Biologics Research Articles

Advancements in Therapeutic Approaches for Proliferative Vitreoretinopathy: A Comprehensive Review.

Proliferative vitreoretinopathy (PVR) is a significant complication of retinal detachment surgery, characterized by the growth of fibrous membranes that can lead to recurrent retinal detachment and vision loss. This comprehensive review aims to summarize the latest advancements in the therapeutic approaches for PVR, encompassing historical perspectives, current surgical techniques, pharmacological interventions, biological and genetic therapies, and novel experimental treatments. Traditional surgical methods, such as vitrectomy, have been refined with advanced instrumentation and techniques to improve outcomes. Pharmacological treatments, including anti-inflammatory and anti-proliferative agents, are being explored to prevent and manage PVR. Emerging therapies, such as stem cell and gene therapy, offer promising new avenues for treatment. Despite these advancements, challenges remain in preventing recurrence and improving long-term outcomes. This review highlights the progress made and identifies areas for future research, emphasizing the importance of continued innovation to enhance patient care and reduce the burden of PVR.

Abatacept retention and clinical effectiveness in patients with rheumatoid arthritis in a real-world setting in Taiwan.

To evaluate real-world abatacept retention and clinical outcomes in patients with rheumatoid arthritis in Taiwan. This prospective, observational study enrolled patients with rheumatoid arthritis aged ≥20 years who received abatacept in real-world practice. The primary endpoint was the abatacept retention rate at 24 months. Patients were categorized into subgroups based on abatacept treatment status and previous biological disease-modifying antirheumatic drug (bDMARD) therapy. Risk factors affecting abatacept retention were determined by regression analysis. A total of 212 patients were enrolled. The overall abatacept retention rate at 24 months among all patients was 59.9% (95% confidence interval 53.0%-66.6%). Patients who were ongoing users of abatacept and bDMARD-naïve had the highest retention rate (76.3%); of these, 31.6% achieved low disease activity or remission after 2 years. Previous treatment with bDMARDs was associated with an increased risk of abatacept discontinuation (hazard ratio 1.99; p = .002). The most common reasons for abatacept discontinuation were drug switch (11.3%) and loss to follow-up (6.1%). Abatacept was well-tolerated with no new safety signals. The 24-month retention rate of abatacept was 59.9%; abatacept was associated with improved clinical outcomes and was well-tolerated in the real-world setting in Taiwan.

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...

Dupilumab as an emerging treatment for refractory allergic fungal rhinosinusitis: a case series and literature review

Background: Allergic Fungal Rhinosinusitis (AFRS) is a chronic, inflammatory, non-invasive fungal disease of the nose, sinuses, and paranasal sinuses. Dupilumab is an emerging biological therapy with promising outcomes in the treatment of patients with refractory AFRS. In this case series, we aimed to assess the effectiveness and safety of dupilumab in the treatment of refractory AFRS. Case description: Our case series included seven patients, all of whom met the inclusion criteria. Of these, four were male (57.1%) and three were female (42.9%). The ages of the patients ranged from 20 to 44 years, with a mean of 30.4. For post-treatment Sinonasal Outcome Test-22 (SNOT-22) scores, six patients (85.7%) reported improvement by one category (two from severe to moderate and four from moderate to mild). Only one patient (14.2%) reported an improvement by two categories (severe to mild). Post-treatment IgE levels ranged from 39 to 590 IU/mL, with a mean of 301.8 IU/mL. There was a significant decrease in the mean IgE level by 93% after dupilumab administration. The average number of surgeries in the included patients ranged from 2 to 4, with a mean of 2.7 surgeries. Post-treatment, none of the patients required revision surgery or steroids after three months of dupilumab therapy. Conclusions: Dupilumab is an emerging biological therapy with promising benefits in the treatment of refractory AFRS. It can be used if functional endoscopic sinus surgery and steroid treatment do not improve symptoms.

