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1.
Eur Cytokine Netw ; 32(1): 8-14, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1477642

ABSTRACT

Cytokine release syndrome is a serious complication of the new coronavirus infection (COVID-19). The aim of the study was to assess effectiveness and safety of the IL-17 antagonist nekatimab for its treatment. The retrospective study included COVID-19 patients with C-reactive protein levels >60 mg/L. Patients received either netakimab (group NET), IL-6 antagonist tocilizumab (group TOC) or no anti-cytokine treatment (group CON). Forty-four patients were enrolled in the NET group, 27 patients in the TOC group, and 47 patients in the CON group. Mortality was lower in the NET group than in TOC and CON groups (2.3% vs. 14.8% and 31.9%; p = 0.018 and p < 0.001). NET group patients required intensive care unit admission (6.8% vs. 25.9% and 46.3%; p = 0.025 and p < 0.001) and mechanical ventilation (4.6% vs. 22.2% and 31.9%; p = 0.022 and p = 0.002) less frequently than patients of the TOC and CON groups. After 7-10 days of anti-cytokine drug administration, a reduction in lung lesion volume (p = 0.016) and an increase in the proportion of patients who did not need oxygen support (p = 0.005) or stayed in prone position (p = 0.044) was observed in the NET group only group; C-reactive protein levels were the same in the TOC and NET groups (p = 0.136) and lower in the CON group (p < 0.001 and p = 0.005). IL-6 levels decreased in the NET group (p = 0.005) and did not change in the TOC group (p = 0.953). There was no difference in the incidence of side effects between groups. The IL-17 antagonist netakimab is effective and safe in the treatment of cytokine release syndrome in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Interleukin-17/antagonists & inhibitors , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/virology , Case-Control Studies , Humans , Interleukin-17/metabolism , Interleukin-6/blood , Lung/pathology , Lung/virology , SARS-CoV-2/physiology , Treatment Outcome
2.
Cytokine ; 146: 155627, 2021 10.
Article in English | MEDLINE | ID: covidwho-1293702

ABSTRACT

BACKGROUND: One of the main pathophysiological mechanisms underlying the severe course of COVID-19 is the hyper-inflammatory syndrome associated with progressive damage of lung tissue and multi-organ dysfunction. IL-17 has been suggested to be involved in hyper-inflammatory syndrome. OBJECTIVE: To evaluate the efficacy and safety of the IL-17 inhibitor netakimab in patients with severe COVID-19. STUDY DESIGN: In our retrospective case-control study we evaluated the efficacy of netakimab in hospitalized patients with severe COVID-19 outside the intensive care unit (ICU). Patients in the experimental group were treated with standard of care therapy and netakimab at a dose of 120 mg subcutaneously. RESULTS: 171 patients with severe COVID-19 were enrolled in our study, and 88 of them received netakimab. On the 3 day of therapy, body temperature, SpO2/FiO2, NEWS2 score, and CRP improved significantly in the netakimab group compared to the control group. Other clinical outcomes such as transfer to ICU (11.4% vs 9.6%), need for mechanical ventilation (10.2% vs 9.6%), 28-day mortality (10.2% vs 8.4%), did not differ between the groups. CONCLUSION: In hospitalized patients with severe COVID-19, anti-IL-17 therapy might mitigate the inflammatory response and improve oxygenation, but do not affect the need for mechanical ventilation and mortality.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/therapy , Hospitalization/statistics & numerical data , Inpatients/statistics & numerical data , Interleukin-17/antagonists & inhibitors , SARS-CoV-2/drug effects , Aged , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/virology , Case-Control Studies , Diarrhea/chemically induced , Dyspnea/chemically induced , Female , Humans , Inflammation/complications , Inflammation/drug therapy , Interleukin-17/immunology , Interleukin-17/metabolism , Length of Stay/statistics & numerical data , Male , Middle Aged , Pilot Projects , Respiration, Artificial , Retrospective Studies , SARS-CoV-2/physiology , Severity of Illness Index , Treatment Outcome
3.
Dermatol Ther ; 33(6): e14512, 2020 11.
Article in English | MEDLINE | ID: covidwho-1140193

