Centre of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Centres, Nieuwegein.
Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein.
Clin Infect Dis. 2020 Feb 3;70(4):595-604. doi: 10.1093/cid/ciz226.
Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear.
We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4-8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration ≥1.3 μg/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone >10 mg/day, thiopurines, methotrexate); (2) anti-tumor necrosis factor agents; (3) combination therapy; and (4) no treatment with immunosuppressive agents (control group).
One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1-3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13-.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29]).
Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy.
Dutch trial register #6315.
炎症性肠病(IBD)患者侵袭性肺炎球菌感染的风险增加。因此,建议接种 13 价肺炎球菌结合疫苗(PCV13),随后在 2 个月后接种 23 价肺炎球菌多糖疫苗(PPSV23)。然而,在接受和不接受免疫抑制药物治疗的 IBD 患者中,这种接种方案诱导的免疫原性水平仍不清楚。
我们前瞻性评估了 IBD 患者接种 PCV13 后再接种 PPSV23 的免疫原性,通过测量接种前和接种后 4-8 周时血清型特异性肺炎球菌免疫球蛋白 G 抗体浓度来评估。接种后反应定义为接种后抗体浓度≥70%所测血清型的 1.3μg/ml。我们分析了 4 种不同药物治疗方案的免疫效果:(1)传统免疫调节剂(即口服泼尼松>10mg/天、硫唑嘌呤、甲氨蝶呤);(2)肿瘤坏死因子拮抗剂;(3)联合治疗;(4)不使用免疫抑制剂(对照组)。
共纳入 141 例 IBD 患者,其中 37 例为对照组。使用免疫抑制剂的患者接种疫苗后反应良好的比例为 59%(61/104),对照组为 81%(30/37)(比值比,0.33[95%置信区间,0.13-0.82])。不同免疫抑制剂联合应用最严重地损害了肺炎球菌疫苗接种的免疫反应(反应率为 52%[15/29])。
虽然 PCV13 序贯接种方案联合 PPSV23 是安全、免疫原性的,因此对大多数 IBD 患者有益,但与对照组相比,接受免疫抑制剂治疗的患者,特别是接受联合治疗的患者,免疫反应受损。因此,最好在开始免疫抑制治疗之前进行疫苗接种。
荷兰临床试验注册中心#6315。