Correlations between Etiopathogenic Factors and Persistence on Anti-IL-17 Therapies in Patients with Psoriasis Vulgaris

With recent advances in the understanding of psoriatic disease, it is increasingly considered a systemic inflammatory condition rather than limited to the skin and joints. A variety of biologics are available today for the treatment of psoriasis, but with them, characteristics such as rapidity of onset, long-term efficacy, safety profile, and effects on comorbidities differ. We designed an observational, non-interventional, retrospective study of patients with severe psoriasis receiving biologic treatment with IL-17 inhibitors and aimed to investigate the correlations between etiopathogenic factors and the efficacy and persistence of these therapies in a group of psoriasis patients from Romania. Study results show that patients treated with ixekizumab had better persistence and high adherence compared to those treated with secukinumab. In this study, ixekizumab demonstrated lower risks of non-persistence, discontinuation, and switching and a higher likelihood of high adherence compared with secukinumab. This study contributes to the understanding of the persistence of anti-IL17 biologic therapies in psoriasis and the factors that may influence it.

Cumulative Benefit Over 52Weeks With Deucravacitinib Versus Apremilast in Moderate to Severe Plaque Psoriasis: POETYK PSO-1 Post Hoc Analysis.

Deucravacitinib demonstrated superior efficacy to apremilast in patients with moderate to severe plaque psoriasis in the POETYK PSO-1 and PSO-2 clinical trials. In the study reported here, we aimed to determine the overall 52-week cumulative clinical benefit of treatment initiated with deucravacitinib versus apremilast and to compare the 52-week cumulative benefit of initiating and staying on deucravacitinib versus initiating apremilast and continuing or switching to deucravacitinib at week 24 of treatment. This post hoc analysis of POETYK PSO-1 data (ClinicalTrials.gov identifier: NCT03624127) determined the cumulative clinical benefit of deucravacitinib 6mg once daily and apremilast 30mg twice daily in adults with moderate to severe plaque psoriasis. Patients treated with apremilast who did not achieve a 50% reduction in the Psoriasis Area and Severity Index (PASI 50) at week 24 were switched to deucravacitinib. The cumulative clinical benefit of deucravacitinib versus apremilast over 52weeks was based on cumulative measures of ≥ 75% improvement from baseline in PASI score (PASI 75) and the proportion of patients with a static Physician Global Assessment score of 0 or 1 (sPGA 0/1). Ratios of area under the curve estimates between treatments were calculated and compared based on analysis of covariance regression models. Patients initiating deucravacitinib (N = 332) had a greater cumulative benefit as measured by the PASI 75 and sPGA 0/1 than those initiating apremilast (N = 168). Over 52weeks, those initiating deucravacitinib experienced 50% more benefit as measured by PASI 75 and 58% more benefit as measured by sPGA 0/1 than those initiating apremilast. Results were consistent with the primary analysis when patients were classified by prior systemic and prior biologic therapy exposure. Results from this analysis corroborate the primary efficacy analysis supporting the use of deucravacitinib compared with apremilast for moderate to severe plaque psoriasis, regardless of prior systemic or biologic use.

A systematic review on the efficacy of the biologic therapies Rituximab, Belimumab and Anifrolumab in Lupus Erythematosus

A systematic review on the efficacy of the biologic therapies Rituximab, Belimumab and Anifrolumab in Lupus Erythematosus

[Artículo traducido] Pitiriasis rubra pilaris: serie de casos multicéntrica de 65 pacientes españoles

IntroductionPRP is a rare entity of unknown etiopathogenesis. Lack of management guidelines makes it a challenge for clinicians. ObjectiveTo add our experience to increase evidence about PRP. MethodsWe performed a retrospective, descriptive and multicentric study of 65 patients with PRP, being the largest European case series of patients with PRP. ResultsPRP was more frequent in male patients with an average age of 51 years, but erythrodermic forms presented in older patients (average age 61 years).Six (75%) paediatric patients and ten (60%) non-erythrodermic adults controlled their disease with topical corticosteroids. On the contrary, 26 (68%) erythrodermic patients required biologic therapy as last and effective therapy line requiring an average of 6.5 months to achieve complete response. ConclusionOur study showed a statistical difference in terms of outcome and response to treatment between children or patients with limited disease and patients who develop erythroderma.