ABSTRACT

The tuberculosis (TB) burden is high in China, with a 32% prevalence of latent tuberculosis infection (LTBI) in Beijing. Screening for LTBI and the chemoprophylaxis of positive patients are recommended prior to biologic therapy. To evaluate the TB-related safety of secukinumab (SEC) in a cohort of plaque psoriasis patients with LTBI receiving different treatments. Plaque psoriasis patients eligible for SEC treatment were screened for TB. LTBI patients (QuantiFeron-TB test positive, QFT+) receiving SEC were closely monitored by chest radiograph, ESR or hs-CRP, and blood counts every 12 to 20 weeks for active TB infection. QFT_patients receiving SEC treatment were screened for LTBI every 6 to 12 months. Of 42 patients treated with SEC, 19 were QFT+ (45.24%). A QFT_patient became QFT+ after 6 months treatment. Two patients started SEC treatment from 2015 to 2016 and were followed up 268 and 216 weeks later, respectively. Three patients received chemoprophylaxis, 17 did not because of safety concerns or being unable to complete the process. During the 16- to 268-week follow-up, no signs of TB reactivation were observed in the 20 LTBI patients receiving SEC. Plaque psoriasis patients with LTBI who received no chemoprophylaxis could be safely treated with SEC.


Subject(s)
Interleukin-17/antagonists & inhibitors , Latent Tuberculosis , Chemoprevention , China/epidemiology , Cohort Studies , Humans , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Latent Tuberculosis/epidemiology
4.
Viral Immunol ; 34(3): 190-200, 2021 04.
Article in English | MEDLINE | ID: covidwho-1099573

ABSTRACT

The initial immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) includes an interferon-dependent antiviral response. A late and uncontrolled inflammatory response characterized by high activity of proinflammatory cytokines and the recruitment of neutrophils and macrophages develops in predisposed individuals and is potentially harmful in some cases. Interleukin (IL)-17 is one of the many cytokines released during coronavirus disease 2019 (COVID-19). IL-17 is crucial in recruiting and activating neutrophils, cells that can migrate to the lung, and are heavily involved in the pathogenesis of COVID-19. During the infection T helper 17 (Th17) cells and IL-17-related pathways are associated with a worse outcome of the disease. All these have practical consequences considering that some drugs with therapeutic targets related to the Th17 response may have a beneficial effect on patients with SARS-CoV-2 infection. Herein, we present the arguments underlying our assumption that blocking the IL-23/IL-17 axis using targeted biological therapies as well as drugs that act indirectly on this pathway such as convalescent plasma therapy and colchicine may be good therapeutic options.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Th17 Cells/immunology , Adaptive Immunity , Adult , COVID-19/classification , COVID-19/drug therapy , Humans , Immunity, Innate , Interleukin-17/antagonists & inhibitors , Interleukin-17/physiology , Interleukin-23/antagonists & inhibitors , Middle Aged
5.
Dermatol Ther ; 33(5): e13687, 2020 09.
Article in English | MEDLINE | ID: covidwho-1006125

