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Basic & Clinical Pharmacology &... Jul 2024This network meta-analysis of randomized controlled trials aimed to determine whether any individual dipeptidyl peptidase-4 (DPP-4) inhibitors increase the risk of acute... (Meta-Analysis)
Meta-Analysis
This network meta-analysis of randomized controlled trials aimed to determine whether any individual dipeptidyl peptidase-4 (DPP-4) inhibitors increase the risk of acute kidney injury (AKI). The Medical Literature Analysis and Retrieval System Online via PubMed, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were systematically searched to identify relevant studies. The primary outcome was AKI. A frequentist network meta-analysis was performed using a random-effects model to account for heterogeneity. Twenty-nine studies involving 56 117 participants were included. There were 918 cases of AKI (1.63%). The risk of bias was generally considered to be low. The only DPP-4 inhibitor that significantly increased the frequency of AKI when compared with placebo was sitagliptin (risk ratio 1.65, 95% confidence interval 1.22-2.23). However, because one study showed significant outliers in the funnel plot, in a highly heterogeneous population composed solely of patients undergoing surgery for coronary artery bypass graft, we conducted a post-hoc sensitivity analysis to exclude this study. The results showed no statistically significant difference in the risk of AKI between sitagliptin and placebo. Individual DPP-4 inhibitors do not appear to increase the risk of AKI. However, sitagliptin may be associated with AKI in patients with underlying severe cardiovascular disease.
Topics: Dipeptidyl-Peptidase IV Inhibitors; Humans; Acute Kidney Injury; Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Randomized Controlled Trials as Topic; Network Meta-Analysis; Risk Factors
PubMed: 38698656
DOI: 10.1111/bcpt.14014 -
Sleep Aug 2021This meta-analysis aimed to explore the effect of non-benzodiazepine sedative hypnotics (NBSH) on continuous positive airway pressure (CPAP) adherence in patients with... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
This meta-analysis aimed to explore the effect of non-benzodiazepine sedative hypnotics (NBSH) on continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA).
METHODS
We conducted a systematic search through PubMed, Medline, the Cochrane Library, EMBASE, Scopus and ClinicalTrials (all searched from inception to August 15, 2020). Publications were limited to articles, clinical conferences and letters, including randomized controlled trials and retrospective studies. We used a random-effects model to calculate the odds ratio (OR) and mean difference (MD) with corresponding confidence interval (CI). Subgroup analyses were conducted to analyze the sources of heterogeneity.
RESULTS
Eight studies fulfilled the inclusion and exclusion criteria for patients newly diagnosed with obstructive sleep apnea. Overall, the use of NBSH was associated with increased use of CPAP per night (MD = 0.62 h; 95% CI = 0.26-0.98) and use for more nights (MD = 12.08%; 95% CI = 5.27-18.88). When a study seriously affecting heterogeneity was removed, more patients adhered well with CPAP use (pooled OR = 2.48; 95% CI = 1.75-3.52) with good adherence defined as CPAP use for >4 h/night on >70% of nights. Among prescribed NBSHs, eszopiclone showed the most significant effect on CPAP adherence.
CONCLUSION
CPAP adherence may increase in OSA patients treated with non-benzodiazepine sedative hypnotics especially eszopiclone. The effect of zolpidem and zaleplon on CPAP adherence requires further investigation by larger scale, randomized, controlled trials.