Ovarian cancer: A review for primary care providers.

Ovarian cancer is the second most common gynecologic cancer in the United States and the deadliest gynecologic cancer worldwide, with a 5-year survival rate of less than 50%. Because of its vague symptoms, more than half of patients present with advanced disease and metastasis. This article reviews the epidemiology, pathogenesis, risk factors, screening, presentation, and diagnosis of ovarian cancer, in addition to providing an overview of the standard approach to treatment and novel targeted biologic therapies.

Ustekinumab in Hidradenitis Suppurativa: A Systematic Review and Meta-analysis.

Hidradenitis suppurativa (HS) is a frequently debilitating, inflammatory skin condition. Patients may have a limited response to adalimumab, currently the only Food and Drug Administration (FDA)-approved biologic treatment for HS. Ustekinumab is an interleukin-12/23 inhibitor that has been utilized in HS, but there is a lack of an updated systematic review on its efficacy and safety. The aim of this study is to perform a systematic review and meta-analysis of the literature on the efficacy and safety of ustekinumab for HS. In October 2022, MEDLINE and Embase databases were searched for articles on ustekinumab in HS. Data extraction was performed on relevant articles by two reviewers. The primary study outcome was the pooled response rate of HS to ustekinumab. A fixed-effects meta-analysis was performed, and Cochran's Q statistic and I squared index were used to assess heterogeneity. Statistical significance was determined at p < 0.05. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. From 2012 to 2022, ten articles (nine case series and one prospective trial) with 88 patients met the inclusion criteria. Patients with reported disease severity had Hurley stage II (17.6%, 12/68) or III (82.4%, 56/68) disease. The majority (80.7%, 71/88) had previously failed at least one biologic treatment. A meta-analysis of all ten studies showed a pooled response rate of 67% (95% CI 0.57-0.76). Study limitations include a small number of patients and randomized controlled trials (RCTs). Ustekinumab may be a helpful treatment option to consider for HS that is recalcitrant to first-line biologic therapies, but RCTs are needed to determine optimal dosing regimens and the specific patient populations that would benefit the most from this agent.

КОРОНАВИРУСНАЯ ИНФЕКЦИЯ COVID-19 У ПАЦИЕНТОВ ПОСЛЕ ТРАНСПЛАНТАЦИИ ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК: ОБЗОР ЛИТЕРАТУРЫ И СОБСТВЕННЫЙ ОПЫТ

The presented literature review presents studies, including our own, on the peculiarities of the course of coronavirus infection in patients after hematopoietic stem cell transplantation (HSCT). It has been shown that patients after HSCT represent an increased risk group for severe COVID-19 and adverse outcomes. The factors that worsen the prognosis of life of patients after HSCT were old age, male gender, uncontrolled/active disease, concomitant diseases, acute course of SARS-CoV-2 COVID19. It is necessary to carry out monitoring, early diagnosis (regular and timely testing for the virus) and the use of effective prevention and treatment protocols in patients after HSCT in a pandemic. Early diagnosis of infection can prevent the spread of the virus, start treatment quickly and take measures to isolate the patient. In the early period after HSCT, patients are at higher risk of developing lower respiratory tract infection, more often need the appointment of antifungal drugs, antibacterial drugs of reserve groups and have greater risks of death from COVID-19. Therapy with genetically engineered biological drugs is not contraindicated in the case of leukopenia and agranulocytosis in this group of patients. As a result of the analysis, there were no differences in the survival rates of patients after autologous and allogeneic HSCT.

