Cecconi Mariana, Ranza Roberto, Titton David C, Moraes Júlio C B, Bertolo Manoel, Bianchi Washington, Brenol Claiton, Carvalho Hellen M, de Castro Glaucio R W, Costa Izaias P, Cunha Maria F L, Duarte Ângela, Fernandes Vander, Freire Marlene, Louzada-Junior Paulo, Macieira José C, Miranda José R S, Pereira Ivanio A, Pinheiro Geraldo R C, Stadler Barbara, Toledo Roberto A, Valim Valeria, Descalzo Miguel A, Pinto Rogerio M C, Laurindo Ieda
From the Universidade Federal de Uberlândia, Uberlândia.
Universidade Federal do Paraná, Curitiba.
J Clin Rheumatol. 2020 Mar;26(2):73-78. doi: 10.1097/RHU.0000000000000935.
The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases.
The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs.
BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI).
A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01-4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15-2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups.
In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.
生物药物的安全性可能存在显著的地区差异。自2009年以来，巴西风湿病学会一直维护着BIOBADABRASIL（巴西生物药物登记处），这是一个用于监测风湿病生物治疗的登记处。
本研究的目的是验证类风湿关节炎（RA）和脊柱关节炎（SpA）患者使用生物药物时严重感染的发病率（IR）。
BIOBADABRASIL前瞻性纳入了开始使用第一种生物药物的风湿病患者或作为平行对照组的合成改善病情抗风湿药物。本研究聚焦于2009年1月至2015年6月期间使用生物药物的RA和SpA患者与对照组相比的严重感染不良事件（SIAEs）。暴露时间设定为从药物开始使用到最后一次给药或审查日期。每1000患者/年计算严重感染不良事件IR，并给出95%置信区间（CI）。
共纳入1698例患者（RA 1121例；SpA 577例），共7119患者/年。肿瘤坏死因子抑制剂（TNFi）治疗的患者中严重感染不良事件比对照组更常见（调整后的IR比值，2.96 [95% CI，2.01 - 4.36]；p < 0.001）。与首次使用TNFi相比，后续使用TNFi与更高的SIAEs发病率相关（调整后的IR比值，1.55 [95% CI，1.15 - 2.08]；p = 0.004）。严重感染不良事件与年龄和皮质类固醇摄入有关。在所有亚组中，呼吸道严重感染不良事件更为频繁。
在BIOBADABRASIL中，与合成改善病情抗风湿药物相比，生物药物，尤其是后续使用的TNFi，与更高的严重感染风险相关。皮质类固醇摄入和年龄是SIAEs的危险因素。在巴西风湿病临床环境中，需要持续监测以跟踪药物的安全性。