Topics: Continuous Positive Airway Pressure; Eszopiclone; Humans; Hypnotics and Sedatives; Retrospective Studies; Sleep Apnea, Obstructive
PubMed: 33769549
DOI: 10.1093/sleep/zsab077 -
Clinical Lymphoma, Myeloma & Leukemia Aug 2019Many new regimens have been applied to newly diagnosed transplant-ineligible multiple myeloma, but no head-to-head research has been performed to compare the efficacy of... (Meta-Analysis)
Meta-Analysis
Many new regimens have been applied to newly diagnosed transplant-ineligible multiple myeloma, but no head-to-head research has been performed to compare the efficacy of these treatments. Currently lenalidomide plus dexamethasone (Rd) is one of the standard treatments. Our aim was to make a comparison of these treatments to Rd by a network meta-analysis. We performed a systematic review and network meta-analysis. We searched PubMed, Embase, and the Cochrane Library for articles published from January 1, 1988, to April 26, 2018, as well as research presented at 5 international conferences (American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, European Society of Medical Oncology, and International Myeloma Working Group) between January 2015 and December 2018. Our interest outcomes were hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS). Bayesian fixed-effects mixed-treatment comparisons were used for this study. A total of 23 articles describing 10,401 participants were included for this network meta-analysis. Lenalidomide and dexamethasone plus daratumumab (HR, 0.57; 95% credible interval [CrI], 0.43-0.73), daratumumab plus bortezomib, melphalan, and prednisone (HR, 0.59; 95% CrI, 0.36-0.91), and the combination of bortezomib with lenalidomide and dexamethasone (RVd) (HR, 0.72, 95% CrI, 0.56-0.90) all showed significant effect compared to Rd for PFS. RVd demonstrated significant benefit compared to Rd (HR, 0.72; 95% CrI, 0.53-0.96) for OS. Our study results suggested that lenalidomide and dexamethasone plus daratumumab; daratumumab plus bortezomib, melphalan, and prednisone; and RVd showed better efficacy than Rd in PFS; and RVd showed better efficacy than Rd in OS in patients with newly diagnosed transplant-ineligible multiple myeloma in the absence of head-to-head research.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Humans; Lenalidomide; Melphalan; Multiple Myeloma; Stem Cell Transplantation; Thalidomide; Treatment Outcome
PubMed: 31130487
DOI: 10.1016/j.clml.2019.04.009 -
Expert Review of Clinical Pharmacology Aug 2022The bleeding risk associated with Bruton's tyrosine kinase inhibitor (BTKi) monotherapy remains to be understood. This systematic review aims to evaluate BTKi... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The bleeding risk associated with Bruton's tyrosine kinase inhibitor (BTKi) monotherapy remains to be understood. This systematic review aims to evaluate BTKi monotherapy related bleeding risk.
RESEARCH DESIGN AND METHODS
PubMed, Embase, and CENTRAL were searched up to 5 December 2021. We included randomized controlled trials (RCTs) comparing BTKi monotherapy with control drugs, or comparing different BTKi monotherapies.
RESULTS
10 studies with 3139 patients were included. Ibrutinib (vs. control drugs) significantly increased the risk of overall bleeding and major bleeding (RR = 2.22, 95% CI 1.80-2.75, P < 0.00001; RR = 1.80, 95% CI 1.02-3.18, P = 0.04, respectively). Acalabrutinib (vs. control drugs) had a significantly increased overall bleeding risk (RR = 3.45, 95% CI 2.39-4.99, p < 0.00001). A significant difference was found in overall bleeding between ibrutinib and acalabrutinib (RR = 1.35, 95% CI 1.11-1.64, P = 0.002). Compared to zanubrutinib, ibrutinib tended to increase the risk of major bleeding (RR = 1.55, 95% CI 0.57-4.18, P = 0.39).
CONCLUSIONS
Ibrutinib and acalabrutinib (vs. control drugs) have a higher risk of bleeding and overall bleeding, respectively. Limited evidence suggests that ibrutinib (vs. acalabrutinib) significantly increases overall bleeding risk, but the differences are not observed in other comparisons.
Topics: Benzamides; Hemorrhage; Humans; Protein Kinase Inhibitors; Pyrazines; Randomized Controlled Trials as Topic
PubMed: 35892246
DOI: 10.1080/17512433.2022.2106968 -
Virology Journal Sep 2020The COVID-19 causing coronavirus is an enveloped RNA virus that utilizes an enzyme RNA dependent RNA polymerase for its replication. Favipiravir (FVP) triphosphate, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The COVID-19 causing coronavirus is an enveloped RNA virus that utilizes an enzyme RNA dependent RNA polymerase for its replication. Favipiravir (FVP) triphosphate, a purine nucleoside analog, inhibits that enzyme. We have conducted this systematic review and meta-analysis on efficacy and safety of the drug FVP as a treatment for COVID-19.
