Home-based treatment of biologics for asthma: who, what, where, when and why.

INTRODUCTION: The advent of biologic therapies for severe asthma has profoundly changed the management of this pathology. The introduction of home administration is therefore an important innovation to optimize the patients' management, even if there are many aspects that need to be clarified and pointed out. AREAS COVERED: This review summarizes the path that led to the possibility of self-administration of biologics, and what the pandemic has changed in the management of these patients. EXPERT OPINION: The growing understanding of asthma phenotypes and endotypes is enabling the careful selection of patients suitable for biologics. In this context, the availability of reliable and simple self-injection devices is important in implementing self-administration. The transition to self-injection is also possible thanks to the high safety profile of biologics. With attention, most patients may potentially be suitable for self-administration. The transition process from hospital to home administration can therefore be carried out correctly by clinicians with adequate expertise in the field of severe asthma and biologic therapies, with the support of other health professionals, pharmacists, and general practitioners. Home administration is probably the best way to guarantee high adherence and high-level satisfaction of patients, even in the long term.

Focus on Marine Animal Safety and Marine Bioresources in Response to the SARS-CoV-2 Crisis.

SARS-CoV-2 as a zoonotic virus has significantly affected daily life and social behavior since its outbreak in late 2019. The concerns over its transmission through different media directly or indirectly have evoked great attention about the survival of SARS-CoV-2 virions in the environment and its potential infection of other animals. To evaluate the risk of infection by SARS-CoV-2 and to counteract the COVID-19 disease, extensive studies have been performed to understand SARS-CoV-2 biogenesis and its pathogenesis. This review mainly focuses on the molecular architecture of SARS-CoV-2, its potential for infecting marine animals, and the prospect of drug discovery using marine natural products to combat SARS-CoV-2. The main purposes of this review are to piece together progress in SARS-CoV-2 functional genomic studies and antiviral drug development, and to raise our awareness of marine animal safety on exposure to SARS-CoV-2.

[Immuno-inflammatory rheumatic diseases and COVID-19: analysis of clinical outcomes according to the data of the register of patients of the Novosibirsk region receiving therapy with genetically engineered biological drugs].

BACKGROUND: Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic. AIM: To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs. MATERIALS AND METHODS: A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020. RESULTS: According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%. CONCLUSION: Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial.

High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62-90) and 89% ORR (95% CI, 75-97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.

Seroconversion after anti-SARS-CoV-2 mRNA vaccinations among moderate-to-severe psoriatic patients receiving systemic biologicals-Prospective observational cohort study.

It is unclear whether biological antipsoriatic therapies affect seroconversion after messenger ribonucleic acid (mRNA)-based antisevere acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) vaccinations. To assess antibody formation and the incidence of side effects after anti-SARS-CoV-2 mRNA vaccinations in psoriatic patients receiving different biologicals compared to healthy controls. 102 moderate-to-severe psoriatic patients (56.2 [±13.5] years) and 55 age-matched healthy (56.4 ± 13.6 years) volunteers were included in our study. Ten to 21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccine, antibody levels specific to the SARS-CoV-2 spike (S) protein receptor binding domain were monitored. The incidence of postvaccination side effects was recorded and compared to real-life data in the literature. Of the 102 patients, 57 (55.88%) received tumor necrosis factor (TNF), 28 (27.45%) received interleukin (IL)-12/23, 16 (15.68%) received IL-17, and 1 (0.99%) received IL-23 inhibitors. No significant differences in the median serum level of anti-SARS-CoV-2S antibody were observed between the study population and the control group (median IQR range: 1681.0 U/mL (600.0-4844.0) versus 1984.0 U/mL (1000.0-3136.0; p = 0.82). The most frequent side effects of the mRNA vaccines within 7 days after the administration of both dosages were arm pain on the side of injection (23.53% and 23.53%), fatigue (9.80% and 13.72%), headache (4.9% and 5.88%), and chills or shivering (4.9% and 8.82%). Detectable antibodies against SARS-CoV-2S protein appear 10-21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccines in moderate-to-severe psoriatic patients receiving biologicals, similar to those of healthy controls.

The course of COVID-19 in patients with severe asthma receiving biological treatment.

OBJECTIVE: In order to decrease the use of systemic corticosteroids and prevent asthma exacerbations, EAACI and GINA made recommendations in favor of severe asthma patients continuing the use of biologicals during the pandemic. However, the course of SARS-CoV-2 infection remains uncertain, especially in patients taking biological therapy for severe asthma. The aim of this study was to demonstrate the clinical course of COVID-19 in severe asthmatic patients receiving biological treatment. METHODS: A total of 75 patients under the care of a tertiary level allergy clinic and receiving omalizumab or mepolizumab, which are the approved biologicals for severe asthma in Turkey, were included in the survey between April 1 and December 31, 2020. A questionnaire was administered via a telephone call by one of the treating physicians. RESULTS: Of the total patients, 46 (61%) were receiving mepolizumab and 29 (39%) omalizumab. Of the patients, 14 (19%) had COVID-19, 9 (64%) had pneumonia, 4 (29%) were hospitalized. A total of 12 (16%) patients interrupted biological treatments because they did not want to attend hospital for injections during the pandemic. The incidence of COVID-19 was higher in patients who have interrupted biological treatment (p < 0.001). In addition, the risk of having COVID-19 was higher in the ones who have interrupted their biological treatment (Relative risk:2.71; 95% Confidence interval:1.21-6.06). Asthma control was better in patients attending regular injections (p = 0.006). CONCLUSION: Severe asthma itself seems to be a risk factor for COVID-19, whether biological treatment has a role in the disease course needs further research.

