Biologics Research Articles

Tuning the Response of Synthetic Mechanogenetic Gene Circuits using Mutations in TRPV4.

Conventional gene therapy approaches for drug delivery generally rely on constitutive expression of the transgene and thus lack precise control over the timing and magnitude of delivery. Synthetic gene circuits with promoters that are responsive to user-defined stimuli can provide a molecular switch that can be utilized by cells to control drug production. Our laboratory has previously developed a mechanogenetic gene circuit that can deliver biologic drugs, such as interleukin-1 receptor antagonist (IL-1Ra), on-demand via the activation of TRPV4, a mechanosensory ion channel that has been shown to be activated transiently in response to physical stimuli such as physiologic mechanical loading or hypo-osmotic stimuli. The goal of this study was to use mutations in TRPV4 to further tune the response of this mechanogenetic gene circuit. Human iPSC-derived chondrocytes harboring targeted gain-of-function mutations of TRPV4 were chondrogenically differentiated. Both mutants - V620I and T89I - showed greater total IL-1Ra production compared to wild type following TRPV4 agonist treatment as well as mechanical or osmotic loading, but with altered temporal dynamics. Gene circuit output was dependent on the degree of TRPV4 activation secondary to GSK101 concentration or strain magnitude during loading. V620I constructs secreted more IL-1Ra compared to T89I across all experimental conditions, indicating that two mutations that cause similar functional changes to TRPV4 can result in distinct circuit activation profiles that differ from wild-type cells. In summary, we successfully demonstrate proof-of-concept that point mutations in TRPV4 that alter channel function can be used to tune the therapeutic output of mechanogenetic gene circuits.

Psoriatic arthritis, biologic therapy experience, body mass index, and onset age of psoriasis were independent factors of secukinumab discontinuation in patients with psoriasis

ABSTRACT Introduction Despite the availability of several treatments for psoriasis (PsO), factors influencing the persistence of secukinumab (SEC) therapy remain inadequately understood. This study aimed to identify predictors of SEC persistence in PsO. Methods A retrospective analysis was conducted on 109 PsO patients who received SEC treatment at least 1 year. Patients were categorized based on continued or discontinued SEC therapy. Results Among the 109 patients, 64 continued SEC treatment while 45 discontinued. Univariate analysis demonstrated that PsA presence and previous biologic therapy use increased the risk of SEC discontinuation 3.56- and 2.33-fold (p = 0.001, %95 CI: 1.66–7.65 and p = 0.032, %95 CI: 1.08–5.04, respectively). Additionally, the risk of SEC discontinuation is 57% higher in patients with a body mass index (BMI) above 26.5 compared to those with a BMI below 26.5 (p = 0.016, %95 CI: 0.22–0.85). Additionally, patients with PsO onset age below 26.5 years were found to have a 2.93-times higher risk of discontinuing SEC compared to those with PsO onset age above 26.5 years (p = 0.004, %95 CI: 1.40–6.13). Conclusion PsA presence, previous biologic therapy experience, BMI, and PsO onset age were identified as independent predictors of SEC discontinuation. These findings underscore the importance of personalized treatment strategies for PsO patients receiving SEC therapy.

Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritis

BackgroundThe Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at...

Designer Solvents for Pharmaceutics: Role of Ionic Liquids/ Deep Eutectic Solvents in Pharmaceutical Formulations

AbstractThe design of biologic and synthetic drugs in the pharmaceutical industry is facing three key challenges, namely, ensuring bioavailability, solubility, and stability. Ionic liquids (ILs) and deep eutectic solvents (DESs), classified as designer solvents, have emerged as excellent solvents for improving the permeability and stability of biotherapeutic drugs. Moreover, they have shown remarkable solubilizing effects for synthetic drugs, particularly in solubilizing active pharmaceutical ingredients (API), and are known as eco‐friendly solvents. Thus, in this review, the development of designer formulations in pharmaceutical industries is reported, and the underlying strategies for designing the most efficient formulations for both biotherapeutics and synthetic drugs are examined.

Filling the gaps in peptide maps with a platform assay for top-down characterization of purified protein samples.

