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United European Gastroenterology Journal Dec 2019Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib.
OBJECTIVES
We aim to summarize the evidence on efficacy and safety of biologics and tofacitinib in moderate-to-severe UC.
METHODS
PubMed, Embase, Scopus, and the Cochrane Library were systematically searched to identify meta-analyses of randomized controlled trials assessing adalimumab, golimumab, infliximab, vedolizumab, and tofacitinib in UC. Efficacy outcomes included induction and maintenance of clinical response, clinical remission and mucosal healing. Safety outcomes included adverse events and serious adverse events.
RESULTS
The overview involved 31 meta-analyses. All four biologics and tofacitinib were superior to placebo regarding efficacy. Indirect comparisons suggested that infliximab may be better than adalimumab and golimumab to induce clinical response and mucosal healing. Safety analyses indicated no increased rates of adverse events, except for infliximab.
CONCLUSIONS
Biologics and tofacitinib are efficacious and safe for treating UC. These findings can support clinical decision-making.
Topics: Biological Factors; Biomarkers; Clinical Trials as Topic; Colitis, Ulcerative; Drug Therapy, Combination; Humans; Molecular Targeted Therapy; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Severity of Illness Index; Treatment Outcome
PubMed: 31839954
DOI: 10.1177/2050640619883566 -
The Cochrane Database of Systematic... Jul 2020Phototherapy is a well-established effective therapy for treating babies with significant neonatal jaundice. Studies have shown that increasing light intensity will... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phototherapy is a well-established effective therapy for treating babies with significant neonatal jaundice. Studies have shown that increasing light intensity will increase its efficiency. A potentially inexpensive and easy way of increasing the intensity of light on the body of the infant may be to hang reflective materials from the sides of phototherapy units.
OBJECTIVES
To assess the effects of reflective materials in combination with phototherapy compared with phototherapy alone for unconjugated hyperbilirubinaemia in neonates.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index of Nursing and Allied Health Literature (CINAHL), on 1 November 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials if the participants, who were term or preterm infants, received phototherapy with curtains made of reflective materials of any type in the treatment arm, and if those in the comparison arm received similar phototherapy without curtains or other intensified phototherapy, such as a double bank of lights.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Of 15 studies identified, we included 12 (1288 babies) in the review - 11 comparing phototherapy with reflective materials and phototherapy alone, and one comparing a single phototherapy light bank with reflective materials with double phototherapy. All reflective materials consisted of curtains on three or four sides of the cot and were made of white plastic (five studies), white linen (two studies), or aluminium (three studies); materials were not specified in two studies. Only 11 studies (10 comparing reflective materials versus none and one comparing reflective curtains and a single bank of lights with a double (above and below) phototherapy unit) provided sufficient data to be included in the meta-analysis. Two excluded studies used the reflective materials in a way that did not meet our inclusion criteria, and we excluded one study because it compared four different phototherapy interventions not including reflective materials. The risk of bias of included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies (281 participants) reported a decline in serum bilirubin (SB) (μmol/L) at four to eight hours (mean difference (MD) -14.61, 95% confidence interval (CI) -19.80 to -9.42; I² = 57%; moderate-certainty evidence). Nine studies (893 participants) reported a decline in SB over 24 hours and showed a faster decline in SB in the intervention group, but heterogeneity (I² = 97%) was too substantial to permit a meaningful estimate of the actual effect size (very low-certainty evidence). Subgroup analysis by type of reflective material used did not explain the heterogeneity. Exchange transfusion was reported by two studies; both reported none in either group. Four studies (466 participants) reported the mean duration of phototherapy, and in each of these studies, it was reduced in the intervention group but there was substantial heterogeneity (I² = 88%), precluding meaningful meta-analysis of data. The only two studies that reported the mean duration of hospital stay in hours showed a meaningful reduction (MD -41.08, 95% CI -45.92 to -36.25; I² = 0; moderate-certainty evidence). No studies reported costs of the intervention, parental or medical staff satisfaction, breastfeeding outcomes, or neurodevelopmental follow-up. The only study that compared use of curtains with double phototherapy reported similar results for both groups. Studies that monitored adverse events did not report increased adverse events related to the use of curtains, including acute life-threatening events, but other rarer side effects could not be excluded.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence shows that the use of reflective curtains during phototherapy may result in greater decline in SB. Very low-certainty evidence suggests that the duration of phototherapy is reduced, and moderate-certainty evidence shows that the duration of hospital stay is also reduced. Available evidence does not show any increase in adverse events, but further studies are needed.
