Effect of a Daily Text Messaging and Directly Supervised Therapy Intervention on Oral Mercaptopurine Adherence in Children With Acute Lymphoblastic Leukemia A Randomized Clinical Trial
Effect of a Daily Text Messaging and Directly Supervised Therapy Intervention on Oral Mercaptopurine Adherence in Children With Acute Lymphoblastic Leukemia A Randomized Clinical Trial
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DOI：
10.1001/jamanetworkopen.2020.14205
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发表时间：
2020-08-27
影响因子：
13.8
通讯作者：
Landier, Wendy
中科院分区：
文献类型：
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作者：
Bhatia, Smita;Hageman, Lindsey;Landier, Wendy
急性淋巴细胞白血病（ALL）患儿口服巯基嘌呤治疗依从性不佳会增加复发风险。一个经常表达的障碍，以遵守是健忘，这往往是克服了父母的vigilances.Objective，以确定是否多组分干预，与教育相比，单独，将导致更高比例的急性淋巴细胞白血病患者谁有巯基嘌呤遵守率95%或更高，为所有研究参与者和患者之间的年龄小于12岁和12岁及以上。依从性干预试验是一项由医生发起的、多机构、平行组、非盲、随机临床试验，于2012年7月16日至2018年8月8日在美国59家儿童肿瘤组机构进行，招募了21岁以下确诊的ALL患者，并接受巯基嘌呤维持治疗。最终随访日期为2019年1月2日。数据分析时间为2019年2月至10月。干预患者按1：1的比例随机分为单独教育组和干预组，干预组包括每日教育和个性化短信提醒，以提示直接监督治疗。4周的基线依从性监测后进行了16周的干预。主要结果和测量主要终点是所有研究参与者在干预期间依从率95%或更高的患者比例，以及12岁以下与12岁及以上的患者比例。（中位年龄8.1岁;四分位距5.3-14.3岁），包括干预组230人和教育组214人。302例患者（68.0%）为男孩，180例（40.5%）为非西班牙裔白色人，170例（38.3%）为西班牙裔人，43例（9.7%）为非洲裔美国人，51例（11.5%）为亚洲人或混合人种/种族。干预组与教育组依从率≥ 95%的患者比例无差异（65% vs 59%;比值比，1.33; 95%CI，1.0-2.0; P = 0.08）。探索性分析显示，在12岁及以上的患者中，干预组的平均（SE）依从率高于教育组（93.1% [1.1%] vs 90.0% [1.3%];差异为3.1%; 95% CI，0.1%-6.0%; P = 0.04）。特别是，在基线依从性低于90%的12岁及以上患者中，干预组的平均（SE）依从率高于教育组（83.4% [2.5%] vs 74.6% [3.4%];差异为8.8%; 95% CI，2.2%-15.4%; P = 0.008）。结论和相关性虽然这种多组分干预并没有导致巯基嘌呤依从率95%或更高的ALL患者比例增加，但它确实确定了一个高危亚群，以作为未来依从性干预策略的目标：基线依从性低的青少年。
IMPORTANCE Suboptimal adherence to oral mercaptopurine treatment in children with acute lymphoblastic leukemia (ALL) increases the risk of relapse. A frequently expressed barrier to adherence is forgetfulness, which is often overcome by parental vigilance.OBJECTIVE To determine whether a multicomponent intervention, compared with education alone, will result in a higher proportion of patients with ALL who have mercaptopurine adherence rates 95% or higher, for all study participants and among patients younger than 12 years and vs those aged 12 years and older.DESIGN, SETTING, AND PARTICIPANTS The adherence intervention trial was an investigator-initiated, multi-institutional, parallel-group, unblinded, randomized clinical trial conducted between July 16, 2012, and August 8, 2018, at 59 Children's Oncology Group institutions in the US, enrolling patients with ALL diagnosed through age 21 years and receiving mercaptopurine for maintenance. The date of final follow-up was January 2, 2019. Data analysis was performed from February to October 2019.INTERVENTIONS Patients were randomized 1:1 to education alone or the intervention package, which consisted of education and personalized text message reminders daily to prompt directly supervised therapy. Four weeks of baseline adherence monitoring were followed with a 16-week intervention.MAIN OUTCOMES AND MEASURES The primary end point was the proportion of patients with adherence rates 95% or higher over the duration of the intervention for all study participants, and for those younger than 12 years vs those aged 12 years and older.RESULTS There were 444 evaluable patients (median age, 8.1 years; interquartile range, 5.3-14.3 years), including 230 in the intervention group and 214 in the education group. Three hundred two patients (68.0%) were boys, 180 (40.5%) were non-Hispanic White, 170 (38.3%) were Hispanic, 43 (9.7%) were African American, and 51 (11.5%) were Asian or of mixed race/ethnicity. The proportion of patients with adherence rates 95% or higher did not differ between the intervention vs education groups (65% vs 59%; odds ratio, 1.33; 95% CI, 1.0-2.0; P = .08). Exploratory analyses showed that among patients aged 12 years and older, those in the intervention group had higher mean (SE) adherence rates than those in the education group (93.1% [1.1%] vs 90.0% [1.3%]; difference, 3.1%; 95% CI, 0.1%-6.0%; P = .04). In particular, among patients aged 12 years and older with baseline adherence less than 90%, those in the intervention group had higher mean (SE) adherence rates than those in the education group (83.4% [2.5%] vs 74.6% [3.4%]; difference, 8.8%; 95% CI, 2.2%-15.4%; P = .008). No safety concerns were identified.CONCLUSIONS AND RELEVANCE Although this multicomponent intervention did not result in an increase in the proportion of patients with ALL who had mercaptopurine adherence rates 95% or higher, it did identify a high-risk subpopulation to target for future adherence intervention strategies: adolescents with low baseline adherence.