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Therapeutic Advances in Urology 2024Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of... (Review)
Review
Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of urothelial cancer. Previously approved systemic therapies, including chemotherapy and immunotherapy, are often impractical due to comorbidities, and outcomes for patients with advanced disease remain poor, even when receiving systemic therapy. In this setting, antibody-drug and bicycle toxin conjugates have emerged as novel treatments, dramatically altering the therapeutic landscape. These drugs harness unique designs consisting of antibody or bicycle peptide, linker, and cytotoxic payload with more targeted delivery than conventional chemotherapy, thus eliminating malignant cells while reducing systemic toxicities. Potential targets investigated in urothelial cancer include Nectin-4, TROP2, HER2, and EphA2. Initial clinical trials demonstrated efficacy in treatment of refractory advanced urothelial cancer, as well as improvement in quality of life. These initial studies led to FDA approval of two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan. Moreover, antibody-drug and bicycle toxin conjugates are being studied in ongoing clinical trials in frontline treatment of advanced disease as well as for localized cancer. These studies highlight the potential for additional future therapies with novel targets, novel antibodies, cytotoxic and immunomodulatory payloads, and unique structural designs enhancing efficacy and safety. There is increasing evidence that combinations with other cancer therapies, especially immunotherapy, improve treatment outcomes. The combination of enfortumab vedotin and pembrolizumab was recently approved for first-line treatment of advanced urothelial carcinoma. Despite the great promise of these novel drugs, robust predictive biomarkers are needed to determine the patients who would maximally benefit. This review surveys the rationale and current state of the evidence for these new drugs and describes future directions actively being explored.
PubMed: 38779496
DOI: 10.1177/17562872241249073 -
Skin Research and Technology : Official... May 2024Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial.... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.
MATERIALS AND METHODS
Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta-analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk-of-bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs).
RESULTS
In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta-regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo.
CONCLUSION
300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.
Topics: Omalizumab; Humans; Chronic Urticaria; Anti-Allergic Agents; Treatment Outcome; Network Meta-Analysis; Randomized Controlled Trials as Topic; Quality of Life; Dose-Response Relationship, Drug
PubMed: 38776128
DOI: 10.1111/srt.13749 -
American Journal of Reproductive... May 2024Seminal plasma hypersensitivity (SPH) is a rare and often misdiagnosed condition characterized by local and/or systemic reactions to seminal plasma proteins following... (Review)
Review
INTRODUCTION
Seminal plasma hypersensitivity (SPH) is a rare and often misdiagnosed condition characterized by local and/or systemic reactions to seminal plasma proteins following exposure to semen. We aimed to summarize key symptomatology, diagnostic features, and management options for SPH.
METHODS
The databases PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Review were searched with key words "seminal plasma hypersensitivity" and "seminal fluid allergy" through September 2023. Exclusion criteria included non-English articles, in vitro studies, publication before 1990, duplicates, and articles with no clinical relevance to SPH in women.
RESULTS
The search yielded 53 articles for review. Of these, 60.5% described systemic SPH and 39.5% described localized.
CONCLUSION
Diagnosis of SPH relies on a thorough patient history and confirmatory skin prick testing. The use of IgE assays is controversial and less accurate for cases of localized SPH. Knowledge of disease immunopathology, systemic versus localized symptom presentation, patient preference, and desire to conceive should guide management options. Artificial insemination has the potential for severe adverse reactions in systemic SPH so necessitates extra procedural precautions. SPH does not appear to impair fertility. Additional research on specific allergens implicated in SPH can aid in the development of more targeted immunotherapy approaches with improved safety and efficacy.
