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Obesity Surgery Jun 2024Bariatric surgery (BS) is the most effective treatment for severe obesity and it has beneficial effects on glycemic control and metabolism outcomes. However, the effects... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bariatric surgery (BS) is the most effective treatment for severe obesity and it has beneficial effects on glycemic control and metabolism outcomes. However, the effects of BS on nutritional outcomes are controversial. Therefore, we aimed to evaluate the changes in several nutritional outcomes after Roux-en-Y gastric bypass (RYGB).
METHODS
A comprehensive search was performed using the following databases: PubMed, Embase, Web of Science, Cochrane Library, WanFang and Chinese National Knowledge Infrastructure. The following outcomes were evaluated: vitamin A, 25-hydroxyvitamin D [25(OH)D], calcium, phosphorus, parathormone (PTH), iron, ferritin, vitamin B12, folate, and zinc. The pooled outcomes were expressed as standard mean difference (SMD) and 95% confidence interval (CI) using a random effects model.
RESULTS
Fifty-six studies including 5645 individuals with obesity met the inclusion criteria. Serum 25(OH)D (SMD = 0.78, 95%CI 0.38 to 1.20, P < 0.001), phosphorus (SMD = 0.48, 95%CI 0.22 to 0.74, P < 0.001), PTH (SMD = 0.35, 95%CI 0.11 to 0.59, P = 0.005), vitamin B12 (SMD = 1.11, 95%CI 0.41 to 1.80, P = 0.002), and folate (SMD = 1.53, 95%CI 0.77 to 2.28, P < 0.001) significantly increased after RYGB compared with the baseline. Serum ferritin (SMD = - 1.67, 95%CI - 2.57 to - 0.77, P < 0.001), vitamin A (SMD = - 0.64, 95%CI - 0.99 to - 0.29, P < 0.001), and plasma zinc (SMD = - 0.58, 95%CI - 1.09 to - 0.06, P = 0.027) significantly decreased after RYGB. No significant changes in serum calcium (SMD = - 0.14, 95%CI - 0.40 to 0.11, P = 0.219) and iron (SMD = 0.26, 95%CI - 0.11 to 0.64, P = 0.165) were observed after RYGB.
CONCLUSIONS
Despite the increased levels of 25(OH)D, phosphorus, vitamin B12 and folate, this meta-analysis revealed the unfavorable nutritional consequences after RYGB.
Topics: Humans; Gastric Bypass; Obesity, Morbid; Vitamin D; Treatment Outcome; Nutritional Status; Calcium; Vitamin B 12; Parathyroid Hormone; Female; Phosphorus; Folic Acid; Vitamin A; Weight Loss; Male; Zinc; Ferritins; Adult
PubMed: 38662252
DOI: 10.1007/s11695-024-07232-2 -
Journal of Cystic Fibrosis : Official... May 2024Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The...
BACKGROUND & AIMS
Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The prognosis of CF has improved with the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Due to the paucity of data and concerns regarding interactions with immunosuppressive drug regimens, there is no general consensus on use of ETI post liver transplantation. The aim of this review is to report the safety and efficacy of ETI in CF patients who underwent liver transplantation.
METHODS
A systematic review was conducted through MEDLINE/Pubmed and EMBASE databases. English-written articles reporting clinical data on liver transplanted CF patients treated with ETI were included. Article quality was evaluated using the Critical Appraisal Checklist for Case Reports.
RESULTS
Twenty cases were retrieved from 6 reports. Temporary discontinuation and/or dose reduction due to elevated transaminases was required in 5 cases. ETI restarted on a reduced dose was tolerated in 3 out of 5 patients, 1 patient tolerated full dose. Tacrolimus dose change was required in 14 cases, in 1 case ETI was discontinued due to tacrolimus toxicity. Improvement in percentage predicted FEV1 was noted in 15/19 patients (median +17 %, range 8 %-38 %).
