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Expert Review of Endocrinology &... 2023To identify a preferred and cost-effective drug among Dipeptidyl peptidase-4 inhibitors (DPP4Is) for Indian patients with T2DM.
OBJECTIVE
To identify a preferred and cost-effective drug among Dipeptidyl peptidase-4 inhibitors (DPP4Is) for Indian patients with T2DM.
METHODS
We performed a systematic literature search using standard databases for relevant literature. Original studies comparing the efficacy and/or safety of different DPP4Is were included. Two authors independently performed the literature search, screening, and collected relevant data from the selected studies. The costs of all brands of individual DPP4Is were noted and compared for lowest, highest, and average cost. Finally, we summarized the information with respect to Efficacy, safety, suitability, and cost to find the most cost-effective DPP4I.
RESULTS
We found 13 eligible studies containing data on 15,720 subjects. These studies showed similar efficacy (or better) and safety with teneligliptin as compared to other DPP4Is. Teneligliptin also showed additional benefits other than the glycemic control. The average cost per tablet of teneligliptin 20 mg was markedly lower as compared to sitagliptin, vildagliptin, and other commonly used DPP4Is. Teneligliptin also outscored other commonly used DPP4Is in India in suitability and seems to have better patient compliance.
CONCLUSIONS
Teneligliptin 20 mg could be considered as the preferred and most cost-effective agent among commonly used DPP4Is for the effective management of patients with T2DM in India.
Topics: Humans; Dipeptidyl-Peptidase IV Inhibitors; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Cost-Benefit Analysis; Blood Glucose; Glycated Hemoglobin; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
PubMed: 37232153
DOI: 10.1080/17446651.2023.2216279 -
The Cochrane Database of Systematic... May 2023Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL).
OBJECTIVES
To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable.
DATA COLLECTION AND ANALYSIS
All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were conducted for the different risk groups (favourable, intermediate, poor) according to the International Metastatic Renal-Cell Carcinoma Database Consortium Score (IMDC) or the Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Our main comparator was sunitinib (SUN). A hazard ratio (HR) or risk ratio (RR) lower than 1.0 is in favour of the experimental arm.
MAIN RESULTS
We included 36 RCTs and 15,177 participants (11,061 males and 4116 females). Risk of bias was predominantly judged as being 'high' or 'some concerns' across most trials and outcomes. This was mainly due to a lack of information about the randomisation process, the blinding of outcome assessors, and methods for outcome measurements and analyses. Additionally, study protocols and statistical analysis plans were rarely available. Here we present the results for our primary outcomes OS, QoL, and SAEs, and for all risk groups combined for contemporary treatments: pembrolizumab + axitinib (PEM+AXI), avelumab + axitinib (AVE+AXI), nivolumab + cabozantinib (NIV+CAB), lenvatinib + pembrolizumab (LEN+PEM), nivolumab + ipilimumab (NIV+IPI), CAB, and pazopanib (PAZ). Results per risk group and results for our secondary outcomes are reported in the summary of findings tables and in the full text of this review. The evidence on other treatments and comparisons can also be found in the full text. Overall survival (OS) Across risk groups, PEM+AXI (HR 0.73, 95% confidence interval (CI) 0.50 to 1.07, moderate certainty) and NIV+IPI (HR 0.69, 95% CI 0.69 to 1.00, moderate certainty) probably improve OS, compared to SUN, respectively. LEN+PEM may improve OS (HR 0.66, 95% CI 0.42 to 1.03, low certainty), compared to SUN. There is probably little or no difference in OS between PAZ and SUN (HR 0.91, 95% CI 0.64 to 1.32, moderate certainty), and we are uncertain