Liquid chromatography-mass spectrometry (LC-MS) intact mass analysis and LC-MS/MS peptide mapping are decisional assays for developing biological drugs and other commercial protein products. Certain PTM types, such as truncation and oxidation, increase the difficulty of precise proteoform characterization owing to inherent limitations in peptide and intact protein analyses. Top-down MS (TDMS) can resolve this ambiguity via fragmentation of specific proteoforms. We leveraged the strengths of flow-programmed (fp) denaturing online buffer exchange (dOBE) chromatography, including robust automation, relatively high ESI sensitivity, and long MS/MS window time, to support a TDMS platform for industrial protein characterization. We tested data-dependent (DDA) and targeted strategies using 14 different MS/MS scan types featuring combinations of collisional- and electron-based fragmentation as well as proton transfer charge reduction. This large, focused dataset was processed using a new software platform, named TDAcquireX, that improves proteoform characterization through TDMS data aggregation. A DDA-based workflow provided objective identification of αLac truncation proteoforms with a two-termini clipping search. A targeted TDMS workflow facilitated the characterization of αLac oxidation positional isomers. This strategy relied on using sliding window-based fragment ion deconvolution to generate composite proteoform spectral match (cPrSM) results amenable to fragment noise filtering, which is a fundamental enhancement relevant to TDMS applications generally.

Patterns of recurrence in patients with CRSwNP who underwent complete FESS.

To analyze recurrence patterns of chronic sinusitis with nasal polyposis (CRSwNP) in patients who underwent complete FESS and identify predisposing factors for different patterns of recurrence. Retrospective analysis of patients with CRSwNP who underwent complete FESS at our tertiary medical center. Recurrence patterns were classified into edema, polyp and normal endoscopy, as well as into early (within 6 months) and late recurrence. Statistical analysis to identify risk factors for recurrence included univariate, multivariate logistic regression and cox regression models. 114 patients were included with an average follow-up of 27 months. 91% were categorized as type-2 inflammation. Recurrence was observed in 65.8% of patients within a mean of 12.9 months. 46.7% had polyp recurrence while 53.3% had edema recurrence. Early recurrence was observed in 41%. Serum eosinophilia > 500 cells/uL was found to be significantly associated with recurrence (RR = 1.62, p-value = 0.046), and particularly with polyp recurrence (RR = 3.9, p-value = 0.001). No predictive factors for early recurrence were identified. Edema recurrence was managed with intranasal corticosteroids while polyp recurrence required systemic therapy including biologic therapy. In this study, two thirds of patients experienced post operative recurrence, either mucosal edema or nasal polyps, with similar frequency during an average follow up of over 2 years. Early recurrence was noted in 41% of recurrent cases. Serum eosinophils > 500 cells/uL was the only risk factor for recurrence on multivariate analysis, more accurate markers are needed for improved treatment allocation to CRSwNP patients.

How to integrate surgery and targeted therapy with biologics for the treatment of hidradenitis suppurativa: Delphi consensus statements from an Italian expert panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified ten areas of interest based on published evidence and personal experience: 1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); 2) tailoring surgery to HS characteristics; 3) wide local excision; 4) pre-surgery biologic treatment; 5) concomitant biologic and surgical treatments; 6) pre- and post-surgery management; 7) antibiotic systemic therapy; 8) biologic therapy after radical surgery; 9) management of adverse events to biologics; 10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Mental Manifestations and Biomarkers of Alcohol Consumption

The purpose of this study is to examine healthcare usage, morbidities, and alcohol consumption monitoring in patients before a diagnosis of mental manifestations to assist in the early identification of individuals at risk. Biological markers of alcoholism are separated into two groups: those biological variables that highlight with great confidence and validate the presence of a predisposition to alcoholism, also called trait markers, or those that highlight alcohol consumption, called markers of alcoholism (“status markers”). Biomarkers are the true “gold standard” for the diagnosis of alcoholism. They are valuable for tracking evolution and progress during biological and psychological therapy and for highlighting relapse. This review compiles the existing data from research on healthcare utilization, comorbidities, and alcohol consumption monitoring in patients before a diagnosis of mental manifestations to aid in the early identification of individuals at risk. This documentary study took place over three to four months by searching for terms on the Science Direct platform, PubMed, Web of Science, and Google Scholar such as alcoholism, alcohol use disorders, alcohol abuse, and biomarkers. Studies reporting on the development, characteristics, and utilization of blood biomarkers for alcohol consumption were included in the search. The initial search included a number of 11.019 articles that contained the keywords biomarkers and alcohol. Finally, a total of 50 research articles were considered. I am involved in clinical studies, meta-analyses, reviews, and case studies regarding alcohol consumption detection, as well as potential alcohol markers.