CONCLUSIONS
In the majority of liver transplanted patients ETI is well tolerated, although adverse events and liver function abnormalities may occur. Close monitoring of liver function and tacrolimus level is warranted. Significant improvement in lung function after ETI initiation is confirmed, highlighting the importance of accessing this medication for this group of patients.
Topics: Humans; Aminophenols; Benzodioxoles; Chloride Channel Agonists; Cystic Fibrosis; Drug Combinations; Indoles; Liver Transplantation; Pyrazoles; Pyridines; Pyrroles; Pyrrolidines; Quinolones
PubMed: 38614868
DOI: 10.1016/j.jcf.2024.04.006 -
World Journal of Gastroenterology Mar 2024() infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric... (Meta-Analysis)
Meta-Analysis
BACKGROUND
() infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for eradication.
AIM
To assess the efficacy of regimens containing P-CABs in eradicating infection.
METHODS
This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated.
RESULTS
A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, = 0.3), respectively.
CONCLUSION
VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating , positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.
Topics: Humans; Anti-Bacterial Agents; Clarithromycin; Helicobacter pylori; Proton Pump Inhibitors; Drug Therapy, Combination; Helicobacter Infections; Pyrroles; Amoxicillin; Treatment Outcome; Randomized Controlled Trials as Topic; Observational Studies as Topic; Benzene Derivatives; Imidazoles; Sulfonamides
PubMed: 38577188
DOI: 10.3748/wjg.v30.i9.1213 -
Hepatology Communications Apr 2024The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We systematically reviewed the literature to answer these questions.
METHODS
Four databases were searched for studies describing the precision of clinical criteria (National Institute on Alcohol Abuse and Alcoholism, European Association for Study of Liver, or classical) and the role of histology in AH. The precision(positive predictive value) of criteria was pooled through random-effects meta-analysis, and its variation was investigated through subgroups and meta-regression of study-level factors with their percent contribution to variation (R2). The risk of bias among studies was evaluated through the QUADAS2 tool (PROSPERO-ID-CRD4203457250).
RESULTS
Of 4320 studies, 18 in the systematic review and 15 (10/5: low/high risk of bias, N=1639) were included in the meta-analysis. The pooled precision of clinical criteria was 80.2% (95% CI: 69.7-89.7, I2:93%, p < 0.01), higher in studies with severe AH (mean-Model for End-Stage Liver Disease > 20) versus moderate AH (mean-Model for End-Stage Liver Disease < 20): 92% versus 67.1%, p < 0.01, and in studies with serum bilirubin cutoff 5 versus 3 mg/dL (88.5% vs.78.8%, p = 0.01). The factors contributing to variation in precision were Model for End-Stage Liver Disease (R2:72.7%), upper gastrointestinal bleed (R2:56.3%), aspartate aminotransferase:aspartate aminotransferase ratio (R2:100%), clinical criteria (R2:40.9%), bilirubin (R2:22.5%), and Mallory body on histology (R2:19.1%).The net inter-pathologist agreement for histologic findings of AH was variable (0.33-0.97), best among 2 studies describing AH through simple and uniform criteria, including steatosis, ballooning, and neutrophilic inflammation. Few studies reported the utility of histology in estimating steroid responsiveness (N = 1) and patient prognosis (N = 4); however, very broad septa, pericellular fibrosis, and cholestasis were associated with mortality. Bilirubinostasis was associated with infection in 1 study.
CONCLUSIONS
Clinical criteria are reasonably precise for diagnosing severe AH, while there is an unmet need for better criteria for diagnosing moderate AH. Histologic diagnosis of AH should be simple and uniform.
Topics: Humans; End Stage Liver Disease; Severity of Illness Index; Hepatitis, Alcoholic; Aspartate Aminotransferases; Bilirubin
PubMed: 38497934
DOI: 10.1097/HC9.0000000000000404 -
BMC Oral Health Mar 2024Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters.
