Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom.
Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom.
复制标题
DOI：
10.1212/nxi.0000000000001008
复制
发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
UK-Childhood Inflammatory Disease Network
中科院分区：
文献类型：
--
作者：
Abdel-Mannan OA;Manchoon C;Rossor T;Southin JC;Tur C;Brownlee W;Byrne S;Chitre M;Coles A;Forsyth R;Kneen R;Mankad K;Ram D;West S;Wright S;Wassmer E;Lim M;Ciccarelli O;Hemingway C;Hacohen Y;UK-Childhood Inflammatory Disease Network
比较新的疾病缓解疗法（DMT）与注射剂在复发缓解型多发性硬化症（RRMS）儿童中的实际有效性。在这项来自英国儿童炎症性脱髓鞘网络的回顾性多中心研究中，我们确定了2012年1月至2018年12月接受DMT的RRMS儿童。从病历中检索临床和临床旁数据。计算治疗前和治疗中的年复发率（ARR）、复发时间、新发MRI病变时间和扩展残疾状态量表（EDSS）评分变化。在103名接受DMT治疗的儿童中，随访3.8年，注射剂治疗的复发率为53/89（59.5%），而新型DMT治疗的复发率为8/54（15%）。注射剂的ARR从1.9降至1.1（p < 0.001），而新型DMT的ARR从1.6降至0.3（p = 0.002）。注射剂组77/89（86.5%）例患者发生新发MRI病变，而新型DMT组26/54（47%）例患者发生新发MRI病变（p = 0.0001）。接受新型DMT治疗的儿童比接受注射剂治疗的患者复发时间、转换治疗时间和新放射学活动时间更长（对数秩p < 0.01）。调整潜在的混杂因素后，多变量分析显示，注射剂与临床复发风险增加12倍相关（调整后的风险比[HR] = 12.12，95% CI = 1.64-89.87，p = 0.015），新发放射学活动的风险增加2倍（校正HR = 2.78，95% CI = 1.08-7.13，p = 0.034）。在治疗开始后2年，38/103（37%）例患者在无临床复发的情况下具有MRI活动。随访期间EDSS评分无变化，仅2例患者出现认知功能障碍。与注射剂相比，新型DMT与患者的临床和放射学复发风险较低相关。我们的研究增加了一个紧迫的转变，在实践中使用更新，更有效的DMT在第一时间的论点的权重。这项研究提供了IV类证据，证明新的DMT（口服或输注）在减少RRMS儿童的临床复发和放射学活性方面上级注射剂（干扰素β/醋酸格拉替雷）。
To compare the real-world effectiveness of newer disease-modifying therapies (DMTs) vs injectables in children with relapsing-remitting multiple sclerosis (RRMS). In this retrospective, multicenter study, from the UK Childhood Inflammatory Demyelination Network, we identified children with RRMS receiving DMTs from January 2012 to December 2018. Clinical and paraclinical data were retrieved from the medical records. Annualized relapse rates (ARRs) before and on treatment, time to relapse, time to new MRI lesions, and change in Expanded Disability Status Scale (EDSS) score were calculated. Of 103 children treated with DMTs, followed up for 3.8 years, relapses on treatment were recorded in 53/89 (59.5%) on injectables vs 8/54 (15%) on newer DMTs. The ARR was reduced from 1.9 to 1.1 on injectables (p < 0.001) vs 1.6 to 0.3 on newer DMTs (p = 0.002). New MRI lesions occurred in 77/89 (86.5%) of patients on injectables vs 26/54 (47%) on newer DMTs (p = 0.0001). Children on newer DMTs showed longer time to relapse, time to switch treatment, and time to new radiologic activity than patients on injectables (log-rank p < 0.01). After adjustment for potential confounders, multivariable analysis showed that injectables were associated with 12-fold increased risk of clinical relapse (adjusted hazard ratio [HR] = 12.12, 95% CI = 1.64–89.87, p = 0.015) and a 2-fold increased risk of new radiologic activity (adjusted HR = 2.78, 95% CI = 1.08–7.13, p = 0.034) compared with newer DMTs. At 2 years from treatment initiation, 38/103 (37%) patients had MRI activity in the absence of clinical relapses. The EDSS score did not change during the follow-up, and only 2 patients had cognitive impairment. Newer DMTs were associated with a lower risk of clinical and radiologic relapses in patients compared with injectables. Our study adds weight to the argument for an imminent shift in practice toward the use of newer, more efficacious DMTs in the first instance. This study provides Class IV evidence that newer DMTs (oral or infusions) are superior to injectables (interferon beta/glatiramer acetate) in reducing both clinical relapses and radiologic activity in children with RRMS.