Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia.
Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia.
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DOI：
10.1002/14651858.cd012349.pub2
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发表时间：
2018-05-08
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影响因子：
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通讯作者：
Estcourt LJ
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作者：
Fortin PM;Fisher SA;Madgwick KV;Trivella M;Hopewell S;Doree C;Estcourt LJ
经常输血的镰状细胞病（SCD）患者和地中海贫血患者（输血依赖或非输血依赖）都有铁超载的危险。铁超载会导致心脏、肝脏和内分泌腺等脆弱器官的铁中毒；可以用铁螯合剂预防和治疗。治疗的强烈要求和不舒服的副作用会对日常活动和健康产生负面影响，这可能会影响依从性。确定和评估干预措施（心理和社会心理、教育、药物干预或多组分干预）的有效性，以提高SCD或地中海贫血患者对铁螯合治疗的依从性。我们检索了CENTRAL （Cochrane图书馆）、MEDLINE、Embase、CINAHL、PsycINFO、Psychology and Behavioral Sciences Collection、Web of Science科学与社会科学会议论文集索引和正在进行的试验数据库（2017年2月1日）。我们检索了Cochrane囊性纤维化和遗传疾病组的血红蛋白病试验注册（2017年12月12日）。对于比较药物或药物变化的试验，只有随机对照试验（rct）符合纳入条件。对于包括心理和社会心理干预、教育干预或多成分干预在内的研究，以依从性为主要结局的非随机对照试验、前后对照研究和中断时间序列研究也符合纳入条件。三位作者独立评估试验资格、偏倚风险和提取数据。使用GRADE评估证据的质量。我们纳入了1997年至2017年间发表的16项随机对照试验（1525名受试者）。大多数参与者患有重度β-地中海贫血；SCD 195例，β-地中海贫血88例。平均年龄11 ~ 41岁。1项试验为药物管理，15项随机对照试验为药物干预。评估的药物是皮下去铁胺和两种口服螯合剂，去铁素和去铁素。我们将本综述中确定的所有结局的证据质量评为低至极低。三个试验使用经过验证的仪器测量生活质量（QoL），但没有提供可分析的数据，也没有报告生活质量的差异。我们不确定去铁酮是否会增加铁螯合治疗的依从性（四项试验，非常低质量的证据）。由于相当大的异质性（参与者的年龄和不同的用药方案），结果不能合并。药物依从性高(去铁倾向（85% ~ 94.9%）；去铁胺（71.6% ~ 93%）。我们不确定去铁蛋白是否会增加粒细胞缺乏症的风险，风险比（RR） 7.88(99%可信区间（CI） 0.18 ~ 352.39)；或对全因死亡率有任何影响，RR 0.44 (95% CI 0.12 ~ 1.63)（1项试验，88名受试者，证据质量非常低）。我们不确定去铁铁素是否会增加铁螯合治疗的依从性，平均差异(MD) -1.40 (95% CI -3.66 - 0.86)（一项试验，197名受试者，证据质量极低）。药物依从性高(去铁氨醇（99%）；去铁胺(100%))。我们不确定去铁昔酮是否能降低地中海贫血相关严重不良事件（SAEs）的风险，RR为0.95 (95% CI 0.41 - 2.17)；或全因死亡率，RR 0.96 (95% CI 0.06 ~ 15.06)（两项试验，240名受试者，证据质量非常低）。我们不确定去铁宁是否降低scd相关疼痛危机的风险，RR 1.05 (95% CI 0.68 - 1.62)；或其他scd相关的SAEs， RR 1.08 (95% CI 0.77 ~ 1.51)（1项试验，195名受试者，极低质量证据）。去铁昔洛FCT可能对依从性影响很小或没有影响，RR 1.10 (95% CI 0.99至1.22)（1项试验，173名受试者，低质量证据）。药物依从性高（FCT为92.9%）；DT(85.3%))。我们不确定去铁昔酮FCT是否会增加SAEs的发生率，RR为1.22 (95% CI 0.62至2.37)；或全因死亡率，RR 2.97 (95% CI 0.12 - 71.81)（1项试验，173名受试者，证据质量极低）。我们不确定去铁胺和去铁胺联合使用是否会增加铁螯合治疗的依从性（非常低质量的证据）。药物依从性高(去铁率为92.7% (37% ~ 100%)~ 93.6% (56% ~ 100%)；去铁胺70.6%（范围25% - 100%）。联合治疗可能对SAEs的风险影响很小或没有影响，RR为0.15 (95% CI为0.01 ~ 2.81)（1项试验，213名受试者，低质量证据）。我们不确定联合治疗是否能降低全因死亡率，RR为0.77 (95% CI为0.18 - 3.35)（两项试验，237名受试者，证据质量非常低）。去铁素和去铁胺联合使用可能对铁螯合治疗的依从性影响很小或没有影响（4项试验，216名受试者，低质量证据）。药物依从性高（去铁胺91.4%至96.1%；去铁胺：82.4%）去铁胺和去铁胺联合使用，可能对SAEs或死亡率的影响很小或没有差异（低质量证据）。3项试验均未发生急性脑损伤，1项试验未报道。两项试验均未发生死亡，两项试验均未报告死亡。去铁素和去铁素联合使用可能改善铁螯合治疗的依从性，RR 0.84 (95% CI 0.72 - 0.99)（1项试验，96名受试者，低质量证据）。药物依从性高（去铁酮和去铁胺：80%；去铁酮和去铁铁：95%）。我们不确定去铁酮和去铁酮是否能降低SAEs的发生率，RR为1.00 (95% CI为0.06 - 15.53)（一项试验，96名受试者，证据质量非常低）。试验中没有死亡病例（低质量证据）。我们不确定药物管理是否能改善与健康相关的生活质量（一项试验，48名受试者，证据质量非常低）。依从性仅在试验的一个组中进行了测量。本综述中纳入的药物比较的依从率高于平均水平，但没有考虑到药物管理或副作用的差异。参与者可能是根据基线时对试验药物的较高依从性来选择的。此外，在临床试验背景下，临床医生的关注和参与增加了，因此高依从率可能是参与试验的人为因素。现实世界中，需要在社区和临床环境中进行实际试验，以检查已证实或未证实的依从性策略，这些策略可能会增加铁螯合治疗的依从性。由于缺乏证据，本综述不能对不同年龄组的干预策略发表评论。
Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia (who are transfusion-dependent or non-transfusion-dependent) are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands; which can be prevented and treated with iron chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and well-being, which may affect adherence. To identify and assess the effectiveness of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) to improve adherence to iron chelation therapy in people with SCD or thalassaemia. We searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, Psychology and Behavioral Sciences Collection, Web of Science Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (01 February 2017). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register (12 December 2017). For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion. For studies including psychological and psychosocial interventions, educational Interventions, or multi-component interventions, non-RCTs, controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion. Three authors independently assessed trial eligibility, risk of bias and extracted data. The quality of the evidence was assessed using GRADE. We included 16 RCTs (1525 participants) published between 1997 and 2017. Most participants had β-thalassaemia major; 195 had SCD and 88 had β-thalassaemia intermedia. Mean age ranged from 11 to 41 years. One trial was of medication management and 15 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral-chelating agents, deferiprone and deferasirox. We rated the quality of evidence as low to very low across all outcomes identified in this review. Three trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL. We are uncertain whether deferiprone increases adherence to iron chelation therapy (four trials, very low-quality evidence). Results could not be combined due to considerable heterogeneity (participants’ age and different medication regimens). Medication adherence was high (deferiprone (85% to 94.9%); deferoxamine (71.6% to 93%)). We are uncertain whether deferiprone increases the risk of agranulocytosis, risk ratio (RR) 7.88 (99% confidence interval (CI) 0.18 to 352.39); or has any effect on all-cause mortality, RR 0.44 (95% CI 0.12 to 1.63) (one trial; 88 participants; very low-quality evidence). We are uncertain whether deferasirox increases adherence to iron chelation therapy, mean difference (MD) -1.40 (95% CI -3.66 to 0.86) (one trial; 197 participants; very-low quality evidence). Medication adherence was high (deferasirox (99%); deferoxamine (100%)). We are uncertain whether deferasirox decreases the risk of thalassaemia-related serious adverse events (SAEs), RR 0.95 (95% CI 0.41 to 2.17); or all-cause mortality, RR 0.96 (95% CI 0.06 to 15.06) (two trials; 240 participants; very low-quality evidence). We are uncertain whether deferasirox decreases the risk of SCD-related pain crises, RR 1.05 (95% CI 0.68 to 1.62); or other SCD-related SAEs, RR 1.08 (95% CI 0.77 to 1.51) (one trial; 195 participants; very low-quality evidence). Deferasirox FCT may make little or no difference to adherence, RR 1.10 (95% CI 0.99 to 1.22) (one trial; 173 participants; low-quality evidence). Medication adherence was high (FCT (92.9%); DT (85.3%)). We are uncertain if deferasirox FCT increases the incidence of SAEs, RR 1.22 (95% CI 0.62 to 2.37); or all-cause mortality, RR 2.97 (95% CI 0.12 to 71.81) (one trial; 173 participants; very low-quality evidence). We are uncertain if deferiprone and deferoxamine combined increases adherence to iron chelation therapy (very low-quality evidence). Medication adherence was high (deferiprone 92.7% (range 37% to 100%) to 93.6% (range 56% to 100%); deferoxamine 70.6% (range 25% to 100%). Combination therapy may make little or no difference to the risk of SAEs, RR 0.15 (95% CI 0.01 to 2.81) (one trial; 213 participants; low-quality evidence). We are uncertain if combination therapy decreases all-cause mortality, RR 0.77 (95% CI 0.18 to 3.35) (two trials; 237 participants; very low-quality evidence). Deferiprone and deferoxamine combined may have little or no effect on adherence to iron chelation therapy (four trials; 216 participants; low-quality evidence). Medication adherence was high (deferoxamine 91.4% to 96.1%; deferiprone: 82.4%) Deferiprone and deferoxamine combined, may have little or no difference in SAEs or mortality (low-quality evidence). No SAEs occurred in three trials and were not reported in one trial. No deaths occurred in two trials and were not reported in two trials. Deferiprone and deferasirox combined may improve adherence to iron chelation therapy, RR 0.84 (95% CI 0.72 to 0.99) (one trial; 96 participants; low-quality evidence). Medication adherence was high (deferiprone and deferoxamine: 80%; deferiprone and deferasirox: 95%). We are uncertain if deferiprone and deferasirox decreases the incidence of SAEs, RR 1.00 (95% CI 0.06 to 15.53) (one trial; 96 participants; very low-quality evidence). There were no deaths in the trial (low-quality evidence). We are uncertain if medication management improves health-related QoL (one trial; 48 participants; very low-quality evidence). Adherence was only measured in one arm of the trial. The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects. Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation. Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy. Due to lack of evidence this review cannot comment on intervention strategies for different age groups.