METHODS
Databases like Pubmed, Pubmed Central, Scopus, Embase, Google Scholar, preprint sites, and clinicaltirals.gov were searched. The studies with the standard of care (SOC) and FVP as a treatment drug were considered as the treatment group and the SOC with other antivirals and supportive care as the control group. Quantitative synthesis was done using RevMan 5.4. Clinical improvement, negative conversion of reverse transcription-polymerase chain reaction (RT-PCR), adverse effects, and oxygen requirements were studied.
RESULTS
We identified a total of 1798 studies after searching the electronic databases. Nine in the qualitative studies and four studies in the quantitative synthesis met the criteria. There was a significant clinical improvement in the FVP group on the 14th day compared to the control group (RR 1.29, 1.08-1.54). Clinical deterioration rates were less likely in the FVP group though statistically not significant (OR 0.59, 95% CI 0.30-1.14) at the endpoint of study (7-15 days). The meta-analysis showed no significant differences between the two groups on viral clearance (day 14: RR 1.06, 95% CI 0.84-1.33), non-invasive ventilation or oxygen requirement (OR 0.76, 95% CI 0.42-1.39), and adverse effects (OR 0.69, 0.13-3.57). There are 31 randomized controlled trials (RCTs) registered in different parts of the world focusing FVP for COVID-19 treatment.
CONCLUSION
There is a significant clinical and radiological improvement following treatment with FVP in comparison to the standard of care with no significant differences on viral clearance, oxygen support requirement and side effect profiles.
Topics: Amides; Antiviral Agents; Betacoronavirus; COVID-19; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Coronavirus Infections; DNA-Directed RNA Polymerases; Databases, Factual; Enzyme Inhibitors; Humans; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; SARS-CoV-2; Standard of Care; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32972430
DOI: 10.1186/s12985-020-01412-z -
Leukemia & Lymphoma Mar 2020Established treatments for transplant-ineligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) include melphalan and prednisone (MP) combined with either... (Meta-Analysis)
Meta-Analysis
Established treatments for transplant-ineligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) include melphalan and prednisone (MP) combined with either bortezomib (VMP) or thalidomide (MPT), or lenalidomide plus low-dose dexamethasone (Rd). New treatments for TNE NDMM include Rd plus bortezomib (RVd) and daratumumab plus VMP (VMP + D), daratumumab plus lenalidomide and dexamethasone (D + Rd). Relative efficacy of these treatments was compared using a network meta-analysis. Eight trials identified by a systematic literature review were included in the primary analysis; hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were used. Rd was superior to other MP-based regimens for OS and PFS. There was strong evidence that, compared with Rd, both D + Rd and RVd improved PFS (HR 0.57; 95% credible interval (CrI) 0.43, 0.73 and HR 0.72; 95% CrI 0.56, 0.91, respectively). However, there was strong evidence only for RVd in respect to OS (HR 0.72; 95% CrI 0.52, 0.96).
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Humans; Lenalidomide; Melphalan; Multiple Myeloma; Network Meta-Analysis; Thalidomide; Treatment Outcome
PubMed: 31709875
DOI: 10.1080/10428194.2019.1683736 -
Clinical Therapeutics Nov 2019Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma that can be either aggressive or indolent. Although MCL usually responds well to initial... (Comparative Study)
Comparative Study
PURPOSE
Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma that can be either aggressive or indolent. Although MCL usually responds well to initial treatment with chemotherapy-based regimens, the disease often relapses or becomes refractory within a few years. Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor with minimal off-target activity. WIthout head-to-head clinical trial data, estimation of the comparative efficacy and safety of new therapeutic entities provides valuable information for patients, clinicians, and health care payers. The objective of this analysis was to compare the efficacy and safety of acalabrutinib versus other targeted therapies employed for the treatment of relapsed/refractory MCL by using matching-adjusted indirect comparisons.