Directional freezing and thawing of biologics in drug substance bottles

Biological drug substance (DS) is typically stored frozen to increase stability. However, freezing and thawing (F/T) of DS can impact product quality and therefore F/T processes need to be controlled. Because active F/T systems for DS bottles are lacking, freezing is often performed uncontrolled in conventional freezers, and thawing at ambient temperature or using water baths.In this study, we evaluated a novel device for F/T of DS in bottles, which can be operated in conventional freezers, generating a directed air stream around bottles. We characterized the F/T geometry and process performance in comparison to passive F/T using temperature mapping and analysis of concentration gradients. The device was able to better control the F/T process by inducing directional bottom-up F/T. As a result, it reduced cryo-concentration during freezing as well as ice mound formation. However, freezing with the device was dependent on freezer performance, i.e. prolonged process times in a highly loaded freezer were accompanied by increased cryo-concentrations. Thawing was faster compared to without the device, but had no impact on concentration gradients and was slower compared to thawing in a water bath.High-performance freezers might be required to fully exploit the potential of directional freezing with this device and allow F/T process harmonization and scaling across sites.

Real-time multivariate statistical monitoring of biopharmaceutical processes with no prior product-specific history

Biologics drug substance manufacturing normally comprises several processing steps including cell culture, purification, etc. Real-time Multivariate Statistical Process Monitoring (RT-MSPM) is an integral need in order to achieve early fault detection and prevention to guarantee robust and efficient process performance. As a part of RT-MSPM framework, Batch Evolution Models (BEMs), which take into account the transient phase of a batch prior to reaching full maturity (steady state), are the standard methods for real-time early fault detection in batch processes. Prior product-specific knowledge and training dataset are critical in order to model time (batch maturity) dependencies. Unlike traditional settings, modern biopharmaceutical manufacturing and clinical facilities use modular designs to enable simultaneous production of multiple medicines and quickly pivot from producing one medicine to another where no prior product-specific historical data might be available. In this article, first, a framework is proposed to detect the steady state operation of a manufacturing scale cell culture bioreactor. This is critical to achieve the ultimate goal to demonstrate feasibility of developing a continuous statistical process monitoring framework to monitor the steady state operation of a batch with no prior product specific history. Steady state time series data from previous step are processed following a systematic approach. The requirements for statistical properties of the processed time series in order to leverage data from different products to monitor a new product are outlined. The new framework establishes a guideline to develop models using datasets from other products with different recipes to monitor new products with no prior product-specific history. A novel software product is developed to test the framework. The framework is successfully applied for real-time monitoring of fast-rate sensors of a manufacturing cell culture bioreactor.

Prevalencia de manifestaciones dermatológicas en pacientes con inmunodeficiencia común variable

Objective: Estimate the prevalence of dermatological manifestations in Mexican patients with common variable immunodeficiency. Methods: Cross-sectional and retrospective study, based on the analysis of records of patients with a diagnosis of common variable immunodeficiency, treated at the Siglo XXI National Medical Center (Mexican Social Security Institute), according to the criteria of the European Society of Immunodeficiencies (ESID). and of which only 3 had a genetic diagnosis with the following mutations: IRF2, CTLA4 and PIK-3, belonging to the Immunodeficiency Clinic of the National Medical Center Siglo XXI (IMSS), to evaluate dermatological manifestations, review of laboratory tests: IgA, IgM, IgG and type of replacement therapy with Immunoglobulin. The statistical analysis was carried out with the SPSS program; Descriptive statistics were used to analyze the data, according to the type of variable to be analyzed. Results: 36 patients were included, of which 55.5% were women; with median age 34 years (18-94). The prevalence of dermatological manifestations was 70% (n = 25). 30.5% had a history of infectious dermatosis and 39.5% had a history of non-infectious dermatosis. The most common dermatosis was irritant contact dermatitis in 13.8% of patients. All received replacement therapy with human immunoglobulin, 33.3% intravenously and the rest subcutaneously. Conclusions: Common variable immunodeficiency is an inborn error of immunity, with different clinical manifestations in various organs and systems (the skin is one of these). Dermatological manifestations are not usually described in patients with common variable immunodeficiency; However, it is important to identify them due to their relationship with certain complications (increased risk of superinfection), due to skin disruption and biological therapies. Keywords: Antibody immunodeficiency; Common variable immunodeficiency; skin diseases.

