假设与链球菌感染(PANDAS)相关的小儿自身免疫性神经精神疾病是由于A组链球菌感染产生的交叉反应性抗体而发生的。先前的研究表明,免疫调节疗法,如静脉注射免疫球蛋白(IVIG),可能导致PANDAS患者症状快速持续改善。
共有35名符合PANDAS和中度至重度强迫症(OCD)标准的儿童被纳入一项随机条目,双盲,安慰剂对照,IVIG的6周试验(连续2天1g/kg/天),其次是对无应答者的可选开放标签治疗,随访12周和24周。主要结果指标为儿童耶鲁-布朗强迫症量表(CY-BOCS)和临床整体印象改善(CGI-I)评分。定义了“响应者”,先验,CY-BOCS总分下降≥30%,并在CGI-I上获得“很多”或“非常多”的评级。
在双盲阶段,IVIG组(n=17)和安慰剂组(n=18)的CY-BOCS评分平均下降24%±31%,IVIG组中有6名应答者(35%),安慰剂组中有4名应答者(22%);这些差异无统计学意义.24名参与者符合双盲输注无应答标准,并在第6周接受了开放标签IVIG。在所有参与者中,CY-BOCS相对于基线的平均改善在第12周为55%±33%,在第24周为62%±33%.
IVIG安全且耐受性良好。组间差异小于预期,双盲比较未能证明IVIG优于安慰剂。观察到的开放标签改进表明,未来的试验将受益于更大的样本量,部分目的是帮助鉴定预测免疫疗法阳性反应的生物标志物。未来的调查重点是PANDAS的自然史也是必要的。临床试验注册信息-静脉内免疫球蛋白用于PANDAS(与链球菌感染相关的小儿自身免疫性神经精神障碍);http://clinicaltrials.gov/;NCT01281969ZIAMH002666。
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are hypothesized to occur as a result of cross-reactive antibodies produced in response to group A streptococcal infections. Previous research suggests that immunomodulatory therapies, such as intravenous immunoglobulin (IVIG), may lead to rapid and sustained symptom improvement in patients with PANDAS.
A total of 35 children meeting criteria for PANDAS and moderate to severe obsessive-compulsive disorder (OCD) were enrolled in a randomized-entry, double-blind, placebo-controlled, 6-week trial of IVIG (1 g/kg/day on 2 consecutive days), followed by optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Primary outcome measures were the Children\'s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions-Improvement (CGI-I) rating. \"Responders\" were defined, a priori, by a ≥ 30% decrease in CY-BOCS total score, and a \"much\" or \"very much\" improved rating on CGI-I.
During the double-blind phase, the mean decrease in CY-BOCS score was 24% ± 31% in the IVIG group (n = 17) and 12% ± 27% in the placebo group (n = 18), with six responders in the IVIG group (35%) versus four (22%) in the placebo group; these differences were not statistically significant. Twenty-four participants met criteria for nonresponse to double-blind infusion and received open-label IVIG at week 6. Among all participants, the mean CY-BOCS improvement from baseline was 55% ± 33% at week 12 and 62% ± 33% at week 24.
IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted. Clinical trial registration information-Intravenous Immunoglobulin for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections); http://clinicaltrials.gov/; NCT01281969ZIAMH002666.