CN115052599A - 以川地匹坦对特应性皮炎的改进治疗 - Google Patents
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Abstract
本公开通常涉及以川地匹坦对瘙痒、特应性皮炎(AD)及其相关症状的治疗的改进。更具体而言,本发明涉及一种在AD患者的治疗中,提高实现最佳治疗响应的可能性的方法,其中所述AD患者的可选择的潜在疗法包括施用有效治疗所述患者AD的量的NK‑1拮抗剂,例如川地匹坦。
Description
相关申请的交叉引用
本专利申请要求于2020年2月25日提交的美国临时专利申请62/981,481号的权益,在此通过参考将其全文并入本文。
背景技术
本发明通常涉及以川地匹坦对瘙痒,特应性皮炎(AD)和相关症状的治疗的改进,更具体而言,本发明涉及到一种在AD患者的治疗中,提高实现最佳治疗响应的可能性的方法,其中所述AD患者的可选择的潜在疗法包括施用有效治疗所述患者AD的量的川地匹坦。
特应性皮炎是一种常见的慢性的复发性的炎症性皮肤病,由皮肤超敏响应引起,其特征是强烈而持续的瘙痒或刺痒的症状,所述症状可能是局部的甚至是广泛的,并且可能不能通过抓挠缓解。美国皮肤协会(AAD)的特应性皮炎指南中将瘙痒列为特应性皮炎的基本特征。其他临床特征包括红斑、剥落、水肿、苔藓样变、渗出和干燥症。因刺痒引起的抓挠可能会导致皮肤粗糙、敏感、肿胀并使皮肤容易感染。AD也被称为特应性湿疹或湿疹,并经常在儿童时期出现。
罹患特应性皮炎的人群中,个体患者的疾病严重程度涵盖多个程度:从轻度到重度。个体患者的AD严重程度可由许多不同方法评估和定量,例如,研究者总体分数(IGA),用于刺痒的100mm单位的视觉模拟量表(VAS),言语打分量表(VRS),皮肤病生活品质指数(DLQI),临床总体变化印象(CGI-C),患者受益指数(PBI),客观和主观的SCORing特应性皮炎(SCORAD)指数,SKINDEX-16,湿疹面积与严重程度指数(EASI),关于瘙痒和AD的患者总体变化印象(PGIC)量表,以及其他测量症状严重程度和特应性皮炎严重程度的方法。
轻度、中度和重度AD可表现为具有不同表现形式和进程的截然不同的实体。根据流行病学研究,轻度AD是最常见的AD类型,影响了美国1200万患有AD的人中约60%。尽管被分类为“轻度”,但较轻度形式的AD仍然以明显并在某些情况下甚至很严重的瘙痒为特征。与重度AD相比,轻度AD表现为具有更少的病灶,所述病灶有轻度红斑和最少的硬结/丘疹或通常代表缓解和复发的渗液/结痂。IGA分数为1或2的患者可被视为患有轻度AD。轻度AD目前通过以下方式治疗:皮肤清洁,局部润肤剂,抗组胺药,局部类固醇,钙调神经磷酸酶抑制剂,cAMP特异性3’,5’-环核苷酸磷酸二酯酶4(PDE4)抑制剂如克立硼罗。然而,在轻度AD患者中对于可能很严重的瘙痒的治疗还有严重的尚未得到满足的需求。
重度AD表现为具有更大量的红斑性病灶,所述的病灶与重度硬结/丘疹或渗液/结痂和慢性病程有关。IGA分数为3或4的患者可被视为有中度到重度AD。重度AD可通过以下方式治疗:局部疗法、光疗和免疫调节药物治疗。
与通过抓挠引起的病灶恶化相关的严重瘙痒,以及与轻度AD相关的睡眠中断持续代表严重的尚未得到满足的医疗需求。具有强效快速作用的耐受性良好的系统性的抗瘙痒试剂可以给患者带来重要价值,并且很有可能在治疗算法中占据主要地位,其中AAD治疗指南目前仅对中度到重度AD并且仅在发现局部疗法和光疗不能充分控制病情后提出且推荐免疫调节药物治疗。
