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Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
Transplant Infectious Disease : An... Aug 2023Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a...
Epidemiology, management, and burden of cytomegalovirus in solid organ transplant recipients in selected countries outside of Europe and North America: A systematic review.
BACKGROUND
Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a systematic review was conducted to describe the epidemiology, management, and burden of CMV post-SOT in selected countries outside of Europe and North America.
METHODS
MEDLINE, Embase, and Cochrane databases were searched for observational studies in SOT recipients across 15 countries in the regions of Asia, Pacific, and Latin America (search period: January 1, 2011 to September 17, 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatment patterns and guidelines, refractory and/or resistant CMV, patient-reported outcomes, and economic burden.
RESULTS
Of 2708 studies identified, 49 were eligible (n = 43/49; 87.8% in adults; n = 34/49, 69.4% in kidney recipients). Across studies, selection of CMV preventive strategy was based on CMV serostatus. Overall, rates of CMV infection (within 1 year) and CMV disease post-SOT were respectively, 10.3%-63.2% (9 studies) and 0%-19.0% (17 studies). Recurrence occurred in 35.4%-41.0% cases (3 studies) and up to 5.3% recipients died of CMV-associated causes (11 studies). Conventional treatments for CMV infection/disease included ganciclovir (GCV) or valganciclovir. Up to 4.4% patients were resistant to treatment (3 studies); no studies reported on refractory CMV. Treatment-related adverse events with GCV included neutropenia (2%-29%), anemia (13%-48%), leukopenia (11%-37%), and thrombocytopenia (13%-24%). Data on economic burden were scarce.
CONCLUSION
Outside of North America and Europe, rates of CMV infection/disease post-SOT are highly variable and CMV recurrence is frequent. CMV resistance and treatment-associated adverse events, including myelosuppression, highlight unmet needs with conventional therapy.
Topics: Adult; Humans; Cytomegalovirus; Cytomegalovirus Infections; Europe; North America; Ganciclovir; Organ Transplantation; Leukopenia
PubMed: 37254966
DOI: 10.1111/tid.14070 -
Expert Opinion on Drug Metabolism &... Apr 2024High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to...
INTRODUCTION
High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment.
AREAS COVERED
A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified.
EXPERT OPINION
This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.
Topics: Humans; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Interactions; Hematologic Neoplasms; Methotrexate; Polymorphism, Genetic; Precision Medicine; Risk Factors
PubMed: 38501267
DOI: 10.1080/17425255.2024.2332366 -
Cureus Dec 2023Ovarian cancer, being one of the prevalent gynecological cancers, warrants a therapy that's both effective and well tolerated. After extensive drug testing, combination... (Review)
Review
Comparison of the Efficacy of Cisplatin/Paclitaxel Versus Carboplatin/Paclitaxel in Improving Survival and Quality of Life in the Advanced Ovarian Cancer Patient Population: A Systematic Review and Meta-Analysis of Randomized Control Trials.
Ovarian cancer, being one of the prevalent gynecological cancers, warrants a therapy that's both effective and well tolerated. After extensive drug testing, combination regimens with paclitaxel plus platinum-based agents such as cisplatin/carboplatin and taxanes, have shown promising results for advanced ovarian cancer. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of two treatment regimens for advanced ovarian cancer: cisplatin/paclitaxel and carboplatin/paclitaxel. PubMed (Medline), Science Direct, and Cochrane Library were searched from inception to March 2023. The meta-analysis included patients with histologically verified International Federation of Gynaecology and Obstetrics (FIGO) stages IIB to IV ovarian carcinoma who received either carboplatin/paclitaxel or cisplatin/paclitaxel. The primary outcomes were progression-free survival (PFS), overall survival (OS), quality of life (QOL), complete response rate (CRR), and partial response rate (PRR). The revised Cochrane Risk of Bias Tool 2.0 was used to assess the quality of the RCTs The five RCTs chosen for this statistical analysis consisted of a total of 2239 participants, with 1109 receiving paclitaxel/cisplatin for treatment and the remaining 1130 receiving carboplatin/paclitaxel. Among all included outcomes, these reported significant findings: QoL (p-value=0.0002), thrombocytopenia (p=<0.00001), neurological toxicity (p-value=0.003), nausea/vomiting (p-value=<0.00001), myalgia/arthralgia (p-value=0.02), and febrile neutropenia (p-value=0.01). We concluded that the carboplatin/paclitaxel doublet endows a better quality of life (QOL) to patients along with significantly fewer gastrointestinal and neurological toxicities when compared with the cisplatin/paclitaxel combination. However, the myelosuppressive effects of carboplatin/paclitaxel remain a point of concern and may require clinical management.
PubMed: 38264391
DOI: 10.7759/cureus.51011 -
Transplant Infectious Disease : An... Aug 2023Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the...
Epidemiology, treatment patterns, and disease burden of cytomegalovirus in hematopoietic cell transplant recipients in selected countries outside of Europe and North America: A systematic review.
BACKGROUND
Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the epidemiology, management, and burden of CMV post-HCT outside of Europe and North America.