Assessment of Analytical Techniques for Precise Quantification of Four Antiviral Drugs in Pharmaceutical Research and Development: A Comprehensive Review

Abstract: Precise measurement of drug concentration in pharmaceutical research is critical, especially for anti-viral drugs like boceprevir, elvitegravir, indinavir, and saquinavir that combat viral infections. It is well-known that analytical techniques play an imperative role in identifying and characterizing active pharmaceutical ingredients in biological samples and drug formulations. Moreover, precise drug assessment directly influences safety, stability, and efficacy while providing in-depth insight into drug pharmacokinetics. Other than this, analytical techniques also aid in identifying impurities, deteriorated products, and potential pollutants. Thus, reliable analytical methods have become crucial for addressing challenges imposed by complex drug formulations. The most commonly used analytical technique is UV spectrophotometry, which does not have the high sensitivity to detect complex drug formulations. In contrast, Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) merges two analytical techniques, chromatography and mass spectrometry, to accurately quantify biological samples. Furthermore, Ultra-Performance Liquid Chromatography (UPLC) provides enhanced resolution, faster analysis in short duration, and low solvent consumption in contrast to HPLC. This comprehensive review aims to critically assess each analytical approach's accuracy, applicability, selectivity, and limitation to provide valuable insights for researchers and analysts. Understanding the weaknesses and strengths of these analytical techniques will enable the researchers to select the suitable analytical method based on their needs and requirements for quality assessment, precise drug quantification, and optimal therapeutic efficiency. Eventually, this review intends to advance pharmaceutical research and development, specifically for anti-viral drugs, by ensuring the effective and secure administration of therapies.

Editorial: Biological therapy for allergic diseases: peculiarities, prospects, and challenges

Editorial: Biological therapy for allergic diseases: peculiarities, prospects, and challenges

Clinical Characteristics of Necrotizing Enterocolitis Diagnosed by Independent Adjudication of Abdominal Radiographs, Laparotomy, or Autopsy in Preterm Infants in the "Connection Trial".

Necrotizing enterocolitis (NEC) classically is diagnosed by radiographic demonstration of pneumatosis intestinalis/portal venous gas (PI/PVG). This study examines clinical characteristics of NEC confirmed by independent evaluation of abdominal radiographs, taken for clinical signs of NEC, or by pathologic findings at laparotomy or autopsy (confirmed NEC [cNEC]). The investigated cohort included 1,382 extremely low birth weight (BW) infants (BW range: 500-1,000 g) with median 27 weeks (range: 23-32) gestational age (GA) at birth. They were randomized into the placebo-controlled "Connection Trial" of the new biological drug candidate IBP-9414 with cNEC as one primary endpoint. Total 119 infants (8.6%) had cNEC diagnosed at median 14 days of age by confirming PI/PVG at X-ray adjudication (n = 111) and/or by surgery/autopsy (n = 21). Sixteen percent of cNEC cases died. Adverse events of NEC were reported in 8.5% of infants and 4.1% had NEC diagnosed by radiology and surgery/autopsy at the participating centers. Regression analyses showed that the risk of cNEC decreased by 11 to 30% for every 100-g increment in BW and single-week increment in GA and associated cNEC with odds ratios (ORs) > 2.0 for gastrointestinal (GI) perforation and obstruction, hypotension, hypokalemia, hypophosphatemia, and death. Comparing risks of cNEC in infants below and above 750-g BW showed higher ORs (2.7-4.3) for GI perforation, hypotension, hypokalemia, and renal complications in the smaller infants, whereas the bigger infants had higher ORs (1.9-3.2) for serious non-GI events, late-onset sepsis (LOS), and death. Predictors of cNEC (hazard ratio, HR > 1.5) included serious non-GI events (mainly infections), hyponatremia, and hyperglycemia, whereas the HR was 0.52 for intravenous antibiotics. After cNEC diagnosis, there were higher rates of GI perforation and obstruction, hypotension, hypokalemia, and LOS. Independent adjudication of abdominal radiographs increased radiological recognition of NEC and proved to be feasible in a multicenter study setting as well as able to diagnose clinically relevant NEC. · Independent adjudication of abdominal radiographs in ELBW infants increased NEC recognition.. · Risk of NEC decreased by 11 to 30% with every 100-g increment in BW and GA week.. · In infants with BW 750 to 1,000 g, the risk of death from NEC was almost twice that in infants with BW 500 to 749 g. · Infants with NEC received antibiotics during one-third and parenteral nutrition during half of the first 7 postnatal weeks..

Clinical Characteristics of Necrotizing Enterocolitis Diagnosed by Independent Adjudication of Abdominal Radiographs, Laparotomy, or Autopsy in Preterm Infants in the "Connection Trial".