Topics: Humans; Male; Allergens; Hypersensitivity; Immunoglobulin E; Insemination, Artificial; Semen; Seminal Plasma Proteins; Skin Tests; Female
PubMed: 38775338
DOI: 10.1111/aji.13865 -
Journal of Neuroimmunology Jun 2024A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift... (Review)
Review
A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift adds complexity to the treatment management of these patients, due to enhanced treatment-associated risks and the possible interplay between immunosenescence and disease-modifying therapies (DMTs). In the present paper, we performed a systematic review of the current evidence concerning the relationship between aging and treatment management in elderly pwMS. Our literature search identified 35 original studies relevant to this topic. The gathered evidence consistently indicates a diminished efficacy of DMTs in older pwMS, particularly in preventing disability accrual. Against this background, high-efficacy therapies (HETs) appear to show less benefit over moderate-low-efficacy DMTs in older patients. These data mainly derive from observational retrospective studies or meta-analyses conducted on randomized clinical trials (RCTs). RCTs, however, exclude pwMS older than 55 years, limiting our ability to acquire robust evidence regarding this patient group. Regarding treatment discontinuation in elderly pwMS with stable disease, the available data, which mainly focuses on older injectable DMTs, suggests that their suspension appears to be relatively safe in terms of disease activity. Nevertheless, the first RCT specifically targeting treatment discontinuation recently failed to demonstrate the non-inferiority of treatment discontinuation over continuation, in terms of MRI activity. On the other hand, the evidence on the impact of discontinuation on disease progression is more conflicting and less robust. Furthermore, there is an important lack of studies concerning sequestering DMTs and virtually no data on the discontinuation of anti-CD20 monoclonal antibodies. De-escalation strategy is gaining attention as a de-risking approach alternative to complete treatment discontinuation. It may be defined as the decision to shift from HETs to less potent DMTs in elderly pwMS who have a stable disease. This strategy could reduce treatment-related risks, while minimizing the risk of disease activity and progression potentially associated with treatment discontinuation. This approach, however, remains unexplored due to a lack of studies. Given these findings, the present scenario underlines the urgent need for more comprehensive and robust studies to develop optimized, data-driven treatment strategies for elderly pwMS and LOMS, addressing the unique challenges of MS treatment and aging.
Topics: Humans; Multiple Sclerosis; Aged; Aging; Immunologic Factors
PubMed: 38761652
DOI: 10.1016/j.jneuroim.2024.578368 -
Pediatric Blood & Cancer Aug 2024This systematic literature review evaluated frontline treatment burden in pediatric and adolescent/young adult (AYA) patients with high-risk classical Hodgkin lymphoma...
This systematic literature review evaluated frontline treatment burden in pediatric and adolescent/young adult (AYA) patients with high-risk classical Hodgkin lymphoma (cHL) among studies originating from the United States. Data were extracted from 32 publications (screened: total, n = 3115; full-text, n = 98) representing 12 studies (randomized controlled trials [RCTs], n = 2; non-comparative, non-randomized, n = 7; observational, n = 3). High-risk disease definitions varied across studies. Five-year event-free survival (EFS)/progression-free survival (PFS) was 86%-100% and 79%-94%, and complete response rates were 35%-100% and 5%-64% for brentuximab vedotin (BV)-containing and chemotherapy-alone regimens, respectively. In identified RCTs, BV-containing compared with chemotherapy-alone regimens demonstrated significantly longer 3-year EFS/5-year PFS. Hematological and peripheral neuropathy were the most commonly reported adverse events of interest, although safety data were inconsistently reported. Few studies evaluated humanistic and no studies evaluated economic burden. Results from studies with the highest quality of evidence indicate an EFS/PFS benefit for frontline BV-containing versus chemotherapy-alone regimens for pediatric/AYA patients with high-risk cHL.
Topics: Adolescent; Child; Humans; Young Adult; Antineoplastic Combined Chemotherapy Protocols; Brentuximab Vedotin; Hodgkin Disease; Prognosis; Survival Rate
PubMed: 38761013
DOI: 10.1002/pbc.31027 -
Diabetes/metabolism Research and Reviews May 2024The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in patients with T1DM, using a systematic review and meta-analysis approach.
METHODS
We systematically searched multiple databases including Medline, Scopus, and others up to 10 January 2024, without language or regional restrictions. We included randomized controlled trials (RCTs) comparing teplizumab with placebo in T1DM patients.
RESULTS
Our analysis incorporated 8 RCTs, predominantly involving participants aged 7-35 years, diagnosed with T1DM and treated with 14-day courses of teplizumab. The primary outcomes included insulin use, C-peptide levels, and HbA1c levels. We observed a significant reduction in insulin use in the teplizumab group standardised mean difference of -0.50 (95% Confidence Interval [CI]: -0.76 to -0.23, p < 0.001; I2 = 49%). C-peptide levels were consistently higher in the teplizumab group, indicating improved endogenous insulin production. However, no significant change was noted in HbA1c levels between the groups. Quality assessment indicated a low risk of bias in most studies.
CONCLUSIONS
Teplizumab has a significant impact on reducing insulin dependence and enhancing endogenous insulin production in T1DM patients. However, its effect on long-term glycaemic control, as indicated by HbA1c levels, remains inconclusive.