Topics: Aluminum; Bedding and Linens; Bias; Bilirubin; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Infant, Premature; Jaundice, Neonatal; Lighting; Phototherapy; Plastics; Randomized Controlled Trials as Topic
PubMed: 32609375
DOI: 10.1002/14651858.CD012011.pub2 -
BMC Gastroenterology Mar 2021There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review...
BACKGROUND/AIMS
There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review we aimed to address pharmacokinetics (PK), safety, and effects on cardiovascular (CV) outcomes of statins in cirrhosis.
METHODS
Our systematic search in several electronic databases and repositories of two regulatory bodies up to 2020-06-11 yielded 22 articles and 2 drug monographs with relevant data.
RESULTS
Rosuvastatin and pitavastatin showed minimal PK changes in Child-Pugh A cirrhosis. Only rosuvastatin was assessed in a repeated dosing PK study. Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials. There was insufficient data to assess CV effects of statins in cirrhosis. Clinical trials in cirrhosis were limited to simvastatin, atorvastatin, and pravastatin. In patients taking simvastatin 40 mg, pooled frequency of rhabdomyolysis was 2%, an incidence 40-fold higher than that reported in non-cirrhosis patients, while this was no rhabdomyolysis observed in patients on simvastatin 20 mg, atorvastatin 20 mg, or pravastatin 40 mg. Drug-induced liver injury was of difficult interpretation due to co-existence of muscle damage. No overt liver failure was reported.
CONCLUSIONS
Simvastatin 40 mg should be avoided in decompensated cirrhosis. Safety data on simvastatin 20 mg or other statins are based on small study sample size. This rarity of evidence combined with lack of data in dose adjustment methods in cirrhosis is a barrier for using statins for CV indications or for investigational use for liver indications.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Pravastatin; Simvastatin
PubMed: 33726685
DOI: 10.1186/s12876-021-01704-w -
Journal of Global Health Dec 2022All term healthy neonates are screened for jaundice before hospital discharge as a standard clinical practice, but methods vary from clinical screening (visual... (Meta-Analysis)
Meta-Analysis
BACKGROUND
All term healthy neonates are screened for jaundice before hospital discharge as a standard clinical practice, but methods vary from clinical screening (visual inspection and/or risk factor assessment) to transcutaneous bilirubin (TcB) or total serum bilirubin (TSB) testing, depending on the setting.
METHODS
This systematic review of randomized and non-randomized studies evaluated the effectiveness of universal TcB and universal TSB screening at discharge compared to clinical screening alone for term healthy neonates. The outcomes were neonatal mortality, readmission for jaundice, severe hyperbilirubinemia (>20 mg/dL), jaundice requiring exchange transfusion, and bilirubin-induced neurological dysfunction (BIND). We searched MEDLINE via Ovid, EBM reviews, Embase, CINAHL, clinical trials databases, and reference lists of retrieved articles. Two authors separately evaluated the risk of bias, extracted data, and synthesized effect estimates using relative risk (RR) for randomized and odds ratio (OR) for non-randomized studies.
