Ortiz-Sanjuán Francisco, Blanco Ricardo, Riancho-Zarrabeitia Leyre, Castañeda Santos, Olivé Alejandro, Riveros Anne, Velloso-Feijoo María L, Narváez Javier, Jiménez-Moleón Inmaculada, Maiz-Alonso Olga, Ordóñez Carmen, Bernal José A, Hernández María V, Sifuentes-Giraldo Walter A, Gómez-Arango Catalina, Galíndez-Agirregoikoa Eva, Blanco-Madrigal Juan, Ortiz-Santamaria Vera, Del Blanco-Barnusell Jordi, De Dios Juan R, Moreno Mireia, Fiter Jordi, Riscos Marina de Los, Carreira Patricia, Rodriguez-Valls María J, González-Vela M Carmen, Calvo-Río Vanesa, Loricera Javier, Palmou-Fontana Natalia, Pina Trinitario, Llorca Javier, González-Gay Miguel A
From the Hospital Universitario Marque[Combining Acute Accent]s de Valdecilla, IDIVAL, Santander (FO-S, RB, LRZ, MCG-V, VC-R, JL, NPF, TP, MAG-G); Hospital Universitario de La Princesa, IIS Princesa Madrid, Madrid (SC); Hospital Universitario Germans Trias i Pujol, Badalona (AO, AR); Hospital Valme, Sevilla (MLV-F); Hospital Universitario de Bellvitge Hospitalet, Barcelona (JN); Hospital San Cecilio, Granada (IJ-M); HU Donostia, San Sebastián (OMA); HRU Carlos Haya, Málaga (CO); HGU, Alicante, Alicante (JAB); Hospital Clinic of Barcelona, Barcelona (MVH); Hospital Ramón y Cajal, Madrid (WASG); Hospital Universitario Basurto, Bilbao (CGA, EGA, JBM); Hospital General Granollers, Granollers, Spain (VOS); H Sant Jaume, Calella (JDBB); HU Álava, Vitoria (JRDD); HU Parc Taulí, Sabadell (MM); HU Son Espases, Palma de Mallorca, Mallorca (JF); Hospital Universitario 12 de Octubre, Madrid (MdlR, PC); Hospital de Jerez, Jerez (MJRV); and Universidad de Cantabria, IDIVAL, Santander, and CIBER Epidemiology and Public Health (CIBERESP), Santander Spain. (JL).
Medicine (Baltimore). 2015 Sep;94(39):e1554. doi: 10.1097/MD.0000000000001554.
Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.
成人斯蒂尔病（AOSD）通常对标准治疗无效。阿那白滞素（ANK）是一种白细胞介素-1受体拮抗剂，已在单例及小系列AOSD患者中显示出疗效。我们评估了ANK在一系列AOSD患者中的疗效。多中心回顾性开放标签研究。由于对标准合成免疫抑制药物无效，且在某些情况下对至少一种生物制剂也无效，因此使用了ANK。招募了41例患者（26例女性/15例男性）。他们的平均年龄为34.4±14岁，在开始使用ANK之前，AOSD的中位病程[四分位间距（IQR）]为3.5[2-6]年。当时最常见的临床特征为关节表现（87.8%）、发热（78%）和皮疹（58.5%）。ANK使临床和实验室指标迅速且持续改善。治疗1年后，关节和皮肤表现的发生率分别降至41.5%和7.3%，发热从78%降至14.6%，贫血从56.1%降至9.8%，淋巴结病从26.8%降至4.9%。实验室指标也有显著改善。泼尼松的中位剂量[IQR]也从开始使用ANK时的20[11.3-47.5]mg/天降至12个月时的5[0-10]mg/天。在中位随访期[IQR]为16[5-50]个月后，最重要的副作用为皮肤表现（n=8）、轻度白细胞减少（n=3）、肌病（n=1）和感染（n=5）。ANK即使在对其他生物制剂无反应的患者中也能使临床和实验室指标迅速且持续改善。然而，关节表现比全身表现更难治疗。
