Vigone Barbara, Caronni Monica, Severino Adriana, Bellocchi Chiara, Baldassarri Anna Rita, Fraquelli Mirella, Montanelli Gaia, Santaniello Alessandro, Beretta Lorenzo
Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Via Pace 9, 20122, Milano, Italy.
Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Via Francesco Sforza 35, Milano, Italy.
Arthritis Res Ther. 2017 Jun 20;19(1):145. doi: 10.1186/s13075-017-1340-y.
Prokinetics are used to treat enteric dismotility symptoms in systemic sclerosis (SSc) patients, but they often lack adequate efficacy. The most effective prokinetics belonging to the serotonin (5-HT) receptor agonists class were withdrawn due to cardiac toxicity in relation to modest 5-HT receptor affinity. Prucalopride is a high-affinity 5-HT receptor agonist with no major cardiac issues, for which the efficacy in SSc has not yet been assessed.
Forty patients with self-reported mild to moderately severe enteric symptoms were enrolled in a cross-over 2 × 2 study. Subjects were randomized 1:1 to prucalopride 2 mg/day or no treatment for one month and vice versa after a 2-week washout period. Before and after each sequence the patients compiled the University of California Los Angeles gastrointestinal tract (UCLA GIT) 2.0 questionnaire and the numbers of complete intestinal movements were recorded. Oro-cecal transit time (OCTT) was evaluated by lactulose breath test in a subgroup of patients. Data were evaluated by mixed linear models corrected for the number of laxatives used during the study periods.
There were 29 subjects who completed the study; 7 subjects withdrew due to side-effects and 4 subjects were not compliant with the study procedures. As compared to dummy treatment, prucalopride was associated with more intestinal evacuations (p < 0.001), improvement of UCLA GIT constipation (-0.672 ± 0.112 vs 0.086 ± 0.115; p < 0.001), reflux (-0.409 ± 0.094 vs 0.01 ± 0.096; p < 0.005) and bloating (-0.418 ± 0.088 vs -0.084 ± 0.09; p = 0.01) scores. Treatment was ranked moderately to more than moderately effective by 22 patients (72.4%). OCTT was significantly reduced during prucalopruide consumption (prucalopride: -20.1 ± 20.1 vs no treatment: 45.8 ± 21.3 minutes; treatment effect = -65.9 minutes; p = 0.035).
The safety profile of prucalopride in SSc is similar to what is known from the literature. In patients with mild to severe gastrointestinal problems, prucalopride may be effective in treating dismotility symptoms, increasing the number of complete bowel movements and improving bowel transit, reducing reflux disease and bloating.
EU Clinical Trial Registry, EudraCT2012-005348-92 . Registered on 19 February 2013.
促动力药用于治疗系统性硬化症（SSc）患者的肠道动力障碍症状，但往往疗效欠佳。最有效的属于5-羟色胺（5-HT）受体激动剂类的促动力药因与适度的5-HT受体亲和力相关的心脏毒性而被撤市。普芦卡必利是一种高亲和力5-HT受体激动剂，无重大心脏问题，其在SSc中的疗效尚未得到评估。
40例自我报告有轻度至中度严重肠道症状的患者参与了一项交叉2×2研究。受试者按1:1随机分为普芦卡必利2mg/天组或1个月不治疗组，2周洗脱期后反之。每个疗程前后，患者填写加利福尼亚大学洛杉矶分校胃肠道（UCLA GIT）2.0问卷，并记录完全肠道蠕动次数。在部分患者亚组中通过乳果糖呼气试验评估口盲肠转运时间（OCTT）。数据通过针对研究期间使用的泻药数量进行校正的混合线性模型进行评估。
29例受试者完成了研究；7例因副作用退出，4例未遵守研究程序。与安慰剂治疗相比，普芦卡必利与更多的肠道排空相关（p<0.001），UCLA GIT便秘评分改善（-0.672±0.112对0.086±0.115；p<0.001）、反流评分改善（-0.409±0.094对0.01±0.096；p<0.005）和腹胀评分改善（-0.418±0.088对-0.084±0.09；p=0.01）。22例患者（72.4%）将治疗评为中度至中度以上有效。服用普芦卡必利期间OCTT显著缩短（普芦卡必利：-20.1±20.1对未治疗：45.8±21.3分钟；治疗效果=-65.9分钟；p=0.035）。
普芦卡必利在SSc中的安全性与文献报道一致。在有轻度至重度胃肠道问题的患者中，普芦卡必利可能有效治疗动力障碍症状，增加完全排便次数，改善肠道转运，减轻反流病和腹胀。
欧盟临床试验注册中心，EudraCT2012-005348-92。于2013年2月19日注册。
