Biologics Research Articles

Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease

ObjectiveImproving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies....

Patient-reported preferences for subcutaneous or intravenous administration of parenteral drug treatments in adults with immune disorders: a systematic review and meta-analysis.

Aim: Several studies have found subcutaneous (SC) and intravenous (IV) administration of similar drugs for long-lasting immunological and autoimmune diseases to have similar clinical effectiveness, meaning that what patients report they prefer is, or should be, a major factor in treatment choices. Therefore, it is important to systematically compile evidence regarding patient preferences, treatment satisfaction and health-related quality of life (HRQL) using SC or IV administration of the same drug. Materials & methods: PubMed database searches were run on 15 October 2021. Studies involving patients with experience of both home-based SC and hospital-based IV administration of immunoglobulins or biological therapies for the treatment of any autoimmune disease or primary immunodeficiencies (PIDs) were included. The outcomes assessed were patient preferences, treatment satisfaction and HRQL. Preference data were meta-analyzed using a random-effects model. Results: In total, 3504 citations were screened, and 46 publications describing 37 studies were included in the review. There was a strong overall preference for SC over IV administration, with similar results seen for PIDs and autoimmune diseases: PID, 80% (95% confidence interval [CI], 64-94%) preferred SC; autoimmune diseases, 83% (95% CI: 73-92%); overall, 82% (95% CI: 75-89%). The meta-analysis also found that 84% (95% CI: 75-92%) of patients preferred administration at home to treatment in hospital. Analysis of treatment satisfaction using the life quality index found consistently better treatment interference and treatment setting scores with SC administration than with IV administration. Conclusion: Compared with IV infusions in hospital, patients tend to prefer, to be more satisfied with and to report better HRQL with SC administration of the same drug at home, primarily due to the greater convenience. This study contributes to evidence-based care of patients with autoimmune diseases or PIDs.

The past 25 years in paediatric rheumatology: insights from monogenic diseases.

The past 25 years have seen major novel developments in the field of paediatric rheumatology. The concept of autoinflammation was introduced to this field, and medicine more broadly, with studies of familial Mediterranean fever, the most common autoinflammatory disease globally. New data on the positive evolutionary selection of familial Mediterranean fever-associated genetic variants might be pertinent to mild gain-of-function variants reported in other disease-associated genes. Genetic studies have unveiled the complexity of human heritability to inflammation and flourishing data from rare monogenic disorders have contributed to a better understanding of general disease mechanisms in paediatric rheumatic conditions. Beyond genomics, the application of other 'omics' technologies, including transcriptomics, proteomics and metabolomics, has generated an enormous dataset that can be applied to the development of new therapies and in the practice of precision medicine. Novel biomarkers for monitoring disease activity and progression have also emerged. A surge in the development of targeted biologic therapies has led to durable remission and improved prognosis for many diseases that in the past caused major complications. Last but not least, the COVID-19 pandemic has affected paediatric rheumatology practice and has sparked new investigations into the link between viral infections and unregulated inflammatory responses in children.

Predictors of initiating biologics in the treatment of psoriasis.

Biologics are among the most effective therapies for psoriasis. However, many patients are only introduced to them at advanced stages of the disease course. Our aim was to identify predictors of initiating biologic therapy in patients with psoriasis and compare patients initiating biologics early versus late in their disease course. Kaplan-Meier curves visualized time to biologic initiation, while Cox regression models further explored variables as predictors of biologic initiation. Mann-Whitney U and chi-squared tests compared patients who started biologics early with those who began biologics later in the disease course. Our primary analysis included 233 psoriasis patients. Cox regression showed that age at diagnosis (P = 0.007), general physical well-being (P = 0.02), and nail psoriasis severity (P = 0.02) were significantly associated with time to biologic initiation. Our secondary analysis, the comparisons between patients starting biologics early versus later in the disease course, included a total of 378 patients. The median (interquartile range [IQR]) age at diagnosis was 34.5 (25.0-51.2) years for patients initiating biologics within 5 years, compared to 22.0 (15.0-32.8) years for patients initiating biologics later (P < 0.0001). The median (IQR) age at initiation was 37.0 (27.0-53.2) and 45.0 (36.0-55.0) years for patients initiating biologics earlier versus later than 5 years (P = 0.04). Age at diagnosis, general well-being, and severity of nail psoriasis significantly predicted future initiation of biologic treatment. Patients initiating biologics early in their disease course were generally older at diagnosis but younger at the time of biologic initiation compared to patients initiating biologics later in their disease course.

