Biologics Research Articles

The history of uveitis: from antiquity to the present day.

This comprehensive review traces the historical understanding and treatment of uveitis from ancient civilisations to modern medicine, a history which reflects the evolution of medical understanding and practice in general. Early descriptions of ocular inflammation appear in Egyptian medical papyri from 1700 BCE, with subsequent contributions from Greek and Roman physicians, including Hippocrates and Galen, who provided foundational observations of ocular inflammatory conditions. Medieval scholarsin the Middle East, particularly Avicenna, preserved and advanced classical knowledge while recognising the systemic nature of ocular inflammation. The Renaissance and Enlightenment periods brought anatomical precision and the emergence of ophthalmology as a distinct specialty, notably through innovations such as Helmholtz's ophthalmoscope in 1851. The twentieth century marked a paradigm shift with the evolution of immunological understanding, leading to the recognition of autoimmune mechanisms and genetic predispositions in uveitis. The introduction of corticosteroids mid-century revolutionised treatment, followed by the development of steroid-sparing immunomodulatory agents and, more recently, targeted biological therapies. Contemporary advances in imaging technology and the establishment of international collaborative groups have standardised classification and treatment approaches. This historical perspective demonstrates the progression from empirical observations to precision medicine in uveitis, highlighting the importance of understanding this evolution for advancing future therapeutic strategies.

The sinus surgery completeness score: a radiological assessment of the extent of endoscopic sinus surgery.

Chronic rhinosinusitis (CRS) often requires endoscopic sinus surgery (ESS) for symptom control. However, there is currently a high reported revision rate. The introduction of biologics offers an alternative treatment, but patient criteria are ambiguous, particularly regarding the definition of "previous ESS." This study aims to introduce the Sinus Surgery Completeness Score (SSCS) to help evaluate the extent of ESS as well as evaluate the extent of sinus surgery in the study cohort. The SSCS was developed by expert rhinologists and anterior skull base surgeons and applied to computed tomography (CT) sinus scans of 41 CRS patients who underwent previous ESS. Inter-rater reliability was assessed, and statistical analysis was performed to correlate SSCS scores with Lund-Mackay (LM) and Sinonasal Outcome Test-22 (SNOT-22) scores. The SSCS demonstrated strong inter-rater reliability (Fleiss Kappa score 0.857). The mean time to complete the SCSS was 2.7min. Most patients had incomplete surgery with a mean SCSS of 7.40 (total 24) with no patients achieving a maximum score. The maxillary sinus was the most dissected subunit, with frontal and sphenoid sinuses being the least. Weak negative correlations were observed between the SSCS and LM and SNOT-22 scores. The SSCS is a useful tool for assessing the completeness of sinus surgery, offering a standardized approach to evaluating surgical outcomes. While further research is needed to elucidate the relationship between surgical completeness and patient outcomes, the SSCS holds promise in guiding patient management including informing decisions regarding eligibility for biologic therapy.

Infiltration of micro-fragmented adipose tissue under local anesthesia for knee osteoarthritis treatment is a safe procedure: A case series

IntroductionKnee osteoarthritis is a debilitating disease that has been increasing in prevalence, especially due to the aging population and rising incidence of obesity. Biological therapies (orthobiologics) have emerged, demonstrating efficacy in improving functional scores, including the injection of microfragmented Adipose Tissue (mFAT). The purpose of this study is to evaluate the safety of adipose tissue harvesting and mFAT injection under local anesthesia. Materials/methodsA case series involving 34 patients who underwent adipose tissue collection from the abdomen under local anesthesia, without sedation, in a sterile environment, and who received the infiltration of microfragmented adipose tissue after single-time preparation, using a fat washing and microfragmentation kit. ResultsEvaluation was performed at the time of the procedure and after 7 days of follow-up. Only ecchymosis (76.5 %) and mild discomfort at the harvested site (70.6 %), as well as mild discomfort at the infiltrated knee (61.8 %), were identified. No major adverse events were identified. ConclusionThe harvesting and injection of mFAT under local anesthesia is safe, with no major adverse events identified during this procedure.

