依那西普治疗多关节型和系统型JRA的长期疗效

Giannini EH, Ilowite NT. EULAR2007. Abstract No:SAT0397.

标签: EULAR2007，EULAR文摘，依那西普，幼年特发性关节炎，长期疗效，中信国健临床通讯

方法：为期3年开放性、非随机的注册资料包括了2～18岁的多关节型和系统型幼年类风湿关节炎(JRA)。单用MTX或依那西普(ETN), 或着两者联用。允许同时使用一种或多种非生物制剂DMARDs。ETN皮下注射剂量为0.4 mg/kg (最大剂量为25 mg) 每周2次，治疗36个月。所有患者均记录以下安全数据：暴露校正的严重不良事件发生率(SAE), 严重的医源性感染 (MII),以及机会感染(OI)。肿瘤、败血症、自身免疫病、死亡也是关心的事件。关节计数以及医生总体评价(PhGA)用于疗效判定。

结果：共纳入601例， MTX、ETN、ETN/MTX组人数分别为198、105和298人。患者大多为女性 (450/601, 75%) 和白种人 (446/601, 74%)。MTX、 ETN、ETN/MTX组病人平均年龄(中位数)分别为9岁(9)、11岁(11)和10岁(10)。多数病人为多关节起病(356/601, 59%)。中断注册登记者：131例MTX(66%)、51例ETN(49%)和146例(49%)ETN/MTX。在MTX、ETN和ETN/MTX组，分别有24人 (12%)、7人 (7%)、和11人 (4%)因病情缓解而停止治疗，并有 35人(18%), 7人(7%), and 51人(17%) 因疗效不佳而停药。总计159例(26%)完成了为期3年的观察。MTX、ETN、ETN/MTX各组每100病人年SAE发生率分别为5.25、 8.36和5.78，每100病人年MII发生率分别为0.95、1.97和1.98。MTX组共有2例OI (0.48/100病人年) ，ETN/MTX组为3例（0.50/100病人年）。MTX组报道了1例狼疮，ETN组和ETN/MTX 组报道了2例败血症。没有淋巴瘤、实体瘤、结核和死亡的报道。另外，与基线时情况相比，36个月时活动关节计数减少如下：MTX组6到0、ETN组5到0、MTX联合ETN组6到1。36个月治疗后，医生总体评分也较基线明显改善，分别为：MTX组4到1; ETN组3到1，MTX联合ETN组4到1。

结论：进行中的注册登记提供的安全性数据和有限的疗效数据肯定了ETN在该人群中长达3年的应用。

请点击查看英文原文或参见以下文字.

[2007] [SAT0397] THE LONG-TERM SAFETY OF ETANERCEPT IN CHILDREN WITH POLYARTICULAR OR SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

E.H. Giannini ¹, N.T. Ilowite ², D.J. Lovell ¹, C.A. Wallace ³, C.E. Rabinovich ⁴, A.O. Reiff ⁵, G. Higgins ⁶, Y. Chon ⁷, S. Lin ⁷

¹Cincinnati Children's Hospital Medical Center, Cincinnati, ²Schneider Children's Hospital, New Hyde Park, ³Children's Hospital and Regional Medical Center, Seattle, ⁴Duke University Medical Center, Durham, ⁵Children's Hospital of Los Angeles, Los Angeles, ⁶Ohio State University and Children's Hospital, Columbus, ⁷Amgen, Thousand Oaks, United States

Background: Etanercept has been approved for use in children with polyarticular course juvenile rheumatoid arthritis (JRA). Analyses of long-term safety data in children with JRA will provide important insight into the prolonged use of etanercept in these patients.

Objectives: To evaluate the long-term safety of etanercept in children with polyarticular or systemic JRA.

Methods: This 3-year, open label, non-randomized registry included patients between 2 and 18 years of age with polyarticular course or systemic JRA, who initiated etanercept and/or methotrexate for ≤ 6 months. JRA patients treated with either methotrexate (MTX), etanercept (ETN), or methotrexate and etanercept in combination (MTX/ETN) were eligible. Co-administration of one or more non-biologic DMARDs was allowed.

Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (to a max dose of 25 mg) twice weekly for up to 36 months. Safety data was reported for all patients including exposure adjusted rates of serious adverse events (SAEs), medically important infections (MIIs), and opportunistic infections (OIs). Events of interest including malignancy, sepsis, autoimmune disorders, and death were also reported. Joint counts and the Physician's Global Assessment (PhGA) were used to assess efficacy.

Results: A total of 601 patients enrolled of which 198 received MTX, 105 received etanercept (ETN), and 298 received MTX/ETN. Most patients were female (450/601, 75%) and Caucasian (446/601, 74%). The mean ages (median) for patients receiving MTX, ETN, or MTX/ETN were 9 (9), 11 (11), and 10 (10) years respectively. Most patients had polyarticular onset arthritis (356/601, 59%). A total of 131 MTX patients (66%), 51 ETN patients (49%), and 146 MTX/ETN (49%) patients discontinued the registry. In the MTX, ENT, and MTX/ENT groups respectively, 24 (12%), 7 (7%), and 11 (4%) patients discontinued because of remission and 35 (18%), 7 (7%), and 51 (17%) discontinued because of an insufficient therapeutic effect. A total of 159 patients (26%) have completed 3 years of observation to date. The rates of SAEs per 100 pt-yrs were 5.25, 8.36, and 5.78, and the rates of MIIs per 100 pt-yrs were 0.95, 1.97, and 1.98 respectively, for patients receiving MTX, ETN, or MTX/ETN. A total of 2 OIs (0.48 per 100 pt-yrs) were reported in patients receiving MTX and 3 OIs were reported in patients receiving MTX/ENT (0.50 per 100 pt-yrs). One case of lupus (MTX) and 2 cases of sepsis (ETN and ETN/MTX) were reported. No cases of lymphoma, malignancy, tuberculosis, or death were reported. In addition, the median number of active joints reported was decreased at 36 months as compared to baseline in patients receiving MTX (6 to 0), ETN (5 to 0), and MTX/ETN (6 to 1). The median PhGA scores were also improved over baseline values as PhGA scores decreased in all patients after 36 months of therapy (MTX, 4 to 1; ETN, 3 to 1; MTX/ETN, 4 to 1).

Conclusion: Safety data and limited efficacy data from this ongoing registry support the use of etanercept in this patient population for up to 3 years.

Citation: Ann Rheum Dis 2007;66(Suppl II):550