JAK inhibition for treatment of psoriatic arthritis in Down syndrome.
JAK inhibition for treatment of psoriatic arthritis in Down syndrome.
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DOI：
10.1093/rheumatology/keab203
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发表时间：
2021-09-01
期刊：
影响因子：
--
通讯作者：
Espinosa JM
中科院分区：
文献类型：
--
作者：
Pham AT;Rachubinski AL;Enriquez-Estrada B;Worek K;Griffith M;Espinosa JM
亲爱的编辑，唐氏综合征（DS）患者，由21三体（T21）引起的疾病，相对于普通人群，显示出几种自身免疫性疾病的患病率增加，包括自身免疫性甲状腺疾病（AITD），乳糜泻，自身免疫性皮肤病和关节病[1]。虽然现在已经确定T21引起IFN和下游Janus激酶（JAK）信号传导的过度活化[2，3]，但是该观察结果的治疗价值仍有待确定。在这里，我们描述了第一例用JAK抑制剂托法替尼作为严重衰弱性PsA的一线疗法有效治疗的DS个体的报道病例。尽管托法替尼被美国食品和药物管理局批准用于治疗典型人群中的PsA，但它被认为不如抑制TNF-α、IL 17、TNF-α和IL 18的一线靶向药物有效。IL 12和/或IL 23信号传导[4]。然而，考虑到T21导致IFN和JAK信号传导升高，我们推断托法替尼将是DS中PsA的优选一线治疗。根据赫尔辛基宣言和本报告的特定知情同意书获得研究知情同意书。本研究获得了科罗拉多多机构审查委员会的批准。该患者是一名27岁女性，患有DS、银屑病、甲状腺功能减退症、乳糜泻和自行消退的房间隔缺损病史。参与者最初向她的初级保健医生（PCP）介绍了左肩关节疼痛，尽管进行了锻炼，布洛芬和热疗，但疼痛仍持续存在。除了高水平的CRP外，她的检查和检查基本上没有什么异常。在持续保守治疗的情况下，她的关节疼痛在四个月内恶化，累及她的左手、肘部和膝盖，尤其是在早晨，导致活动受限，导致她不得不回家。随着关节炎症状的恶化，她的牛皮癣也恶化了。
DEAR EDITOR, People with Down syndrome (DS), the condition caused by trisomy 21 (T21), display increased prevalence of several autoimmune conditions relative to the general population, including autoimmune thyroid disease (AITD), celiac disease, autoimmune skin conditions and arthropathies [1]. Although it is now well established that T21 causes hyperactivation of IFN and downstream Janus kinase (JAK) signalling [2, 3], the therapeutic value of this observation remains to be defined. Here, we describe the first reported case of an individual with DS who was effectively treated with the JAK inhibitor tofacitinib as a first-line therapy for severely debilitating PsA.Although tofacitinib is approved by the United States Food and Drug Administration for the treatment of PsA in the typical population, it is considered less effective than first-line targeted agents that inhibit TNF-a, IL17, IL12 and/or IL23 signalling [4]. However, given that T21 causes elevated IFN and JAK signalling, we reasoned that tofacitinib would be a preferable first-line treatment for PsA in DS. Informed consent for research was obtained in accordance with the Declaration of Helsinki and specific consent obtained for this report. This study was approved by the Colorado Multiple Institutional Review Board. This patient is a 27-year-old woman with DS, psoriasis, hypothyroidism, celiac disease and a history of self-resolving atrial septal defect. The participant initially presented to her primary care physician (PCP) with left shoulder joint pain that persisted despite exercise, ibuprofen and heat therapy. Her exam and workup were largely unremarkable except for high levels of CRP. With continued conservative management, her joint pain worsened over four months to involve her left hand, elbow and knee, especially in the morning, resulting in mobility limitations that caused her to be homebound. As the signs of arthritis worsened, so did her psoriasis.
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影响因子：
7.7
作者：
Sullivan, Kelly D.;Lewis, Hannah C.;Espinosa, Joaquin M.
通讯作者：
Espinosa, Joaquin M.
DOI：
10.1073/pnas.1908129116
发表时间：
2019-11-26
影响因子：
11.1
作者：
Araya, Paula;Waugh, Katherine A.;Espinosa, Joaquin M.
通讯作者：
Espinosa, Joaquin M.
影响因子：
--
作者：
Taylor, William;Gladman, Dafna;Mielants, Herman
通讯作者：
Mielants, Herman
影响因子：
16.6
作者：
Powers, Rani K.;Culp-Hi, Rachel;Espinosa, Joaquin M.
通讯作者：
Espinosa, Joaquin M.
影响因子：
13.3
作者：
Singh, Jasvinder A.;Guyatt, Gordon;Reston, James
通讯作者：
Reston, James