Rheumatology Unit, Department of Medicine DIMED, Padova University Hospital, Giustiniani 2, 35128, Padua, Italy.
Clin Rheumatol. 2021 Nov;40(11):4569-4580. doi: 10.1007/s10067-021-05799-0. Epub 2021 Jun 16.
We aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of multiple therapies in psoriatic arthritis (PsA).
We enrolled consecutive PsA patients attending our unit and undergoing bDMARDs during 2004-2020. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were recorded. Disease activity and functional and clinimetric scores were recorded at baseline and yearly and were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Effectiveness was evaluated over time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of response and failure of multiple bDMARDs. Kaplan-Meier curves were used to assess differences in time-to-first bDMARD discontinuation. Infections and adverse events were recorded.
Two hundred sixty-four patients were included (117 (44.32%) females, mean age 56 years, mean PsA duration 15 years); 117 (44.32%) switched bDMARDs at least once. Switchers were mostly females, with higher Psoriasis Area and Severity Index and worse Health Assessment Questionnaire at baseline. Mean time-to-first bDMARD discontinuation was 72 months; 2-year and 5-year retention rates were 75% and 60%, respectively. Survival curves for anti-TNFα/anti-IL12/23/anti-IL17 were similar (p = 0.66). Main reasons for switching were inefficacy (67.52%) and adverse events (25.7%). Female sex was associated with a higher risk of first bDMARD discontinuation (HR = 2.39; 95% CI: 1.50-3.81) and failure of multiple bDMARDs (OR = 1.99; 95% CI: 1.07-3.69); initiating therapy before 2015 was protective (HR = 0.40; 95% CI: 0.22-0.73).
Survival rate was good for anti-TNFα and other bDMARDs. Female sex was a predictor of first bDMARD discontinuation, unlike mechanism of action, comorbidities, and BMI. Key Points • Drug survival in PsA patients was confirmed be greater for the first bDMARD administered. • In case of failure of the first bDMARD, switching/swapping proved a good treatment option, as reflected by a persistent satisfactory effectiveness with second-line bDMARDs and so subsequent switches. • Female sex may constitute a predisposing risk factor for flare and therapeutic switches. • Discontinuation or switching of biologics due to mechanism of action, comorbidities tolerability and BMI did not seem to impact first bDMARD withdrawal.
评估(a)首生物性疾病修饰抗风湿药物(bDMARD)失败的潜在预测因素,以及(b)银屑病关节炎(PsA)中与多种治疗失败相关的因素。
我们招募了 2004 年至 2020 年期间在我们科室就诊并接受 bDMARD 治疗的连续 PsA 患者。记录疾病特征、既往/正在进行的治疗、合并症和随访时间。在基线和每年记录疾病活动度和功能及临床计量评分,并在转换者和非转换者之间以及根据转换原因在转换者内部进行比较。使用描述性统计数据评估随时间推移的疗效;使用多变量 Cox 和逻辑回归模型评估反应和多种 bDMARD 失败的预测因素。使用 Kaplan-Meier 曲线评估首次 bDMARD 停药时间的差异。记录感染和不良事件。
共纳入 264 例患者(117 例[44.32%]为女性,平均年龄 56 岁,平均 PsA 病程 15 年);117 例(44.32%)至少转换了一次 bDMARD。转换者主要为女性,基线时 Psoriasis Area and Severity Index 和 Health Assessment Questionnaire 更高。首次 bDMARD 停药的平均时间为 72 个月;2 年和 5 年的保留率分别为 75%和 60%。抗 TNFα/抗 IL12/23/抗 IL17 的生存曲线相似(p=0.66)。转换的主要原因是无效(67.52%)和不良反应(25.7%)。女性是首次 bDMARD 停药(HR=2.39;95%CI:1.50-3.81)和多种 bDMARD 失败(OR=1.99;95%CI:1.07-3.69)的更高风险相关因素;2015 年前开始治疗是保护性的(HR=0.40;95%CI:0.22-0.73)。
抗 TNFα 和其他 bDMARD 的生存率良好。与作用机制、合并症和 BMI 不同,女性是首次 bDMARD 停药的预测因素。
关键点
• 在接受治疗的 PsA 患者中,首用 bDMARD 的药物存活期更长。
• 对于首用 bDMARD 失败的患者,转换/交换证明是一种良好的治疗选择,因为二线 bDMARD 的后续效果持续令人满意,随后的转换也同样如此。
• 女性可能构成疾病发作和治疗转换的易感风险因素。
• 由于作用机制、合并症的耐受性和 BMI,生物制剂的停药或转换似乎不会影响首次 bDMARD 的停药。