Division of Rheumatology, Hospital Universitario Marques de Valdecilla, University of Cantabria, Santander, Spain.
Clin Exp Rheumatol. 2009 Nov-Dec;27(6):920-5.
The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies.
The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain).
Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection.
Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.
使用生物制剂治疗后，风湿性疾病患者的发病率和死亡率有了显著改善。然而，接受这些药物治疗的患者中观察到细菌感染的频率增加。本研究旨在确定因严重风湿性疾病对常规治疗无效而接受 TNF-α拮抗剂治疗的一大群风湿性疾病患者中非伤寒沙门氏菌感染的发生率和临床表现。
将在西班牙风湿性疾病生物治疗不良事件登记处（BIOBADASER）发现的非伤寒沙门氏菌感染率与未接受 TNF-α拮抗剂治疗的 EMECAR（类风湿关节炎的发病率和临床表现）研究中的类风湿关节炎（RA）患者队列中观察到的感染率进行比较。BIOBADASER 登记处发现的感染率也与在西班牙北部韦斯卡（Huesca）的人群中报告的非 RA 历史对照队列中的感染率进行了比较。
在接受抗 TNF-α治疗的患者系列中观察到 17 例非伤寒沙门氏菌感染。BIOBADASER 的非伤寒沙门氏菌发病率为 0.73/1000 患者年（95%置信区间 [CI]：0.45-1.17）。EMECAR 队列的发病率为 0.44/1000 患者年。与未接受生物治疗的患者相比，接受 TNF-α抑制剂治疗的 RA 患者患非伤寒沙门氏菌病的相对风险为 2.07（95%CI：0.27-15.73）（p=0.480），而接受 TNF-α拮抗剂治疗的风湿性疾病患者与非 RA 西班牙对照队列相比，非伤寒沙门氏菌感染的相对风险为 0.63（95%CI：0.38-1.04）（p=0.07）。17 例非伤寒沙门氏菌感染患者中有 9 例出现严重全身感染。
与接受常规 DMARD 治疗的 RA 患者或普通人群相比，接受抗 TNF-α治疗的风湿性疾病患者中非伤寒沙门氏菌感染的发生率并未显著增加。然而，一旦发生非伤寒沙门氏菌感染，至少有 50%的 TNF-α 患者会出现严重并发症。这一事实表明，抗 TNF-α 治疗可能导致沙门氏菌传播而不是感染。
