Teledermatology in the provision of biologics through COVID-19 in a rural dermatology practice-A retrospective review.

COVID-19 compounded existing barriers to healthcare for rural patients. We completed a retrospective chart review of patients receiving Pharmaceutical Benefits Scheme subsidised biologics at a Modified Monash Model 3 dermatology practice during the pandemic and examined factors contributing to successful continuation of care, particularly teledermatology. Our experience is instructive in the provision of medical dermatology to regional patients.

FDA Approvals of Biologics in 2022.

The year 2022 witnessed the control of the COVID-19 pandemic in most countries through social and hygiene measures and also vaccination campaigns. It also saw a decrease in total approvals by the U.S. Food and Drug Administration (FDA). Nevertheless, there was no fall in the Biologics class, which was boosted through the authorization of 15 novel molecules, thus maintaining the figures achieved in previous years. Indeed, the decrease in approvals was only for the category of small molecules. Monoclonal antibodies (mAbs) continued to be the drug class with the most approvals, and cancer remained the most targeted disease, followed by autoimmune conditions, as in previous years. Interestingly, the FDA gave the green light to a remarkable number of bispecific Biologics (four), the highest number in recent years. Indeed, 2022 was another year without the approval of an antimicrobial Biologic, although important advancements were made in targeting new diseases, which are discussed herein. In this work, we only analyze the Biologics authorized in 2022. Furthermore, we also consider the orphan drugs authorized. We not only apply a quantitative analysis to this year's harvest, but also compare the efficacy of the Biologics with those authorized in previous years. On the basis of their chemical structure, the Biologics addressed fall into the following classes: monoclonal antibodies; antibody-drug conjugates; and proteins/enzymes.

Immunogenicity, efficacy, and safety of CoronaVac and Pfizer/BioNTech mRNA vaccines in patients with psoriasis receiving systemic therapies: A prospective cohort study.

BACKGROUND AND OBJECTIVES: Evidence of immune response to COVID-19 vaccine in psoriasis patients on biological agents is lacking. This study aimed to evaluate SARS-CoV-2 antibody levels following vaccination with CoronaVac or Pfizer/BioNTech mRNA in patients using biological agents or methotrexate, high-titer antibody levels achievement rate, and impact of medications on immunogenicity. METHODS: This noninterventional, prospective cohort study included 89 patients and 40 controls vaccinated with two doses of inactivated (CoronaVac) or Pfizer/BioNTech mRNA vaccines. Anti-spike and neutralising antibodies were analysed before and three to six weeks after the second dose. Adverse effects and symptomatic COVID-19 were assessed. RESULTS: Median anti-spike and neutralising antibody titers after CoronaVac were significantly lower in patients than controls (57.92 U/mL vs 125.4 U/mL, and 1/6 vs 1/32, respectively, p < 0.05). Patients were less likely to achieve high-titer anti-spike antibody levels (25.6 % vs 50 %). Infliximab was associated with attenuated vaccine response. Pfizer/BioNTech vaccine induced comparable median anti-spike (2,080 U/mL vs 2,976.5 U/mL,) and neutralising antibody levels (1/96 vs 1/160) in patients and controls, respectively (p > 0.05). High-titer anti-spike and neutralising antibodies development rates were comparable among patients and controls (95.2 % vs 100 %, and 30.4 % vs 50.0 %, respectively, p > 0.05). Nine (10.1 %) COVID-19 cases- all mild - were identified. Psoriasis flare was seen in 6.74 %, mostly after Pfizer/BioNTech vaccine. CONCLUSION: Psoriasis patients treated with biological agents and methotrexate developed similar response to mRNA vaccine but weaker response to inactivated vaccine. Infliximab reduced response to the inactivated vaccine. Adverse effects were more frequent with mRNA vaccine, but none was severe.

Long-Term Efficacy and Safety of Risankizumab for Moderate to Severe Psoriasis: A 2-Year Real-Life Retrospective Study.

