van Assen Sander, Holvast Albert, Benne Cornelis A, Posthumus Marcel D, van Leeuwen Miek A, Voskuyl Alexandre E, Blom Marlies, Risselada Anke P, de Haan Aalzen, Westra Johanna, Kallenberg Cees G M, Bijl Marc
Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Groningen, Groningen, The Netherlands.
Arthritis Rheum. 2010 Jan;62(1):75-81. doi: 10.1002/art.25033.
For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination.
Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4-8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity.
Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for no strains in the rituximab-treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination.
Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6-10 months after rituximab administration. Previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. RA activity was not influenced.
对于类风湿关节炎（RA）患者，建议每年接种流感疫苗。然而，其在接受利妥昔单抗治疗的患者中的疗效尚不清楚。本研究的目的是调查流感疫苗在接受利妥昔单抗治疗的RA患者中的疗效，并调查利妥昔单抗治疗后体液免疫反应可能被抑制的持续时间。我们还评估了流感疫苗接种的安全性以及既往流感疫苗接种的影响。
对23例接受利妥昔单抗治疗的RA患者（11例在利妥昔单抗治疗后4 - 8周[早期利妥昔单抗亚组]，12例在利妥昔单抗治疗后6 - 10个月[晚期利妥昔单抗亚组]）、20例接受甲氨蝶呤（MTX）治疗的RA患者和29例健康对照者接种三价流感亚单位疫苗。使用血凝抑制试验在接种前和接种后28天测量针对3种疫苗株的抗体水平。采用28个关节疾病活动评分（DAS28）评估RA活动度。
接种疫苗后，MTX治疗组和健康对照组中所有流感毒株的抗流感抗体几何平均滴度（GMT）均显著升高，但利妥昔单抗治疗组中无一毒株升高。然而，在晚期利妥昔单抗亚组中，接种疫苗时CD19 +细胞未重新增殖的情况下，A/H3N2和A/H1N1毒株的GMT有所升高。对于A/H3N2和A/H1N1毒株，利妥昔单抗治疗组的血清转化和血清保护发生率低于MTX治疗组，而对于A/H1N1毒株，利妥昔单抗治疗组的血清保护发生率低于健康对照组。与利妥昔单抗治疗组中未接种疫苗的患者相比，既往接种过疫苗的患者接种A/H1N1毒株前后的GMT更高。接种疫苗后DAS28未改变。
利妥昔单抗降低了RA患者接种流感疫苗后的体液免疫反应，在利妥昔单抗给药6 - 10个月后反应有适度恢复。利妥昔单抗治疗的患者既往接种流感疫苗可提高接种前后的滴度。RA活动度未受影响。