Anti-Cytokine Active Immunotherapy Based on Supramolecular Peptides for Alleviating IL-1β-Mediated Inflammation.

IL-1β is a principal proinflammatory cytokine underlying multiple local and systemic chronic inflammatory conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and type 2 diabetes. Passive immunotherapies and biologic drugs targeting IL-1β, while offering significant clinical benefit, nevertheless have limitations such as significant non-response rates, induction of anti-drug antibodies, and high costs. Here, an active immunotherapy raising antibody responses against IL-1β employing self-assembling peptide nanofibers is described. The nanofibers contain defined quantities of B-cell epitopes from IL-1β and exogenous T helper epitopes and employ the Q11 self-assembling peptide platform. Without adjuvant, the nanofibers raised durable anti-IL-1β antibody responses that inhibit IL-1β activity in vitro and in vivo. In a mouse model of imiquimod-induced psoriasis, prophylactic immunizations with the nanofibers diminished symptoms of epidermal thickening. This therapeutic effect is associated with biasing the immune response toward an anti-inflammatory IgG1/Th2 phenotype and a lowered expression of proinflammatory genes in the skin. Further, anti-IL-1β nanofibers induced therapeutic immunosuppressive CD62L+ Treg cells. This technology represents a potential alternative for passive immunotherapies and other biologics for treating chronic inflammatory conditions.

Safety and efficacy of biologic drugs in children or adolescents with atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Children and adolescents suffering from moderate-to-severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p-value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08-8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71-10.02), EASI 50 (OR 8.89; 95% CI 6.18-12.78) and EASI 90 (8.30; 95% CI 4.81-14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34-9.90) or 4 points or more (OR 8.09; 95% CI 5.19-12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58-1.07), and conjunctivitis (OR 2.08; 95% CI 1.00-4.33). In this meta-analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population.

Prescribing patterns and persistence of biological therapies for psoriasis management: a retrospective cohort study from Saudi Arabia

Background Biological therapies are effective for psoriasis, but patient responses vary, often requiring therapy switching or discontinuation. Objectives To identify physicians’ prescribing patterns of biological therapies at a referral tertiary center in Saudi Arabia and assess the probability of biologic persistence following treatment initiation. Methods We conducted a retrospective study of biologic-naïve adult psoriasis patients who initiated therapy from October 2013 to July 2022 in Dammam. Descriptive statistics and a Kaplan-Meier analysis evaluated treatment persistence at 6, 12, 24, and 36 months. Results A total of 151 patients received adalimumab (n = 89), etanercept (n = 17), risankizumab (n = 30), ustekinumab (n = 14), and ixekizumab (n = 1). At 6 months, all therapies demonstrated 100% persistence. At 12 months, persistence was highest for ustekinumab (100%) and lowest for etanercept (88.2%). At 24 months, ustekinumab maintained 100% persistence, followed by risankizumab (96.6%), adalimumab (94.3%), and etanercept (76.4%). At 36 months, risankizumab had the highest persistence (96.6%), followed by adalimumab (83.1%), ustekinumab (78%), and etanercept (70.6%). The most common reasons for discontinuation were lack of effectiveness and intolerability. Conclusion This study shows changing psoriasis treatment patterns with new therapies. Risankizumab demonstrated high long-term persistence, while etanercept and ustekinumab showed declining persistence, suggesting evolving treatment considerations.

Use of Glucagon-like peptide 2 (GLP-2) analogs in inflammatory bowel disease

Introduction: Inflammatory bowel disease (IBD) is a chronic condition that involves long-term treatment and chronic idiopathic inflammation within the gastrointestinal tract. The predominant forms of IBD are: Crohn's disease and ulcerative colitis. These diseases cause significant physical as well as psychological dysfunction - patients with this condition are thought to have an increased risk of depression as well as anxiety. Standard treatment for IBD most commonly includes aminosalicylates, corticosteroids, immunomodulatory drugs, and biologic therapy. In some cases, particularly when it comes to Crohn's disease, it is necessary to remove a portion of the inflamed bowel. Multiple segmental bowel resections can result in the rare but serious complication of short bowel syndrome, which leads to intestinal failure and necessitates parenteral nutrition. Glucagon-like peptide-2 exhibits intestinotropic properties and also acts as a growth factor in the gastrointestinal tract, thereby increasing intestinal perfusion, causing increased absorption of nutrients, and enhancing proliferative mechanisms while inhibiting apoptotic processes. Methods: We carefully reviewed the medical literature on inflammatory bowel disease, short bowel syndrome and the potential treatment of this condition with GLP-2 and its analogs. The materials for the analysis we presented came from the PubMed database. Conclusions: Glucagon-like peptide 2 (GLP-2) analogs may prove to be new treatments for short bowel syndrome (SBS). They exhibit growth-stimulating effects on the intestinal membrane and promote normal function.