METHODS
Individual data from 124 patients treated with acalabrutinib in the Phase II ACE-LY-004 trial were adjusted to match average baseline characteristics of populations from studies using alternative targeted treatment regimens for relapsed/refractory MCL (for monotherapy: ibrutinib, bortezomib, lenalidomide, and temsirolimus; for combination therapies: ibrutinib + rituximab, bendamustine + rituximab, and lenalidomide + rituximab). Patient populations were matched on age, sex, race, Eastern Cooperative Oncology Group performance status, Simplified MCL International Prognostic Index score, tumor bulk, lactate dehydrogenase concentration, extranodal disease, bone marrow involvement, and number of previous treatment regimens. Outcomes assessed included overall response rate (ORR), complete response (CR) rate, overall survival (OS), progression-free survival (PFS), and adverse events.
FINDINGS
After matching, acalabrutinib was associated with significant increases in ORR and CR rate (estimated treatment difference [95% CI]) versus ibrutinib (ORR, 9.3% [0.3-18.3]; CR, 14.9% [5.4-24.3]), bortezomib (ORR, 50.6% [40.2-61.0]; CR, 18.8% [9.1-28.5]), lenalidomide (ORR, 38.1% [27.1-49.1]; CR, 43.5% [34.8-52.3]), and temsirolimus (ORR, 40.7% [31.0-50.4]; CR, 27.1% [19.2-35.0]). PFS (hazard ratio [95% CI]) with acalabrutinib was significantly increased versus bortezomib (0.36 [0.26-0.51]), lenalidomide (0.65 [0.48-0.89]), lenalidomide + rituximab (0.57 [0.35-0.93]), and temsirolimus (0.33 [0.24-0.45]). Acalabrutinib was associated with significantly increased OS (hazard ratio) versus bortezomib (0.36 [0.22-0.61]) and temsirolimus (0.32 [0.23-0.44]). The overall safety profile of acalabrutinib was similar or better compared with the monotherapies; however, infection risk increased versus bendamustine + rituximab, and anemia increased risk versus lenalidomide + rituximab and ibrutinib + rituximab.
IMPLICATIONS
This comparison of targeted therapies used in the treatment of relapsed/refractory MCL showed that acalabrutinib has the potential to provide increased response rates, with trends for increased PFS and OS, and an improved safety profile.
Topics: Adenine; Antineoplastic Agents; Benzamides; Bortezomib; Humans; Lenalidomide; Lymphoma, Mantle-Cell; Neoplasm Recurrence, Local; Piperidines; Pyrazines; Pyrazoles; Pyrimidines; Rituximab; Sirolimus; Treatment Outcome
PubMed: 31699438
DOI: 10.1016/j.clinthera.2019.09.012 -
Pharmacotherapy Jun 2020Voxelotor, a sickle hemoglobin polymerization inhibitor, was approved by the U.S. Food and Drug Administration to treat sickle cell disease (SCD) in November 2019. This...
Voxelotor, a sickle hemoglobin polymerization inhibitor, was approved by the U.S. Food and Drug Administration to treat sickle cell disease (SCD) in November 2019. This article reviews published data about voxelotor treatment of SCD based on a search of MEDLINE, Embase, and International Pharmaceutical Abstracts. In a phase I/II trial, voxelotor demonstrated a dose-dependent pharmacokinetic and pharmacodynamic response and was well tolerated in healthy volunteers and patients with SCD. In a multi-center, randomized, double-blind, phase III trial (HOPE trial), a significantly higher percentage of patients randomized to voxelotor had increased hemoglobin (> 1 g/dl from baseline) compared to placebo. A greater reduction of hemolytic markers was also observed in the voxelotor-treated group, whereas the incidence of adverse effects was comparable. Three case series or reports also demonstrated the efficacy and safety of voxelotor use in a limited number of SCD patients in the real-world situation, although one patient with SCD, severe anemia, and a history of autoantibody-mediated hemolysis failed to respond to voxelotor. An ongoing trial (HOPE-KIDS) is designed to establish the use of voxelotor in younger pediatric patients with SCD. There is a theoretical concern that voxelotor may impair oxygen delivery, due to modification of the oxygen affinity of hemoglobin, which needs to be further evaluated. As a first-in-class hemoglobin modulator, voxelotor offers a new treatment option targeting the root cause of SCD.
