Anti IL-17 in psoriasis

Ly, Karen; Smith, Mary Patricia; Thibodeaux, Quinn; Reddy, Vidhatha; Liao, Wilson; Bhutani, Tina

doi:10.1080/1744666x.2020.1679625

Cited by 67 publications

(60 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL‐17A, IL‐22, and GM‐CSF are mainly derived from Th17 cells and involved in recruiting more inflammatory cells 31 . Previous studies of anti‐IL‐17 antibodies in treating psoriasis revealed a marked efficacy, however, it was not sufficient to change the clinical endpoint 32 . Relatively speaking, IL‐6 is involved in multiple pathways of adaptive immunity with context‐dependent pro and anti‐inflammatory properties.…”

Section: Discussionmentioning

confidence: 99%

In‐depth peripheral CD4⁺ T profile correlates with myasthenic crisis

Huan

Luo

Zhong

et al. 2021

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in‐hospital mortality. We aimed to identify immune signatures using in‐depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally. Methods We studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow‐up visits occurred prospectively from crisis to 6 months off‐mechanical ventilation. The frequencies of 20 CD4+ T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis. Results Patients in crisis exhibited a proinflammatory CD4+T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P < 0.001), Tnaive in Tfh cells (P < 0.001), ICOS−Tfh cells (P = 0.017), and T central memory in Tfh (P = 0.022) compared with controls, and increased frequencies of Tregs (P = 0.026) and Tfh17 (P = 0.045) compared with non‐crisis MG. Cytokine cascade was identified in crisis including the ones associated with Th1 (IL‐1β/2/12p70/18/27/IFN‐γ/TNF‐α), Th2 (IL‐4/5/13), Th17 (IL‐6/17A/21/22/23/GM‐CSF), Th9 (IL‐9), and Treg (IL‐10). Longitudinally, seven immune biomarkers including Tregs, IL‐2/4/17A/IFN‐γ/TNF‐α/GM‐CSF had significant correlations with MG‐activities of daily living score. Interpretation Vigorous inflammatory CD4+ T signatures were identified in MC and are associated with clinical severity. Future research is needed to explore its potential candidacy for therapeutic intervention and predicting impending crisis.

show abstract

Section: Discussionmentioning

confidence: 99%

In‐depth peripheral CD4⁺ T profile correlates with myasthenic crisis

Huan

Luo

Zhong

et al. 2021

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…Recently, a better understanding of the pathophysiology of plaque psoriasis has led to the identification of several promising biological targets. While the pathogenesis of plaque psoriasis is undoubtedly multifactorial, the interleukin-23/T helper 17 pathway has been shown to play a crucial role in the disease [5]. In this pathway, interleukin-17A (IL-17A) is the primary effector: overexpression of this IL-17A results in hyperplasia and an overly robust inflammatory response in epiderma, leading to skin plaques and the systemic inflammation which is characteristic of psoriasis.…”

Section: Introductionmentioning

confidence: 99%

In which patients the best efficacy of secukinumab? Update of a real-life analysis after 136 weeks of treatment with secukinumab in moderate-to-severe plaque psoriasis

Galluzzo

D’Adamio

Silvaggio

et al. 2019

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Background: There is limited long-term, real-world evidence on the efficacy and safety in patients with plaque psoriasis treated with secukinumab. We present results at 136 weeks in a real-world setting with focus on special populations. Research design and methods: Retrospective analysis of 151 patients with chronic plaque psoriasis who initiated treatment with secukinumab between September 2015 and May 2019. Secukinumab 300 mg was administered once weekly for 5 weeks followed by once monthly. Main outcome measures: Clinical and laboratory assessments were performed up to 136 weeks. Results: At 16 weeks, 90%, 79%, and 63% of patients achieved Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100, respectively, compared with 79%, 72%, and 55% of patients after 136 weeks of therapy with secukinumab. Fifteen of the 151 patients experienced an adverse event, the most common of which was candida infection (4%). Biological treatment naïve was significantly associated with response to therapy at 1 and 2 years (P < 0.0001). There were no safety issues in patients with infection with HBV, HCV or mycobacterium tuberculosis. Conclusions: Our results confirm the rapidity of action of secukinumab as well as its long-lasting efficacy and good safety in real-world clinical practice.

show abstract

“…Thus, targeting IL-17 immunologically can be an effective strategy to prevent acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) ( Pacha et al, 2020 ). There are treatment for IL-17 such as IL17 inhibitors ( Hohenberger et al, 2018 ) that are used as standard of care for certain inflammatory conditions ( Ly et al, 2019 ); and further drug repurposing investigation are underway ( Hohenberger et al, 2018 ) including for the viral infection ( de Almeida Nagata et al, 2014 ) and COVID-19 ( Bulat et al, 2020 ). However, there are some limitations as adverse events that limit its scope for SOC and repurposing such as likelihood of nasopharyngitis, infections ( Loft et al, 2020 ), major adverse cardiovascular events (MACE) ( Zeng et al, 2020 ), inflammatory bowel disease (IBD) are some of the prominent AEs ( Loft et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Repurposing Treatment of Wernicke–Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile

Vatsalya

Frimodig

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Coronavirus disease identified in 2019 (COVID-19) can be complicated by the Th17 cell-mediated IL-17 proinflammatory response. We tested if thiamine can effectively lower the Th17 response in a clinical study [Proinflammatory state in alcohol use disorder patients termed as disease controls (DC)] and corroborated the results using an in vitro study. We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19. Three-week 200 mg dose of thiamine was administered to sixteen DC patients. Eight healthy volunteers (HV) were also included in this investigation. A subsequent in vitro study was performed to validate the effectiveness of thiamine [100 mg/day equivalent (0.01 μg/ml)] treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264.7) treated with ethanol. Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19) and effective and safe dose ranges of thiamine. We developed a pharmacokinetic profile for thiamine dose range as a novel intervention strategy in COVID-19. DC group showed significantly elevated proinflammatory cytokines compared to HV. Thiamine-treated DC patients showed significant lowering in IL-17 and increase in the IL-22 levels. In humans, a range of 79–474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm. A literature review showed that several neurological symptoms of COVID-19 (∼45.5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment. Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19. Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role.

show abstract

Anti IL-17 in psoriasis

Cited by 67 publications

References 73 publications

In‐depth peripheral CD4⁺ T profile correlates with myasthenic crisis

In‐depth peripheral CD4⁺ T profile correlates with myasthenic crisis

In which patients the best efficacy of secukinumab? Update of a real-life analysis after 136 weeks of treatment with secukinumab in moderate-to-severe plaque psoriasis

Repurposing Treatment of Wernicke–Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile

Contact Info

Product

Resources

About

Anti IL-17 in psoriasis

Cited by 67 publications

References 73 publications

In‐depth peripheral CD4+ T profile correlates with myasthenic crisis

In‐depth peripheral CD4+ T profile correlates with myasthenic crisis

In which patients the best efficacy of secukinumab? Update of a real-life analysis after 136 weeks of treatment with secukinumab in moderate-to-severe plaque psoriasis

Repurposing Treatment of Wernicke–Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile

Contact Info

Product

Resources

About

In‐depth peripheral CD4⁺ T profile correlates with myasthenic crisis

In‐depth peripheral CD4⁺ T profile correlates with myasthenic crisis