Long-term real-world evidence of SB5 (adalimumab biosimilar) treatment in patients with moderate-to-severe psoriasis from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR)

Background SB5 (adalimumab-bwwd) is an adalimumab biosimilar targeting tumor necrosis factor (TNF) for the treatment of chronic inflammatory diseases, including moderate-to-severe chronic plaque psoriasis. Objectives To assess the four-year persistence associated with the effectiveness and safety of SB5 in patients with psoriasis in the UK and Ireland. Methods This prospective study included 1195 SB5-treated patients using British Association of Dermatologists’ Biologic Interventions Register (BADBIR) between 01 June 2018 and 31 August 2022. Persistence was defined as the time from biologic therapy initiation to discontinuation and Kaplan-Meier analysis was used to evaluate SB5 discontinuation rates. Cox regression was used to investigate the effect of covariates on the time-to-first-discontinuation of SB5 with the potential covariates. Results SB5 one-, two-, three-, and four-year discontinuation rates were 26.5%, 37.2%, 41.9%, and 43.3%, respectively. Tested covariates such as switching, age, sex, body mass index (BMI), and duration of psoriasis did not significantly affect the discontinuation rate of SB5. Conclusions Median persistence of SB5 in predominantly bio-naïve psoriasis patients was about 2.5 years in clinical practice. The results suggest that SB5 can be confidently used for patients with psoriasis, offering comparable outcomes to reference adalimumab.

Biosimilars - An Overview

Biosimilars are the biologic medical products highly similar to an already approved reference biologic with no clinically meaningful difference in terms of safety,purity,and potency .they are developed after the original biologics patent expires and are subjected to rigorous regulatory evaluation to ensure their efficacy and safety .Biosimilars offer a cost - effective alternative to biologics ,fostering in the pharmaceutical market and increasing patient access to treatments fo br various chronic and life threatening diseases and auto immune disorders. Biosimilars are made from the same type of sources (eg:living organisms like bacteria(e.coli, bacilius subtilis) mammalian cells lines (HEK293,NSO) plant based system (tobacco ,corn ). Biosimilars is a biologic medication.

Clinical, Immunologic, and Genetic Characteristics in Patients with Syndrome of Undifferentiated Recurrent Fevers (SURF).

Syndrome of Undifferentiated Recurrent Fevers (SURF) is characterized by recurrent fevers and autoinflammation without a confirmed molecular diagnosis of a Hereditary Recurrent Fever syndrome (HRF), and not fulfilling criteria for Periodic Fever, Adenitis, Pharyngitis, Aphthous stomatitis syndrome (PFAPA). The goal of this study was to characterize clinical features of SURF patients compared to PFAPA, and to analyze their cytokine signature, genetic variations, and responses to treatment. We enrolled 46 patients followed at Cincinnati Children's Hospital Medical Center. Baseline data and inflammatory cytokines were collected at enrollment, and their clinical course was followed. Cytokine analysis was performed using a cytokine multiplex assay. Many patients had specific or whole exome genetic testing. The prevalence of rash and arthralgias were higher in SURF compared to PFAPA. Pharyngitis and adenopathy were less frequent. A subset of SURF patients clustered together with elevated pro-inflammatory cytokines and more frequently required biologic therapy. Focused analysis of WES data revealed that variants of unknown clinical significance (VUCS) were frequently identified in genes implicated in B cell development, immunodeficiencies, and inflammatory bowel disease risk. Treatments for SURF patients commonly included on-demand steroids, colchicine, and anti-IL1 therapy. Our findings suggest SURF is a heterogeneous group but has distinct clinical and immunologic features from disorders like PFAPA. Patients have frequent VUCS, which may have relevance to disease pathogenesis. A subset of patients showed more inflammation and increased need for biologic use. Further research is necessary to define whether there exist distinct SURF endotypes and to better predict treatment outcomes.

Integrating Micro- and Nanostructured Platforms and Biological Drugs to Enhance Biomaterial-Based Bone Regeneration Strategies.