ABSTRACT

Coronavirus disease 2019 (COVID-19) is responsible for at least 2 546 527 cases and 175 812 deaths as of April 21, 2020. Psoriasis and atopic dermatitis (AD) are common, chronic, inflammatory skin conditions, with immune dysregulation as a shared mechanism; therefore, mainstays of treatment include systemic immunomodulating therapies. It is unknown whether these therapies are associated with increased COVID-19 susceptibility or worse outcomes in infected patients. In this review, we discuss overall infection risks of nonbiologic and biologic systemic medications for psoriasis and AD and provide therapeutic recommendations. In summary, in patients with active infection, systemic conventional medications, the Janus kinase inhibitor tofacitinib, and biologics for psoriasis should be temporarily held until there is more data; in uninfected patients switching to safer alternatives should be considered. Interleukin (IL)-17, IL-12/23, and IL-23 inhibitors are associated with low infection risk, with IL-17 and IL-23 favored over IL-12/23 inhibitors. Pivotal trials and postmarketing data also suggest that IL-17 and IL-23 blockers are safer than tumor necrosis factor alpha blockers. Apremilast, acitretin, and dupilumab have favorable safety data and may be safely initiated and continued in uninfected patients. Without definitive COVID-19 data, these recommendations may be useful in guiding treatment of psoriasis and AD patients during the COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , Dermatitis, Atopic/drug therapy , Psoriasis/drug therapy , SARS-CoV-2 , Humans , Immunologic Factors/adverse effects , Interleukin-17/antagonists & inhibitors , Interleukin-23/antagonists & inhibitors , Janus Kinase Inhibitors/adverse effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors
6.
Expert Opin Biol Ther ; 21(2): 271-277, 2021 02.
Article in English | MEDLINE | ID: covidwho-939506

ABSTRACT

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.


Subject(s)
Biological Products/therapeutic use , Biological Therapy/methods , COVID-19/epidemiology , Psoriasis/drug therapy , Adult , Aged , Aged, 80 and over , Biological Products/pharmacology , COVID-19/diagnosis , Chronic Disease , Cohort Studies , Female , Humans , Incidence , Interleukin-17/antagonists & inhibitors , Italy/epidemiology , Male , Middle Aged , Pandemics , Psoriasis/diagnosis , Psoriasis/epidemiology , Receptors, Interleukin/antagonists & inhibitors , Risk Assessment/methods , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Young Adult
8.
J Immunol ; 205(4): 892-898, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-638521

ABSTRACT

SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age >65. The mechanisms underlying the susceptibility to critical illness are poorly understood. Of interest, these comorbidities have previously been associated with increased signaling of Th17 cells. Th17 cells secrete IL-17A and are important for clearing extracellular pathogens, but inappropriate signaling has been linked to acute respiratory distress syndrome. Currently there are few treatment options for SARS-CoV-2 infections. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. These findings provide a basis for testing the potential use of therapies directed at modulation of Th17 cells and IL-17A signaling in the treatment of COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Interleukin-17/antagonists & inhibitors , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Th17 Cells/drug effects , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Critical Illness , Female , Humans , Interleukin-17/metabolism , Male , Pandemics , Pneumonia, Viral/virology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/virology , Risk Factors , SARS-CoV-2 , Signal Transduction/drug effects , Signal Transduction/immunology , Th17 Cells/immunology
12.
Expert Opin Biol Ther ; 20(8): 829-830, 2020 08.
Article in English | MEDLINE | ID: covidwho-574667

ABSTRACT

INTRODUCTION: In light of the current Covid-19 pandemic and the ongoing, extensive debate about the use of biological agents in psoriatic patients, we felt compelled to relate our experience in the use of secukinumab in the same cohort before and during the lockdown in Italy. Areas covered: Secukinumab was not discontinued, and there were no cases of confirmed infection with SARS-CoV-2 in this cohort. Expert opinion: In our practice, there is no evidence favoring the discontinuation of secukinumab in these patients. We also present a brief commentary on the use of biological agents in patients with moderate-to-severe plaque psoriasis.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus , Biological Factors/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Psoriasis/drug therapy , Severity of Illness Index , Aged , Antibodies, Monoclonal, Humanized/pharmacology , Biological Factors/pharmacology , Biological Therapy/methods , COVID-19 , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/immunology , Female , Humans , Interleukin-17/antagonists & inhibitors , Interleukin-17/immunology , Italy , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Psoriasis/complications , Psoriasis/immunology , SARS-CoV-2 , Treatment Outcome
13.
Metabolism ; 109: 154282, 2020 08.
Article in English | MEDLINE | ID: covidwho-457485