Risankizumab is a humanized IgG monoclonal antibody inhibitor of IL23 and has been recently approved by the EMA and the FDA for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. Its efficacy and safety have been reported by clinical trials and real-life studies. However, even if long-term data from trials have already been reported (up to 172 weeks), data on long-term real-life experiences are still limited. The aim of our study was to investigate the long-term (2 years) efficacy and safety of risankizumab for psoriasis management in a real-life setting. A monocentric retrospective study was performed, enrolling 168 patients affected by moderate to severe psoriasis who were undergoing treatment with risankizumab. Psoriasis severity and safety outcomes were evaluated at each follow-up visit (week 16, week 28, week 52, week 88, week 104). A statistically significant reduction of psoriasis severity scores was reported from week 16 and was maintained up to week 104. Moreover, interesting results in terms of safety have been collected, without any serious adverse events registered. Our long-term real-life monocentric retrospective study confirmed the efficacy and safety of risankizumab up to 104 weeks of treatment. However, further studies are required to confirm our results and to increase available data to establish the best evidence-based biologic selection algorithm.

Respiratory Reviews in Asthma 2022.

Asthma is a chronic inflammatory disease of the airways characterized by varying and recurrent symptoms, reversible airway obstruction, and bronchospasm. In this paper, clinical important studies on asthma published between March 2021 and February 2022 were reviewed. A study on the relationship between asthma and chronic rhinosinusitis, bronchiectasis, and hormone replacement therapy was published. A journal on the usefulness of fractional exhaled nitric oxide for the prediction of severe acute exacerbation was also introduced. Studies on the effect of inhaler, one of the most important treatments for asthma, were published. Studies on the control of severe asthma continued. Phase 2 and 3 studies of new biologics were also published. As the coronavirus disease 2019 (COVID-19) pandemic has been prolonged, many studies have explored the prevalence and mortality of COVID-19 infection in asthma patients.

Aerosol pulmonary immune engineering.

Aerosolization of immunotherapies poses incredible potential for manipulating the local mucosal-specific microenvironment, engaging specialized pulmonary cellular defenders, and accessing mucosal associated lymphoid tissue to redirect systemic adaptive and memory responses. In this review, we breakdown key inhalable immunoengineering strategies for chronic, genetic, and infection-based inflammatory pulmonary disorders, encompassing the historic use of immunomodulatory agents, the transition to biological inspired or derived treatments, and novel approaches of complexing these materials into drug delivery vehicles for enhanced release outcomes. Alongside a brief description of key immune targets, fundamentals of aerosol drug delivery, and preclinical pulmonary models for immune response, we survey recent advances of inhaled immunotherapy platforms, ranging from small molecules and biologics to particulates and cell therapies, as well as prophylactic vaccines. In each section, we address the formulation design constraints for aerosol delivery as well as advantages for each platform in driving desirable immune modifications. Finally, prospects of clinical translation and outlook for inhaled immune engineering are discussed.

A Decade of Clinical Advances in Chronic Rhinosinusitis: 2012-2022.

The field of chronic rhinosinusitis (CRS) is constantly evolving. In the past 10 years, key advancements in basic and translational research as well as clinical studies have improved our understanding and management of CRS. Notably, treatment options have expanded to include novel therapeutic drugs, devices, and surgical techniques. Assessments of patient symptoms and their impact on quality of life have become more standardized. Progress has also been made in both determining the true prevalence of CRS and recognizing comorbidities that can impact CRS severity. Practice guidelines have also shifted from expert opinion to more data-driven analyses. This review highlights major clinical advancements made in the field of CRS over the past 10 years as well as identifies current gaps in knowledge that can form the basis for new areas of study over the next decade.

The Impact of Immune-Modulating Treatments for Dermatological Diseases on the Risk of Infection with SARS-CoV-2 and Outcomes Associated with COVID-19 Illness.

Purpose of Review: Immune-modulating treatments are used in dermatology for a variety of conditions. The authors aim to review the data regarding the safety of these treatments during the COVID-19 pandemic, namely the risk of infection with SARS-CoV-2 and the outcomes associated with COVID-19-related illness. Recent Findings: Several large-scale studies found no increased risk of COVID-19 infection for patients on TNF-α inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, dupilumab, and methotrexate. They also found that these patients did not have worse outcomes when infected with COVID-19. The data regarding JAK inhibitors, rituximab, prednisone, cyclosporine, mycophenolate mofetil, and azathioprine are more mixed. Summary: Based on current research and guidelines from the American Academy of Dermatology and the National Psoriasis Foundation, dermatology patients on immune-modulating therapies can continue treatment during the COVID-19 pandemic when they are not infected with SARS-CoV-2. For patients who have COVID-19, guidelines encourage individualized assessment of the benefits and risks of continuing or temporarily withholding treatment.