Bone defects resulting from congenital anomalies and trauma pose significant clinical challenges for orthopedics surgeries, where bone tissue engineering (BTE) aims to address these challenges by repairing defects that fail to heal spontaneously. Despite numerous advances, BTE still faces several challenges, i.e., difficulties in detecting and tracking implanted cells, high costs, and regulatory approval hurdles. Biomaterials promise to revolutionize bone grafting procedures, heralding a new era of regenerative medicine and advancing patient outcomes worldwide. Specifically, novel bioactive biomaterials have been developed that promote cell adhesion, proliferation, and differentiation and have osteoconductive and osteoinductive characteristics, stimulating tissue regeneration and repair, particularly in complex skeletal defects caused by trauma, degeneration, and neoplasia. A wide array of biological therapeutics for bone regeneration have emerged, drawing from the diverse spectrum of gene therapy, immune cell interactions, and RNA molecules. This review will provide insights into the current state and potential of future strategies for bone regeneration.

Cost and Cost Effectiveness of Treatments for Psoriatic Arthritis: An Updated Systematic Literature Review.

Psoriatic arthritis (PsA) is an inflammatory disease characterised by a variety of clinical manifestations. Considering the economic burden posed by PsA and the increasing number of treatment options, economic evaluations are required to better allocate available resources. This work aims to update a previous published literature review on PsA cost-of-illness and cost-effectiveness analysis. A search was performed of English-language literature between January 2017 and March 20, 2024 in Medline/PubMed, Embase and Cochrane library using the terms 'psoriatic arthritis', 'cost of illness' and 'cost effectiveness'. Data on decision model, time horizon, population, treatment options, perspective, type of costs, relevant results and authors' conclusion were extracted from the reviewed articles. Finally, the quality of the included studies was evaluated. Twenty-seven studies met the inclusion criteria: 16 cost-of-illness and 11 cost-effectiveness/cost-utility analyses. PsA is characterised by high direct and indirect costs. Drug costs as well as hospitalisation and absenteeism were the major drivers of the observed costs. The cost-effectiveness analyses reported the dominance or the cost effectiveness of biologic therapies compared with non-biologic PsA treatment. Biological options like bimekizumab and ixekizumab have demonstrated a better cost-effectiveness profile in PsA patients compared with other treatments (i.e., other biological treatments). There was an increased number of economic evaluations compared with the previous review. PsA is still associated with significant economic burden worldwide. The main cost was represented by therapies, specifically biological therapies. Amongst the biological therapies, bimekizumab and ixekizumab appear to provide the most economic benefit. Finally, new economic studies are needed to enrich knowledge on the economic burden of subgroups of PsA patients as well as early treatment of PsA with new therapies.

Changes in immature granulocyte levels and their association with disease activation following biologic therapy in patients with ankylosing spondylitis

IntroductionAS is a chronic disease with an inflammatory serum microenvironment characterized by increased oxidative stress (OS). Along with OS, reactive oxygen species (ROS) are elevated in patients with AS. Overexpression of ROS causes active inflammatory processes leading to the secretion of pro-inflammatory factors, including tumor necrosis factor-alpha (TNF-α). Immature granulocytes (IG) are essential to the chronic inflammatory process. This may mean that IG can be a parameter used in the follow-up of chronic inflammatory diseases such as AS. ObjectiveWe aimed to evaluate the change in IG in patients with AS who were on biologic medication for six months after diagnosis and to assess its relationship with disease activity, remission, and BASDAI score. MethodsThis single-center, retrospective study was conducted between January 2020 and January 2022. For the study, 68 patients were included in the patient group and 74 patients in the control group. Demographic and laboratory data were recorded and compared in the groups. Then, the patient group was divided into two groups: pre-biologic drug and post-biologic drug. Hemogram data, IG, ESR, CRP, and BASDAI data were recorded for both groups. Correlation analysis was performed between the results of IG data and hemogram and laboratory data. ConclusionIn our study, WBC, neutrophil, IG, and IG% ratios were significantly higher in AS patients compared to the control group. Neutrophil, IG, and IG% levels were significantly decreased in the AS group compared to pretreatment and post-treatment comparisons. In addition, IG levels were correlated with WBC, neutrophil, CRP, and ESR levels. This study hypothesized that IG values may be a valuable parameter for monitoring AS disease severity, response to treatment, and disease activation after biological drug use.