Budget impact analysis of introducing fruquintinib for metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy and biologics in the United States from the payer perspective

ABSTRACT Aims Fruquintinib is a selective small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 recently approved in the United States (US) for the treatment of adult patients with mCRC who have previously been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type and medically appropriate, anti-epidermal growth factor receptor therapy. This study aimed to estimate the 5-year budget impact of fruquintinib from a US payer perspective (commercial and Medicare). Materials and Methods A budget impact model was developed to compare two scenarios: a reference scenario in which patients received regorafenib, trifluridine/tipiracil, or trifluridine/tipiracil with bevacizumab and an alternative scenario in which patients received reference scenario treatments or fruquintinib. Market shares were evenly divided across available options. A 5-year time horizon and a hypothetical health plan of 1 million members was assumed. The model included epidemiological inputs to estimate the eligible population; clinical inputs for treatment duration, progression-free survival, overall survival, and adverse event (AE) frequency; and cost inputs for treatment, AEs, disease management, subsequent therapy, and terminal care costs. Budget impact was reported as total, per member per year (PMPY), and per member per month (PMPM). Results The model estimated an eligible population of 194 patients (39 per year) over 5 years. In the base case, the estimated 5-year budget impact of fruquintinib was $4,077,073 ($0.82 PMPY and 0.07 PMPM) for a commercial health plan. During the first year, the estimated budget impact was $627,570 ($0.63 PMPY and 0.05 PMPM). Results were robust across sensitivity analyses. PMPM costs from the Medicare perspective were greater than the base-case (commercial) ($0.17 vs. $0.07) due to higher incidence of CRC in that population. Conclusions Fruquintinib is associated with a low budget impact for payers based on proposed thresholds in the US.

Drug survival analysis of etanercept compared with monoclonal antibody tumour necrosis factor-α inhibitors in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a propensity score-matched analysis from the Czech ATTRA registry

Objectives To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Methods Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. Results We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. Conclusions We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.

Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients.

Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly. The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence. Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months. We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.

A novel approach to investigate severe asthma and COPD: the 3D Ex Vivo Respiratory Mucosa Model

Biologic drugs have been shown to enhance the treatment of severe asthma and COPD. Monoclonal antibodies against specific targets have dramatically changed the management of these conditions. Although the inflammatory pathways of asthma and COPD have already been clearly outlined, alternative mechanisms of action remain mostly unexplored. They could provide additional insights into these diseases and their clinical management. In vivo or in vitro models have thus been developed to test alternative hypotheses. This study describes sophisticated ex vivo models that mimic the response of human respiratory mucosa to disease triggers, aiming to narrow the gap between laboratory studies and clinical practice. These models successfully replicate crucial aspects of these diseases, such as inflammatory cell presence, cytokine production, and changes in tissue structure, offering a dynamic platform for investigating disease processes and evaluating potential treatments, such as monoclonal antibodies. The proposed models have the potential to enhance personalized medicine approaches and patient-specific treatments, helping to advance the understanding and management of respiratory diseases. This article illustrates the replication of asthma and COPD conditions in a laboratory setting and the potential applications of this methodology.

From Psoriasis to Psoriatic Arthritis: Decoding the Impact of Treatment Modalities on the Prevention of Psoriatic Arthritis.

Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis. This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group1, topical therapy; group2, phototherapy; group3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group4, biologic DMARDs which was also stratified according to biologic class. The PsA incidence rate was lower in the biologic agents' group versus the methotrexate group (HR 0.46 [95%CI 0.35-0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95%CI 1.65-2.07]). Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor.

GRAPPA Point-Counterpoint: Should Biologics Be Used for Mild Psoriasis?

Psoriasis (PsO) is commonly classified as mild, moderate, or severe, usually based on body surface area (BSA) or other validated measures. Although most dermatologists agree that mild PsO should be treated with topical therapies, there are circumstances where mild or limited PsO should be treated with biologics, even as first line. A debate about use of topical vs biologic therapy was presented at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting. Arguments in favor of using biologics when patients have mild disease on limited BSA included presence of psoriatic arthritis (PsA) and symptoms on special sites (ie, scalp, face, body folds, genitals, nails, palms, soles). New data suggest that treating limited or early PsO may decrease the risk of developing PsA. Arguments against using biologics for mild PsO focused on the definition of mild PsO, citing that limited BSA with PsA and significant quality of life impact should not be defined as mild. Truly mild PsO should be treated with topical agents, given their safety and relative low cost. The availability of newer agents like roflumilast and tapinarof have expanded therapeutic choice and have data supporting their use for treatment of special sites.

