*仅供医学专业人士阅读参考
小编按:
今天小编带给大家的是来自Ulrike Blume-Peytavi团队于2026年1月发表在BJD的一篇文章:Cinainu 治疗儿童斑秃的有效性与安全性:一项国际、双盲、随机、安慰剂对照的 Ⅱ/Ⅲ 期临床试验(Efficacy and safety of Cinainu in paediatric alopecia areata: an international, double-blind, randomized,placebo-controlled, phase II/III trial.)
作者团队介绍
Ulrike Blume-Peytavi
1.柏林夏里特大学医学中心皮肤病学与变态反应学正教授,皮肤病学、性病学与变态反应学系副主任,毛发与皮肤科学临床研究中心主任,儿童皮肤病学单元负责人。
2.发表超 370 篇科学论文,主编《毛发生长与疾病教科书》《德国儿童皮肤病学图谱》。
3.欧洲毛发研究学会、女性皮肤病学会创始成员及前主席,德国儿童皮肤病学协会前主席,柏林皮肤病学协会前主席及董事。
研究背景
斑秃是一种自身免疫介导的非瘢痕性脱发病,全球终身发病率约 2%,19%-36% 的病例发生于儿童和青少年,且起病越早预后越差,该病会严重损害患者生活质量,还易引发抑郁、焦虑等心理问题。其发病核心为免疫紊乱,涉及 IL-8、JAK 依赖信号通路等关键机制,目前获批的口服 JAK 抑制剂仅适用于成人及青少年重度斑秃,儿童中重度患者无获批治疗方案,且尚无外用药物获批用于任何年龄段的斑秃治疗,临床需求未被满足。Cinainu 是含四种植物提取物的外用溶液,具备抗炎、抗凋亡、抗氧化特性,且在成人雄激素性脱发等疾病中显示出良好疗效,为填补儿童斑秃治疗空白提供了潜在可能。
研究目的
评估外用制剂 Cinainu 治疗 2-17 岁中重度斑秃儿童及青少年患者的有效性与安全性,同时探究该药物的治疗效果能否在停药后持续,为其成为儿童中重度斑秃的临床治疗方案提供循证医学证据。
研究对象
研究纳入保加利亚、法国、德国、印度 12 个中心的 2-17 岁斑秃患者,共计 114 例患者接受筛选,107 例纳入意向治疗人群(ITT),并按 2:1 随机分为 Cinainu 组(71 例)和安慰剂组(36 例)。其中 62 例经研究者和专家双重确认符合中重度斑秃标准(SALT 评分 25-95 分)、当前发病期 6 个月至 3 年且无合并其他脱发治疗的患者,纳入全分析集(FAS)作为主要疗效分析人群,该人群平均年龄约 11 岁,男女比例接近,约半数为首次发病,74%-78% 合并眉毛、睫毛等部位受累。
研究方法
本研究为国际多中心、双盲、随机、安慰剂对照的 Ⅱ/Ⅲ 期临床试验(RAAINBOW 试验),包含 4 周筛选期、24 周双盲治疗期和 24 周无治疗随访期。患者按年龄调整剂量外用 Cinainu 或外观气味一致的安慰剂,2-15 岁每次 7 喷、>15 岁每次 8 喷,每日两次涂抹全头皮。以基线至 24 周 SALT 评分相对变化为主要疗效终点,以 SALT 评分改善≥40% 的应答率、生活质量评分(CDLQI、EQ-VAS)变化等为次要终点,同时记录治疗中出现的不良事件评估安全性。采用混合重复测量模型(MMRM)分析连续变量,卡方检验分析二分类变量,通过多种缺失数据插补方法进行敏感性分析,确保结果可靠性。
研究结果
疗效方面,FAS 人群中 Cinainu 组基线至 24 周 SALT 评分相对改善率显著优于安慰剂组,校正均数差 26.3%(P=0.0488),26.2% 的患者达到应答标准,远高于安慰剂组的 5.0%(P=0.0484),且患者 CDLQI、EQ-VAS 生活质量评分均获显著改善。停药随访至 48 周时,Cinainu 的疗效持续并提升,SALT 评分相对改善率校正均数差达 39.4%(P=0.0033),45.2% 患者达到应答标准,47.6% 患者 SALT 评分≤20 分,均显著高于安慰剂组。安全性方面,Cinainu 组无严重不良事件报告,治疗中出现的不良事件发生率(39%)与安慰剂组(47%)无差异,且均为局部、短暂的轻至中度反应,仅 1 例因严重面部头皮湿疹停药,药物相关不良事件发生率更低(6% vs 11%)。
结果解读
过去十年内加拿大梅毒的发病率持续上升。城市和农村地区的异性恋人群的梅毒发病率均升高,男男性行为者的梅毒发病率升高尤为显著。在同时感染艾滋病病毒的人群中,尤其是CD4 T细胞计数低于350个细胞/μL(0.35×10^9/L)的患者中,神经梅毒更为常见。一项回顾性研究显示约40%的患者出现眼部受累,包括葡萄膜炎、视网膜病变及视力丧失。三分之一的患者表现出认知障碍,三分之一的患者有神经系统症状,如头痛、失语、幻听和中风。精神症状的发生时间各异,轻躁狂症状并不常见,不到10%的神经梅毒患者出现该症状。 神经系统后遗症通常是永久性的,但该患者在静脉青霉素治疗后完全康复。
1.结论:本研究证实 Cinainu 外用溶液治疗 2-17 岁中重度斑秃儿童及青少年具有显著的临床疗效,不仅能有效改善脱发症状,还能提升患者生活质量,且疗效在停药后 24 周仍持续增强,提示其可能对斑秃的免疫病理机制产生长效调节作用。同时,Cinainu 耐受性良好,无药物相关严重不良事件,安全性与安慰剂相当,为儿童及青少年中重度斑秃提供了首个经随机对照试验证实的安全有效的外用治疗方案,填补了临床未满足的治疗需求,也可作为 JAK 抑制剂治疗后的潜在维持治疗选择。
2.局限性:本研究意向治疗人群的疗效未达统计学意义,因纳入了自发缓解率较高的轻度斑秃患者,干扰了疗效评估;研究仅设置了 24 周治疗 + 24 周随访的观察周期,未评估 Cinainu 长期连续用药的疗效和安全性;未探索不同用药剂量、频率对治疗效果的影响,也未分析该药物对极重度斑秃(SALT≥95 分)患者的作用,后续仍需扩大样本量、延长观察周期开展进一步研究。
