美国耶鲁大学医学院Brett King团队研究了利特昔替尼治疗成人和青少年斑秃的疗效和安全性。相关论文发表在2023年4月13日出版的《柳叶刀》杂志上。

斑秃的特点是头皮、面部或体毛无疤痕脱落。课题组研究了口服选择性双JAK3/TEC家族激酶抑制剂利特昔替尼治疗斑秃患者的疗效和安全性。

研究组在18个国家的118个地点进行了一项随机、双盲、多中心、2b–3期临床试验，招募年龄在12岁及以上的斑秃患者和至少50%的头皮脱发患者，随机分配接受口服利特昔替尼或安慰剂，每天一次，持续24周，伴或不伴4周的负荷剂量（50 mg、30 mg、10 mg、200 mg负荷剂量，之后50 mg；或200 mg负荷剂量，之后30 mg），然后是24周的延长期，在此期间，利特昔替尼继续其分配的剂量，最初分配至安慰剂组的患者改为利特昔替尼50 mg或200 mg负荷剂量，然后是50 mg。

采用互动反应系统进行随机分组，并根据基线疾病严重程度和年龄进行分层。申办者、患者和研究人员双盲接受治疗，所有患者都接受了相同数量的药片以保持双盲。主要终点是脱发严重程度工具（SALT）评分在第24周达到20分或更低。在所有指定的患者中评估主要终点，无论他们是否接受治疗。

2018年12月3日至2021年6月24日，1097名患者接受了筛查，718名患者被随机分配接受利特昔替尼200 mg + 50 mg （n=132）、200 mg + 30 mg（n=130）、50 mg（n=130）、30 mg（n=132）、10 mg（n=63）、安慰剂至50 mg（n=66）或安慰剂至200 mg + 50 mg（n＝65）。718例患者中446例（62%）为女性，272例（38%）为男性。488例（68%）为白人，186例（26%）为亚洲人，27例（4%）为黑人或非裔美国人。在随机分配的718名患者中，104名患者停止了治疗（34名退出，19名不良事件[AEs]，12名医生决定，12名无效，13名失去随访，5名转入长期研究转移，4名怀孕，2名方案偏离，1名因新冠肺炎而拒绝参加随访，1名因新冠肺炎而延迟参加最后一次随访，还有1名不依从）。

在第24周，利特昔替尼200 mg + 50 mg组124名患者中有38名（31%），200 mg + 30 mg组121名患者中有27名（22%），50 mg组124名患者中有29名（23%），30 mg组119名患者中17名（14%），安慰剂组130名患者中有2名（2%）的SALT评分为20分或更低。安慰剂组和利特昔替尼200 mg + 50 mg组之间基于SALT评分20或更低的应答率差异为29.1%，200 mg + 30 mg组为20.8%，50 mg组为21.9%，30 mg组为12.8%。

截至第48周（包括随访期），利特昔替尼200 mg + 50 mg组131名患者中有108名（82%）报告了不良事件 ，200 mg + 30 mg组129名患者中有105名（81%），50 mg组130名患者中有110名（85%），30 mg组132名患者中有106名（80%），10 mg组62名患者中有47名（76%），安慰剂组转至利特昔替尼 200 mg + 50 mg延长组65名患者中有54名（83%），安慰剂组转至50 mg组的66名患者中有57名（86%）。各组之间每种不良事件的发生率相似，没有患者死亡。

研究结果表明，利特昔替尼对12岁及以上的斑秃患者有效且耐受性良好。对于系统治疗的斑秃患者，利特昔替尼可能是一种合适的治疗选择。

附：英文原文

Title: Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b–3 trial

Author: Brett King, Xingqi Zhang, Walter Gubelin Harcha, Jacek C Szepietowski, Jerry Shapiro, Charles Lynde, Natasha A Mesinkovska, Samuel H Zwillich, Lynne Napatalung, Dalia Wajsbrot, Rana Fayyad, Amy Freyman, Debanjali Mitra, Vivek Purohit, Rodney Sinclair, Robert Wolk

Issue&Volume: 2023-04-13

Abstract:

Background

Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata.

Methods

In this randomised, double-blind, multicentre, phase 2b–3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807.

Findings

Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg+50 mg (n=132), 200 mg+30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg+50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg+50 mg group, 27 (22%) of 121 patients in the 200 mg+30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg+50 mg group was 29·1% (95% CI 21·2–37·9; p<0·0001), 20·8% (13·7–29·2; p<0·0001) for the 200 mg+30 mg group, 21·9% (14·7–30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7–20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg+50 mg group, 105 (81%) of 129 patients in the 200 mg+30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg+50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths.

Interpretation

Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy.

DOI: 10.1016/S0140-6736(23)00222-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00222-2/fulltext