METHODS
Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger's test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11.
RESULTS
By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals.
CONCLUSION
The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.
Topics: Humans; Stomatitis, Aphthous; Vitamin B 12 Deficiency; Folic Acid Deficiency; Folic Acid; Vitamin B 12; Hemoglobins; Ferritins
PubMed: 38493289
DOI: 10.1186/s12903-024-04072-5 -
BMC Gastroenterology Mar 2024Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based... (Meta-Analysis)
Meta-Analysis
Comparison of vonoprazan and proton pump inhibitors for the treatment of gastric endoscopic submucosal dissection-induced ulcer: an updated systematic review and meta-analysis.
BACKGROUND
Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection.
METHODS
The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate.
RESULTS
Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs.
CONCLUSIONS
Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan.
SYSTEMATIC REVIEW REGISTRATION
Identifier CRD42024509227.
Topics: Humans; Proton Pump Inhibitors; Stomach Ulcer; Ulcer; Endoscopic Mucosal Resection; Stomach Neoplasms; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Pyrroles; Sulfonamides
PubMed: 38491413
DOI: 10.1186/s12876-024-03198-8 -
Italian Journal of Pediatrics Mar 2024Home phototherapy (HPT) remains a contentious alternative to inpatient phototherapy (IPT) for neonatal hyperbilirubinemia. To guide evidence-based clinical... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Home phototherapy (HPT) remains a contentious alternative to inpatient phototherapy (IPT) for neonatal hyperbilirubinemia. To guide evidence-based clinical decision-making, we conducted a meta-analysis of randomized clinical trials (RCTs) and cohort studies and assessed the comparative risks and benefits of HPT and IPT.
METHODS
PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technique Journals Database, ClinicalTrials.gov, and International Clinical Trial Registry Platform trial were searched from inception until June 2, 2023. We included RCTs and cohort studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Cochrane Collaboration Risk of Bias tool and the Newcastle-Ottawa scale. The outcome measures were phototherapy duration, daily bilirubin level reduction, exchange transfusion, hospital readmission, parental stress scale, and complications. We used fixed- or random-effects meta-analysis models, assessed heterogeneity (I), conducted subgroup analyses, evaluated publication bias, and graded evidence quality.
RESULTS
Nine studies (998 patients) were included (four RCTs, five cohort studies). HPT was associated with longer phototherapy duration (SMD = 0.55, 95% CI: 0.06-1.04, P = 0.03). Cohort study subgroup analysis yielded consistent results (SMD = 0.90; 95% CI: 0.69 to 1.11, P < 0.001, I = 39%); the RCTs were not significantly different (SMD = -0.04; 95% CI: -0.15 to 0.08, P = 0.54, I = 0%). Hospital readmission was higher with HPT (RR = 4.61; 95% CI: 1.43-14.86, P = 0.01). Daily bilirubin reduction (WMD = -0.12, 95% CI: -0.68 to 0.44, P = 0.68) or complications were not significantly different (RR = 2.29; 95% CI: 0.31-16.60, P = 0.41). The evidence quality was very low. HPT was associated with lower parental stress (SMD = -0.44, 95% CI: -0.71 to -0.16, P = 0.002). None of three included studies reported exchange transfusion.
CONCLUSIONS
The current evidence does not strongly support HPT efficacy for neonatal hyperbilirubinemia, as high-quality data on long-term outcomes are scarce. Future research should prioritize well-designed, large-scale, high-quality RCTs to comprehensively assess HPT risks and benefits.
Topics: Humans; Infant, Newborn; Bilirubin; Clinical Decision-Making; Hyperbilirubinemia, Neonatal
PubMed: 38433210
DOI: 10.1186/s13052-024-01613-0 -
The American Journal of Clinical... Mar 2024The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention.