Biological strategies in rotator cuff repair: a clinical application and molecular background.

Conventional repair of rotator cuff tears bears a variable but significant risk of incomplete healing. Biological therapies that accompany surgical rotator cuff repair include platelet-rich plasma, stem cells of different origins, and biological scaffolds. Biological therapies facilitate the regeneration of the correct microarchitecture of the tendon attachment to the bone and reduce failures after surgical rotator cuff repair.

Longitudinal multi-trajectory phenotypes of severe eosinophilic asthma on type 2 biologics treatment

BackgroundLimited understanding exists regarding the progression trajectory of severe eosinophilic asthma (SEA) patients on type 2 biologics therapies. ObjectiveWe aim to explore distinct longitudinal phenotypes of these patients based on crucial asthma biomarkers. MethodsWe enrolled 101 adult patients with SEA. Of these, 51 were treated with anti-IL5/IL5Rα or anti-IL5/IL5RαR antibody, and 50 with anti-IL-4Rα antibody. Multi-trajectory analysis, an extension of univariate group-based trajectory modeling, was used to categorize patients based on their trajectories of forced expiratory volume in 1 s (FEV1), blood eosinophil counts (BEC), and fractional exhaled nitric oxide (FeNO) levels at baseline, and after 1, 6, and 12 months of treatment. Associations between trajectory-based clusters and clinical parameters were examined. ResultsAmong anti-IL5/IL5Rα antibody-treated patients, 2 clusters were identified. The cluster characterized by higher baseline BEC and lower FEV1 showed a better response, with improvements in FEV1 and reductions in BEC over time. Among anti-IL-4Rα antibody-treated, 3 clusters were identified. Clusters with moderate BEC and FeNO at baseline demonstrated better improvements in FEV1 and reductions in FeNO, despite increased BEC during follow-up. Conversely, individuals with extremely low FeNO and high BEC at baseline were more likely to experience poorer progression, demonstrating an increase in FeNO and a reduction in FEV1. ConclusionTo optimally monitor treatment response in SEA patients on type 2 biologics, integrating longitudinal biomarker features is essential.

Combination of granulocyte–monocyte apheresis and ustekinumab: Multicentre and retrospective study

ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. Patients and methodsA retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. ResultsSeventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35–61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5–7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. ConclusionGMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.

Recent Advances in Pharmaceutical Design: Unleashing the Potential of Novel Therapeutics.

Pharmaceutical design has made significant advancements in recent years, leading to the development of novel therapeutics with unprecedented efficacy and safety profiles. This review highlights the potential of these innovations to revolutionize healthcare and improve patient outcomes. The application of cutting-edge technologies like artificial intelligence, machine learning, and data mining in drug discovery and design has made it easier to find potential drug candidates. Combining big data and omics has led to the discovery of new therapeutic targets and personalized medicine strategies. Nanoparticles, liposomes, and microneedles are examples of advanced drug delivery systems that allow precise control over drug release, better bioavailability, and targeted delivery to specific tissues or cells. This improves the effectiveness of the treatment while reducing side effects. Stimuli-responsive materials and smart drug delivery systems enable drugs to be released on demand when specific internal or external signals are sent. Biologics and gene therapies are promising approaches in pharmaceutical design, offering high specificity and potency for treating various diseases like cancer, autoimmune disorders, and infectious diseases. Gene therapies hold tremendous potential for correcting genetic abnormalities, with recent breakthroughs demonstrating successful outcomes in inherited disorders and certain types of cancer. Advancements in nanotechnology and nanomedicine have paved the way for innovative diagnostic tools and therapeutics, such as nanoparticle-based imaging agents, targeted drug delivery systems, gene editing technologies, and regenerative medicine strategies. Finally, the review emphasizes the importance of regulatory considerations, ethical challenges, and future directions in pharmaceutical design. Regulatory agencies are adapting to the rapid advancements in the field, ensuring the safety and efficacy of novel therapeutics while fostering innovation. Ethical considerations regarding the use of emerging technologies, patient privacy, and access to advanced therapies also require careful attention.