备注:Cinainu 是一种由瑞士生物制药公司 Legacy Healthcare 研发的创新型外用植物药,目前主要用于治疗中度至重度斑秃(Alopecia Areata),特别是针对儿童和青少年群体。 药物性质:Cinainu 是一种多靶点植物候选药物,由洋葱(Allium cepa)、柠檬(Citrus limon)、可可(Theobroma cacao)和瓜拉纳(Paullinia cupana)四种植物提取物组成。作用机制:它通过抗炎、抗凋亡和抗氧化特性发挥作用,能调节毛囊周期并激活内皮细胞,同时不产生免疫抑制相关副作用。剂型:无油、无粘性、快速吸收且无味的外用溶液。
参考文献
Thompson AR, Tziotzios C, Nesnas J et al. Lifetime incidence and healthcare disparities in alopecia areata: a UK population-based cohort study. Br J Dermatol 2024; 191:924–35.
Harries M, Macbeth AE, Holmes S et al. The epidemiology of alopecia areata: a population-based cohort study in UK primary care. Br J Dermatol 2022; 186:257–65.
Cranwell WC, Lai VW, Photiou L et al. Treatment of alopecia areata: an Australian expert consensus statement. Australas J Dermatol 2019; 60:163–70.
Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol 2015; 8:397–403.
Prendke M, Kanti-Schmidt V, Wilborn D, et al. Quality of life in children and adolescents with alopecia areata – a systematic review. J Eur Acad Dermatol Venereol 2023; https://doi.org/10.1111/jdv.18848 (Epub ahead of print).
Macbeth AE, Holmes S, Harries M et al. The associated burden of mental health conditions in alopecia areata: a population-based study in UK primary care. Br J Dermatol 2022; 187:73–81.
Sinclair RD. Alopecia areata and suicide of children. Med J Aust 2014; 200:145.
Christensen T, Yang JS, Castelo-Soccio L. Bullying and quality of life in pediatric alopecia areata. Skin Appendage Disord 2017; 3:115–18.
Altunisik N, Ucuz I, Turkmen D. Psychiatric basics of alopecia areata in pediatric patients: evaluation of emotion dysregulation, somatization, depression, and anxiety levels. J Cosmet Dermatol 2022; 21:770–5.
King BA, Craiglow BG. Janus kinase inhibitors for alopecia areata. J Am Acad Dermatol 2023; 89:S29–32.
Ebrahim A, Salem R, El Fallah A, Younis E. Serum interleukin-15 is a marker of alopecia areata severity. Int J Trichol 2019; 11:26.
Barahmani N, Lopez A, Babu D et al. Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy. Clin Exp Dermatol 2010; 35:409–16.
Kuwano Y, Fujimoto M, Watanabe R et al. Serum chemokine profiles in patients with alopecia areata. Br J Dermatol 2007; 157:466–73.
Glickman JW, Dubin C, Renert-Yuval Y et al. Cross-sectional study of blood biomarkers of patients with moderate to severe alopecia areata reveals systemic immune and cardiovascular biomarker dysregulation. J Am Acad Dermatol 2021; 84:370–80.
Larsen CG, Anderson AO, Appella E et al. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science 1989; 243:1464–6.
Matsushima K, Yang D, Oppenheim JJ. Interleukin-8: an evolving chemokine. Cytokine 2022; 153:155828.