Necrotizing enterocolitis (NEC) classically is diagnosed by radiographic demonstration of pneumatosis intestinalis/portal venous gas (PI/PVG). This study examines clinical characteristics of NEC confirmed by independent evaluation of abdominal radiographs, taken for clinical signs of NEC, or by pathologic findings at laparotomy or autopsy (confirmed NEC [cNEC]). The investigated cohort included 1,382 extremely low birth weight (BW) infants (BW range: 500-1,000 g) with median 27 weeks (range: 23-32) gestational age (GA) at birth. They were randomized into the placebo-controlled "Connection Trial" of the new biological drug candidate IBP-9414 with cNEC as one primary endpoint. Total 119 infants (8.6%) had cNEC diagnosed at median 14 days of age by confirming PI/PVG at X-ray adjudication (n = 111) and/or by surgery/autopsy (n = 21). Sixteen percent of cNEC cases died. Adverse events of NEC were reported in 8.5% of infants and 4.1% had NEC diagnosed by radiology and surgery/autopsy at the participating centers. Regression analyses showed that the risk of cNEC decreased by 11 to 30% for every 100-g increment in BW and single-week increment in GA and associated cNEC with odds ratios (ORs) > 2.0 for gastrointestinal (GI) perforation and obstruction, hypotension, hypokalemia, hypophosphatemia, and death. Comparing risks of cNEC in infants below and above 750-g BW showed higher ORs (2.7-4.3) for GI perforation, hypotension, hypokalemia, and renal complications in the smaller infants, whereas the bigger infants had higher ORs (1.9-3.2) for serious non-GI events, late-onset sepsis (LOS), and death. Predictors of cNEC (hazard ratio, HR > 1.5) included serious non-GI events (mainly infections), hyponatremia, and hyperglycemia, whereas the HR was 0.52 for intravenous antibiotics. After cNEC diagnosis, there were higher rates of GI perforation and obstruction, hypotension, hypokalemia, and LOS. Independent adjudication of abdominal radiographs increased radiological recognition of NEC and proved to be feasible in a multicenter study setting as well as able to diagnose clinically relevant NEC. · Independent adjudication of abdominal radiographs in ELBW infants increased NEC recognition.. · Risk of NEC decreased by 11 to 30% with every 100-g increment in BW and GA week.. · In infants with BW 750 to 1,000 g, the risk of death from NEC was almost twice that in infants with BW 500 to 749 g. · Infants with NEC received antibiotics during one-third and parenteral nutrition during half of the first 7 postnatal weeks..

Features of psoriasis treatment with infection COVID-19

Background. Today, one of the difficult tasks in modern dermatology is the management of patients with chronic dermatoses, including psoriasis, due to a new coronavirus infection. The general condition of the patients, as well as concomitant therapy for the underlying disease, may subsequently produce severe side effects and complicate the treatment of concomitant skin pathology in patients in this category. Aim. The purpose of our study was to optimize the treatment of patients with psoriasis against the background of COVID-19 infection. Methods. Our study included 34 patients with psoriasis who were hospitalized at the Zangiota Clinical Hospital, specializing in patients with COVID-19 infection from 2020 to 2022. Also, all patients were divided according to the severity of the underlying disease according to the “Temporary recommendations for the management of patients infected with COVID-19”, fifth version of 2020. The severity of the psoriatic process was assessed using the PASI index. Results. If patients have a psoriatic process, it is more rational to use biological drugs for the treatment of COVID-19 infection due to the absence of exacerbation of the psoriatic process in dynamics. Conclusion. Treatment of patients with COVID-19 infection with casivirimab + imdevimab showed a positive effect on the dynamics of skin elements and the absence of relapses during three months of observation. While standard therapy for coronavirus infection gives a good regression of skin elements on the 10th day of therapy, after a month there is a progression of the skin process, the appearance of itching and new elements of psoriasis.

Research perspective in the clinical management of Kawasaki disease.

This study examines research perspective in the clinical diagnosis, treatment, and prevention of cardiovascular complications in Kawasaki Disease (KD). Starting with an overview of the disease, it introduces KD's clinical manifestations, etiology, epidemiological features, and its impact on the cardiovascular system. Subsequently, the study discusses in detail the diagnostic methods, pathological mechanisms, and treatment strategies for KD, including foundational and emerging approaches such as high-dose intravenous immunoglobulin and aspirin therapy, biologic therapy, and corticosteroid pulse therapy. Additionally, it outlines strategies for preventing cardiovascular complications, including early risk assessment and long-term management. The study also explores the intersection of the COVID-19 pandemic with an increase in KD-like symptoms, emphasizing the need for further studies on the association between SARS-CoV-2 and KD. Lastly, it explores future research directions to enhance understanding of KD and improve patient outcomes and quality of life. This study provides valuable insights into the comprehensive treatment and management of KD and highlights avenues for future research.