Topics: Adolescent; Humans; Antibodies, Monoclonal, Humanized; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Child; Young Adult; Adult
PubMed: 38757421
DOI: 10.1002/dmrr.3806 -
Translational Breast Cancer Research :... 2023Antibody-drug conjugate (ADC) is an emerging therapy that bestows advanced breast tumors with encouraging clinical activity and manageable toxicity; however, the...
Antibody-drug conjugate monotherapy refines the oncological efficacy as compared to therapy of physicians' choices in advanced breast cancers: a systematic review and meta-analysis.
BACKGROUND
Antibody-drug conjugate (ADC) is an emerging therapy that bestows advanced breast tumors with encouraging clinical activity and manageable toxicity; however, the outcomes of phase 2/3 randomized controlled trials (RCTs) are heterogeneous. Our study aims to assess the clinical utilities [i.e., objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS)], and treatment-related adverse events (AEs) of ADC monotherapy (defined as the study cohort) versus the therapy of physician's choice (TPC) (defined as the control cohort) in participants with advanced breast tumors.
METHODS
We conducted a computerized retrieval to identify RCTs from MEDLINE, Web of Science, Cochrane Library, Embase databases, and ClinicalTrials.gov until April 4, 2023. Screening, data extraction, and quality assessment were performed in duplicate.
RESULTS
A total of 10 RCTs were involved, with 5,089 unique patients. A binary random-effect model Mantel-Haenszel method was employed to pool data due to the considerable heterogeneity. The primary outcome measure was odds ratio (OR) with the corresponding 95% confidential interval (CI) of ORR and CBR. The secondary outcome measure represented hazard ratio (HR) of PFS and OS and OR of the frequency of any grade/grade ≥3 AEs. The pooled results showed an insignificant difference of ORR (OR =1.64; 95% CI: 0.86-3.13; P=0.136) and CBR (OR =1.43; 95% CI: 0.89-2.31; P=0.142) in the study cohort than the control cohort. The pooled effect on PFS (HR =0.62; 95% CI: 0.50-0.74; P<0.001) and on OS (HR =0.70; 95% CI: 0.57-0.83; P<0.001) both indicated a significant superiority of the study cohort. The frequency of any grade AEs (OR =1.03; 95% CI: 0.75-1.41; P=0.849) and that of grade ≥3 AEs (OR =0.83; 95% CI: 0.57-1.21; P=0.342) were both observed a nonsignificant difference between the cohorts. These domains, i.e., allocation concealment, blinding of participants and personnel, and blinding of outcome assessment, had the high risk of bias over 50%.
CONCLUSIONS
Compared to physician's choice, ADC monotherapy overall confirms a considerable refinement in survival benefits plus a similar safety profile in advanced breast tumors.
PubMed: 38751489
DOI: 10.21037/tbcr-23-14 -
International Journal of Technology... May 2024Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs...
OBJECTIVES
Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown.
METHODS
A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies.
RESULTS
Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations.
CONCLUSIONS
Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.
Topics: Humans; Cost-Benefit Analysis; Hematologic Neoplasms; Immunoglobulins, Intravenous; Agammaglobulinemia; Hospitalization; Immunoglobulins
PubMed: 38751245
DOI: 10.1017/S026646232400028X -
Sao Paulo Medical Journal = Revista... 2024Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated promising results.
OBJECTIVES
We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis.
DESIGN AND SETTING
Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
METHODS
The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds.
RESULTS
Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: -1.58; 95% confidence interval -2.50, -0.66, P = 0.0008; I2 = 68.4%, P = 0.0031).
CONCLUSION
Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results.
SYSTEMATIC REVIEW REGISTRATION
CRD42021278726, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278726.
Topics: Humans; Hemophilia A; Antibodies, Bispecific; Antibodies, Monoclonal, Humanized; Hemorrhage
PubMed: 38747872
DOI: 10.1590/1516-3180.2023.0102.R1.20022024 -
Age and Ageing May 2024This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three... (Meta-Analysis)
Meta-Analysis
This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this.
Topics: Humans; Probiotics; Randomized Controlled Trials as Topic; Aged; Influenza Vaccines; Administration, Oral; COVID-19 Vaccines; Vaccination; Middle Aged; COVID-19; Influenza, Human; SARS-CoV-2
PubMed: 38745493
DOI: 10.1093/ageing/afae033