whether CAB improves OS when compared to SUN (HR 0.84, 95% CI 0.43 to 1.64, very low certainty). The median survival is 28 months when treated with SUN. Survival may improve to 43 months with LEN+PEM, and probably improves to: 41 months with NIV+IPI, 39 months with PEM+AXI, and 31 months with PAZ. We are uncertain whether survival improves to 34 months with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. Quality of life (QoL) One RCT measured QoL using FACIT-F (score range 0 to 52; higher scores mean better QoL) and reported that the mean post-score was 9.00 points higher (9.86 lower to 27.86 higher, very low certainty) with PAZ than with SUN. Comparison data were not available for PEM+AXI, AVE+AXI, NIV+CAB, LEN+PEM, NIV+IPI, and CAB. Serious adverse events (SAEs) Across risk groups, PEM+AXI probably increases slightly the risk for SAEs (RR 1.29, 95% CI 0.90 to 1.85, moderate certainty) compared to SUN. LEN+PEM (RR 1.52, 95% CI 1.06 to 2.19, moderate certainty) and NIV+IPI (RR 1.40, 95% CI 1.00 to 1.97, moderate certainty) probably increase the risk for SAEs, compared to SUN, respectively. There is probably little or no difference in the risk for SAEs between PAZ and SUN (RR 0.99, 95% CI 0.75 to 1.31, moderate certainty). We are uncertain whether CAB reduces or increases the risk for SAEs (RR 0.92, 95% CI 0.60 to 1.43, very low certainty) when compared to SUN. People have a mean risk of 40% for experiencing SAEs when treated with SUN. The risk increases probably to: 61% with LEN+PEM, 57% with NIV+IPI, and 52% with PEM+AXI. It probably remains at 40% with PAZ. We are uncertain whether the risk reduces to 37% with CAB. Comparison data were not available for AVE+AXI and NIV+CAB.
AUTHORS' CONCLUSIONS
Findings concerning the main treatments of interest comes from direct evidence of one trial only, thus results should be interpreted with caution. More trials are needed where these interventions and combinations are compared head-to-head, rather than just to SUN. Moreover, assessing the effect of immunotherapies and targeted therapies on different subgroups is essential and studies should focus on assessing and reporting relevant subgroup data. The evidence in this review mostly applies to advanced clear cell RCC.
Topics: Male; Female; Adult; Humans; Carcinoma, Renal Cell; Axitinib; Nivolumab; Network Meta-Analysis; Sunitinib
PubMed: 37146227
DOI: 10.1002/14651858.CD013798.pub2 -
Pharmaceuticals (Basel, Switzerland) Mar 2023Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary... (Review)
Review
Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary metabolites found in plants and are used in traditional medicine to treat diverse human diseases. Considering this, the synthesis of naphthoquinone derivatives has been explored to contain compounds with potential biological activity. It has been reported that the chemical modification of naphthoquinones improves their pharmacological properties by introducing amines, amino acids, furan, pyran, pyrazole, triazole, indole, among other chemical groups. In this systematic review, we summarized the preparation of nitrogen naphthoquinones derivatives and discussed their biological effect associated with redox properties and other mechanisms. Preclinical evaluation of antibacterial and/or antitumoral naphthoquinones derivatives is included because cancer is a worldwide health problem, and there is a lack of effective drugs against multidrug-resistant bacteria. The information presented herein indicates that naphthoquinone derivatives could be considered for further studies to provide drugs efficient in treating cancer and multidrug-resistant bacteria.
PubMed: 37111253
DOI: 10.3390/ph16040496 -
Korean Journal of Anesthesiology Dec 2023Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery.
METHODS
CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis.
RESULTS
We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs.
CONCLUSIONS
Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.
