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Abstract：
BACKGROUND: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).
METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI).
RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time.
CONCLUSIONS: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as \"difficult to treat\" due to failure of previous b-DMARD therapy.
METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI).
RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time.
CONCLUSIONS: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as \"difficult to treat\" due to failure of previous b-DMARD therapy.
摘要：
背景：Filgotinib（FIL）是一种选择性JAK1抑制剂，其亲和力比JAK2高30倍，已被批准用于治疗中度至重度活动性类风湿关节炎（RA），在对一种或多种改善疾病的抗风湿药（DMARDs）反应不足或不耐受的成年人中。
方法：我们进行了回顾性研究，多中心研究，以评估FIL200mg每日治疗的疗效和安全性，三个月和六个月后，在120名受RA影响的患者中，在托斯卡纳和翁布里亚风湿病中心管理。分析了以下临床记录：人口统计学数据，吸烟状况,以前存在合并症(带状疱疹-HZ-感染，静脉血栓栓塞-VTE-,主要不良心血管事件-MAC-，癌症,糖尿病,和高血压），疾病持续时间,存在抗瓜氨酸化蛋白抗体（ACPA），类风湿因子（RF），生物故障的数量，和以前使用的csDMARD。在基线,在FIL治疗3（T3）和6（T6）个月后，我们评估了类固醇的平均剂量,csDMARDs摄入量，临床指标(DAS28，CDAI，HAQ,病人和医生PGA，VAS),红细胞沉降率（ESR），C反应蛋白(CRP),体重指数（BMI）。
结果：在基线时，平均病程为9.4±7.5年；既往HZ感染的患病率，VTE,MACE,癌症分别为4.12%，0%,7.21%,和0.83%，分别。总的来说,76.3%的患者失败了一种或多种生物制剂(一种生物失败，20.6%；两次生物失效，27.8%；三次生物故障，16.5%；四个生物故障，10.3%;5种生物失效,1.1%）。经过3个月的FIL治疗，所有临床指标结果均较基线显着改善，以及6个月后。此外，ESR和CRP在T3和T6时显着降低。记录了2例HZ，虽然没有新的MACE，VTE,或在观察时间内记录癌症。
结论：尽管回顾性研究和观察期仅有6个月的局限性，用FIL治疗RA患者的真实数据表明，这种Jak抑制剂治疗在CV方面是安全的，VTE事件,和癌症的发生，并且在由于先前的b-DMARD治疗失败而被确定为“难以治疗”的人群中也有效。
方法：我们进行了回顾性研究，多中心研究，以评估FIL200mg每日治疗的疗效和安全性，三个月和六个月后，在120名受RA影响的患者中，在托斯卡纳和翁布里亚风湿病中心管理。分析了以下临床记录：人口统计学数据，吸烟状况,以前存在合并症(带状疱疹-HZ-感染，静脉血栓栓塞-VTE-,主要不良心血管事件-MAC-，癌症,糖尿病,和高血压），疾病持续时间,存在抗瓜氨酸化蛋白抗体（ACPA），类风湿因子（RF），生物故障的数量，和以前使用的csDMARD。在基线,在FIL治疗3（T3）和6（T6）个月后，我们评估了类固醇的平均剂量,csDMARDs摄入量，临床指标(DAS28，CDAI，HAQ,病人和医生PGA，VAS),红细胞沉降率（ESR），C反应蛋白(CRP),体重指数（BMI）。
结果：在基线时，平均病程为9.4±7.5年；既往HZ感染的患病率，VTE,MACE,癌症分别为4.12%，0%,7.21%,和0.83%，分别。总的来说,76.3%的患者失败了一种或多种生物制剂(一种生物失败，20.6%；两次生物失效，27.8%；三次生物故障，16.5%；四个生物故障，10.3%;5种生物失效,1.1%）。经过3个月的FIL治疗，所有临床指标结果均较基线显着改善，以及6个月后。此外，ESR和CRP在T3和T6时显着降低。记录了2例HZ，虽然没有新的MACE，VTE,或在观察时间内记录癌症。
结论：尽管回顾性研究和观察期仅有6个月的局限性，用FIL治疗RA患者的真实数据表明，这种Jak抑制剂治疗在CV方面是安全的，VTE事件,和癌症的发生，并且在由于先前的b-DMARD治疗失败而被确定为“难以治疗”的人群中也有效。