Safety and Immunogenicity Following the Second and Third Doses of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents with Juvenile-Onset Autoimmune Inflammatory Rheumatic Diseases: A Prospective Multicentre Study.

BACKGROUND: To explore the long-term safety and dynamics of the immune response induced by the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) compared with healthy controls. METHODS: This international prospective study included adolescents with AIIRDs and controls vaccinated with two (AIIRDs n = 124; controls n = 80) or three (AIIRDs n = 64; controls n = 30) doses of the BNT162b2 vaccine, evaluated for vaccine side-effects, disease activity, COVID-19 breakthrough infection rates and severity, and anti-spike S1/S2 IgG antibody titers in a sample from both groups. RESULTS: The vaccination safety profile was favorable, with most patients reporting mild or no side-effects. The rheumatic disease remained stable at 98% and 100% after the second and third doses, respectively. The two-dose vaccine induced comparable seropositivity rates among patients (91%) and controls (100%), (p = 0.55), which declined within 6 months to 87% and 100%, respectively (p = 0.3) and increased to 100% in both groups after the third vaccine dose. The overall post-vaccination COVID-19 infection rate was comparable between patients and controls, 47.6% (n = 59) and 35% (n = 28), respectively; p = 0.5278, with most infections occurring during the Omicron surge. In relation to the last vaccination, time-to-COVID-19 infection was similar between patients and controls, at a median of 5.5 vs. 5.2 months, respectively (log-rank p = 0.1555). CONCLUSION: The safety profile of three doses of the BNT162b2 mRNA vaccine was excellent, with adequate humoral response and similar efficacy among patients and controls. These results support the recommendation for vaccinating adolescents with juvenile-onset AIIRDs against COVID-19.

ADULT STILL'S DISEASE: NEW HORIZONS.

Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.

ADULT STILL'S DISEASE: NEW HORIZONS.

Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.

Immunopharmacology/Musculoskeletal System Pharmacology: Overview

The rapid technological advancement over the past few decades has profoundly influenced the scientific approaches that shape the therapeutic landscape. Undoubtedly, immunopharmacology is an important player in the modern era of transition toward precision medicine that is largely defined by the identification of patient-specific therapies. According to the Immunopharmacology Section - ImmuPhar of the International Union of Basic and Clinical Pharmacology (IUPHAR), immunopharmacology is considered to be the youngest area of pharmacology dealing with the selective modulation, mostly up- or down-regulation, of specific immune responses that are often accomplished by immune cell subsets with specialized functions. Although the recent biotechnological progress has made available new classes of drugs with improved selectivity and/or specificity, agents possessing immunomodulating activities have been used in clinical practice for more than 70years. A pertinent example from the late 1940s is the counteraction of the inflammatory response upon administration of cortisone in patients with rheumatoid arthritis. © 2022 Elsevier Inc. All rights reserved

Formulation of Biologics for Alternative Routes of Administration: Current Problems and Perspectives

Introduction: Biologics (biopharmaceuticals) present new promising therapies for many diseases such as cancers, chronical inflammatory diseases and today's biggest challenge - COVID-19. Research: Today, most biologics have been synthetized using modern methods of biotechnology, in particular DNA recombinant technology. Current pharmaceutical forms of protein/peptide biopharmaceuticals are intended for parenteral route of administration due to their instability and large size of molecules. In order to improve patient compliance, many companies are working on developing adequate forms of biopharmaceuticals for alternative, non-invasive routes of administration. The aim of this work is to review current aspirations and problems in formulation of biopharmaceuticals for alternative (non-parenteral) routes of administration and to review the attempts to overcome them. These alternative routes of administration could be promising in prevention and treatment of COVID-19, among other serious diseases. Conclusion(s): The emphasis is on stabilizing monoclonal antibodies into special formulations and delivery systems;their application should be safer, more comfortable and reliable. When it comes to hormones, vaccines and smaller peptides, some companies have already registered drugs intended for nasal and oral delivery.Copyright © 2022 Sciendo. All rights reserved.

