Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis
Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis
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DOI：
10.1136/ard.2006.065615
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发表时间：
2007-07-01
影响因子：
27.4
通讯作者：
Wolbink, Gerrit Jan
中科院分区：
文献类型：
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作者：
Bartelds, Geertje M.;Wijbrandts, Carla A.;Wolbink, Gerrit Jan
背景：相当大比例的类风湿性关节炎(RA)患者对阿达利单抗治疗没有反应或失去初始反应。无反应的一个原因是患者产生了抗阿达单抗抗体。目的：评估抗阿达单抗抗体的形成及其与血清阿达单抗浓度和临床反应的关系。方法：连续121例接受阿达单抗治疗的类风湿关节炎患者，在治疗前和治疗后28周检测血清阿达单抗浓度和抗阿达单抗抗体，以及临床反应变量。结果：在治疗28周期间，21例患者(17%)检测到抗阿达单抗抗体。EULAR无反应者的抗体阳性率显著高于有反应者(34%对5%；p=0.032)。有抗体的患者的疾病活动性(平均(SD)deltaDAS280.65(1.35))比无抗体的患者(平均deltaDAS281.70(1.35))改善更少(p=0.001)。随访期间有抗体的患者在28周时的血清阿达单抗浓度低于无抗体的患者(中位数1.2 mg/L，范围0-5.6vs11.0 mg/L，范围2.0-33.0；p，0.001)。良好应答者的血清阿达利单抗浓度高于中等应答者(p=0.021)和无应答者(p=0.001)。同时使用甲氨蝶呤的抗阿达单抗组(52%)低于无抗体组(84%)(p=0.003)。结论：抗阿达单抗血清抗体与阿达单抗血药浓度降低和阿达单抗治疗无效有关。
Background: A substantial proportion of patients with rheumatoid arthritis ( RA) do not respond, or lose initial response, to adalimumab treatment. One explanation for non- response is that patients develop antiadalimumab antibodies.Objectives: To evaluate the incidence of formation of antibody against adalimumab and the association with serum adalimumab concentrations and clinical response.Methods: In a cohort of 121 consecutive patients with RA treated with adalimumab, serum adalimumab concentrations and antibodies against adalimumab were measured together with clinical response variables before and up to 28 weeks after the start of treatment.Results: Anti- adalimumab antibodies were detected in 21 patients ( 17%) during 28 weeks of treatment. EULAR non- responders had antibodies significantly more often than good responders ( 34% vs 5%; p = 0.032). Patients with antibodies showed less improvement in disease activity ( mean ( SD) delta DAS28 0.65 ( 1.35)) than patients without antibodies ( mean delta DAS28 1.70 ( 1.35)) ( p = 0.001). Patients with antibodies during follow- up had lower serum adalimumab concentrations at 28 weeks than patients without antibodies ( median 1.2 mg/l, range 0.0 - 5.6 vs median 11.0 mg/ l, range 2.0 - 33.0, respectively; p, 0.001). Good responders had higher serum adalimumab concentrations than moderate responders ( p = 0.021) and non- responders ( p = 0.001). Concomitant methotrexate use was lower in the group with antiadalimumab antibodies ( 52%) than in the group without antibodies ( 84%) ( p = 0.003).Conclusions: Serum antibodies against adalimumab are associated with lower serum adalimumab concentrations and non- response to adalimumab treatment.