Biological therapies, asthma and coronavirus disease 2019.

PURPOSE OF REVIEW: As of June 2021, coronavirus disease 2019 (COVID-19) exceeded 180 million reported cases and was responsible for almost 4 million deaths globally. Asthma affects approximately 262 million people worldwide and is an important cause of morbidity and mortality. Presently, it appears asthma is neither associated with an increased risk of contracting COVID-19 nor with a risk of severe COVID-19 or COVID-19 related death. Regarding the severe asthma patients on biologics, questions remain. The purpose of this review is to discuss the evidence regarding the relationship between asthma, biologics and COVID-19. RECENT FINDINGS: The available evidence does not suggest that severe asthmatics on treatment with biologics have a higher risk of severe acute respiratory syndrome coronavirus 2 infection compared to the general population. It does not appear that they have a higher risk of severe disease or COVID-19 related death either. SUMMARY: This review suggests that treatment with biologics for severe asthma is safe and should be maintained during the COVID-19 pandemic. However, more studies are needed to address this question and the role of biological therapy on different asthma phenotypes.

Safety of biologics in inflammatory bowel disease patients with COVID-19.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) remain highly concerned that either their disease or medications-namely, biologics-may increase the risk of severe coronavirus-2019 (COVID-19). We aimed to assess the safety of biologics in Inflammatory bowel disease (IBD) patients with COVID-19. METHODS: We systematically reviewed multiple databases to find relevant articles reporting the effect of biologics on "severe" COVID-19 in IBD patients. Those in the form of case series (> 10 patients), case-control, and cohort studies were included. Severe COVID-19 was defined as intensive care unit (ICU) admission, mechanical ventilation, and/or mortality. Pooled analysis with multivariate regression was performed. RESULTS: A total of 12 studies with 2681 patients were included. The proportion of females was (48.3%, 95% confidence interval (CI) 47.0-49.5%). The proportion of UC patients was (44.8%, 95% CI 41.0-48.5%). Overall, in IBD patients, the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality was 5.1%, 6.1%, and 4.5%, respectively. Use of biologics did not show a moderating effect on mechanical ventilation (p = 0.68), ICU admission (p = 0.27), or mortality (p = 0.20). CONCLUSIONS: Our findings advocate for the continued biologic therapy in IBD patients during the COVID-19 pandemic. Nevertheless, the incidence, severity, and outcomes related to COVID-19 in IBD patients' needs to be reassessed as data continues to emerge.

The impact of COVID-19 pandemic on psoriasis patients, and their immunosuppressive treatment: a cross-sectional multicenter study from Turkey.

BACKGROUND: Immunosuppressive therapy has been a great concern during the pandemic. This study aimed to evaluate the pandemic's impact on psoriasis patients treated with immunosuppressive drugs. MATERIAL AND METHODS: The multicenter study was conducted in 14 tertiary dermatology centers. Demographic data, treatment status, disease course, and cases of COVID-19 were evaluated in patients with psoriasis using the immunosuppressive treatment. RESULTS: Of 1827 patients included, the drug adherence rate was 68.2%. Those receiving anti-interleukin (anti-IL) drugs were more likely to continue treatment than patients receiving conventional drugs (OR = 1.50, 95% CI, 1.181-1.895, p = .001). Disease worsening rate was 24.2% and drug dose reduction increased this rate 3.26 and drug withdrawal 8.71 times. Receiving anti-TNF or anti-IL drugs was associated with less disease worsening compared to conventional drugs (p = .038, p = .032; respectively). Drug withdrawal causes were 'unable to come' (39.6%), 'COVID concern' (25.3%), and 'physician's and patient's co-decision' (17.4%). Four patients had COVID-19 infection with mild symptoms. The incidence was 0.0022% while it was 0.0025% in the general population. CONCLUSION: Our study shows that psoriasis patients using systemic immunosuppressive do not have a higher, but even lower COVID-19 risk than the general population, and treatment compliance with biological drugs is higher.

Systemic Medications of Dermatological Importance in COVID-19.

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.

Can we safely use systemic treatment in atopic dermatitis during the COVID-19 pandemic? Overview of selected conventional and biologic systemic therapies.

Introduction: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical community has faced major challenges that affect disease management in all areas. Dermatologists and immunologists have to choose appropriate treatment strategy taking into consideration the risk of infection and possible exacerbation of the course of the disease in patients with confirmed infection. Management of atopic dermatitis (AD) in moderate to severe cases is based on systemic therapy such as cyclosporine, azathioprine, methotrexate and dupilumab.Areas covered: A literature search in PubMed database was performed until 6 March 2021. In this review, the authors discuss non-biologic and biologic systemic medications for AD and provide an overview of therapeutic recommendations during COVID-19 pandemic.Expert opinion: In case of an active COVID-19 infection, conventional systemic treatment and biological treatment needs to be stopped until clinical recovery. Noninfected patients with systemic treatment of AD should continue their therapy via self-application. The authors can conclude that understanding of dupilumab therapy is better recognized in context AD treatment during COVID-19 pandemic in comparison to cyclosporine, azathioprine and methotrexate. However, this systemic immunosuppressants still require further investigation and literature complementation.