Target Therapy in Chronic Arthritis: The Unmet Needs, State-of-the-Art on Dual Biologic Treatments, and Future Perspectives

Since the early 1990s, the introduction of biologic disease-modifying antirheumatic drugs (b-DMARDs) in managing rheumatological diseases has revolutionised the course of inflammatory chronic arthritis, improving the quality of life, slowing the radiographic progression, avoiding disability, preserving workability, and reducing mortality [...]

Mitophagy and its regulatory mechanisms in the biological effects of nanomaterials.

Mitophagy is a selective cellular process critical for the removal of damaged mitochondria. It is essential in regulating mitochondrial number, ensuring mitochondrial functionality, and maintaining cellular equilibrium, ultimately influencing cell destiny. Numerous pathologies, such as neurodegenerative diseases, cardiovascular disorders, cancers, and various other conditions, are associated with mitochondrial dysfunctions. Thus, a detailed exploration of the regulatory mechanisms of mitophagy is pivotal for enhancing our understanding and for the discovery of novel preventive and therapeutic options for these diseases. Nanomaterials have become integral in biomedicine and various other sectors, offering advanced solutions for medical uses including biological imaging, drug delivery, and disease diagnostics and therapy. Mitophagy is vital in managing the cellular effects elicited by nanomaterials. This review provides a comprehensive analysis of the molecular mechanisms underpinning mitophagy, underscoring its significant influence on the biological responses of cells to nanomaterials. Nanoparticles can initiate mitophagy via various pathways, among which the PINK1-Parkin pathway is critical for cellular defense against nanomaterial-induced damage by promoting mitophagy. The role of mitophagy in biological effects was induced by nanomaterials, which are associated with alterations in Ca2+ levels, the production of reactive oxygen species, endoplasmic reticulum stress, and lysosomal damage.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort

IntroductionBiological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. MethodsMulticenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included.Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients’ colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). ResultsA total of 1090 patients were included. After induction, at approximately 12–14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response.At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab – 9 patients (37.5%) – compared to the other biological treatments analyzed.With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments.As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. ConclusionsBiological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy.In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

The role of Interleukin-38 in modulating T cells in chronic Colitis: A mouse model study

BackgroundInterleukin (IL)-38 belongs to the IL-36 subfamily within the IL-1 family. Patients with inflammatory bowel diseases (IBD) exhibit higher levels of IL-38 in their intestinal tissue compared to healthy controls, suggesting that IL-38 may play a role in the pathogenesis of IBD. However, IL-38′s impact on T cell-mediated immune responses in gastrointestinal inflammation has not been investigated. Therefore, the objective of this work was to elucidate the role of IL-38 in modulating T cells in a mouse model of dextran sulfate sodium (DSS)-induced chronic colitis. MethodsRecombinant IL-38 (rIL-38) was administered intraperitoneally (i.p.) to mice with chronic colitis induced by DSS. Clinical symptoms, length of colon, and histologic alterations were assessed. Cytokine production was quantified using ELISA, and helper T (Th) cell subsets were evaluated via flow cytometry. ResultsAdministration of recombinant IL-38 (rIL-38) alleviated DSS-induced chronic colitis. In addition, animals with chronic colitis treated with rIL-38 exhibited a significant decrease in the spontaneous production of inflammatory cytokines by neutrophils in the lamina propria. Furthermore, rIL-38 treatment increased the absolute numbers and percentages of regulatory T cells (Tregs) but decreased the absolute numbers and percentages of Th1 and Th17 cells. Moreover, rIL-38 treatment also decreased IL-17A-producing γδT cells substantially. ConclusionThis study’s results show that IL-38 reduces the effects of chronic colitis caused by DSS by boosting Treg reactions and reducing Th1/Th17 reactions and IL-17A-producing γδT cells in LPL. Therefore, we propose that IL-38 has the potential to be utilized as a biological therapy agent for IBD.

