Latiglutenase Improves Symptoms in Seropositive Celiac Disease Patients While on a Gluten-Free Diet.
Latiglutenase Improves Symptoms in Seropositive Celiac Disease Patients While on a Gluten-Free Diet.
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DOI：
10.1007/s10620-017-4687-7
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发表时间：
2017-09
影响因子：
3.1
通讯作者：
Khosla C
中科院分区：
文献类型：
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作者：
Syage JA;Murray JA;Green PHR;Khosla C
乳糜泻(CD)是一种广泛的疾病，由饮食中的面筋引发，并使用终身无面筋饮食(GFD)治疗；然而，无意中接触面筋可导致发作症状。之前的一项试验是在有持续性损伤的有症状的受试者中进行的，该试验是一种口服两种重组面筋特异性蛋白酶的混合物。组织学改善的主要终点没有达到，可能是由于试验效果。在这项事后分析中，我们根据研究参与者的血清阳性情况，研究了乳胶酶对减轻亚组患者症状的有效性。这项研究包括有症状的CD患者，在随机分组前接受GFD至少一年。患者接受乳胶酶或安慰剂治疗12周。在完成的398名患者中，173名(43%)在基线时血清阳性。每天记录症状，并编制每周症状评分。用协方差分析(ANCOVA)计算P值。在血清阳性而不是血清阴性的患者中，发现症状的严重程度和频率有统计学意义的剂量依赖性的降低。与安慰剂组(n=54)相比，服用最高剂量(900 mg，n=14)的患者腹痛和腹胀的严重程度分别降低了58%和44%。从第6周到第12周，症状改善增加。随着基线症状严重程度的增加，也有更大的症状改善的趋势。血清阳性的CD患者在随餐服用乳胶酶后症状有所改善，并将从这种治疗的可用性中受益。
Celiac disease (CD) is a widespread condition triggered by dietary gluten and treated with a lifelong gluten-free diet (GFD); however, inadvertent exposure to gluten can result in episodic symptoms. A previous trial of latiglutenase (clinicaltrials.gov; NCT01917630), an orally administered mixture of two recombinant gluten-specific proteases, was undertaken in symptomatic subjects with persistent injury. The primary endpoint for histologic improvement was not met, presumably due to a trial effect. In this post hoc analysis we investigated the efficacy of latiglutenase for reducing symptoms in subgroups of the study participants based on their seropositivity. The study involved symptomatic CD patients following a GFD for at least one year prior to randomization. Patients were treated for 12 weeks with latiglutenase or placebo. Of 398 completed patients 173 (43%) were seropositive at baseline. Symptoms were recorded daily and weekly symptom scores were compiled. P-values were calculated by analysis of covariance (ANCOVA). A statistically significant, dose-dependent reduction was detected in the severity and frequency of symptoms in seropositive but not seronegative patients. The severity of abdominal pain and bloating was reduced by 58% and 44%, respectively, in the cohort receiving the highest latiglutenase dose (900 mg, n=14) relative to placebo (n=54). Symptom improvement increased from week 6 to week 12. There was also a trend toward greater symptom improvement with greater baseline symptom severity. Seropositive CD patients show symptomatic improvement from latiglutenase taken with meals and would benefit from the availability of this treatment.