Topics: Humans; Pregnancy; Female; Diclofenac; Ketorolac; Celecoxib; Cesarean Section; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Pain
PubMed: 37066603
DOI: 10.4097/kja.23014 -
Hematology/oncology and Stem Cell... Apr 2023Renal cell carcinoma (RCC) is the most common kidney cancer in adults (approximately 90%), and clear cell RCC (ccRCC) is the most frequent histologic subtype... (Review)
Review
Renal cell carcinoma (RCC) is the most common kidney cancer in adults (approximately 90%), and clear cell RCC (ccRCC) is the most frequent histologic subtype (approximately 75%). We reviewed the safety and efficacy of checkpoint inhibitors (CPIs) in ccRCC, identifying 5927 articles in PubMed, Embase, Cochrane, and Web of Science. Ten randomized control (N = 7765) and 10 non-randomized (N = 572) studies were included. Overall, 4819 patients treated with CPI combinations were compared with everolimus, sunitinib, or placebo. Overall response rates (ORR) were 9-25% with nivolumab (niv), 42% with niv + ipilimumab (ipi), 55.7% with niv + cabozantinib, 56% with niv + tivozanib vs. 5% with everolimus. ORR was 51.5-58% with avelumab + axitinib vs. 25.5% with sunitinib. ORR was 59.3-73% with pembrolizumab + tyrosine kinase inhibitor vs. 25.7% with sunitinib. ORR was 32-36% with atezolizumab + bevacizumab vs. 29-33% with sunitinib. In patients with PD-L1+ve and -ve ccRCC, niv, atezolizumab, ipi, and pembrolizumab were safe and effective alone and when combined with cabozantinib, tivozanib, axitinib, levantinib, and pegilodecakin. Atezolizumab + bevacizumab was safe and effective in ccRCC with high PD-L1 expression. Pembrolizumab was safe and effective in preventing recurrence in ccRCC patients with nephrectomy. Additional randomized, double-blind, multicenter clinical trials are needed to confirm these results.
Topics: Adult; Humans; Carcinoma, Renal Cell; Sunitinib; Axitinib; Everolimus; B7-H1 Antigen; Bevacizumab; Kidney Neoplasms; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37023219
DOI: 10.56875/2589-0646.1027 -
Clinical Pharmacokinetics Apr 2023Ruxolitinib is a tyrosine kinase inhibitor targeting the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways. Ruxolitinib is used to...
BACKGROUND AND OBJECTIVE
Ruxolitinib is a tyrosine kinase inhibitor targeting the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways. Ruxolitinib is used to treat myelofibrosis, polycythemia vera and steroid-refractory graft-versus-host disease in the setting of allogeneic stem-cell transplantation. This review describes the pharmacokinetics and pharmacodynamics of ruxolitinib.
METHODS
Pubmed, EMBASE, Cochrane Library and web of Science were searched from the time of database inception to march 15, 2021 and was repeated on November 16, 2021. Articles not written in English, animal or in vitro studies, letters to the editor, case reports, where ruxolitinib was not used for hematological diseases or not available as full text were excluded.
RESULTS
Ruxolitinib is well absorbed, has 95% bio-availability, and is bound to albumin for 97%. Ruxolitinib pharmacokinetics can be described with a two-compartment model and linear elimination. Volume of distribution differs between men and women, likely related to bodyweight differences. Metabolism is mainly hepatic via CYP3A4 and can be altered by CYP3A4 inducers and inhibitors. The major metabolites of ruxolitinib are pharmacologically active. The main route of elimination of ruxolitinib metabolites is renal. Liver and renal dysfunction affect some of the pharmacokinetic variables and require dose reductions. Model-informed precision dosing might be a way to further optimize and individualize ruxolitinib treatment, but is not yet advised for routine care due to lack of information on target concentrations.
CONCLUSION
Further research is needed to explain the interindividual variability of the ruxolitinib pharmacokinetic variables and to optimize individual treatment.
Topics: Animals; Humans; Female; Janus Kinases; Protein Kinase Inhibitors; Pyrazoles; Nitriles
PubMed: 37000342
DOI: 10.1007/s40262-023-01225-7 -
American Journal of Clinical Oncology Jun 2023Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a valuable strategy for treating ovarian cancer, and the drug pazopanib is a potent, multitarget tyrosine kinase inhibitor. However, treatment with pazopanib in combination with chemotherapy remains controversial. We performed a systematic review and meta-analysis to clarify the efficacy and side effects of pazopanib combined with chemotherapy in the treatment of advanced ovarian cancer.
