary alveolar proteinosis development. However, further clinical studies conducted in larger RA populations are needed to confirm these promising results. This review summarizes the biological role of GM-CSF in RA and the preclinical and clinical data on mavrilimumab and other monoclonal antibodies targeted on this pathway as an alternative therapeutic option in RA patients who are unresponsive to conventional biological drugs.
| S-EPMC5245809 | biostudies-literature
Project description:Psoriasis is a chronic, immune-mediated, inflammatory, and debilitating skin disease with significant impact on patients' quality of life. Its pathogenesis is complex and not yet fully understood. However, the IL-23/IL-17 axis is currently considered the main pathogenic pathway in psoriasis. Guselkumab is a fully human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that binds to the p19 subunit of IL-23. It is the first of its class, already approved by the US Food and Drug Administration (FDA), as well as the European Medicines Agency (EMA) for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for either systemic therapy or phototherapy. Several clinical trials have demonstrated potential benefits of guselkumab over other already approved immunomodulators in terms of safety and efficacy. The results of the head-to-head trial ECLIPSE were recently released and are addressed in this review. They contribute to the increasing confidence in guselkumab, demonstrating great potential for long-term treatment of psoriasis. However, further long-term data and additional comparative studies will be essential for positioning guselkumab in the therapeutic armamentarium for psoriasis.
| S-EPMC6668503 | biostudies-literature
Project description:Brodalumab is a fully human monoclonal antibody targeting the IL-17 receptor A leading to an inhibition of the biological effect of IL-17A, IL-17F, IL-17A/F heterodimer, IL-17C and IL-17E isoforms. It has shown to be efficacious in the treatment of moderate to severe plaque psoriasis (210 mg administered subcutaneously at weeks 0, 1 and 2 followed by 210 mg every 2 weeks [Q2W+1]). A population pharmacokinetic model based on psoriasis patients only from six clinical trials was developed to describe the pharmacokinetics and identify sources of variability. In patients with psoriasis, Brodalumab exhibits non-linear pharmacokinetics due to target-mediated drug disposition resulting in concentration-dependent clearance. The pharmacokinetics was best described by a two-compartment model with linear absorption and combined linear and Michaelis-Menten elimination. The subcutaneous bioavailability of Brodalumab was 55%, absorption rate was 0.30 day-1 , and body-weight was found to affect the volume of distribution and clearance. For a reference patient with plaque psoriasis (body-weight of 90 kg), the estimates were 0.16 L/d for linear serum clearance, 6.1 mg/d for the maximum non-linear clearance rate, and 4.7 and 2.4 L for central and peripheral volume of distribution, respectively. For the approved dosing regimen, time to maximum concentration was 4 days and 90% of steady-state was achieved after 10 weeks for a reference patient. Following last dose at steady-state, 90% of the population of reference patients will reach serum concentrations below lower limit of quantification after 45 days.
| S-EPMC6850607 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease primarily affecting synovial joints and is characterized by persistent high-grade systemic inflammation. Proinflammatory cytokines, particularly interleukin-6 (IL-6), are of crucial importance in the pathogenesis of the disease, driving both joint inflammation and extra-articular comorbidities. Tocilizumab, a humanized IL-6 receptor-inhibiting monoclonal antibody, has been the first, and, to date, the only, IL-6 inhibitor approved for the treatment of RA. Many studies have demonstrated the potency and effectiveness of tocilizumab in controlling disease activity and radiological progression of RA. These successful results have encouraged the development of novel IL-6 inhibitors, among which a promising agent is sirukumab (SRK), a human anti-IL-6 monoclonal antibody currently under evaluation in Phase II/III studies in patients with RA, systemic lupus erythematosus, giant-cell arteritis, and major depressive disorder. The evidence to date indicates SRK as an effective and well-tolerated new therapeutic tool for patients with active RA, with some preliminary data suggesting a specific beneficial impact on relevant systemic complications associated with the disease, such as depression and cardiovascular disease. Conversely, although pathophysiological considerations make plausible the hypothesis that IL-6 blockade with SRK may also be beneficial in the treatment of many diseases other than RA (either autoimmune or not), available clinical data in patients with systemic lupus erythematosus do not seem to support this view, also giving rise to potentially relevant concerns about drug safety. If large Phase III clinical trials currently in progress in patients with RA confirm the efficacy and tolerability of SRK, then in the long term, this drug could, in the near future, occupy a place in the treatment of the disease, potentially also opening the doors to a more extended use of SRK in a wide range of disorders in which IL-6 plays a key pathogenic role.
| S-EPMC5044992 | biostudies-literature
Project description:Despite advances in the treatment of multiple myeloma, it remains an incurable disease, with relapses and resistances frequently observed. Recently, immunotherapies, in particular, monoclonal antibodies, have become important treatment options in anticancer therapies. Elotuzumab is a humanized monoclonal antibody to signaling lymphocytic activation molecule F7, which is highly expressed on myeloma cells and, to a lower extent, on selected leukocyte subsets such as natural killer cells. By directly activating natural killer cells and by antibody-dependent cell-mediated cytotoxicity, elotuzumab exhibits a dual mechanism of action leading to myeloma cell death with minimal effects on normal tissue. In several nonclinical models of multiple myeloma, elotuzumab was effective as a single agent and in combination with standard myeloma treatments, supporting the use of elotuzumab in patients. In combination with lenalidomide and dexamethasone, elotuzumab showed a significant increase in tumor response rates and progression-free survival in patients with relapsed and/or refractory multiple myeloma. This review summarizes the nonclinical and clinical development of elotuzumab as a single agent and in combination with established therapies for the treatment of multiple myeloma.
| S-EPMC5063562 | biostudies-literature
Project description:IntroductionBrodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited.MethodsThe aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients' demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded.ResultsAt week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab.ConclusionOur data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.
| S-EPMC10352451 | biostudies-literature
Project description:Asthma is a heterogeneous disease, which may be classified into phenotypes and endotypes based on clinical characteristics and molecular mechanisms. The best described endotype of severe asthma is type 2 (T2)-high asthma, characterized by release of inflammatory cytokines by T helper 2 (TH2) cells and type 2 innate lymphoid cells cells. Prostaglandin D2 contributes to T2 inflammation through binding of the G-protein-coupled receptor chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2). Fevipiprant is an oral competitive antagonist of CRTH2. Early-phase trials have demonstrated safety and potential efficacy in patients with asthma, specifically, improvement in FEV1 and eosinophilic airway inflammation. However, no clear biomarker identified patients who responded favorably to fevipiprant, although patients with moderate-to-severe asthma and evidence of T2 inflammation may be more likely to respond to treatment. Additional studies are needed to determine the efficacy and target population for use of this drug in patients with asthma.
| S-EPMC6324611 | biostudies-literature