RESULTS
For universal TcB at discharge, we included one randomized trial enrolling 1858 participants and four non-randomized studies enrolling 375 956 participants. No study reported neonatal mortality. The randomized trial suggested that universal TcB at discharge may decrease readmission for jaundice (risk ratio (RR) = 0.24, 95% confidence interval (CI) = 0.13 to 0.46; low certainty evidence) and severe hyperbilirubinemia (RR = 0.27, 95% CI = 0.08 to 0.97; low certainty evidence), but the effect on jaundice requiring exchange transfusion (RR = 0.20, 95% CI = 0.01 to 41.6) and BIND (RR = 0.33, 95% CI = 0.01 to 8.17) was uncertain. Meta-analysis of non-randomized studies suggested that TcB may decrease severe hyperbilirubinemia (odds ratio (OR) = 0.25, 95% = CI 0.12 to 0.52; low certainty evidence) and jaundice requiring exchange transfusion (OR = 0.28, 95% CI = 0.19 to 0.42; low certainty evidence), but the effect on readmission for jaundice was uncertain (OR = 1.01, 95% CI = 0.38 to 2.7; very low certainty evidence). For universal TSB, we included three studies from the United States enrolling 490 426 participants. The effect on severe hyperbilirubinemia (OR = 0.37, 95% CI = 0.15 to 0.88), jaundice requiring exchange transfusion (OR = 0.53, 95% CI = 0.13 to 2.25) and readmission for jaundice (OR = 1.01, 95% CI = 0.62 to 1.67) was uncertain.
CONCLUSIONS
Universal TcB at discharge may improve clinical outcomes for term healthy neonates. Evidence for universal TSB is uncertain.
REGISTRATION
PROSPERO 2020 CRD42020187279.
Topics: Infant, Newborn; Humans; United States; Patient Discharge; Bilirubin; Hyperbilirubinemia; Jaundice
PubMed: 36579719
DOI: 10.7189/jogh.12.12007 -
Systematic Reviews May 2020Development of cognitive decline represents substantial issues in today's society, steadily gaining importance with increasing life expectancy. One potential approach to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Development of cognitive decline represents substantial issues in today's society, steadily gaining importance with increasing life expectancy. One potential approach to preventing cognitive decline is to lower homocysteine by administering vitamin B. In this systematic review and meta-analysis, we address this topic and investigate whether oral supplementation of vitamin B can successfully prevent cognitive decline in cognitively unimpaired individuals.
METHODS
A computerized systematic literature search was conducted using the electronic databases PubMed, Embase, and the Cochrane Library. Eligibility criteria included oral supplementation with vitamin B (B, B, folic acid, and B) and the absence of cognitive impairment. A meta-analysis was conducted with "global cognition" as the primary outcome of this review. Secondary outcomes were changes in cognitive function in other cognitive domains reported in the included studies. Risk of bias was assessed according to the Cochrane Risk of Bias tool and the GRADE approach to establish the overall certainty of the evidence.
RESULTS
The meta-analysis did not yield a significant overall effect of supplementation with vitamin B on cognitive function (Z = 0.87; p = 0.39; SMD, 0.02; 95% CI, - 0.034, 0.08). A sensitivity analysis focusing on specific risk factors did not alter this result. Some studies reported isolated significant effects of the intervention on secondary outcomes. However, these findings were outnumbered by the number of cognitive tests that did not yield significant effects.
DISCUSSION
We found no overall evidence that oral vitamin B supplementation prevented cognitive decline. The isolated significant effects that were reported could be attributed to methodological issues. The results of this review do not provide evidence that population groups with certain risk factors would profit more from the intervention than others. Our findings do not apply to forms of administration other than oral supplementation nor do they offer information regarding the treatment of cognitively impaired individuals via the administration of vitamin B.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017071692.
Topics: Cognitive Dysfunction; Dietary Supplements; Folic Acid; Humans; Vitamin B 12; Vitamin B Complex
PubMed: 32414424
DOI: 10.1186/s13643-020-01378-7 -
Annals of Palliative Medicine Feb 2022This study aimed to investigate the efficacy and safety of mecobalamin combined with vestibular rehabilitation training in acute vestibular neuritis and to improve the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to investigate the efficacy and safety of mecobalamin combined with vestibular rehabilitation training in acute vestibular neuritis and to improve the clinical therapeutic effect in vestibular nerve disease.