瘙痒感可至少部分地由内源性神经肽物质P(SP)通过与多种皮肤细胞上表达的神经激肽(NK-1)受体结合的作用而诱导。NK-1R在人体不同组织中表达,在神经元组织中具有主要活性。神经元组织中的SP和NK-1R相互作用在局部调节神经源性炎症以及通过中枢神经系统调节疼痛感知途径。其他组织,包括内皮细胞和免疫细胞,也表现出SP和NK-1R活性。天然配体SP对NK-1R的激活涉及许多生理过程,包括疼痛感、行为应激源、渴望以及恶心和呕吐过程。SP在神经组织或周围组织中的不适当过度表达可能导致病理状况,例如物质依赖、焦虑、恶心/呕吐和瘙痒。NK-1R拮抗剂可能具有减少这种对NK-1R过度刺激的能力,因此可以解决这些状况中症状的潜在病理生理问题。NK-1R拮抗剂包括阿瑞匹坦(aprepitant),卡索匹坦(casopitant),依洛匹坦(ezlopitant),福沙匹坦(fosaprepitant),奈妥匹坦(netupitant),罗拉匹坦(rolapitant),司洛匹坦(serlopitant),川地匹坦(川地匹坦),维替匹坦(vestipitant),沃氟匹坦(vofopitant)。
川地匹坦是高效的、选择性的、具有中枢渗透和口服活性的NK-1受体拮抗剂,其结构如下式I所示:
川地匹坦在美国专利7,320,994中公开,其包含6个主要的结构组分:3,5-双-三氟甲基苯基部分、两个吡啶环、三唑环、氯苯基环和甲酮。川地匹坦的化学名称为2-[1-[[3,5-双(三氟甲基)苯基]甲基]-5-(4-吡啶基)-1H-1,2,3-三唑-4-基]-3-吡啶基](2-氯苯基)-甲酮,或者{2-[1-(3,5-双三氟甲基苄基)-5-吡啶-4-基-1H-[1,2,3]三唑-4-基]-吡啶-3-基}-(2-氯苯基)-甲酮,也被称为LY686017和VLY-686。美国专利7,320,994描述了使用化合物例如川地匹坦来治疗与速激肽过量相关的病况的方法,尤其是与速激肽过量的相关病况是抑郁症和焦虑的情况下。
美国专利7,320,994进一步描述了在其他此类疾病中使用化合物,如川地匹坦等的作用,即,由于这些化合物抑制了与速激肽过量有关的生理作用。该专利描述了此类化合物在治疗许多与速激肽受体激活相关其他疾病中的有用性,包括:精神病,精神分裂症和其他精神疾病;神经退行性疾病,例如痴呆,包括阿尔茨海默氏型老年性痴呆、阿尔茨海默氏病、与艾滋病相关的痴呆和唐氏综合征;脱髓鞘疾病,例如多发性硬化症和肌萎缩性侧索硬化症以及其他神经病理性疾病,例如周围神经病、糖尿病和化疗引起的神经病以及疱疹后神经痛和其他神经痛;急性和慢性阻塞性气道疾病,例如成人呼吸窘迫综合征、支气管肺炎、支气管痉挛、慢性支气管炎、驾驶性咳嗽和哮喘;炎症性疾病,例如炎症性肠病、银屑病、纤维炎、骨关节炎和类风湿性关节炎;肌肉骨骼系统疾病,例如骨质疏松症;过敏,例如湿疹和鼻炎;过敏性病症,如毒藤病;眼病,例如结膜炎和春季结膜炎等;皮肤疾病,例如接触性皮炎、特应性皮炎、荨麻疹和其他湿疹样皮炎;成瘾病症,例如酗酒;与压力有关的躯体疾病;反射性交感神经营养不良,例如肩/手综合征;恶劣心境障碍;不良免疫反应,例如移植组织的排斥反应以及与免疫增强或抑制有关的疾病,例如系统性红斑狼疮;与内脏神经元控制有关的胃肠道病症或疾病,例如溃疡性结肠炎、克罗恩病和肠易激综合征;膀胱功能障碍,例如膀胱逼尿肌反射亢进和失禁;动脉粥样硬化;纤维蛋白和胶原蛋白疾病,例如硬皮病和嗜酸性筋膜炎;良性前列腺增生的刺激性症状;与血压有关的疾病,例如高血压;或由血管扩张和血管痉挛性疾病(如心绞痛,偏头痛和雷诺氏病)引起的血流障碍;呕吐,包括化疗引起的恶心和呕吐;和疼痛或伤害感受,例如,归因于上述病况中的任一种或与之相关的疼痛或伤害感受。最后,该专利描述了这些化合物预计在月0.001mg/kg/天至月100mg/kg/天的量有效。