Understanding and Managing Severe Asthma in the Context of COVID-19.

Coronavirus disease 2019 (COVID-19) continues to spread across the world. Since the beginning of the pandemic, the question of whether asthma is a risk factor for getting the infection or for poor outcomes motivated a great debate. In the field of severe asthma and its treatment during COVID-19 pandemic, several issues are also pending. A literature review focused on the management of severe asthma patients in the context of COVID-19 is performed. The available evidence suggests that severe asthma patients do not have an increased risk of poor COVID-19 outcomes and that it is safe to treat asthmatic patients with inhaled corticosteroids (ICS) and biologics during the pandemic, even though some studies indicate that high doses of ICS may predispose to COVID-19. The chronic use of oral corticosteroid (OCS) might be associated with poor COVID-19 outcomes, although there is no complete agreement. There is very limited evidence concerning the use of triple therapy for asthma in the context of this pandemic. Ultimately, severe asthma patients should maintain their medication during the COVID-19 pandemic, including biologic agents. More studies are needed to address the role of asthma medications and asthma's different phenotypes on the incidence and course of COVID-19.

Mapping knowledge structure and research of the biologic treatment of asthma: A bibliometric study.

Background: Bronchial asthma (asthma) is a chronic inflammatory disease of the airways, involving a variety of cells and cellular components, that manifests clinically as recurrent episodes of wheezing, shortness of breath, with or without chest tightness or cough, airway hyperresponsiveness, and variable airflow limitation. The number of people with asthma has reached 358 million worldwide and asthma causes huge economic loss. However, there is a subset of patients who are not sensitive to existing drugs and the existing drugs have many adverse effects. Therefore, it's important to find new drugs for asthma patients. Methods: Publications related to biologics in asthma published from 2000 to 2022 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: TS=(biologic* OR "biologic* product*" OR "biologic* therap*" OR biotherapy* OR "biologic* agent*" OR Benralizumab OR "MEDI-563" OR Fasenra OR "BIW-8405" OR Dupilumab OR SAR231893 OR "SAR-231893" OR Dupixent OR REGN668 OR "REGN-668" OR Mepolizumab OR Bosatria OR "SB-240563" OR SB240563 OR Nucala OR Omalizumab OR Xolair OR Reslizumab OR "SCH-55700" OR SCH55700 OR "CEP-38072" OR CEP38072 OR Cinqair OR "DCP-835" OR DCP835 OR Tezspire OR "tezepelumab-ekko" OR "AMG-157" OR tezspire OR "MEDI-9929" OR "MEDI-19929" OR MEDI9929 OR Itepekimab OR "REGN-3500"OR REGN3500 OR "SAR-440340"OR SAR440340 OR Tralokinumab OR "CAT-354" OR Anrukinzumab OR "IMA-638" OR Lebrikizumab OR "RO-5490255"OR "RG-3637"OR "TNX-650"OR "MILR1444A"OR "MILR-1444A"OR"PRO301444"OR "PRO-301444"OR Pitrakinra OR altrakincept OR "AMG-317"OR"AMG317" OR Etokimab OR Pascolizumab OR "IMA-026"OR Enokizumab OR "MEDI-528"OR "7F3COM-2H2" OR 7F3COM2H2 OR Brodalumab OR "KHK-4827" OR "KHK4827"OR "AMG-827"OR Siliq OR Ligelizumab OR "QGE-031" OR QGE031 OR Quilizumab OR Talizumab OR "TNX-901" OR TNX901 OR Infliximab OR Etanercept OR "PRS-060") AND TS=asthma*. The document type was set to articles and review articles and the language restriction was set to English. Three different analysis tools including one online platform, VOS viewer1.6.18, and CiteSpace V 6.1.R1 software were used to conduct this bibliometric study. Results: This bibliometric study included 1,267 English papers published in 244 journals from 2,012 institutions in 69 countries/regions. Omalizumab, benralizumab, mepolizumab, and tezepelumab in relation to asthma were the research hotspots in the field. Conclusion: This study systematically uncovers a holistic picture of existing literature related to the biologic treatment of asthma over the past 20 years. We consulted scholars in order to understand key information in this field from the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics.