OBJECTIVE
Our aim was to determine the optimal dosage range of a combination of folic acid, vitamin B12, and vitamin B6 supplementation in stroke prevention.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase database for randomized controlled trials published between January 1966 and April 2023, whose participants received B-vitamin supplementation and that reported the number of stroke cases. Relative risk (RR) was used to measure the effect of combined supplementation on risk of stroke using a fixed-effects model. Risk of bias was assessed with the Cochrane risk-of-bias algorithm.
RESULTS
The search identified 14 randomized controlled trials of folic acid combined with vitamin B12 and vitamin B6 supplementation for stroke prevention that included 76,664 participants with 2720 stroke cases. In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively. Further analysis showed that a dosage of folic acid ≤0.8 mg/d and vitamin B12 ≤0.4 mg/d was best for stroke prevention (RR: 0.65; 95% CI: 0.48, 0.86) in these areas. In contrast, no benefit of combined supplementation was found in fortified areas (RR: 1.04; 95% CI: 0.94, 1.16).
CONCLUSIONS
Our meta-analysis found that the folic acid combined with vitamin B12 and vitamin B6 supplementation strategy significantly reduced the risk of stroke in areas without and with partial folic acid fortification. Combined dosages not exceeding 0.8 mg/d for folic acid and 0.4 mg/d for vitamin B12 supplementation may be more effective for populations within these areas. This trial was registered at PROSPERO asCRD42022355077.
Topics: Humans; Vitamins; Vitamin B 12; Folic Acid; Vitamin B 6; Stroke; Dietary Supplements
PubMed: 38432716
DOI: 10.1016/j.ajcnut.2023.12.021 -
International Journal of Nursing Studies May 2024Practices related to umbilical cord clamping at birth should be evidence-based. Deferred cord clamping, compared to immediate cord clamping, shows benefits for preterm... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Practices related to umbilical cord clamping at birth should be evidence-based. Deferred cord clamping, compared to immediate cord clamping, shows benefits for preterm neonates but this may also apply to healthy term neonates. Different blood sampling techniques are used to measure effect of deferred and immediate cord clamping.
OBJECTIVE
To assess the statistical and effect size differences between blood biomarkers from umbilical cord and capillary blood samples of healthy term neonates following either immediate or deferred cord clamping.
DESIGN
Systematic review and meta-analysis.
METHODS
The databases PubMed, Medline, CENTRAL, CINAHL and EMBASE were systematically searched. We included studies with a randomised clinical trial design comparing deferred and immediate cord clamping among healthy term neonates born by a spontaneous vaginal birth, reporting on blood biomarkers. Studies including caesarean births and premature births/neonates were excluded. Study attributes, sampling technique, blood biomarkers, mean differences, and standard deviations were extracted. The standardised mean differences (SMD) and sampling errors were calculated for effect size estimation. Meta-analyses were performed if ≥2 studies reported the same outcome using RevMan 5. Subgroup analyses distinguished effects from umbilical cord and capillary blood samples. Moderator tests and publication bias analyses were performed using JASP.
RESULTS
Fifteen studies were included for analysis. The biomarkers haematocrit, haemoglobin, and bilirubin were reported in ≥2 studies and thus eligible for pooling. No differences were found in haemoglobin (SMD -0.04, 95%CI -0.57 to 0.49) or bilirubin values (SMD 0.13, 95%CI -0.03 to 0.28) between umbilical cord blood samples collected after deferred or immediate cord clamping. Deferred cord clamping led to lower haematocrit values (SMD -0.3, 95%CI -0.53 to -0.07). Higher haematocrit (SMD 0.67, 95%CI 0.37 to 0.97) and haemoglobin values (SMD 0.76, 95%CI 0.56 to 0.97) from capillary blood samples, collected 2 to 72 h postpartum, showed when cord clamping was deferred. No effect was found on bilirubin values (SMD 0.13, 95%CI -0.03 to 0.28) irrespective of the sampling technique.
