Background

Although biologics represent a major advance in rheumatoid arthritis (RA), many patients fail to achieve adequate responses to these agents. We examined whether combined positivity to three well-characterized autoantibodies predicts treatment response among RA patients initiating biologics.

Methods

The study included biologic-naïve patients initiating anti-TNF treatment, biologic-exposed patients switching to rituximab or tocilizumab, and patients (biologic naïve or exposed) initiating abatacept. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, and IgG antibodies to malondialdehyde-acetaldehyde (MAA) were measured using banked enrollment serum. The relationship between the number of autoantibodies positive (0–3) and treatment response (absolute improvement in 28-joint Disease Activity Score [DAS28-CRP] or improvement > 1.2) at 6 months was examined using multivariable linear and logistic regression.

Results

Of 1,229 patients initiating biologics, 79% were women; 89% were Caucasian. The number of baseline RA-related autoantibodies positive was associated with improved treatment response in a dose-dependent fashion. Compared to patients seronegative for all autoantibodies, adjusting for covariates, those positive for all three were more than twice (OR 2.35; 95% CI 1.57–3.51) as likely to achieve DAS28 improvement > 1.2 units. Associations of autoantibody positivity with biologic treatment response were strongest for anti-CCP antibody, persisted in analyses limited to biologic naïve patients, and did not appear to differ markedly among different agents examined.

Conclusion

An expanded autoantibody profile appears to significantly predict RA treatment response to biologic treatment in a dose-dependent fashion. Incorporating these serologic profiles with additional biomarkers or other informative patient characteristics could provide an opportunity to personalize RA management.

中文翻译：

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类风湿关节炎患者自身抗体谱的扩展与对生物疗法的治疗反应之间的关联

背景

尽管生物制剂代表类风湿关节炎（RA）的重大进展，但许多患者未能对这些药物取得足够的反应。我们检查了对三个特征明确的自身抗体的综合阳性是否可预测RA病人在开始使用生物制剂时的治疗反应。

方法

这项研究包括未接受过抗TNF治疗的初生物学患者，接受过利妥昔单抗或托珠单抗治疗的生物接触患者以及未接受abatacept治疗的（未接受过生物治疗的）患者。使用库存入组血清测量类风湿因子（RF），抗环瓜氨酸肽（CCP）抗体和抗丙二醛-乙醛（MAA）的IgG抗体。使用多变量线性和逻辑回归分析了6个月时自身抗体阳性（0–3）数量与治疗反应（28关节疾病活动评分[DAS28-CRP]的绝对改善或改善> 1.2）之间的关系。

结果

在1,229例开始使用生物制剂的患者中，女性占79％；89％是白人。基线RA相关自身抗体阳性的数量与剂量依赖性治疗反应的改善有关。与对所有自身抗体呈阴性的患者（校正协变量）相比，对所有三个抗体呈阳性的患者，其DAS28改善均> 1.2单位的可能性是两倍以上（OR 2.35； 95％CI 1.57–3.51）。自身抗体阳性与生物治疗反应的相关性对于抗CCP抗体最强，在仅限于单纯生物学患者的分析中持续存在，并且在所检查的不同药物之间似乎无显着差异。

结论

扩展的自身抗体谱似乎以剂量依赖性方式显着预测RA治疗对生物治疗的反应。将这些血清学特征与其他生物标志物或其他信息丰富的患者特征相结合，可以提供个性化RA管理的机会。