Xing L, Dai Z, Jabbari A et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 2014; 20:1043–9.
King B, Ohyama M, Kwon O et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med 2022; 386:1687–99.
King B, Senna MM, Mesinkovska NA et al. Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: results from the phase 3 randomized, controlled trial (THRIVE-AA1). J Am Acad Dermatol 2024; 91:880–8.
King B, Zhang X, Harcha WG et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. Lancet 2023; 401:1518–29.
King B, Ko J, Kwon O et al. Baricitinib withdrawal and retreatment in patients with severe alopecia areata: the BRAVE-AA1 randomized clinical trial. JAMA Dermatol 2024; 160:1075–81.
Carmichael AR, Lovell KK, Prieto K et al. Patient preferences in the treatment of alopecia areata: a review of the literature. JAAD Rev 2025; 3:21–5.
Shen P, Lin W, Deng X et al. Potential implications of quercetin in autoimmune diseases. Front Immunol 2021; 12:689044.
Marefati N, Ghorani V, Shakeri F et al. A review of anti-inflammatory, antioxidant, and immunomodulatory effects of Allium cepa and its main constituents. Pharmaceut Biol 2021; 59:285–300.
Cucé L, Rodrigues CJ, Patriota RCR. Cellium® GC: evaluation of a new natural active ingredient in 210 mg/ml topical solution, through scalp biopsy. Surg Cosmet Dermatol 2011; 3:123–8.
Orasan O, Oprean R, Saplonţai-Pop A et al. Antimicrobial activity and thiosulfinates profile of a formulation based on Allium cepa L. extract. Open Chemistry 2017; 15:175–81.
Liu JW, Harti S, Mello A, Cauwenbergh G. A topical botanical lotion increases and remodels scalp collagen content through longer anagen phase, opening new perspectives. J Am Acad Dermatol 2016; 74:AB132.
Katoulis AC, Liakou AI, Alevizou A et al. Efficacy and safety of a topical botanical in female androgenetic alopecia: a randomized, single-blinded, vehicle-controlled study. Skin Appendage Disord 2018; 4:160–5.
Kang D, Kim I-R, Park YH et al. Impact of a topical lotion, CG428, on permanent chemotherapy-induced alopecia in breast cancer survivors: a pilot randomized double-blind controlled clinical trial (VOLUME RCT). Support Care Cancer 2020; 28:1829–37.
Solomon JA. Development of uniform protocol for alopecia areata clinical trials. J Investig Dermatol Symp Proc 2015; 17:63–6.
Olsen EA, Hordinsky MK, Price VH et al. Alopecia areata investigational assessment guidelines – part II. National Alopecia Areata Foundation. J Am Acad Dermatol 2004; 51:440–7.
Lewis-Jones MS, Finlay AY. The Children’s Dermatology Life Quality Index (CDLQI): initial validation and practical use. Br J Dermatol 2010; 132:942–9.
Cheng LJ, Schieskow S, Chen LA, et al. Head-to-head comparisons of the distributional characteristics and measurement properties of the 3-level and 5-level versions of the EQ-5D-Y: a systematic review. Value Health 2025; S1098-3015(25)02303-4. https://doi.org/10.1016/j.jval.2025.03.020 (Epub ahead of print).
Ito T. Advances in the management of alopecia areata. J Dermatol 2012; 39:11–17.
Tosti A, Bellavista S, Iorizzo M. Alopecia areata: a long term follow-up study of 191 patients. J Am Acad Dermatol 2006; 55:438–41.
Messenger AG, McKillop J, Farrant P et al. British Association of Dermatologists’ guidelines for the management of alopecia areata 2012. Br J Dermatol 2012; 166:916–26.
Scherrer B, Guiraud J, Addolorato G et al. Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: a meta-regression analysis to develop an enrichment strategy. Alcohol Clin Exp Res 2021; 45:1722–34.
Barton VR, Toussi A, Awasthi S, Kiuru M. Treatment of pediatric alopecia areata: a systematic review. J Am Acad Dermatol 2022; 86:1318–34.
Samuel C, Cornman H, Kambala A, Kwatra SG. A review on the safety of using JAK inhibitors in dermatology: clinical and laboratory monitoring. Dermatol Ther (Heidelb) 2023; 13:729–49.
European Medicines Agency. ICH E9 Statistical principles for clinical trials – scientific guideline. 1998. Available at: https://www.ema.europa.eu/en/ich-e9-statistical-principles-clinical-trials-scientific-guideline (last accessed 14 August 2025).
King BA, Mesinkovska NA, Craiglow B et al. Development of the alopecia areata scale for clinical use: results of an academic-industry collaborative effort. J Am Acad Dermatol 2022; 86:359–64.
文字编辑:刘迪
南医大二附院皮肤科研究生
指导审核:张瑞丽
南医大二附院皮肤科主任、主任医师
扫一扫,了解更多内容