Background:
Thalassaemia is a genetic disorder disease, one of the most clinically relevant haemoglobinopathies in paediatric population. It interferes with the synthesis of haemoglobin chain. For the sake of maintaining the serum haemoglobin at a normal level, regular blood cell transfusion is required to the patients with thalassaemia. In general, patients with thalassaemia are often diagnosed at an early age and need to take a life-long iron chelating therapy to prevent the multi-organ failure caused by iron-overload. The safety issue is considered a very importance aspect in the treatment among paediatric population and young people.
In the past decades, numerous randomised controlled trials (RCTs) and meta-analysis regarding the efficacy and safety of iron chelating agents including deferoxamine, deferiprone, deferasirox, in reducing iron accumulation among patients with thalassaemia had been published, yet limited meta-analysis reveal the same issue among paediatric population and young adults. Further evidence and understanding are therefore needed to confirm whether or not the iron chelating agents are safe among young patients with thalassaemia.
Objective:
To conduct a meta-analysis to evaluate the safety of iron chelating agents in paediatric population and young adults with thalassaemia.
Methods:
Literature search was carried out in PubMed, EMBASE, BIOSIS Previews, Science Citation Index Expanded and Cochrane Library databases. This meta-analysis of observational studies was conducted following the PRISMA and MOOSE statements.
Selection Criteria
All prospective uncontrolled cohort studies were eligible to include. Articles were assessed according to the age range of its participants and the quality of the reported adverse effects. All enrolled studies should record countable cases of adverse effects of paediatric population and young patients up to 25 years of age, diagnosed with alpha/beta thalassaemia or sickle cell disease and under the treatment of iron chelating agents.
Data Collection and analysis
Two reviewers independently retrieved the data and conducted the quality assessment for each of the included studies. Agency for healthcare research and quality assessment tool was used to evaluate the general risk of bias, whilst the quality of harms was assessed with the Mcharm question criterions. Meta-analysis was carried out for detecting the entire proportion value of six adverse effects including liver abnormality, renal abnormality, rash, abdominal pain/discomfort, nausea and neutropenia, and the forest plot was generated accordingly. The I2 was estimated to assess the methodological quality of each outcome. Random or fixed model was used for the analysis. The sensitivity analysis was conducted to assess the robust of the result.
Results
A total of 8199 articles were identified in the initial database search. After removal of duplications, update from other sources and exclusion based on the exclusion criteria, 25 full articles were retrieved and 14 uncontrolled cohort studies were included in this review. Eight hundred and fifty-four patients up to 25 years of age were included in the analysis. The general quality of the studies was moderate while the quality of adverse effects was low to moderate. Out of the 14 included studies, nine were under the deferasirox treatment; five for deferiprone therapy. No study included deferoxamine. Most adverse effects were observed among the paediatric patients under deferasirox treatment. The meta-analysis of pooled proportion under deferasirox were 17.23% (95%CI, 8.78-25.68%) for liver abnormality, 11.58% (95%CI, 5.91-17.25%) for renal abnormality, 5.41% (95%CI, 3.23-7.58%) for rash, 11.03% (95%CI, 1.83-20.22%) for abdominal pain/discomfort and 5.77% (95%CI, 1,50-10.03%) for nausea. Only one study reported case of neutropenia in the patients under deferasirox, whereas more cases were recorded within the paediatric patients with deferiprone, estimated proportion of 5.98% (95%CI, 2.79-9.16%). However, the meta-analysis of estimated proportion for liver abnormality in paediatric patients with deferiprone was 10.08% (95%CI, 2.67-17.49%), abdominal pain/discomfort was 4.31% (95%CI, 1.65-6.98%). Only one study reported case of renal abnormality, rash and nausea respectively in the patients with deferasirox, which a meta-analysis could not be conducted.
Conclusions
Among paediatric population and young patients with thalassaemia disease, most drug-related adverse effects were liver injury among patients under both deferasirox and deferiprone. For patients under deferasirox, the proportions of the risk of abdominal pain/discomfort and renal abnormality were in a secondary high-level, whereas the proportions of the risk of rash and nausea were comparatively very low. Few adverse effects were detected among young patients with deferiprone. In addition, the proportion of liver abnormality and abdominal pain/discomfort were lower for deferiprone than deferasirox. Further investigation is needed to assess the safety and efficacy between different dosage of iron chelating agents and the risk of other adverse effects among paediatric population, which are necessary to guide the clinical practice in the treatment of paediatric patients with thalassaemia. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/208520 |
| Date | January 2014 |
| Creators | Li, Niya, 李妮婭 |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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