METHODS
The MEDLINE, Embase, and Cochrane databases were searched for observational studies and treatment guidelines in HCT recipients across 15 selected countries from Asia-Pacific, Latin America, and Middle East (search period: 1 January 2011-17 September 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatments, refractory, resistant CMV, and burden.
RESULTS
Of 2708 references identified, 68 were eligible (67 studies and one guideline; 45/67 studies specific to adult allogeneic HCT recipients). The rates of CMV infection and disease within 1 year of allogeneic HCT were 24.9%-61.2% (23 studies) and 2.9%-15.7% (10 studies), respectively. Recurrence occurred in 19.8%-37.9% of cases (11 studies). Up to 10% of HCT recipients died of CMV-related causes. In all countries, first-line treatment for CMV infection/disease involved intravenous ganciclovir or valganciclovir. Conventional treatments were associated with serious adverse events such as myelosuppression (10.0%) or neutropenia only (30.0%, 39.8%) and nephrotoxicity (11.0%) (three studies), frequently leading to treatment discontinuation (up to 13.6%). Refractory CMV was reported in 2.9%, 13.0%, and 28.9% of treated patients (three studies) with resistant CMV diagnosed in 0%-10% of recipients (five studies). Patient-reported outcomes and economic data were scarce.
CONCLUSION
The incidence of CMV infection and disease post-HCT is high outside of North America and Europe. CMV resistance and toxicity highlight a major unmet need with current conventional treatments.
Topics: Adult; Humans; Cytomegalovirus; Hematopoietic Stem Cell Transplantation; Transplant Recipients; Cytomegalovirus Infections; Cost of Illness; Europe; North America
PubMed: 37287436
DOI: 10.1111/tid.14083 -
Journal of Clinical Medicine Oct 2023This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active... (Review)
Review
This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active and inactive metabolites that influence their therapeutic effects. The research examines the role of genetic polymorphisms in the enzyme thiopurine S-methyltransferase (TPMT) in predicting the therapeutic response and adverse effects of thiopurine treatment. The TPMT genotype variations impact the individual responses to thiopurines. Patients with reduced TPMT activity are more susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and minimize AEs. Patients with higher 6-TGN levels tend to have better clinical responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping for TPMT before or during treatment initiation is suggested to tailor dosing strategies and enhance treatment efficacy while reducing the risk of myelosuppression. In conclusion, this study highlights the importance of considering genetic variations and metabolite levels in optimizing thiopurine therapy for IBD patients, focusing on balance therapeutic efficacy with the prevention of adverse effects and contributing to personalized treatment and better patient outcomes.
PubMed: 37959208
DOI: 10.3390/jcm12216742 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal... (Review)
Review
INTRODUCTION
Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.
MATERIALS AND METHODS
Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.
RESULTS
From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.
CONCLUSIONS
This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.
Topics: Adult; Humans; Kidney Transplantation; Living Donors; Immune Tolerance; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Transplantation Tolerance
PubMed: 37709652
DOI: 10.1016/j.trre.2023.100792 -
Medicine Oct 2023Caffeic acid tablets (CFA) are a proprietary Chinese medicine in treating thrombocytopenia. The efficacy and safety of CFA compared with other platelet-raising drugs for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Caffeic acid tablets (CFA) are a proprietary Chinese medicine in treating thrombocytopenia. The efficacy and safety of CFA compared with other platelet-raising drugs for the treatment of thrombocytopenia have been widely reported in the literature, but there is no systematic evaluation. Therefore, we designed this meta-analysis to further establish the efficacy and safety of CFA in treating thrombocytopenia.
METHODS
A computerized search was conducted in the Chinese biomedical database (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, Chinese Scientific Journal Database (VIP), PubMed, and Web of Science databases using the keywords "caffeic acid tablets" and "thrombocytopenia." All randomized controlled trials were selected for the timeframe of build to 02/2023 and then screened and analyzed using RevMan 5.4 and stata17.0 software.
RESULTS
A total of 35 publications with an overall 2533 patients were included in the study. The results of the meta-analysis showed that CFA were effective in the treatment of thrombocytopenia with a statistically significant difference [relative risk ratio (RR) = 1.24, 95% CI (1.17, 1.31), P < .00001] and in increasing platelet counts [standardized mean difference (SMD) = 1.50, 95% CI (1.09, 1.91), P < .00001], white blood cell count [SMD = 1.08, 95% CI (0.77, 1.39), P < .00001], and neutrophil count [SMD = 0.73, 95% CI (0.19, 1.28), P = .009], and CFA reduced myelosuppression [RR = 0.19, 95% CI (0.1, 0.37), P < .00001] and adverse effects [RR = 0.75, 95% CI (0.58, 0.96), P = .02].
CONCLUSION
CFA can effectively improve the clinical outcome of patients with thrombocytopenia with a good safety profile and are worth promoting. However, due to the low quality and small sample size of the included literature, a larger sample size and more standardized, high-quality studies are needed to validate these results.