CONCLUSIONS
Blood collected after deferred umbilical cord clamping showed increased haemoglobin and haematocrit values up to 72 h after birth, opposed to bilirubin values. Clinical evaluation of blood biomarkers from the umbilical cord shows different values compared to capillary blood. Sampling time and technique therefore seem essential in estimating the effects of deferred cord clamping.
TWEETABLE ABSTRACT
This meta-analysis shows that sampling time and technique are essential in estimating the effects of deferred cord clamping on neonatal blood values.
Topics: Humans; Infant, Newborn; Umbilical Cord Clamping; Fetal Blood; Biomarkers; Umbilical Cord; Hemoglobins; Bilirubin; Pregnancy; Female
PubMed: 38417349
DOI: 10.1016/j.ijnurstu.2024.104718 -
The Cochrane Database of Systematic... Feb 2024Management of congenital hemophilia A and B is by prophylactic or on-demand replacement therapy with clotting factor concentrates. The effects of newer non-clotting... (Review)
Review
BACKGROUND
Management of congenital hemophilia A and B is by prophylactic or on-demand replacement therapy with clotting factor concentrates. The effects of newer non-clotting factor therapies such as emicizumab, concizumab, marstacimab, and fitusiran compared with existing standards of care are yet to be systematically reviewed.
OBJECTIVES
To assess the effects (clinical, economic, patient-reported, and adverse outcomes) of non-clotting factor therapies for preventing bleeding and bleeding-related complications in people with congenital hemophilia A or B compared with prophylaxis with clotting factor therapies, bypassing agents, placebo, or no prophylaxis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, electronic databases, conference proceedings, and reference lists of relevant articles and reviews. The date of the last search was 16 August 2023.
SELECTION CRITERIA
Randomized controlled trials (RCTs) evaluating people with congenital hemophilia A or B with and without inhibitors, who were treated with non-clotting factor therapies to prevent bleeds.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed studies for eligibility, assessed risk of bias, and extracted data for the primary outcomes (bleeding rates, health-related quality of life (HRQoL), adverse events) and secondary outcomes (joint health, pain scores, and economic outcomes). We assessed the mean difference (MD), risk ratio (RR), 95% confidence interval (CI) of effect estimates, and evaluated the certainty of the evidence using GRADE.
MAIN RESULTS
Six RCTs (including 397 males aged 12 to 75 years) were eligible for inclusion. Prophylaxis versus on-demand therapy in people with inhibitors Four trials (189 participants) compared emicizumab, fitusiran, and concizumab with on-demand therapy in people with inhibitors. Prophylaxis using emicizumab likely reduced annualized bleeding rates (ABR) for all bleeds (MD -22.80, 95% CI -37.39 to -8.21), treated bleeds (MD -20.40, 95% CI -35.19 to -5.61), and annualized spontaneous bleeds (MD -15.50, 95% CI -24.06 to -6.94), but did not significantly reduce annualized joint and target joint bleeding rates (AjBR and AtjBR) (1 trial; 53 participants; moderate-certainty evidence). Fitusiran also likely reduced ABR for all bleeds (MD -28.80, 95% CI -40.07 to -17.53), treated bleeds (MD -16.80, 95% CI -25.80 to -7.80), joint bleeds (MD -12.50, 95% CI -19.91 to -5.09), and spontaneous bleeds (MD -14.80, 95% CI -24.90 to -4.71; 1 trial; 57 participants; moderate-certainty evidence). No evidence was available on the effect of bleed prophylaxis using fitusiran versus on-demand therapy on AtjBR. Concizumab may reduce ABR for all bleeds (MD -12.31, 95% CI -19.17 to -5.45), treated bleeds (MD -10.10, 95% CI -17.74 to -2.46), joint bleeds (MD -9.55, 95% CI -13.55 to -5.55), and spontaneous bleeds (MD -11.96, 95% CI -19.89 to -4.03; 2 trials; 78 participants; very