Gladman Dafna D, Dougados Maxime, Marzo-Ortega Helena, Cadatal Mary Jane, Agarwal Ekta, Kinch Cassandra D, Nash Peter
Schroeder Arthritis Institute, Krembil Research Institute, Department of Medicine, Toronto Western Hospital, Toronto, ON, Canada.
Department of Rheumatology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Université de Paris Cité, Paris, France.
Rheumatol Adv Pract. 2025 Jan 21;9(2):rkaf008. doi: 10.1093/rap/rkaf008. eCollection 2025.
To assess long-term tofacitinib efficacy and safety in patients with PsA with or without prior biologic DMARD (bDMARD) exposure.
Data were pooled post hoc from three phase 3 and one long-term extension (LTE) PsA studies and stratified by TNF inhibitor-inadequate responder (TNFi-IR) or bDMARD-naïve patient status at the phase 3 study baseline. Data were reported as all tofacitinib (patients receiving one or more tofacitinib doses) or average tofacitinib 5 and 10 mg twice daily (patients receiving an average total daily dose <15 and ≥15 mg, respectively). Drug survival to month 51, efficacy to month 42 and safety were assessed descriptively.
A total of 408 TNFi-IR patients (including 29 TNFi-experienced with unknown IR status) and 562 bDMARD-naïve patients were included. At baseline, TNFi-IR patients were more likely to be ≥65 years old, have cardiovascular/venous thromboembolism risk and have longer disease duration bDMARD-naïve patients. Drug survival was numerically shorter in TNFi-IR bDMARD-naïve patients. Tofacitinib efficacy was generally sustained to month 42, regardless of prior bDMARD treatment. Minimal disease activity/ PsA Disease Activity Score ≤3.2/>75% Psoriasis Area and Severity Index improvement response rates were numerically lower in TNFi-IR bDMARD-naïve patients to month 42, but rates of achieving an HAQ Disability Index ≤0.5 and enthesitis/dactylitis resolution were similar. In TNFi-IR bDMARD-naïve patients, treatment-emergent adverse event incidence rates were higher and serious adverse event, serious infection and herpes zoster incidence rates were numerically higher (CI overlapped).
These findings support long-term tofacitinib efficacy and safety in TNFi-IR and bDMARD-naïve patients. However, the benefit-risk profile appeared more favourable in bDMARD-naïve patients, likely due to differences in baseline characteristics and risk factors between subgroups.
ClinicalTrials.gov: NCT01877668, NCT01882439, NCT03486457, NCT01976364.
评估托法替布对有或无生物性改善病情抗风湿药（bDMARD）治疗史的银屑病关节炎（PsA）患者的长期疗效和安全性。
对三项3期和一项长期扩展（LTE）PsA研究进行事后数据汇总，并根据3期研究基线时肿瘤坏死因子抑制剂反应不足者（TNFi-IR）或初治bDMARD患者状态进行分层。数据报告为所有接受托法替布治疗的患者（接受一剂或多剂托法替布治疗）或平均每日两次服用5毫克和10毫克托法替布的患者（分别接受的平均每日总剂量<15毫克和≥15毫克）。对至第51个月的药物留存率、至第42个月的疗效和安全性进行描述性评估。
共纳入408例TNFi-IR患者（包括29例肿瘤坏死因子抑制剂治疗史未知的患者）和562例初治bDMARD患者。在基线时，TNFi-IR患者比初治bDMARD患者更可能年龄≥65岁，有心血管/静脉血栓栓塞风险，且病程更长。TNFi-IR患者的药物留存率在数值上低于初治bDMARD患者。无论既往是否接受bDMARD治疗，托法替布的疗效一般可持续至第42个月。至第42个月时，TNFi-IR患者的最小疾病活动度/PsA疾病活动评分≤3.2/银屑病面积和严重程度指数改善率在数值上较低，但达到健康评估问卷残疾指数≤0.5以及肌腱端炎/指（趾）炎缓解的比例相似。在TNFi-IR患者和初治bDMARD患者中，治疗中出现的不良事件发生率更高，严重不良事件、严重感染和带状疱疹的发生率在数值上更高（置信区间重叠）。
这些研究结果支持托法替布在TNFi-IR患者和初治bDMARD患者中的长期疗效和安全性。然而，初治bDMARD患者的获益风险比似乎更有利，这可能是由于亚组之间基线特征和风险因素存在差异。
ClinicalTrials.gov：NCT01877668、NCT01882439、NCT03486457、NCT01976364。
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