METHODS
The PubMed, Embase, and Cochrane databases were systematically searched for relevant randomized controlled trials published up to September 2, 2022. The primary outcomes of eligible studies included overall response rate (ORR), disease control rate, 1-year progression-free survival (PFS) rate, 2-year PFS rate, 1-year overall survival (OS) rate, 2-year OS rate, and adverse events.
RESULT
Outcomes from a total of 518 recurrent or persistent ovarian cancer patients from 5 studies were analyzed in this systematic review. Pooled results showed that pazopanib plus chemotherapy, when compared with chemotherapy alone, significantly improved the ORR (pooled risk ratio=1.400; 95% CI, 1.062-1.846; P = 0.017) but not the disease control rate, 1-year PFS, 2-year PFS, 1-year OS, or 2-year OS. Moreover, pazopanib increased the risk of neutropenia, hypertension, fatigue, and liver dysfunction.
CONCLUSION
Pazopanib plus chemotherapy improved patient ORR but did not improve survival; it also increased the occurrence of several adverse events. Further large-sample clinical trials are needed to verify these results to guide pazopanib use in patients with ovarian cancer.
Topics: Humans; Female; Ovarian Neoplasms; Pyrimidines; Sulfonamides; Indazoles; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36877187
DOI: 10.1097/COC.0000000000000999 -
Medicine Mar 2023Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with edaravone injection (ERI) for the treatment of acute cerebral infarction is not well determined. Therefore, we evaluated the efficacy of ERI combined with SXN versus that of ERI alone in patients with acute cerebral infarction.
METHODS
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases were searched up to July 2022. Randomized controlled trials comparing the outcomes of efficacy rate, neurologic impairment, inflammatory factors, and hemorheology were included. Odds ratio or standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to present the overall estimates. The quality of the included trials was evaluated by the Cochrane risk of bias tool. The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses.
RESULTS
Seventeen randomized controlled trials were included consisting of 1607 patients. Compared to ERI alone, treatment with ERI plus SXN had a greater effective rate than ER alone (odds ratio = 3.94; 95% CI: 2.85, 5.44; I2 = 0%, P < .00001), a lower National Institute of Health Stroke Scale (SMD= -1.39; 95% CI: -1.73, -1.05; I2 = 71%, P < .00001), lower neural function defect score (SMD= -0.75; 95% CI: -1.06,-0.43; I2 = 67%, P < .00001), and lower level of neuron-specific enolase (SMD= -2.10; 95% CI: -2.85, -1.35; I2 = 85%, P < .00001). ERI plus SXN treatment provided significant improvements in whole blood high shear viscosity (SMD = -0.87; 95% CI: -1.17, -0.57; I2 = 0%, P < .00001), and whole blood low shear viscosity (SMD = -1.50; 95% CI: -1.65, -1.36; I2 = 0%, P < .00001) compared to ERI alone.
CONCLUSION
ERI plus SXN showed better efficacy than ERI alone for patients with acute cerebral infarction. Our study provides evidence supporting the application of ERI plus SXN for acute cerebral infarction.
Topics: Humans; Edaravone; Stroke; Brain Ischemia; Acute Disease; Cerebral Infarction
PubMed: 36862906
DOI: 10.1097/MD.0000000000032929 -
Journal of Cutaneous Medicine and... 2023Lichen Planus (LP) is a dermatological disorder characterized by violaceous papules that affect the cutaneous region, nails, scalp, and mucous membranes. Current... (Review)
Review
BACKGROUND
Lichen Planus (LP) is a dermatological disorder characterized by violaceous papules that affect the cutaneous region, nails, scalp, and mucous membranes. Current molecular and clinical studies point to the Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway as a potential effector of LP pathology.