ABSTRACT

The most severe presentation of COVID-19 is characterized by a hyperinflammatory state attributed to the massive pro-inflammatory cytokine release, called "cytokine storm". Several specific anti-inflammatory/immunosuppressive agents are being evaluated by ongoing clinical trials; however, there is currently insufficient evidence for their efficacy and safety in COVID-19 treatment. Given the role of phosphodiesterase 4 (PDE) 4 and cyclic adenosine monophosphate in the inflammatory response, we hypothesize that selective PDE4 inhibition may attenuate the cytokine storm in COVID-19, through the upstream inhibition of pro-inflammatory molecules, particularly TNF-α, and the regulation of the pro-inflammatory/anti-inflammatory balance. Conversely, other anti-cytokine agents lead to the downstream inhibition of specific targets, such as IL-1, IL-6 or TNF-α, and may not be efficient in blocking the cytokine storm, once it has been triggered. Due to their mechanism of action targeting an early stage of the inflammatory response and ameliorating lung inflammation, we believe that selective PDE4 inhibitors may represent a promising treatment option for the early phase of COVID-19 pneumonia before the cytokine storm and severe multiorgan dysfunction take place. Furthermore, PDE4 inhibitors present several advantages including an excellent safety profile; the oral route of administration; the convenient dosing; and beneficial metabolic properties. Interestingly, obesity and diabetes mellitus type 2 have been reported to be risk factors for the severity of COVID-19. Therefore, randomized clinical trials of PDE4 inhibitors are necessary to explore their potential therapeutic effect as an adjunct to supportive measures and other therapeutic regiments.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Phosphodiesterase 4 Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , COVID-19 , Coronavirus Infections/etiology , Coronavirus Infections/immunology , Cyclic AMP/metabolism , Humans , Interleukin-17/antagonists & inhibitors , Obesity/complications , Pandemics , Pneumonia, Viral/etiology , Pneumonia, Viral/immunology , SARS-CoV-2
14.
J Thorac Oncol ; 15(7): e101-e103, 2020 07.
Article in English | MEDLINE | ID: covidwho-291629

ABSTRACT

The coronavirus disease 2019 outbreak is evolving rapidly worldwide. The lungs are the target of the primary infection and patients with lung cancer seem to have a poor prognosis. To our knowledge, this is the first reported investigation of a possible role of interleukin-17 target therapy in patients with lung cancer and concomitant severe acute respiratory syndrome-coronavirus-2 infection.


Subject(s)
Betacoronavirus , Coronavirus Infections , Interleukin-17 , Lung Neoplasms , Pandemics , Pneumonia, Viral , Respiratory Distress Syndrome , Betacoronavirus/drug effects , Betacoronavirus/physiology , COVID-19 , Chemokines, CXC/metabolism , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Drug Discovery , Humans , Inflammation/immunology , Interleukin-17/antagonists & inhibitors , Interleukin-17/immunology , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Molecular Targeted Therapy/methods , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/immunology , SARS-CoV-2 , Th17 Cells/immunology , Up-Regulation/drug effects
15.
J Immunother Cancer ; 8(1)2020 05.
Article in English | MEDLINE | ID: covidwho-220167

ABSTRACT

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as 'cytokine storm'. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Immunotherapy , Interleukin-6/antagonists & inhibitors , Interleukin-6/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/drug therapy , Societies, Medical , Adoptive Transfer , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Humans , Inflammation/complications , Inflammation/drug therapy , Inflammation/immunology , Inflammation/pathology , Interferon-gamma/antagonists & inhibitors , Interleukin-1/antagonists & inhibitors , Interleukin-17/antagonists & inhibitors , Interleukin-23/antagonists & inhibitors , Interleukin-6/genetics , Interleukin-6/metabolism , Janus Kinases/antagonists & inhibitors , Neoplasms/immunology , Neoplasms/therapy , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , STAT Transcription Factors/antagonists & inhibitors , Severe Acute Respiratory Syndrome/pathology , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors
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