A REVIEW OF ANIMAL MODELS FOR BONE FRACTURE NONUNION AND THEIR ROLE IN STUDYING BIOLOGICAL THERAPY EFFICACY

The bone healing impairment, such as non-union fractures after injuries of long bones, lead to loss of working capacity and result in significant financial costs, which emphasizes the socioeconomic significance of the problem. However, it is not known which method of modeling the non-union bone fractures is more optimal for further research into the effectiveness of biological therapy aimed at treating bone healing impairment. For a detailed study of methods of non-union fracture treatment of, it is necessary to determine the developed animal models. The objective was to analyze the existing animal models of fracture nonunion in long bones in vivo and to consider the possibility of their further use to evaluate the effectiveness of the use of modern biotechnologies for the in the management of fracture nonunion. It was found that the majority of developed animal models of atrophic long bone non-union were created using small animals, namely rats, mice, and rabbits. A more common method of modeling bone non-union is performing an osteotomy with the formation of a defect of different widths between the bone fragments and subsequent removal of the periosteum proximal and distal to the osteotomy site; damage to the endosteum or removal of bone marrow. Also, in such animal models, researchers use a silicone spacer, a polysulfone plate, or a latex-silicone foil to physically prevent fracture union. In these animal models, studies using mesenchymal stromal cells, platelet-rich plasma or bone morphogenetic protein-2 (BMP-2) have already been conducted for the management of non-union bone fractures. At the same time, the clinical results of the application of various biological therapies are ambiguous, which determines the conduct of further experimental studies, in particular, in vivo. However, there are disagreements about which in vivo modeling methods give a reproducible result and prevent bone union, which determines the need for further analysis of existing modeling tools for conducting research in this direction.

Research perspective in the clinical management of Kawasaki disease

This study examines research perspective in the clinical diagnosis, treatment, and prevention of cardiovascular complications in Kawasaki Disease (KD). Starting with an overview of the disease, it introduces KD's clinical manifestations, etiology, epidemiological features, and its impact on the cardiovascular system. Subsequently, the study discusses in detail the diagnostic methods, pathological mechanisms, and treatment strategies for KD, including foundational and emerging approaches such as high-dose intravenous immunoglobulin and aspirin therapy, biologic therapy, and corticosteroid pulse therapy. Additionally, it outlines strategies for preventing cardiovascular complications, including early risk assessment and long-term management. The study also explores the intersection of the COVID-19 pandemic with an increase in KD-like symptoms, emphasizing the need for further studies on the association between SARS-CoV-2 and KD. Lastly, it explores future research directions to enhance understanding of KD and improve patient outcomes and quality of life. This study provides valuable insights into the comprehensive treatment and management of KD and highlights avenues for future research.

IBD Patients with Primary or Secondary Nonresponse to Ustekinumab Benefit from Dose Escalation or Reinduction

Ustekinumab is a monoclonal antibody approved for the treatment of IBD. This drug has a well-established efficacy; however, patients may not respond or lose response. The availability of other biological therapies prompts the need for comparative data between different agents to suggest first- or second-line strategies. Aim of this review is to compare the effectiveness of ustekinumab to other biologics in Crohn’s disease and ulcerative colitis, as well as report the available data on dose escalation and reinduction. A systematic electronic search of the English literature was performed up to November 2023, using Medline (PubMed), Web of Science, Scopus and the Cochrane Library. Conference proceedings were also screened. Out of 659 citations, 80 relevant articles were selected and included in the present narrative review. Head-to-head comparisons of different biological drugs are relatively scarce, mostly deriving from indirect comparison or retrospective studies. Overall available data indicate similar effectiveness in the treatment of IBD patients. Dose escalation and reinduction strategies are well documented, but the optimal treatment schedule is still to be defined. Response and remission rates vary in different studies, and a proportion of patients fail to achieve clinical and endoscopic outcomes. However, both approaches are effective and safe in nonresponders and secondary loss of response. IBD patients may benefit from dose escalation or reinduction. Both strategies prove effective in regaining response in a proportion of patients, avoiding unnecessary early switch. Head-to-head trials are still needed to determine the exact placement of this drug compared to other biologics.