OBJECTIVE
This systematic review summarizes the current reported literature outcomes for patients receiving JAK inhibitors to treat LP.
METHODS
MEDLINE and Embase were searched on 16 October, 2022, and 15 original articles were included, with 56 LP patients.
RESULTS
(mean age: 54.5 years, range: 26-81 years, male: 26.8%). The treatment outcomes were included for the following JAK inhibitors: tofacitinib ( = 30), baricitinib ( = 16), ruxolitinib ( = 12), and upadacitinib ( = 2). Patient outcomes were classified into complete resolution, partial resolution, and no resolution. Patients achieving complete resolution represented 25% ( = 4/16) in the baricitinib group, 10% ( = 3/30) in the tofacitinib group, 16.7% ( = 2/12) in the ruxolitinib group, and 100% (2/2) in the upadacitinib group. Partial resolution patients represented 31.3% ( = 5/16) of baricitinib patients, 60% ( = 18/30) of tofacitinib patients, and 83% ( = 10/12) of ruxolitinib patients. 43.8% ( = 7/16) of baricitinib patients and 10% ( = 9/30) of tofacitinib patients had no resolution of lesions.
CONCLUSION
This review also highlights the significance of utilizing a uniform outcome measure for LP, as it aids in reporting more generalizable results, reduces reporting bias, and ultimately lead to improved clinical outcomes for LP patients.
Topics: Humans; Male; Middle Aged; Janus Kinase Inhibitors; Pyrazoles; Lichen Planus
PubMed: 36815857
DOI: 10.1177/12034754231156100 -
European Journal of Clinical... Jun 2023Inflammation is closely related to cancer prognosis. The effect of celecoxib, a nonsteroidal anti-inflammatory drug, on the prognosis of patients with cancer remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammation is closely related to cancer prognosis. The effect of celecoxib, a nonsteroidal anti-inflammatory drug, on the prognosis of patients with cancer remains uncertain. To assess the association between celecoxib plus standard chemotherapy and cancer prognosis, we conducted a systematic review and meta-analysis of published studies.
METHODS
PubMed, EMBASE, and the Cochrane Library were searched from inception until July 2022 for randomized controlled trials reporting the prognosis of patients with cancer treated with celecoxib plus standard chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Meta-analysis was performed using Review Manager software version 5.4. The following search terms were used in the databases: ((((celecoxib)) AND ((((((((cancer) OR (carcinoma)) OR (sarcoma)) OR (neoplasms)) OR (tumor)) OR (tumour)) OR (tumors)) OR (tumours))) AND ((survival) OR (mortality))) AND (((Clinical Trials, Randomized) OR (Trials, Randomized Clinical)) OR (Controlled Clinical Trials, Randomized)).
RESULTS
Overall, 13 randomized controlled trials, including 8957 patients with cancer, were included in the analysis. Compared to conventional chemotherapy alone, 1-year OS and 1-year PFS rates were not significantly improved with celecoxib adjuvant therapy (OS: p = .38; PFS: p = .65). In addition, no differences were observed between the celecoxib and placebo groups in 3-year overall (p = .98), 3-year progression-free (p = .40), 5-year overall (p = .59), or 5-year progression-free (p = .56) survival rates. An increase in the risk ratio of leukopenia (p = .02) and thrombocytopenia (p = .05) was also observed, suggesting that celecoxib promotes hematologic toxicity. No increased risk of cardiovascular (p = .96) and gastrointestinal (p = .10-.91) events was observed.
CONCLUSIONS
The addition of celecoxib to standard chemotherapy did not improve OS or PFS rates of patients with cancer. Additionally, celecoxib can increase hematologic toxicity without increasing the risk of gastrointestinal or cardiovascular reactions. Further randomized controlled trials are necessary to clarify its effects and applications.
Topics: Humans; Celecoxib; Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36807298
DOI: 10.1111/eci.13973