Topics: Anemia, Sickle Cell; Benzaldehydes; Biomarkers; Dose-Response Relationship, Drug; Hematologic Agents; Hemoglobin, Sickle; Humans; Polymerization; Pyrazines; Pyrazoles; Randomized Controlled Trials as Topic
PubMed: 32343424
DOI: 10.1002/phar.2405 -
Expert Review of Hematology Dec 2020A variety of molecular-targeted drugs have been widely used in hematological malignancies and have shown great advances. Nevertheless, as the use of drugs in clinical...
INTRODUCTION
A variety of molecular-targeted drugs have been widely used in hematological malignancies and have shown great advances. Nevertheless, as the use of drugs in clinical practice increases, the problem of relapse or of the disease being refractory to treatment is becoming apparent. This problem is closely related to the C-X-C chemokine receptor 4 (CXCR4).
AREAS COVERED
This review focuses mainly on the effect of CXCR4 on molecular-targeted drug resistance in hematological malignancies as well as the clinical efficacy of CXCR4 antagonists combined with molecular-targeted drugs. Relevant literatures published between 2006 and 2020 were searched using PubMed/Medline for this review.
EXPERT OPINION
Monoclonal antibodies and non-antibody molecular-targeted drugs provide new therapeutic approaches for B-lineage malignancies and leukemia, but the clinical activity of these drugs is affected by CXCR4. In general, high CXCR4 expression or mutation inhibits the effects of molecular-targeted drugs, but there are exceptions, and in studies of proteasome inhibitors bortezomib (Bz) in multiple myeloma (MM), low CXCR4 expression or loss of CXCR4 was associated with Bz resistance (BzR) and poor treatment outcomes. Given that CXCR4 is a critical mediator of molecular-targeted drug resistance, numerous studies have combined molecular-targeted drugs with CXCR4 antagonists, which synergistically enhance the anti-proliferative/pro-apoptotic effect of molecular-targeted drugs.
Topics: Antineoplastic Agents; Antineoplastic Agents, Immunological; Bortezomib; Cell Lineage; Chemokine CXCL12; Drug Resistance, Neoplasm; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Molecular Targeted Therapy; Multiple Myeloma; Neoplasm Proteins; Protease Inhibitors; Receptors, CXCR4; Signal Transduction; Waldenstrom Macroglobulinemia
PubMed: 33170753
DOI: 10.1080/17474086.2020.1839885 -
Leukemia & Lymphoma Mar 2020For patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible, bortezomib-melphalan-prednisone (VMP) demonstrated superior efficacy based on...
The effects of different schedules of bortezomib, melphalan, and prednisone for patients with newly diagnosed multiple myeloma who are transplant ineligible: a matching-adjusted indirect comparison.
For patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible, bortezomib-melphalan-prednisone (VMP) demonstrated superior efficacy based on the VISTA trial. In subsequent trials, twice-weekly bortezomib was limited to the first cycle or completely replaced with once-weekly bortezomib to reduce toxicity. Following a systematic literature review, the efficacy and safety of modified VMP schedules (pooled data from the once-weekly bortezomib VMP arm of the GIMEMA trial and the VMP arm of the ALCYONE trial) were compared to the VISTA schedule using naïve and unanchored matching-adjusted indirect comparison (MAIC). Median progression-free survival was similar between VISTA and modified VMP (20.7 months [95% CI, 18.4-24.3] vs 19.6 months [95% CI, 18.8-21.0]). Peripheral neuropathy was significantly reduced with modified VMP versus VISTA VMP (all grades: naïve, 32.1% vs 46.8% and MAIC, 32.1% vs 46.7%; both < .0001). These findings support a modified VMP dosing schedule for patients with NDMM who are transplant ineligible.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Humans; Melphalan; Multiple Myeloma; Prednisone; Treatment Outcome
PubMed: 31686561
DOI: 10.1080/10428194.2019.1675881