A systematic review of adherence to iron chelation therapy among children and adolescents with thalassemia
Annals of medicine. 2022;54(1):326-342
INTRODUCTION Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents. METHODS This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria. RESULTS Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report (n = 15/36, 41.7%), and pill count (n = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills (n = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence (n = 29) or "quantitatively" as a percentage of medication taken out of those prescribed (n = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis. CONCLUSIONS Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients.Key messagesPredictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort.Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes.Inadequate adherence to ICT is associated with increased lifetime health costs.There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients.
Efficacy and Tolerability of Twice-Daily Dosing Schedule of Deferasirox in Transfusion-Dependent Paediatric Beta-Thalassaemia Patients: A Randomized Controlled Study
Journal of pharmacy practice. 2022;:8971900211038301
BACKGROUND Deferasirox has proved good efficacy and acceptable safety for the management of thalassaemia patients. However, some patients are unresponsive or intolerant to once-daily administration of deferasirox even at a high dose. The current study evaluated the effectiveness and tolerability of twice-daily dosing of deferasirox among transfusion-dependent paediatric beta-thalassaemia patients. METHODS This prospective randomized single-blinded parallel study included all transfusion-dependent paediatric beta-thalassaemia patients prescribed with deferasirox, who visit the study site for their regular blood transfusions and follow-up. The enrolled patients were randomized into intervention and control groups by using a simple block randomization method. In the intervention group, the once-daily dosing of deferasirox was changed to twice-daily dosing with the same total daily dose. Whereas, in the control group, the patients continued with the once-daily deferasirox dosing. The serum ferritin levels of both groups were determined on the enrolment day and after 6 months of follow-up. RESULTS Forty-one patients were included for analysis. A statistically significant mean decrease in serum ferritin levels was detected in the intervention group, while the serum ferritin levels of the control group significantly increased from baseline. The twice-daily dosing of deferasirox was better tolerated by the thalassaemia patients when compared to once-daily dosing. CONCLUSION This study concludes that twice-daily dosing of deferasirox with the same total daily dose significantly enhances the iron chelation efficacy and tolerability among transfusion-dependent paediatric beta-thalassaemia patients when compared to once-daily regimen.
Risk factors for bleeding in people living with Hemophilia A and B treated with regular prophylaxis: a systematic review of the literature
Journal of thrombosis and haemostasis : JTH. 2022
BACKGROUND Knowledge about the risk for bleeding in patients with hemophilia (PWH) would be relevant for patients, stakeholders, and policy makers. OBJECTIVES to perform a systematic review of the literature on risk assessment models (RAMs) and risk factors for bleeding in PWH on regular prophylaxis. METHODS We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception through August 2019. In duplicate, reviewers screened the articles for inclusion, extracted data, and assessed the risk for bias using the QUIPS tool. A qualitative synthesis of the results was not performed due to high heterogeneity in risk factors, outcomes definition and measurement, and statistical analysis of the results. RESULTS From 1843 search results, 10 studies met the inclusion criteria. No RAM for the risk for bleeding in PWH was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact. CONCLUSIONS Our findings suggest that plasma factor levels, history of bleeds, and physical activity should be considered for the derivation analysis when building a RAM for bleeding in PWH, and the role of other risk factors, including antithrombotic treatment and obesity, should be explored.
People living with haemophilia (PWH) A and B treated with regular prophylaxis (10 studies).
Systematic review on risk assessment models and risk factors for bleeding.
No risk assessment model was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact.
Safety of Ferric Carboxymaltose in Children: Report of a Case Series from Greece and Review of the Literature
Paediatric drugs. 2022
BACKGROUND Parenteral iron is generally considered safe in adults, and severe adverse events are extremely rare. Ferric carboxymaltose (FCM), a third-generation parenteral iron product, is not licensed for pediatric use. OBJECTIVE The aim of this study was to present our data on the safety of FCM in children with iron deficiency (ID) and/or iron deficiency anemia (IDA) and to investigate through a systematic literature review articles reporting on the safety of FCM use in children with ID/IDA. PATIENTS AND METHODS Safety data regarding children treated with FCM for ID/IDA from four pediatric departments in Greece over a 26-month period are presented. Additionally, a literature search was performed in PubMed, Scopus, and Google Scholar on December 4, 2021 for articles reporting on the use of FCM in children with ID/IDA. Review articles, guidelines, case reports/case series, and reports on the use of FCM for conditions other than ID/IDA were excluded. Identified articles were screened for all reported adverse events (AE) that were graded according to the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS In our cohort, 37 children with ID/IDA received 41 FCM infusions. All infusions were tolerated well. In addition, 11 articles reporting 1231 infusions of FCM in 866 children were identified in the literature. Among them, 52 (6%) children developed AE that were graded as mild or moderate (grades I-III). CONCLUSIONS Our patient cohort and this literature review provide further evidence for the good safety profile of FCM in children, although well-designed prospective clinical trials with appropriate safety endpoints are still required.