已知可通过多种可生物利用的施用途径来治疗性地施用川地匹坦。美国专利7,320,994公开了通过口服和胃肠外途径(例如口服)、通过吸入、皮下、肌内、静脉内、经皮、鼻内、直肠、眼、局部、舌下和颊内施用川地匹坦,通常优选口服施用来进行治疗。此外,国际专利申请公开WO 2016/141341中公开了使用川地匹坦对瘙痒和特应性皮炎的治疗。认为川地匹坦安全,耐受性良好。
以药物治疗患者通常需要医师确定患者对该药物有响应的可能性以及该处方药物可能提供的治疗益处的程度。许多因素可与处方决定相关,包括患者的病史和患者症状的严重程度。对于一些药物来讲,特殊诊断测验可以提供识别能从特定药物中受益的患者的判断。这些伴随诊断检测课用于将患者在测试表明几乎没有或根本没有显著治疗响应的预期的情况下排除在该药物治疗之外。对此,美国食品药品监督管理局指南中规定伴随诊断可以识别最可能受益于特定治疗产品的患者,https://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm407297.htm。
发明内容
在本发明的一方面,提供了一种在特应性皮炎(AD)患者的治疗中提高实现最佳治疗响应的可能性的方法。在各种实施方式中,对所述患者施用有效治疗特应性皮炎的量的NK-1拮抗剂可能是选择疗法。特别是,NK-1拮抗剂可以是川地匹坦或其药学上可接受的盐,并且可特别是美国专利7,381,826描述的晶型IV或晶型V的川地匹坦。
所述方法包括以足以评估患者AD严重程度的方式检测所述患者,其中,IGA分数为1或2,和/或BSA分数为10%以下表明轻度AD。IGA分数为3或4,和/或BSA分数大于10%表明非轻度AD,即中度到重度AD。如果基于IGA和/或BSA分数确定患者患有轻度AD,该方法包括开处方使所述患者使用有效治疗其特应性皮炎的量的NK-1拮抗剂,例如川地匹坦。之后向所述患者施用有效量的川地匹坦。有效治疗所述患者AD的量的川地匹坦可以是100至400mg/天、150至400mg/天、100至300mg/天、150至300mg/天、100至200mg/天、170至340mg/天或170至255mg/天。特定的实施方式中,所述量可为170mg/天的川地匹坦,或者为每天施用两次(bid)85mg。如果基于IGA或BSA分数,没有对所述患者开NK-1拮抗剂,如川地匹坦,该方法包括评估(1)是否有除NK-1拮抗剂(如川地匹坦)外的替代药物疗法,或者(2)使用NK-1拮抗剂,如川地匹坦是否是治疗所述患者的更适合的药物干预手段。
本发明的这些和其他方面、优点和突出特征将从以下具体描述和附图中变得显而易见,这些具体描述和附图公开了本发明的实施方式。
附图说明
图1示出了此例描述的EPIONE研究中最差瘙痒强度数字评定量表(WI-NRS)的每周变化。
图2A-2D示出了此例中描述的EPIONE研究中的研究人群的基线特征。特别是,图2A示出了由IGA1和2(轻度)和IGA3和4(中度和重度)定义的AD不同的内型和临床表现。图2B示出了由IGA1和2(轻度)和IGA3和4(中度和重度)定义的内型的临床变体分布。图2C示出了由IGA1和2(轻度)和IGA3和4(中度和重度)定义的内型的嗜酸性粒细胞计数的明显区别。图2D显示的棉棒图展示出丝聚蛋白(FLG)中已识别的变体的位点和频次。与IGA1和2的AD患者(轻度)相比,观察到稀少LOF变体在IGA3和4的AD患者(中度和重度)中有明显聚集。