This article reports on an American Society of Pharmacology and Therapeutics, Division of Drug Metabolism and Disposition symposium held at Experimental Biology on April 2nd, 2022, in Philadelphia. As of July 2022, over 500 million people have been infected with SARS-CoV-2 (the virus causing COVID-19) and over 12,000,000,000 vaccine doses have been administered. Clinically significant interactions between viral infections and hepatic drug metabolism were first recognized over 40 years ago during a cluster of pediatric theophylline toxicity cases attributed to reduced hepatic drug metabolism amidst an influenza B outbreak. Today, a substantive body of research supports that the activated innate immune response generally decreases hepatic cytochrome P450 (CYP) activity. The interactions extend to drug transporters and other organs and have the potential to impact drug absorption, distribution, metabolism, and excretion (ADME). Based on this knowledge, altered ADME is predicted with SARS-CoV-2 infection or vaccination. The report begins with a clinical case exploring the possibility of SARS-CoV-2 vaccination increasing clozapine levels. This is followed by discussions of how SARS-CoV-2 infection or vaccines alter the metabolism and disposition of complex drugs, such as nanoparticles and biologics and small molecule therapies. The review concludes with a discussion of the effects of viral infections on placental amino acid transport and their potential to impact fetal development. The session improved our understanding of the impact of emerging viral infections and vaccine technologies on drug metabolism and disposition, which will help mitigate drug toxicity and improve drug and vaccine safety and effectiveness. Significance Statement Altered pharmacokinetics of small molecule and complex molecule drugs and fetal brain distribution of amino acids following SARS-CoV-2 infection or immunization are possible. The proposed mechanisms involve decreased liver CYP metabolism of small molecules, enhanced innate immune system metabolism of complex molecules and altered placental and fetal blood-brain barrier amino acid transport, respectively. Future research is needed to understand the effects of these interactions on adverse drug responses, drug and vaccine safety and effectiveness and fetal neurodevelopment.

Immunotherapy in atopic dermatitis.

In the past decade, the emergence of biologics targeting human cytokine networks has advanced a new era in atopic dermatitis therapy. Dupilumab, in particular, the most widely studied and used IL-4/IL-13 inhibitor, has been considered a milestone in the treatment of patients with moderate-to-severe atopic dermatitis. In addition to the IL-4 and IL-13 pathways, many other cytokines and receptors have been newly targeted as therapeutic options. In this review, the authors provide an overview of the approved and tested biologics and JAK inhibitors for the treatment of atopic dermatitis, including their advantages and limitations.

COVID-19 vaccination in psoriasis patients receiving systemic treatment: A prospective single-center study.

Background: The rate of seroconversion after COVID-19 vaccination in patients with moderate to severe psoriasis requiring systemic treatment is poorly understood. Objectives: The aim of this prospective single-center cohort study performed between May 2020 and October 2021 was to determine the rate of seroconversion after COVID-19 vaccination in patients under active systemic treatment for moderate to severe psoriasis. Methods: Inclusion criteria were systemic treatment for moderate to severe psoriasis, known COVID-19 vaccination status, and repetitive anti-SARS-CoV-2-S IgG serum quantification. The primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination. Results: 77 patients with a median age of 55.9 years undergoing systemic treatment for moderate to severe psoriasis were included. The majority of patients received interleukin- (n=50, 64.9%) or tumor necrosis factor (TNF)-α inhibitors (n=16, 20.8%) as systemic treatment for psoriasis; nine patients (11.7%) were treated with methotrexate (MTX) monotherapy, and one patient each received dimethyl fumarate (1.3%), respectively apremilast (1.3%). All included patients completed COVID-19 vaccination with two doses over the course of the study. Serum testing revealed that 74 patients (96.1%) showed an anti-SARS-CoV-2-S IgG seroconversion. While all patients on IL-17A, -12 or -12/23 inhibitors (n=50) achieved seroconversion, three of 16 patients (18.8%) receiving MTX and/or a TNF-α inhibitor as main anti-psoriatic treatment did not. At follow-up, none of the patients had developed symptomatic COVID-19 or died from COVID-19. Conclusions: Anti-SARS-CoV-2-S IgG seroconversion rates following COVID-19 vaccination in psoriasis patients under systemic treatment were high. An impaired serological response, however, was observed in patients receiving MTX and/or TNF-α inhibitors, in particular infliximab.