Prevalencia de manifestaciones dermatológicas en pacientes con inmunodeficiencia común variable

Objective: Estimate the prevalence of dermatological manifestations in Mexican patients with common variable immunodeficiency. Methods: Cross-sectional and retrospective study, based on the analysis of records of patients with a diagnosis of common variable immunodeficiency, treated at the Siglo XXI National Medical Center (Mexican Social Security Institute), according to the criteria of the European Society of Immunodeficiencies (ESID). and of which only 3 had a genetic diagnosis with the following mutations: IRF2, CTLA4 and PIK-3, belonging to the Immunodeficiency Clinic of the National Medical Center Siglo XXI (IMSS), to evaluate dermatological manifestations, review of laboratory tests: IgA, IgM, IgG and type of replacement therapy with Immunoglobulin. The statistical analysis was carried out with the SPSS program; Descriptive statistics were used to analyze the data, according to the type of variable to be analyzed. Results: 36 patients were included, of which 55.5% were women; with median age 34 years (18-94). The prevalence of dermatological manifestations was 70% (n = 25). 30.5% had a history of infectious dermatosis and 39.5% had a history of non-infectious dermatosis. The most common dermatosis was irritant contact dermatitis in 13.8% of patients. All received replacement therapy with human immunoglobulin, 33.3% intravenously and the rest subcutaneously. Conclusions: Common variable immunodeficiency is an inborn error of immunity, with different clinical manifestations in various organs and systems (the skin is one of these). Dermatological manifestations are not usually described in patients with common variable immunodeficiency; However, it is important to identify them due to their relationship with certain complications (increased risk of superinfection), due to skin disruption and biological therapies. Keywords: Antibody immunodeficiency; Common variable immunodeficiency; skin diseases.

Radiomics and machine learning analysis of liver magnetic resonance imaging for prediction and early detection of tumor response in colorectal liver metastases.

The aim of this study was to demonstrate the effectiveness of a machine learning-based radiomics model for distinguishing tumor response and overall survival in patients with unresectable colorectal liver metastases (CRLM) treated with targeted biological therapy. We prospectively recruited 17 patients with unresectable liver metastases of colorectal cancer, who had been given targeted biological therapy as the first line of treatment. All patients underwent liver magnetic resonance imaging (MRI) three times up until 8 weeks after chemotherapy. We evaluated the diagnostic performance of machine learning-based radiomics model in tumor response of liver MRI compared with the guidelines for the Response Evaluation Criteria in Solid Tumors. Overall survival was evaluated using the Kaplan-Meier analysis and compared to the Cox proportional hazard ratios following univariate and multivariate analyses. Performance measurement of the trained model through metrics showed the accuracy of the machine learning model to be 76.5%, and the area under the receiver operating characteristic curve was 0.857 (95% confidence interval [CI], 0.605-0.976; P < 0.001). For the patients classified as non-progressing or progressing by the radiomics model, the median overall survival was 17.5 months (95% CI, 12.8-22.2), and 14.8 months (95% CI, 14.2-15.4), respectively (P = 0.431, log-rank test). Machine learning-based radiomics models could have the potential to predict tumor response in patients with unresectable CRLM treated with biologic therapy.