图3A-3D示出了刺痒调节中物质P的作用。瘙痒相关联的机制包括白细胞介素和神经肽,白细胞介素和神经肽与神经发生炎症反应,例如物质P和致痒原-角化细胞连接相关。在轻度AD人群中(图3C),存在相对少量的刺痒调节因子包括,细胞因子、血清素、组胺和嗜酸性粒细胞,物质P是刺痒中的主要因子。相反,在更严重的AD人群中(图3D),除物质P以外的越来越多的因子参与刺痒的成因。
附图仅旨在描绘本公开的典型方面,因此不应认为限制本公开的范围。
具体实施方式
在本发明的各种实施方式中,本文所述的方法包括在罹患特应性皮炎(AD)的患者的治疗中提高实现最佳治疗响应的可能性的方法,并且特别是,其中对所述患者施用有效剂量的NK-1拮抗剂可能是治疗AD的选择疗法。本领域已知的NK-1拮抗剂包括阿瑞匹坦、卡索匹坦、依洛匹坦、福沙匹坦、奈妥匹坦、罗拉匹坦、司洛匹坦、川地匹坦、维替匹坦和沃氟匹坦。在此描述的特定实施方式和实施例中,NK-1拮抗剂可特定为川地匹坦。然而,应认识到本领域技术人员可用川地匹坦以外的NK-1拮抗剂以所述方式治疗患者来影响患者的瘙痒和/或AD。
在AD患者的治疗中提高实现最佳治疗响应的可能性的一种这样的方法中,提供者首先确认患者具有与一个或多个皮肤病灶相关的报道的瘙痒。本文的“提供者”可指医疗服务提供者,例如,医师、其他医疗服务的从业人员,或者有执照的药物处方人员。提供者可以检测或评估患者的临床表现是否符合AD和与之相关的瘙痒的诊断,以及确定瘙痒和潜在AD的严重程度。
特别是,提供者可以根据皮肤病灶的外观和程度确定AD的类型,并且利用大量诊断工具和标准中的任一种表征病灶的物理外观。所述诊断工具和标准的实例包括,例如,研究者总体分数(IGA),用于刺痒100mm单位的视觉模拟量表(VAS),言语打分量表(VRS),皮肤病生活品质指数(DLQI),临床总体变化印象(CGI-C),患者受益指数(PBI),客观和主观的SCORing特应性皮炎(SCORAD)指数,SKINDEX-16,湿疹面积与严重程度指数(EASI),关于瘙痒和AD的患者总体变化印象(PGIC)量表,以及其他本领域已知的症状严重程度和特应性皮炎严重程度的测量方法。提供者可以进一步评估和确定患者受AD影响的体表面积(BSA),该数据是以百分数形式提供。这些因素可用于确定患者是否罹患轻度、中度或重度AD。
特别是,IGA、BSA或者IGA和BSA可用于确定AD疾病的严重程度。IGA分数为1或2,BSA小于或等于(≤)10%,或者IGA为1或2并且BSA≤10%的患者可被确定为患有轻度AD。IGA分数为3或4,BSA大于10%,或者IGA为3或4并且有BSA大于10%的患者可被确定为患有中度或重度AD。
在其他实施方式中,其他评估方式也可以单独或者互相组合使用,或者与IGA和BSA组合使用,或者以前述中的任何组合使用,进而确定和/或确认AD的严重程度。特别是,提供者可以评估生化和遗传标志物来确定患者是否罹患轻度AD,或者患者是否倾向罹患轻度AD。例如,在一个实施方式中,提供者可以进行,或请求进行评估患者嗜酸性粒细胞血液计数的诊断测验。这可以通过进行例如全血计数(CBC),白细胞分类计数,或者嗜酸性粒细胞绝对计数来进行。前述的任何测验都可以对从要治疗的患者体内采集的生物样本进行,例如,待治疗患者的血液样本。正常参考限值内的嗜酸性粒细胞计数可与轻度AD相关(图2C)。