Comparison of the effects of calcium channel blockers plus iron chelation therapy versus chelation therapy only on iron overload in children and young adults with transfusion-dependent thalassemia: A randomized double-blind placebo-controlled trial
Pediatric blood & cancer. 2022;:e29564
BACKGROUND Myocardial iron deposition is a significant cause of morbidity and mortality in patients with transfusion-dependent thalassemia (TDT). Amlodipine, L-type calcium channel blocker with regular chelation therapy may reduce myocardial iron overload. Lack of randomized trials prompted this study to assess the effect of calcium channel blocker (amlodipine) in combination with iron chelation therapy on iron overload in patients with TDT. METHODS Sixty-four eligible patients were randomized to receive either amlodipine and chelation (group A) or chelation alone (group B) in double-blind placebo-controlled trial. Myocardial iron concentration (MIC) using T2* magnetic resonance imaging (MRI), liver iron concentration (LIC), left ventricular ejection fraction (LVEF), and serum ferritin were measured at baseline and 12 months. RESULTS In the amlodipine group, mean cardiac T2* value significantly increased from 18.11 ± 8.47 to 22.15 ± 7.61 (p = .002) at 12 months, whereas in control group, there was a nonsignificant increase (p = .62) in cardiac T2* value from 19.50 ± 8.84 to 20.03 ± 9.07. There was a significant decrease in MRI-derived MIC in the amlodipine group compared to control group (1.93 ± 1.61 to 1.29 ± 0.90, p = .01). Changes in the LVEF (p = .45), MRI-derived LIC (p = .09), and serum ferritin (p = .81) were not significant between the two groups. CONCLUSION Amlodipine is safe and when combined with chelation therapy appears to be more effective in reducing cardiac iron overload than chelation only in children and young adults with TDT.
Two trade names of deferasirox (Osveral® and Exjade®) in reduction of iron overload parameters in major beta-thalassemia patients: A randomized open labeled clinical trial
Caspian journal of internal medicine. 2022;13(1):61-69
BACKGROUND Beta-thalassemia major patients typically require chronic transfusion and iron-chelating agents to reduce serum iron overload. Osveral(®) is an available Iranian brand name of deferasirox used by majority of thalassemic patients. The aim of this study was to compare the efficacy of Osveral(®) vs. Exjade(®) in major beta- thalassemia patients. METHODS In this randomized clinical trial, all patients received a single daily dose of 30 mg/kg either of Osveral(®) or Exjade(®) for 6 months. Primary outcome was the mean of bimonthly changes in serum ferritin concentration and secondary outcomes included mean changes of heart and liver MRI T2* after a year. RESULTS Finally, 80 patients completed the study. The mean serum ferritin level at the end of sixth month significantly decreased in Osveral(®) and Exjade(®) groups (p<0.01). After a year, means cardiac MRI T2* in Osveral(®) group were changed from 25.9±9.6 ms to 25.4±9.7 ms and in Exjade(®) group from 24.8±9.2 ms to 26.9±5.9 ms, with no significant difference (P=0.43). Mean liver MRI T2* for Osveral(®) and Exjade(®) groups were 8.6±6.4 ms (baseline 6.3±4.7) and 6.3±4 ms (baseline 4.9±3.5), respectively and there was no significant difference between two study arms (P=0.1). CONCLUSION Osveral(®) decreased significantly the serum ferritin level and improved heart and liver iron overload as efficient as Exjade(®). It can be a suitable cost-effective alternative agent in beta-thalassemia major patients.
A Systematic Review on the Management of Transfusion-Related Acute Lung Injury in Transfusion-Dependent Sickle Cell Disease
The onset of respiratory distress and acute lung injury (ALI) following a blood transfusion is known as transfusion-related acute lung injury (TRALI), although its pathophysiology remains unknown. Even though sickle cell disease (SCD) has been studied for more than a century, few therapeutic and management strategies adequately address the emergence of TRALI. TRALI, an immune-mediated transfusion response that can result in life-threatening consequences, is diagnosed based on clinical signs and symptoms. Early detection and treatment increase the chances of survival and, in most cases, result in a complete recovery. Our objective is to provide a firm grasp of the present status of SCD-related TRALI care and therapy. After exploring multiple databases, this study offers evidence-based guidelines to aid clinicians and other healthcare professionals make decisions concerning transfusion assistance for SCD and the management of transfusion-related complications. Other risk factors for acute lung injury including sepsis aspiration should be ruled out throughout the diagnostic process. Several recent studies have shown that immunotherapy or immunological targets can effectively prevent these complications. Red cell transfusions, red cell antigen matching optimization, and iron chelation can also help reduce negative consequences. It is to be noted that poor clinical outcomes can be avoided by early detection and treatment of hemolytic transfusion reactions. Finally, preventing the onset of TRALI may be the most effective therapeutic strategy for SCD patients who rely on blood transfusions for survival.