METHODS
We performed a literature search of the PubMed, Medline, China National Knowledge Infrastructure (CNKI), and other databases from the date of establishment of the database until the present. The search terms included "mecobalamin", "vestibular rehabilitation training", "vestibular rehabilitation therapy", and "vestibular neuritis". References of the comparative study of vestibular rehabilitation training and vestibular rehabilitation training combined with mecobalamin were screened. Boolean logic retrieval was adopted, and Review Manager software was employed.
RESULTS
Meta-analysis was conducted on a total of four studies with a low risk of bias. The activities specific balance confidence scale (ABC) scores of the two groups were heterogeneous (Chi2=8.56, I2=88%, P=0.003), and a fixed-effect model (FEM) analysis indicated that there were no significant differences in the ABC between the groups after treatment (Z=0.67, P=0.50). It may be that mecobalamin combined with vestibular rehabilitation training effectively alleviated the symptoms of vestibular neuritis in the experimental group, thereby reducing the canal paresis (CP) value. In addition, there was no heterogeneous dizziness handicap inventory (DHI) between the groups after treatment (Chi2=20.75, I2=86%, P=0.0001); finite element method (FEM) analysis showed that the DHI of the experimental group after 6 months of treatment was notably lower compared to that of the control group (Z=3.20, P=0.001).
DISCUSSION
Mecobalamin combined with vestibular rehabilitation training can effectively improve vertigo and other symptoms of acute vestibular neuritis patients, with high effectiveness and safety.
Topics: Dizziness; Humans; Vertigo; Vestibular Neuronitis; Vitamin B 12
PubMed: 35249325
DOI: 10.21037/apm-21-3171 -
The Journal of Headache and Pain Jul 2022In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA).
METHODS
Data included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II-IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings.
RESULTS
Across 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9-45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant.
CONCLUSIONS
The efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words.
Topics: Adult; Benzamides; Double-Blind Method; Female; Humans; Middle Aged; Migraine Disorders; Network Meta-Analysis; Piperidines; Pyridines; Pyrroles; Randomized Controlled Trials as Topic
PubMed: 35790906
DOI: 10.1186/s10194-022-01440-w -
Irish Journal of Medical Science Jun 2024This systematic review and network meta-analysis aimed to evaluate the three different administration routes of vitamin B12: oral, intramuscular (IM), and sublingual... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and network meta-analysis aimed to evaluate the three different administration routes of vitamin B12: oral, intramuscular (IM), and sublingual (SL) routes.
METHODS
We searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL Register of Controlled Trials). We included only comparative studies. We performed a frequentist network meta-analysis to measure network estimates for the relative outcomes. Moreover, we conducted a pairwise meta-analysis using a random effect model to obtain direct estimates for outcomes. All outcomes were continuous, and the relative treatment effects were pooled as mean difference (MD) with 95% confidence intervals.
RESULTS
Thirteen studies were included in the meta-analysis, with a total of 4275 patients. Regarding increasing vitamin B12 levels, the IM route ranked first, followed by the SL route (MD = 94.09 and 43.31 pg/mL, respectively) compared to the oral route. However, these differences did not reach statistical significance owing to the limited number of studies. Regarding the hemoglobin level, the pooled effect sizes showed no difference between all routes of administration that could reach statistical significance. However, the top two ranked administration routes were the oral route (78.3) and the IM route (49.6).
CONCLUSION
All IM, oral, and SL routes of administration of vitamin B12 can effectively increase the level of vitamin B12 without significant differences between them, as thought previously. However, the IM route was the top-ranked statistically but without clinical significance. We found no significant difference among studied administrated routes in all other CBC parameters and homocysteine levels.
Topics: Humans; Administration, Oral; Administration, Sublingual; Dietary Supplements; Hemoglobins; Injections, Intramuscular; Network Meta-Analysis; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 38231320
DOI: 10.1007/s11845-023-03602-4 -
The Cochrane Database of Systematic... Oct 2020Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review.