另一实施方式中,提供者可以对从待治疗患者采集的生物样本进行基因型分析,进而鉴定遗传变体,例如,丝聚蛋白(FLG)基因中的遗传变体。FLG是S100融合型蛋白(SFTP家族)的一员,定位于1号染色体q21。FLG编码丝聚蛋白,即皮肤屏障结构蛋白。生物学样品可以包括,例如,血液、血清、唾液、尿液等,如本领域中已知。患者FLG基因的突变累积与患者的非轻度(例如,中度到重度)AD的严重程度相关,而患者FLG基因的非累积突变与患者的轻度AD相关(图2D)。
运用前述的严重程度指数,例如,IGA分数1或2,或者BSA指数≤10%,和相关的生物标志物,包括相对较低的嗜酸性粒细胞计数,FLG基因型分析,和其他测量方法中的一种或多种,患者可以被鉴定为罹患轻度AD或者非轻度(中度到重度)AD。如此例的描述所示,罹患轻度AD的患者相较于非轻度AD的患者,更可能对川地匹坦的治疗有响应。
如果根据IGA分数,BSA分数,和/或本文描述的其他指标确定患者罹患与轻度AD相关的瘙痒症,可以开处方使所述患者使用有效治疗其特应性皮炎的量的NK-1拮抗剂,如川地匹坦。在各种实施方式中,治疗患者瘙痒或特应性皮炎的川地匹坦的有效量可为如100至400mg/天、150至400mg/天、100至300mg/天、150至300mg/天、100至200mg/天、170至340mg/天或170至255mg/天。在某些实施方式中,有效量可为170mg/天,或者为每天施用两次(bid)85mg。随后可以以所述量向该患者施用NK-1拮抗剂,如川地匹坦,以治疗该患者的瘙痒和/或潜在的AD。川地匹坦给药的第一整天后,可立即显示出抗瘙痒作用和夜晚睡眠的明显改善。
如果基于前述的指标,例如,IGA分数和BSA分数,没有对患者开NK-1拮抗剂,如川地匹坦处方,即该患者没有诊断为罹患轻度AD,则提供者可接下来评估(1)是否有除NK-1拮抗剂,如川地匹坦以外的替代药物疗法,或者(2)使用NK-1拮抗剂,如川地匹坦是否是治疗所述患者的更适合的药物干预手段。在(1)的情况下,更加合适的治疗方法选自在本领域已知的哪些。这种替代的示例可见于https://www.mayoclinic.org/diseases-conditions/ atopic-dermatitis-eczema/diagnosis-treatment/drc-20353279,并且包括局部药物(例如,皮质类固醇乳膏或软膏,钙调磷酸酶抑制药,或抗生素乳膏或软膏)和全身药物(例如,口服皮质类固醇激素,包括泼尼松或是注射剂如达必妥)。
根据测量,可施用替代性药物疗法或者NK-1拮抗剂,如川地匹坦。在向患者施用川地匹坦而不是基于IGA和/或BSA分数的情况下,需要更加密切地监视患者对该治疗的响应,因为对川地匹坦治疗显示响应的AD患者可能在川地匹坦给药的第一整天后就产生反应。提供者可以至少通过施用后的这一窗口时间监视患者,从而评估用川地匹坦是否获得满意的治疗响应。
本领域技术人员将会理解,可以通过组合上述优选实施方式或参考本文给出的实施例来选择另外优选的实施方式。
实施例:EPIONE研究
在患有重度瘙痒的特应性皮炎(AD)患者中开展随机安慰剂对照的III期实验,所述患者的疾病严重程度表现范围由研究者总体分数(IGA)确定为轻度(23%)到中度(64%)和重度(13%)。该研究中,患者(n=341)按照1:1随机分组以接受川地匹坦或者安慰剂8周的治疗时间。研究中川地匹坦组的患者每天施用两次(bid)85mg的川地匹坦。在基线和随机化后定期以许多症状和疾病严重程度量表对患者进行评估。
第8周时,由最差瘙痒强度数字评定量表(WI-NRS)测定,研究中川地匹坦组和对照组的患者都表现出对瘙痒症重要且有意义的改善。川地匹坦的改善幅度高于安慰剂组,不过治疗之间的差异在统计学上不显著。