Prevalence of transfusion-transmitted infections in multiple blood transfusion-dependent thalassemic patients in Asia: A systemic review
International journal of immunopathology and pharmacology. 2022;36:3946320221096909
BACKGROUND Thalassemia is a hereditary hemolytic anemia marked by a defect in synthesizing one or more globin chains in hemoglobin. In Pakistan, approximately 10,000 patients with thalassemia are primarily dependent on blood transfusions. The β-thalassemia patients require blood transfusions and iron chelation therapy. Patients who need blood transfusions are at an increased risk of contracting transfusion-transmitted infections (TTIs) such as hepatitis B and C viruses (HBV and HCV, respectively), as well as the human immunodeficiency virus (HIV). OBJECTIVE This systemic review aims to assess the prevalence of TTIs in transfusion-dependent β-thalassemia patients in Asia. METHODS The data for the systematic review were gathered from PubMed, Google Scholar, the Directory of Open Access Journals (DOAJ), and ScienceDirect using the following keywords: "prevalence, HBV, HCV, HIV, thalassemia, and transfusion-transmitted infections (TTIs)," and so on. This review includes the research articles that address the prevalence of viral infections in thalassemic patients following blood transfusion. RESULTS A preliminary search of various databases identified 231 potential studies. 157 duplicate studies were eliminated, and the eligibility of 59 full-length articles was determined. Only 43 studies met the inclusion criteria. Among the 43 studies analyzed, 11 reported a high prevalence of HCV alone in thalassemic patients, while 21 reported a high prevalence of HCV and HBV infection in thalassemic patients. Eight studies reported the prevalence of all three TTIs examined, namely, HCV, HBV, and HIV, in patients with transfusion-dependent thalassemia. CONCLUSION Preventable transfusion-transmitted infections occur frequently, and robust national policies and hemovigilance are required to detect and mitigate the infection risk.
Health State Utilities for Sickle Cell Disease: A Catalog Prepared From a Systematic Review
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2022;25(2):276-287
OBJECTIVES Sickle cell disease (SCD) is a complex, chronic condition that impairs health-related quality of life of affected individuals and their caregivers. As curative therapies emerge, comprehensive cost-effectiveness models will inform their value. These models will require descriptions of health states and their corresponding utility values that accurately reflect health-related quality of life over the disease trajectory. The objectives of this systematic review were to develop a catalog of health state utility (HSU) values for SCD, identify research gaps, and provide future directions for preference elicitation. METHODS Records were identified through searches of PubMed and Embase, Tufts Medical Center Cost-Effectiveness Analysis Registry, reference lists of relevant articles, and consultation with SCD experts (2008-2020). We removed duplicate records and excluded ineligible studies. For included studies, we summarized the study characteristics, methods used for eliciting HSUs, and HSU values. RESULTS Five studies empirically elicited utilities using indirect methods (EQ-5D) (n = 3) and Short Form-6 Dimension (n = 2); these represent health states associated with general SCD (n = 1), SCD complications (n = 2), and SCD treatments (n = 3). Additionally, we extracted HSUs from 7 quality-adjusted life-years-based outcome research studies. The HSU among patients with general SCD without specifying complications ranged from 0.64 to 0.887. Only 36% of the HSUs used in the quality-adjusted life-year-based outcomes research studies were derived from individuals with SCD. No study estimated HSUs in caregivers. CONCLUSIONS There is a dearth of literature of HSUs for use in SCD models. Future empirical studies should elicit a comprehensive set of HSUs from individuals with SCD and their caregivers.
Efficacy and safety of intravenous iron with different frequencies for renal anaemia: A systematic review and meta-analysis
Journal of clinical pharmacy and therapeutics. 2022
WHAT IS KNOWN AND OBJECTIVE To evaluate the efficacy and safety of intravenous iron supplementation in patients with renal anaemia. METHODS We searched the PubMed, Embase, Cochrane Library, and Web of Science from their inception until 17 September 2021, for randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous iron at different frequencies. The observed efficacy indicators included transfer saturation (TSAT), serum ferritin (SF) and haemoglobin (HGB). Outcomes of interest included allergies, infections, all-cause mortality and cardiovascular events. RESULTS AND DISCUSSION Of the 751 eligible studies, 7 RCTs met the inclusion criteria. The RCTs showed that there were no significant differences between the low-frequency high-dose group (1-2 doses, >200 mg/dose) and the high-frequency low-dose group (4-5 doses, ≤200 mg/dose) in the increase in TSAT (WMD = 1.90; 95% CI = -2.04 to 5.84; I(2) = 0%), SF (WMD = 15.70; 95% CI = -32.20 to 70.61; I(2) = 0%) and HGB (WMD = -0.00; 95% CI = -0.43 to 0.42; I(2) = 0%). There was also no significant difference in the occurrence of outcome events, including allergies (RR = 1.84; 95% CI = 0.95 to 3.57; I(2) = 45%), infections (RR = 0.61; 95% CI = 0.20-1.86; I(2) = 0%), cardiovascular events (RR = 0.88; 95% CI = 0.67-1.15; I(2) = 48%) and all-cause mortality (RR = 0.74; 95% CI = 0.40-1.35; I(2) = 0%). WHAT IS NEW AND CONCLUSION Frequencies of intravenous iron supplementation with similar doses share similar safety and efficacy in patients with renal anaemia. However, a single dose or two doses of intravenous iron are more cost-effective and patient friendly. These findings may provide evidence for the clinical application of intravenous iron supplementation for patients with renal anaemia.