OBJECTIVES
To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy.
SEARCH METHODS
We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020.
SELECTION CRITERIA
We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI-based targeted therapy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression-free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health-related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach.
MAIN RESULTS
We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons. 1. Pazopanib versus sunitinib Pazopanib may result in little to no difference in PFS as compared to sunitinib (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.90 to 1.23; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 420 per 1000 in this trial at 12 months, this corresponds to 18 fewer participants experiencing PFS (95% CI 76 fewer to 38 more) per 1000 participants. Pazopanib may result in little to no difference in OS compared to sunitinib (HR 0.92, 95% CI 0.80 to 1.06; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 27 more OSs (95% CI 19 fewer to 70 more) per 1000 participants. Pazopanib may result in little to no difference in SAEs as compared to sunitinib (risk ratio (RR) 1.01, 95% CI 0.94 to 1.09; 1 study, 1102 participants; low-certainty evidence). Based on the control event risk of 734 per 1000 in this trial, this corresponds to 7 more participants experiencing SAEs (95% CI 44 fewer to 66 more) per 1000 participants. 2. Sunitinib versus avelumab and axitinib Sunitinib probably reduces PFS as compared to avelumab plus axitinib (HR 1.45, 95% CI 1.17 to 1.80; 1 study, 886 participants; moderate-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 130 fewer participants experiencing PFS (95% CI 209 fewer to 53 fewer) per 1000 participants. Sunitinib may result in little to no difference in OS (HR 1.28, 95% CI 0.92 to 1.79; 1 study, 886 participants; low-certainty evidence). Based on the control event risk of 890 per 1000 in this trial at 12 months, this would result in 29 fewer OSs (95% CI 78 fewer to 8 more) per 1000 participants. Sunitinib may result in little to no difference in SAEs (RR 1.01, 95% CI 0.93 to 1.10; 1 study, 873 participants; low-certainty evidence). Based on the control event risk of 705 per 1000 in this trial, this corresponds to 7 more SAEs (95% CI 49 fewer to 71 more) per 1000 participants. 3. Sunitinib versus pembrolizumab and axitinib Sunitinib probably reduces PFS as compared to pembrolizumab plus axitinib (HR 1.45, 95% CI 1.19 to 1.76; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 590 per 1000 in this trial at 12 months, this corresponds to 125 fewer participants experiencing PFS (95% CI 195 fewer to 56 fewer) per 1000 participants. Sunitinib probably reduces OS (HR 1.90, 95% CI 1.36 to 2.65; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 880 per 1000 in this trial at 12 months, this would result in 96 fewer OSs (95% CI 167 fewer to 40 fewer) per 1000 participants. Sunitinib may reduce SAEs as compared to pembrolizumab plus axitinib (RR 0.90, 95% CI 0.81 to 1.02; 1 study, 854 participants; low-certainty evidence) although the CI includes the possibility of no effect. Based on the control event risk of 604 per 1000 in this trial, this corresponds to 60 fewer SAEs (95% CI 115 fewer to 12 more) per 1000 participants. 4. Sunitinib versus nivolumab and ipilimumab Sunitinib may reduce PFS as compared to nivolumab plus ipilimumab (HR 1.30, 95% CI 1.11 to 1.52; 1 study, 847 participants; low-certainty evidence). Based on the control event risk of 280 per 1000 in this trial at 30 months' follow-up, this corresponds to 89 fewer PFSs (95% CI 136 fewer to 37 fewer) per 1000 participants. Sunitinib reduces OS (HR 1.52, 95% CI 1.23 to 1.89; 1 study, 847 participants; high-certainty evidence). Based on the control event risk 600 per 1000 in this trial at 30 months, this would result in 140 fewer OSs (95% CI 219 fewer to 67 fewer) per 1000 participants. Sunitinib probably increases SAEs (RR 1.37, 95% CI 1.22 to 1.53; 1 study, 1082 participants; moderate-certainty evidence). Based on the control event risk of 457 per 1000 in this trial, this corresponds to 169 more SAEs (95% CI 101 more to 242 more) per 1000 participants.