在基线疾病严重程度和治疗组之间观察到明显的相互作用(p=0.0004),其中疾病的严重程度由研究者总体分数(IGA)在1至4分的范围内测量。这表明具有不同基线疾病严重程度的研究参与者经历了不同的治疗结果。
当考虑基线疾病严重程度和疗法的相关作用时,在完整实验人群中在预设的第8周终点时,与安慰剂相比,川地匹坦组中观察到WI-NRS的显著更大改善(p=0.0217)。在包括第2、4、6和8周的所有随机化后访问时的治疗阶段都可以看到类似的效果(表1)。
表1.EPIONE结果总结
1.P值来自于MMRM分析。
2.P值来自于费希尔精确检验。
亚组分析显示出疾病严重程度为轻度的患者(受试患者中的23%,IGA 1,2)表现出与安慰剂相比最大程度的改善。具体而言,轻度AD组中川地匹坦在每一访问时间与安慰剂相比都显著地改善了WI-NRS分数(表1,图1)。分类WI-NRS响应者分析(>4点改善)表明72.5%的川地匹坦患者具有在临床上有意义的响应,相比之下安慰剂患者是33.3%。
这些结果表明治疗轻度AD中川地匹坦有巨大且明显的抗瘙痒效果,这与患者每日日记记录一致。对于轻度AD患者而言,响应时间过程也表明川地匹坦给药第一整天后立即显示出抗瘙痒作用,这表明巨大且即刻的治疗作用。对夜晚睡眠也观察到相似的改善,重度瘙痒的患者的夜晚睡眠经常中断。
此外,结果显示:轻度和非轻度(例如,重度)AD表现为具有需许多不同致病因素和进程的截然不同的内型。如图2C所示,与轻度AD(IGA 1,2)相比,非轻度,即中度到重度AD(IGA 3,4)与明显更高计数的嗜酸性粒细胞有关。嗜酸性粒细胞是炎症反应的介质,也负责在病灶中募集其他免疫细胞。嗜酸性粒细胞直接或间接地参与引起瘙痒和炎症的介质的产生和分泌,这些介质包括组胺、血清素、物质P、NGF和许多白细胞介素细胞因子。这样,与轻度和重度AD相关的严重瘙痒很可能有不同的介质(图3A-3D)。
而且,全基因组测序分析(WGAS)表明特定的遗传标志物与轻度v.s.非轻度(即,中度和重度)AD相关。例如,患者丝聚蛋白(FLG)基因上罕见功能丧失(LOF)突变的积累与患者的非轻度(如,轻度和中度)AD患者的严重程度相关,而患者FLG基因的突变的非积累与患者的轻度AD相关(图2D)。
川地匹坦在轻度AD中表现为产生大量迅速的抗瘙痒效果,在第一整天治疗时提供显著且迅速的刺痒减少,同时具有相对安全的特性。这对于有轻度AD病灶但仍罹患严重瘙痒的大多数AD患者可提供急需的疗法。
已经出于展示和说明的目的而提出本发明的各方面的前述描述。其目的不在于将本发明穷尽或限制到所公开的精确形式,而是可以进行改动或变化。意图将可能对本领域技术人员显而易见的这样的改动或变化包含在所附权利要求限定的本发明范围内。
Claims (14)
1.一种在特应性皮炎患者的治疗中提高实现最佳治疗响应的可能性的方法,对所述特应性皮炎患者施用有效治疗特应性皮炎的量的川地匹坦可能是选择疗法,所述方法包括:
以足以评估所述患者的研究者总体分数(IGA)和体表面积(BSA)分数中的一个或两个的方式检查所述患者;和
如果所述患者的IGA分数为2以下,或者所述患者的BSA分数为10%以下,或者所述患者的IGA分数为2以下并且BSA分数为10%以下,则开具使所述患者使用有效治疗其特应性皮炎的量的川地匹坦的处方,从而向所述患者施用所述量的川地匹坦;和
如果基于所述的IGA或BSA分数没有对所述患者开具川地匹坦处方,则评估(1)是否有除川地匹坦外的替代药物疗法,或者(2)川地匹坦是否是治疗所述患者的更适合的药物干预手段。