IBD Patients with Primary or Secondary Nonresponse to Ustekinumab Benefit from Dose Escalation or Reinduction

Ustekinumab is a monoclonal antibody approved for the treatment of IBD. This drug has a well-established efficacy; however, patients may not respond or lose response. The availability of other biological therapies prompts the need for comparative data between different agents to suggest first- or second-line strategies. Aim of this review is to compare the effectiveness of ustekinumab to other biologics in Crohn’s disease and ulcerative colitis, as well as report the available data on dose escalation and reinduction. A systematic electronic search of the English literature was performed up to November 2023, using Medline (PubMed), Web of Science, Scopus and the Cochrane Library. Conference proceedings were also screened. Out of 659 citations, 80 relevant articles were selected and included in the present narrative review. Head-to-head comparisons of different biological drugs are relatively scarce, mostly deriving from indirect comparison or retrospective studies. Overall available data indicate similar effectiveness in the treatment of IBD patients. Dose escalation and reinduction strategies are well documented, but the optimal treatment schedule is still to be defined. Response and remission rates vary in different studies, and a proportion of patients fail to achieve clinical and endoscopic outcomes. However, both approaches are effective and safe in nonresponders and secondary loss of response. IBD patients may benefit from dose escalation or reinduction. Both strategies prove effective in regaining response in a proportion of patients, avoiding unnecessary early switch. Head-to-head trials are still needed to determine the exact placement of this drug compared to other biologics.

A Comprehensive Review of Biologics in Phase III and IV Clinical Trials for Atopic Dermatitis

Atopic dermatitis (AD) is a skin condition characterized by significant challenges and a substantial deterioration in the life quality for affected patients. The therapeutic landscape for AD has witnessed a transformative shift with the emergence of biologic therapies. Our focus centers on biologics currently undergoing phase III and IV clinical trials, deeming them to hold the highest potential for significant clinical relevance. To identify biologic drugs under development in phase III and IV clinical trials, we searched ClinicalTrials.gov. Additional relevant trials were identified through JapicCTI/ Japan Registry of Clinical Trials (jRCT) with a citation search. A search in MEDLINE and EMBASE was performed. There have been 76 clinical trials identified concerning biologic drugs: dupilumab (34 trials), lebrikizumab (14 trials), tralokinumab (10 trials), rocatinlimab (7 trials), amlitelimab (2 trials), nemolizumab (6 trials), MG-K10 (1 trial), CM310 (1 trial), 611 (1 trial). A search in MEDLINE revealed 132 articles concerning phase III and IV clinical trials for AD treatment. A total of 39 articles concerned biologic drugs covering 23 clinical trials. A search in EMBASE revealed 268 relevant articles, allowing us to identify results of an additional six clinical trials. The safety and efficacy of these biologics are comprehensively addressed in this review. This comprehensive review aims to explore the current landscape of biologic therapies for AD, delving into the latest research findings, clinical trial outcomes, and the diverse mechanisms of action employed by these novel interventions.

A Comprehensive Review of Biologics in Phase III and IV Clinical Trials for Atopic Dermatitis

Atopic dermatitis (AD) is a skin condition characterized by significant challenges and a substantial deterioration in the life quality for affected patients. The therapeutic landscape for AD has witnessed a transformative shift with the emergence of biologic therapies. Our focus centers on biologics currently undergoing phase III and IV clinical trials, deeming them to hold the highest potential for significant clinical relevance. To identify biologic drugs under development in phase III and IV clinical trials, we searched ClinicalTrials.gov. Additional relevant trials were identified through JapicCTI/ Japan Registry of Clinical Trials (jRCT) with a citation search. A search in MEDLINE and EMBASE was performed. There have been 76 clinical trials identified concerning biologic drugs: dupilumab (34 trials), lebrikizumab (14 trials), tralokinumab (10 trials), rocatinlimab (7 trials), amlitelimab (2 trials), nemolizumab (6 trials), MG-K10 (1 trial), CM310 (1 trial), 611 (1 trial). A search in MEDLINE revealed 132 articles concerning phase III and IV clinical trials for AD treatment. A total of 39 articles concerned biologic drugs covering 23 clinical trials. A search in EMBASE revealed 268 relevant articles, allowing us to identify results of an additional six clinical trials. The safety and efficacy of these biologics are comprehensively addressed in this review. This comprehensive review aims to explore the current landscape of biologic therapies for AD, delving into the latest research findings, clinical trial outcomes, and the diverse mechanisms of action employed by these novel interventions.