low-certainty evidence), but not target joint bleeds (MD -1.00, 95% CI -3.26 to 1.26). Emicizumab prophylaxis resulted in an 11.31-fold increase, fitusiran in a 12.5-fold increase, and concizumab in a 1.59-fold increase in the proportion of participants with no bleeds. HRQoL measured using the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) physical and total health scores was improved with emicizumab, fitusiran, and concizumab prophylaxis (low-certainty evidence). Non-serious adverse events were higher with non-clotting factor therapies versus on-demand therapy, with injection site reactions being the most frequently reported adverse events. Transient antidrug antibodies were reported for fitusiran and concizumab. Prophylaxis versus on-demand therapy in people without inhibitors Two trials (208 participants) compared emicizumab and fitusiran with on-demand therapy in people without inhibitors. One trial assessed two doses of emicizumab (1.5 mg/kg weekly and 3.0 mg/kg bi-weekly). Fitusiran 80 mg monthly, emicizumab 1.5 mg/kg/week, and emicizumab 3.0 mg/kg bi-weekly all likely resulted in a large reduction in ABR for all bleeds, all treated bleeds, and joint bleeds. AtjBR was not reduced with either of the emicizumab dosing regimens. The effect of fitusiran prophylaxis on target joint bleeds was not assessed. Spontaneous bleeds were likely reduced with fitusiran (MD -20.21, 95% CI -32.12 to -8.30) and emicizumab 3.0 mg/kg bi-weekly (MD -15.30, 95% CI -30.46 to -0.14), but not with emicizumab 1.5 mg/kg/week (MD -14.60, 95% CI -29.78 to 0.58). The percentage of participants with zero bleeds was higher following emicizumab 1.5 mg/kg/week (50% versus 0%), emicizumab 3.0 mg/kg bi-weekly (40% versus 0%), and fitusiran prophylaxis (40% versus 5%) compared with on-demand therapy. Emicizumab 1.5 mg/kg/week did not improve Haem-A-QoL physical and total health scores, EQ-5D-5L VAS, or utility index scores (low-certainty evidence) when compared with on-demand therapy at 25 weeks. Emicizumab 3.0 mg/kg bi-weekly may improve HRQoL measured by the Haem-A-QoL physical health score (MD -15.97, 95% CI -29.14 to -2.80) and EQ-5D-5L VAS (MD 9.15, 95% CI 2.05 to 16.25; 1 trial; 43 participants; low-certainty evidence). Fitusiran may result in improved HRQoL shown as a reduction in Haem-A-QoL total score (MD -7.06, 95% CI -11.50 to -2.62) and physical health score (MD -19.75, 95% CI -25.76 to -11.94; 1 trial; 103 participants; low-certainty evidence). The risk of serious adverse events in participants without inhibitors also likely did not differ following prophylaxis with either emicizumab or fitusiran versus on-demand therapy (moderate-certainty evidence). Transient antidrug antibodies were reported in 4% (3/80) participants to fitusiran, with no observed effect on antithrombin lowering. A comparison of the different dosing regimens of emicizumab identified no differences in bleeding, safety, or patient-reported outcomes. No case of treatment-related cancer or mortality was reported in any study group. None of the included studies assessed our secondary outcomes of joint health, clinical joint function, and economic outcomes. None of the included studies evaluated marstacimab.
AUTHORS' CONCLUSIONS
Evidence from RCTs shows that prophylaxis using non-clotting factor therapies compared with on-demand treatment may reduce bleeding events, increase the percentage of individuals with zero bleeds, increase the incidence of non-serious adverse events, and improve HRQoL. Comparative assessments with other prophylaxis regimens, assessment of long-term joint outcomes, and assessment of economic outcomes will improve evidence-based decision-making for the use of these therapies in bleed prevention.
Topics: Male; Adult; Humans; Hemophilia A; Blood Coagulation Factors; Hemorrhage; Hemarthrosis; Heme
PubMed: 38411279
DOI: 10.1002/14651858.CD014544.pub2