The use of biological and targeted synthetic basic anti-inflammatory drugs in elderly patients with rheumatoid arthritis: for or against

Due to the global aging of the population and increasing life expectancy, the population of elderly patients with rheumatoid arthritis is growing, both due to patients with onset after 60 years of age (EORA), and elderly patients in whom the disease started at a young age. Treatment of such patients is associated with a number of difficulties, which is associated with the characteristics of the aging of the immune system and the body as a whole, and the burden of comorbid conditions. Elderly patients, unlike young ones, have a higher risk of developing adverse events when prescribed both basic and biological drugs. These features lead to a more “gentle” treatment strategy for elderly patients, limited use of adequate doses of basic drugs and a low number of prescriptions of biological drugs among doctors. This article provides current data on the safety and effectiveness of the use of biological and targeted synthetic disease-modifying anti-inflammatory drugs in elderly patients with rheumatoid arthritis.

Monoclonal Antibody Treatment for Relapse Prevention in Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system that can lead to devastating neurological disabilities such as blindness and impaired mobility. Given that NMOSD can cause severe neurological deteriorations even with a single episode, exploring effective relapse prevention strategies in NMOSD is imperative. Recently, various biological monoclonal antibody therapies targeting diverse mechanisms have shown efficacy in preventing relapses in NMOSD, as evidenced by clinical trials. These monoclonal antibody therapies include complement inhibition (eculizumab and ravulizumab), B-cell depletion (rituximab and inebilizumab), and interleukin-6 receptor blockade (tocilizumab and satralizumab) mechanisms. Some of these therapies are now reimbursable, and this review summarizes their mechanisms, administration methods, reimbursement status in Korea, efficacy, and safety profiles in clinical practice.

Monoclonal Antibody Treatment for Relapse Prevention in Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system that can lead to devastating neurological disabilities such as blindness and impaired mobility. Given that NMOSD can cause severe neurological deteriorations even with a single episode, exploring effective relapse prevention strategies in NMOSD is imperative. Recently, various biological monoclonal antibody therapies targeting diverse mechanisms have shown efficacy in preventing relapses in NMOSD, as evidenced by clinical trials. These monoclonal antibody therapies include complement inhibition (eculizumab and ravulizumab), B-cell depletion (rituximab and inebilizumab), and interleukin-6 receptor blockade (tocilizumab and satralizumab) mechanisms. Some of these therapies are now reimbursable, and this review summarizes their mechanisms, administration methods, reimbursement status in Korea, efficacy, and safety profiles in clinical practice.

Soluble CD26: From Suggested Biomarker for Cancer Diagnosis to Plausible Marker for Dynamic Monitoring of Immunotherapy.

Soluble CD26 (sCD26), a glycoprotein with dipeptidyl peptidase (DPP4) enzymatic activity, can contribute to early diagnosis of colorectal cancer and advanced adenomas and has been studied, including for prognostic purposes, across various other types of cancer and disease. The latest research in this field has confirmed that most, though not all, serum/plasma sCD26 is related to inflammation. The shedding and/or secretion of sCD26 from different immune cells are being investigated, and blood DPP4 activity levels do not correlate very strongly with protein titers. Some of the main substrates of this enzyme are key chemokines involved in immune cell migration, and both soluble and cell-surface CD26 can bind adenosine deaminase (ADA), an enzyme involved in the metabolism of immunosuppressor extracellular adenosine. Of note, there are T cells enriched in CD26 expression and, in mice tumor models, tumor infiltrating lymphocytes exhibited heightened percentages of CD26+ correlating with tumor regression. We employed sCD26 as a biomarker in the follow-up after curative resection of colorectal cancer for the early detection of tumor recurrence. Changes after treatment with different biological disease-modifying antirheumatic drugs, including Ig-CTLA4, were also observed in rheumatoid arthritis. Serum soluble CD26/DPP4 titer variation has recently been proposed as a potential prognostic biomarker after a phase I trial in cancer immunotherapy with a humanized anti-CD26 antibody. We propose that dynamic monitoring of sCD26/DPP4 changes, in addition to well-known inflammatory biomarkers such as CRP already in use as informative for immune checkpoint immunotherapy, may indicate resistance or response during the successive steps of the treatment. As tumor cells expressing CD26 can also produce sCD26, the possibility of sorting immune- from non-immune-system-originated sCD26 is discussed.