Giant Cell Arteritis: A review of current knowledge and new biological treatment options

Introduction and objective Giant cell arteritis (GCA) is the most common primary systemic vasculitis in Europe. It mainly affects individuals over the age of fifty, its incidence increases with age. The most common clinical manifestation is bilateral headache accompanied by systemic symptoms. The disease may be associated with serious complications, such as permanent vision loss, stroke or rupture of aortic aneurysm. The aim of this study is to discuss the current knowledge about giant cell arteritis and new possibilities of biological treatment. Review methodsTo prepare this review, PubMed and Google Scholar databases were used, searching the following terms: “giant cell arteritis,” “temporal arteritis,” “giant cell arteritis biological treatment,” “giant cell arteritis biological therapy,” “giant cell arteritis treatment,” “giant cell arteritis epidemiology.” The search results were limited to publications from 2007 to 2024, as well as key studies from earlier years, including original papers and randomized, double-blind, placebo-controlled studies. Brief description of the state of knowledgeThe pathogenesis of GCA remains unclear. Since inflammatory factors appear to play an important role, new therapeutic strategies are aimed in direction to interfere these pathways. Setting a diagnosis of GCA requires imaging studies or a temporal artery biopsy. The results of current treatment with high doses of glucocorticoids are unsatisfying, which has led to ongoing research into new therapeutic options. SummaryEarly diagnosis and initiation of treatment are crucial for preventing occurrence of complications. Although the current treatment regimen is effective, it leads to many side effects and does not prevent relapses. This highlights the need to better understand the pathomechanism of the disease to develop more precise therapeutic strategies, including biological treatment.

Role of innate immune receptors in the psoriasis development

Psoriasis is an immune-mediated autoimmune inflammatory skin disease with a prevalence of 2 to 3% worldwide. In the psoriasis development and pathogenesis an important role is played by disorders in the immune system. Disruption of the innate and adaptive immune response mechanisms with the involvement of keratinocytes leads to the initiation and maintenance of inflammation. Immune reactions are activated in the skin, in which various cells participate (macrophages, dendritic cells, mast cells, innate immune lymphoid cells, melanocytes, keratinocytes, Langerhans cells and γδT cells; T and B cells; epithelial endothelial and stromal cells of the skin), each of which expresses pattern recognition receptors that respond to pathogens and cell damage itself. Many of these receptors, in particular toll-like receptors and NOD-like receptors play an important role in the pathogenesis of psoriasis. The associated innate receptors signaling cascades that activate in the skin cells may become potential targets for the treatment of this disease. To date, there are several approved drugs for biological therapy of psoriasis. The study of the role of the innate immune cells receptors in inflammatory skin pathologies requires further exploration and new developments.

Determinants of Cost-Effectiveness results of Biological Therapies for Severe Asthma: a systematic methodological assessment

Objective: to assess the associations between cost-effectiveness analysis’ (CEA) methodological characteristics and Incremental Cost-Effectiveness Ratio (ICER) outcomes and conclusions, in biological treatments for asthma. Study design and settingWe included CEAs comparing biological treatments to standard care, in adults with severe asthma. We performed a search in MEDLINE, EMBASE, and Web of Science (Sep 2022). We extracted and summarised CEA’s characteristics and critically appraised the studies using the extended Consensus Health Economic Criteria (e-CHEC). In those reporting benefits as quality-adjusted life years (QALY), we conducted bivariate and regression analyses. ResultsWe identified 33 CEAs that showed overall good quality (above 66.6% of compliance) with variable results across e-CHEC sections. We included 28 cost-utility analysis (CUA) on biological treatments in asthma in our analysis. Only industry sponsorship showed significant differences in the bivariate analysis (p=0.021 for the difference in ICER medians, and p=0.027 for the different percentage in reported cost-effectiveness). In the regression adopting a non-lifetime horizon and non-use of a model (β = 4.25 and β = 0.16, p<0.05), significantly associated in the multivariate ananlysis. Only non industry sponsorship showed a significant association with the drug being reported as not cost-effective, both in the bivariate and multivariate analysis (OR = 13.2, and OR = 20.15 p<0.05). ConclusionOur study identified significant limitations, including poor reporting practices and the impact of industry sponsorship on outcomes, with notable effects on cost-effectiveness conclusions.These findings highlight the need for policymakers and healthcare decision-makers to meticulously consider methodological rigour and potential biases in economic evaluations.