Calvo Margarita, Tejos-Bravo Macarena, Passi-Solar Alvaro, Espinoza Fernanda, Fuentes Ignacia, Lara-Corrales Irene, Pope Elena
Physiology Department, Biological Sciences Faculty, Pontificia Universidad Católica de Chile, Santiago, Chile.
Millennium Nucleus for the Study of Pain, Santiago, Chile.
JAMA Dermatol. 2024 Dec 1;160(12):1314-1319. doi: 10.1001/jamadermatol.2024.3767.
Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB.
To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the Douleur Neuropathique 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023.
Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups.
Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention.
In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated.
The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial.
ClinicalTrials.gov Identifier: NCT03928093.
隐性营养不良性大疱性表皮松解症（RDEB）患者会经历神经性疼痛和瘙痒。目前缺乏关于RDEB患者这些症状的任何治疗方法的证据。
测试普瑞巴林治疗RDEB患者神经性疼痛和瘙痒的疗效。
设计、地点和参与者：2019年1月1日至2020年12月31日在加拿大多伦多和智利圣地亚哥的2个地点进行了一项口服普瑞巴林（50 - 300毫克/天）与安慰剂对比的随机、双盲、交叉试验。符合参与条件的患者被诊断为RDEB，年龄在8至40岁之间，非怀孕或哺乳期（女性），并且有神经性疼痛和瘙痒的证据，定义为远端热感觉丧失（通过热滚轮确认）、神经病理性疼痛4问卷（DN4）得分4分或更高，以及10分视觉模拟量表（VAS）得分大于4分。患有具有临床重要性或控制不佳的医学或精神疾病、普瑞巴林不耐受或过敏的患者被排除。在41名筛查的患者中，3名不符合条件，28名拒绝入组。2021年至2023年进行了数据分析。
参与者以随机顺序接受普瑞巴林和匹配的安慰剂（滴定至最大耐受剂量300毫克/天），以便在参与者内部和组间进行比较。
干预前后普瑞巴林和安慰剂治疗之间的平均疼痛和瘙痒评分差异（使用VAS测量）。
总共10名参与者被随机分为2组，第1组6名患者（平均[标准差]年龄，26.7[8.1]岁；3名女性[50%]），第2组4名患者（平均[标准差]年龄，26.5[7.8]岁，2名女性[50%]）。第1组接受普瑞巴林 - 安慰剂序列，而第2组接受安慰剂 - 普瑞巴林序列。与基线相比，在控制序列和治疗期时，普瑞巴林显著降低平均（标准差）疼痛评分1.9（1.5）分，而安慰剂降低0.1（2.0）分。与基线相比，普瑞巴林的作用是使瘙痒轻度但显著降低（平均[标准差]分，0.9[2.2]），而安慰剂没有降低（0.1[2.5]）。普瑞巴林的平均剂量总体耐受性良好。
这项随机交叉试验的结果表明，与安慰剂相比，普瑞巴林在RDEB患者中显著降低了与基线相比的疼痛和瘙痒评分。这项可行性研究提供了普瑞巴林治疗RDEB疼痛和瘙痒疗效的初步数据，并收集了重要数据以指导更大队列试验的设计。
ClinicalTrials.gov标识符：NCT03928093。