AUTHORS' CONCLUSIONS
Based on the low to high certainty of evidence, several combinations of immune checkpoint inhibitors appear to be superior to single-agent targeted therapy in terms of PFS and OS, and with a favourable AE profile. Some single-agent targeted therapies demonstrated a similar or improved oncological outcome compared to others; minor differences were observed for AE within this group. The certainty of evidence was variable ranging from high to very low and all comparisons were based on single trials.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Immunological; Axitinib; Bevacizumab; Bias; Carcinoma, Renal Cell; Everolimus; Humans; Indazoles; Ipilimumab; Kidney Neoplasms; Phenylurea Compounds; Progression-Free Survival; Protein Kinase Inhibitors; Pyrimidines; Quality of Life; Quinolines; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Sirolimus; Sorafenib; Sulfonamides; Sunitinib
PubMed: 33058158
DOI: 10.1002/14651858.CD012796.pub2 -
BMJ Open Aug 2020The optimum systemic therapies for advanced/metastatic renal cell carcinoma (RCC) of favourable, intermediate and poor risk have not been established. We aimed to... (Meta-Analysis)
Meta-Analysis
What is the optimum systemic treatment for advanced/metastatic renal cell carcinoma of favourable, intermediate and poor risk, respectively? A systematic review and network meta-analysis.
PURPOSE
The optimum systemic therapies for advanced/metastatic renal cell carcinoma (RCC) of favourable, intermediate and poor risk have not been established. We aimed to compare and rank the effects associated with systemic therapies in the first-line setting.
METHODS
We searched PubMed, Cochrane databases, Web of Science and ClinicalTrials.gov for randomised controlled trials (RCT) published up to February 2020 of all available treatments for advanced/metastatic RCC. Analysis was done on a Bayesian framework.
RESULTS
15 unique RCTs including 8995 patients were identified. For advanced/metastatic RCC of favourable risk, avelumab plus axitinib was associated with a significantly higher improvement in progression-free survival (PFS) than sunitinib (HR 0.57, 95% CI 0.34 to 0.96). For intermediate-risk patients, cabozantinib, nivolumab plus ipilimumab, pembrolizumab plus axitinib and avelumab plus axitinib were associated with significantly higher improvement in PFS than sunitinib (HR 0.63, 95% CI 0.44 to 0.97; HR 0.66, 95% CI 0.53 to 0.81; HR 0.58, 95% CI 0.44 to 0.80; HR 0.62, 95% CI 0.47 to 0.83, respectively); pembrolizumab plus axitinib and nivolumab plus ipilimumab were associated with significantly higher improvement in overall survival (OS) than sunitinib (HR 0.53, 95% CI 0.34 to 0.81; HR 0.66, 95% CI 0.50 to 0.87, respectively). For poor-risk patients, nivolumab plus ipilimumab and pembrolizumab plus axitinib were associated with significantly higher improvement in PFS than sunitinib (HR 0.57, 95% CI 0.43 to 0.76; HR 0.48, 95% CI 0.30 to 0.82, respectively); nivolumab plus ipilimumab and pembrolizumab plus axitinib were significantly more efficacious for OS than sunitinib (HR 0.57, 95% CI 0.39 to 0.883; HR 0.43, 95% CI 0.23 to 0.80, respectively). For OS, there were 81% and 78% probabilities that pembrolizumab plus axitinib was the best option for intermediate-risk and poor-risk patients, respectively.
CONCLUSION
Avelumab plus axitinib might be the optimum treatment for advanced/metastatic RCC of favourable risk. Pembrolizumab plus axitinib might be the optimum treatment for intermediate-risk and poor-risk patients.
Topics: Axitinib; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Network Meta-Analysis; Sunitinib
PubMed: 32859659
DOI: 10.1136/bmjopen-2019-034626