Topics: Humans; Drugs, Chinese Herbal; Caffeic Acids; Thrombocytopenia; Drug-Related Side Effects and Adverse Reactions
PubMed: 37800784
DOI: 10.1097/MD.0000000000035353 -
Journal of Ethnopharmacology Jan 2024Transcatheter arterial chemoembolization (TACE) is recommended as the first-line therapy for unresected primary liver cancer (PLC), but only partial patients could... (Meta-Analysis)
Meta-Analysis
ETHNOPHARMACOLOGICAL RELEVANCE
Transcatheter arterial chemoembolization (TACE) is recommended as the first-line therapy for unresected primary liver cancer (PLC), but only partial patients could benefit from TACE due to the serious adverse reactions. Clearing heat and resolving toxin (CHRT), one of most critical traditional Chinese medicine (TCM) therapeutic principles, has been widely used in the treatment of PLC patients especially after TACE. However, there is no enough clinical evidence to confirm the efficacy and safety of the combined therapy.
AIM OF THE STUDY
To comprehensively evaluate the efficacy and safety of the combined CHRT-CHF with TACE in the treatment of PLC.
MATERIALS AND METHODS
7 databases were searched from their inception until February 1, 2023. The primary outcomes included survival rate (1-, 2-year), objective response rate (ORR) and disease control rate (DCR), liver function indicators (AST, ALT), adverse reactions including fever, upper digestive tract side and myelosuppression, AFP were selected as the secondary outcomes. RevMan5.4 software was used to evaluate the quality of included studies; meta-analysis, subgroup analysis, meta-regression analysis, publication bias and trial sequential analyses (TSA) was conducted by Stata software 12.0.
RESULTS
There were 40 RCTs involving 3649 patients. Patients treated with TACE plus CHRT-CHF showed significantly better 1-, 2-year survival (respectively: OR, 2.23 [1.67-2.97]; OR, 2.13 [1.56-2.92]), ORR (OR, 2.14 [1.82-2.52]), DCR (OR, 2.13 [1.73-2.62]) compared with TACE alone. There was a decreased incidence of aspartate transaminase (AST), alanine transaminase (ALT), alpha-fetoprotein (AFP) and postembolization syndrome (PES) in patients receiving the combined TACE with CHRT-CHF compared with TACE alone. Subgroup analysis found that lower proportion (20-30%) of CHRT-CHF significantly enhanced survival rate and DCR, higher proportion (≥40%) of CHRT-CHF reduced PES after TACE treatment.
CONCLUSION
The efficacy and safety of the combined CHRT-CHF with TACE were validated in this meta-analysis, the optimal proportion of CHRT-CHF in enhancing the efficacy may be 20-30%; Additionally, higher proportion (≥40%) of CHRT-CHF appears to reduce PES after TACE treatment. The potential role of combined relative proportion of CHRT-CHF with TACE should be emphasized in clinic.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Chemoembolization, Therapeutic; Hot Temperature; Treatment Outcome
PubMed: 37625603
DOI: 10.1016/j.jep.2023.117072 -
Cancer Treatment Reviews Jul 2024There is a need to improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC), especially in recurrent...
A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopharyngeal carcinoma: Charting the course of future therapies.
INTRODUCTION
There is a need to improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC), especially in recurrent unresectable and metastatic (R/M) setting. Antibody-drug conjugates (ADC) and bispecific antibodies (BsAb) may deliver promising results.
METHODS
We conducted a systematic literature review to identify ADC and BsAb clinical trials, involving patients with HNSCC and NPC, from database creation to December 2023. We reported trial characteristics, overall response rate (ORR), overall survival (OS), and grade ≥ 3 treatment-related adverse events (trAEs).
RESULTS
23 trials (65 % phase I) were found, involving 540 R/M patients (355 [20trials] HNSCC and 185 [5trials] NPC). There were 13 ADC (n = 343) and 10 BsAb (n = 197) trials. 96 % patients were refractory to standard of care treatments. ORR ranged from 0 to 100 %, with the highest ORR for GEN1042 plus chemoimmunotherapy. ORRs for monotherapies were 47 % for ADC, and 0-37 % for BsAb. MRG003 reached in HNSCC 43 % and NPC 47 %. BL-B01D1 54 % in NPC. Longest median OS was seen with MRG003 and KN046. Grade ≥ 3 trAEs were 28-60 % in ADC trials, and 3-33 % BsAb. Grade ≥ 3 myelosuppressive trAEs were typically seen in 8 ADC trials, while 4 BsAb showed infusion-related reactions (IRR). Four treatment-related deaths were reported (1 pneumonitis), all ADC trials.
CONCLUSION
ADC and BsAb antibodies show promise in R/M HNSCC and NPC. Results are premature by small sample sizes and lack of control arm. ADC mainly caused myelosuppression and a pneumonitis case, and BsAb IRR. Further research is warranted in this setting.
Topics: Humans; Antibodies, Bispecific; Head and Neck Neoplasms; Immunoconjugates; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 38820656
DOI: 10.1016/j.ctrv.2024.102772