Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound.
Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound.
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DOI：
10.1007/s00296-021-04956-7
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发表时间：
2021-10
影响因子：
4
通讯作者：
Batalov AZ
中科院分区：
文献类型：
--
作者：
Karalilova RV;Batalov ZA;Sapundzhieva TL;Matucci-Cerinic M;Batalov AZ
系统性硬化症（SSc）是一种罕见的自身免疫性结缔组织疾病，其特征是皮肤和内脏器官的纤维化，自身免疫驱动的损伤和血管病变。目前批准的改善疾病的治疗方法疗效有限，治疗的指导是减轻器官并发症。因此，对于发现新的有效治疗选择存在未满足的需求。最近有证据表明JAK/STAT信号通路在SSc患者中被显著激活。为了评估托法替尼（TOF）与甲氨蝶呤（MTX）相比在系统性硬化症（SSc）中对皮肤和肌肉骨骼受累的疗效和安全性。在这项为期52周的初步研究中，66例SSc患者入组：33例患者接受5 mg口服TOF，每日两次; 33例患者接受10 mg MTX每周一次。dcSSc和lcSSc患者的比例相似（dcSSc：42% TOF组和36% MTX组; lcSSc：58% TOF组和64% MTX组）。主要结局是改良Rodnan皮肤评分（mRSS）的变化。次要结局包括超声（US）皮肤厚度和肌肉骨骼受累（US 10 SSc评分）。通过治疗记录手指溃疡（DU）和不良事件（AE）。两组在基线时的结局指标特征和中位数相似。第52周时，TOF中位mRSS显著低于MTX（p < 0.001），平均降低13分，而MTX为2.57分。TOF组的平均改善百分比比MTX组高44%。TOF中位超声皮肤厚度显著低于MTX（p < 0.001），MTX组平均减少0.31 mm，MTX组平均减少0.075 mm。TOF组的US 10 SSc中位评分显著较低（p = 0.002）;平均降低10.21，MTX组为5.27。在TOF组中观察到DU愈合，没有新的发生。从基线到第52周，两组之间的AE数量无显著差异。TOF在减少SSc的mRSS、皮肤厚度和肌肉骨骼受累方面的疗效高于MTX，安全性也令人满意。
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.
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影响因子：
2
作者：
Khanna D;Furst DE;Clements PJ;Allanore Y;Baron M;Czirjak L;Distler O;Foeldvari I;Kuwana M;Matucci-Cerinic M;Mayes M;Medsger T Jr;Merkel PA;Pope JE;Seibold JR;Steen V;Stevens W;Denton CP
通讯作者：
Denton CP
影响因子：
4.9
作者：
Li H;Furst DE;Jin H;Sun C;Wang X;Yang L;He J;Wang Y;Liu A
通讯作者：
Liu A
DOI：
10.1002/art.40358
发表时间：
2018-03
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Gordon JK;Martyanov V;Franks JM;Bernstein EJ;Szymonifka J;Magro C;Wildman HF;Wood TA;Whitfield ML;Spiera RF
通讯作者：
Spiera RF
影响因子：
27.4
作者：
Naredo, Esperanza;D'Agostino, Maria Antonietta;Bruyn, George A. W.
通讯作者：
Bruyn, George A. W.
影响因子：
27.4
作者：
Kaloudi, Olga;Bandinelli, Francesca;Matucci-Cerinic, Marco
通讯作者：
Matucci-Cerinic, Marco