University of Nebraska Medical Center & VA Nebraska-Western Iowa Health Care System, 986270 Nebraska Medical Center, Omaha, NE 68198-6270, United States.
Albany Medical College and The Center of Rheumatology, 43 New Scotland Ave, Albany, NY 12208, United States; Corrona LLC, 1440 Main St, Waltham, MA, 02451 and Columbia University, New York, NY 10027, United States.
Int Immunopharmacol. 2021 Feb;91:107260. doi: 10.1016/j.intimp.2020.107260. Epub 2020 Dec 23.
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.
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.
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.
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.
尽管生物制剂代表了类风湿关节炎（RA）治疗的重大进展，但许多患者对这些药物的反应并不充分。我们研究了在开始使用生物制剂的 RA 患者中，三种特征明确的自身抗体同时阳性是否可预测治疗反应。
该研究纳入了开始接受抗 TNF 治疗的生物制剂初治患者、转换为利妥昔单抗或托珠单抗的生物制剂暴露患者，以及开始使用阿巴西普的生物制剂初治或暴露患者。采用储存的入组血清检测类风湿因子（RF）、抗环瓜氨酸肽（CCP）抗体和丙二醛-乙醛（MAA）IgG 抗体。采用多变量线性和逻辑回归分析比较基线时自身抗体阳性（0-3 种）数目与 6 个月时治疗反应（28 关节疾病活动度评分[DAS28-CRP]绝对改善或改善>1.2）之间的关系。
在 1229 例开始使用生物制剂的患者中，79%为女性；89%为白种人。基线时 RA 相关自身抗体阳性的数目与剂量依赖性治疗反应改善相关。与所有自身抗体均阴性的患者相比，校正混杂因素后，三种抗体均阳性的患者 DAS28 改善>1.2 单位的可能性是其两倍多（OR 2.35；95%CI 1.57-3.51）。抗 CCP 抗体与生物制剂治疗反应的相关性最强，在仅限于生物制剂初治患者的分析中仍持续存在，且在不同检查的药物之间似乎差异不大。
更广泛的自身抗体谱似乎以剂量依赖性方式显著预测 RA 对生物制剂治疗的反应。将这些血清学谱与其他生物标志物或其他有意义的患者特征相结合，可能为 RA 管理的个体化提供机会。