2.如权利要求1所述的方法,所述方法还包括:
如果基于所述的IGA或BSA分数没有对所述患者开具川地匹坦处方,则向该患者施用除川地匹坦外的替代药物疗法。
3.如权利要求1所述的方法,所述方法还包括:
如果基于所述的IGA或BSA分数没有对所述患者开具川地匹坦处方,则确定川地匹坦是治疗所述患者的合适的药物干预手段,并且向该患者施用川地匹坦。
4.如权利要求1~3中任一项所述的方法,其中,有效治疗所述患者的瘙痒症或特应性皮炎的川地匹坦的量为100至400mg/天、150至400mg/天、100至300mg/天、150至300mg/天、100至200mg/天、170至340mg/天或170至255mg/天。
5.如权利要求4所述的方法,其中,有效治疗所述患者的瘙痒症或特应性皮炎的川地匹坦的量为170mg/天。
6.如权利要求5所述的方法,其中,有效治疗所述患者的瘙痒症或特应性皮炎的川地匹坦的量是85mg bid。
7.一种在特应性皮炎患者的治疗中提高实现最佳治疗响应的可能性的方法,对所述特应性皮炎患者施用有效治疗特应性皮炎的量的NK-1拮抗剂可能是选择疗法,所述方法包括:
以足以评估所述患者的研究者总体分数(IGA)和体表面积(BSA)分数中的一个或两个的方式检查所述患者;和
如果所述患者的IGA分数为2以下,或者所述患者的BSA分数为10%以下,或者所述患者的IGA分数为2以下并且BSA分数为10%以下,则开具使所述患者使用有效治疗其特应性皮炎的量的NK-1拮抗剂的处方,从而向所述患者施用所述量的NK-1拮抗剂;和
如果基于所述的IGA或BSA分数没有对所述患者开具NK-1拮抗剂处方,则评估(1)是否有除NK-1拮抗剂外的替代药物疗法,或者(2)NK-1拮抗剂是否是治疗所述患者的更适合的药物干预手段。
8.如权利要求7所述的方法,所述方法还包括:
如果基于所述的IGA或BSA分数没有对所述患者开具NK-1拮抗剂处方,则向该患者施用除NK-1拮抗剂外的替代药物疗法。
9.如权利要求7所述的方法,所述方法还包括:
如果基于所述的IGA或BSA分数没有对所述患者开具NK-1拮抗剂处方,则确定NK-1拮抗剂是治疗所述患者的合适的药物干预手段,并且向该患者施用NK-1拮抗剂。
10.如权利要求7~9中任一项所述的方法,其中,所述NK-1拮抗剂选自由以下组成的组:阿瑞匹坦、卡索匹坦、依洛匹坦、福沙匹坦、奈妥匹坦、罗拉匹坦、司洛匹坦、川地匹坦、维替匹坦和沃氟匹坦。
11.如权利要求10所述的方法,其中,所述NK-1拮抗剂是川地匹坦。
12.如权利要求11所述的方法,其中,有效治疗所述患者的瘙痒症或特应性皮炎的川地匹坦的量为100至400mg/天、150至400mg/天、100至300mg/天、150至300mg/天、100至200mg/天、170至340mg/天或170至255mg/天。
13.如权利要求12所述的方法,其中,有效治疗所述患者的瘙痒症或特应性皮炎的川地匹坦的量为170mg/天。
14.如权利要求13所述的方法,其中,有效治疗所述患者的瘙痒症或特应性皮炎的川地匹坦的量是85mg bid。
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CN107427502A (zh) * | 2015-03-04 | 2017-12-01 | 万达制药公司 | 使用川地匹坦的治疗方法 |
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