Application of Drug Repurposing Approach for Therapeutic Intervention of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti- inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.

Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma.

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.

Mirikizumab: A promising breakthrough in Crohn's disease treatment.

Crohn's disease (CD) is a chronic, progressive inflammatory bowel disorder characterized by persistent inflammation and noncontiguous "skip lesions" throughout the gastrointestinal tract. With a prevalence of 100-300 cases per 100,000 individuals, CD is most common in Western Europe and North America. Symptoms include abdominal pain, diarrhea, fever, weight loss, and anemia, with severe cases leading to complications such as perianal abscesses and cutaneous fistulas. Treatment involves pharmaceutical interventions, bowel rest, and sometimes surgery, with biological therapies like ustekinumab and mirikizumab gaining prominence. The VIVID-1 trial assessed mirikizumab in patients with moderately to severely active CD. By Week 12, mirikizumab significantly outperformed placebo in clinical response (45.4% vs. 19.6%, p < 0.000001). By Week 52, it showed higher clinical remission rates (54.1% vs. 19.6%) and demonstrated non-inferiority to ustekinumab in clinical remission (p = 0.51). The SEQUENCE study compared risankizumab to ustekinumab, with risankizumab showing superior reductions in inflammatory markers and higher biologic remission rates at Weeks 8, 24, and 48. Both treatments had similar safety profiles, with common adverse events including COVID-19, anemia, and headache. Mirikizumab, based on the VIVID-1 trial outcomes, is a promising addition to CD therapy. It demonstrated significant clinical responses and remission rates, warranting further research on its long-term efficacy and safety. Updating professional guidelines and addressing affordability will ensure broader access and improved management of CD.

Navigating through the healthcare system with atopic dermatitis: Analysing patient journeys in Germany.

Atopic dermatitis (AD), which can significantly impact quality of life, is a complex, heterogeneous skin disease affecting all ages and therefore can lead to very different patient journeys. Understanding the patient journey within the healthcare system is essential for improving care outcomes. To explore the patient journey of individuals with AD in Germany, with a specific focus on the utilization of Internet resources throughout this process. A cross-sectional study using a self-administered questionnaire was conducted from June 2021 to February 2022. Participants were recruited from dermatology private practices, a university hospital and online platforms. The study included 276 participants (62.3% female; mean age: 46.3 ± 18.4 years; mean disease duration: 26.9 ± 17.5 years; mean DLQ Index: 10.0 ± 5.6). Around 191 participants were currently receiving medical treatment, with 9.1% receiving biologic therapy. Most of the people initially contacted a GP (42.4%) and were diagnosed by a dermatologist first (57.6%). Around 47.1% were currently in treatment by a dermatologist, seeking dermatological care on average 4.5 times a year. Almost all individuals (86.2%) have already consulted more than one physician during their patient journey. Overall, participants consulted a median of five physicians, while those with severe AD consulted a median of six physicians. Initial symptoms to diagnosis and between consulting two different physicians both had a median duration of 6 months. Dissatisfaction with treatment outcomes emerged as a common reason for changing physicians. Approximately 76.4% of participants used the Internet for disease-related information, primarily relying on Google. Overall, 63% found the information quality unsatisfactory. The study underlines the widespread utilization of medical treatment and the proactive healthcare-seeking behaviour during a long patient journey. Dissatisfaction with treatment outcomes, alternative medicine and the quality of the Internet sources emphasize the potential for improving the comprehensive disease management to improve care outcomes.

Contemporary Concise Review 2023: Asthma.

Asthma research and management needs to meet the priorities of the end user-patients, carers and clinicians. A better understanding of the natural history of asthma and the progression of disease has highlighted the importance of early identification of patients with asthma and the potential role of early intervention. Management of mild asthma requires a consistent approach with the same detail and consideration used when managing severe disease. Evidence around treatable traits approaches continues to evolve, supporting the role of a personalized medicine in asthma. Oral corticosteroid (OCS) stewardship continues to be an urgent issue in asthma management. Strategies to taper OCS doses and the implementation of biologic therapies for their steroid sparing benefits will be important steps to address this problem. The concept of remission in asthma provides an ambitious target and treatment outcome.

Analytical Characterization for Similarity Assessment Between an Aflibercept Biosimilar SB15 and Reference Product (Eylea®).

SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15.