Benucci Maurizio, Gobbi Francesca Li, Bandinelli Francesca, Damiani Arianna, Infantino Maria, Grossi Valentina, Manfredi Mariangela, Parisi Simone, Fusaro Enrico, Batticciotto Alberto, Sarzi-Puttini Piercarlo, Atzeni Fabiola, Meacci Francesca
Rheumatology Unit, Azienda Sanitaria di Firenze, S. Giovanni di Dio Hospital, Via Torregalli 3, 50143, Florence, Italy.
Allergology and Immunology Laboratory, S.Giovanni di Dio Hospital, Florence, Italy.
Immunol Res. 2017 Feb;65(1):419-422. doi: 10.1007/s12026-016-8843-5.
Biosimilar infliximab (INX) was recently approved by the European Medicine Agency for the treatment of rheumatoid arthritis, ankylosing spondylitis (AS), Crohn's disease, ulcerative colitis, psoriatic arthritis (PsA), and psoriasis on the grounds that its pharmacokinetics, safety, and efficacy were comparable to those of innovator INX. The aim of this study was to investigate the real-life efficacy, safety, and immunogenicity of switching from innovator to biosimilar INX in patients with spondyloarthritis (SpA). Forty-one patients attending three Italian rheumatology centres with a previous diagnosis of SpA and clinically inactive or moderate disease activity (ASDAS-CRP < 2.1; 22 with AS, five with enteropathic arthritis, 10 with PsA, and four with undifferentiated SpA), who had been treated for more than 6 months with innovator INX in accordance with the ASAS/EULAR guidelines, were switched to biosimilar INX for pharmaco-economic reasons (Tuscany Law No. 450 of 7 April 2015) and followed up for 6 months. A record was kept of their BASDAI, BASFI, ASDAS-CRP, DAS28-CRP (in the presence of peripheral disease), MASES, VAS pain scores, the duration of morning stiffness, and adverse events (AEs). At the time of the switch, the patients had a median age of 50.9 years (range 23-80), a median disease duration of 124.5 months (range 14-372), and a median duration of treatment with innovator INX of 73.7 months (range 6-144). After 6 months of biosimilar INX therapy, there were no statistical differences in their median BASDAI (2.73 ± 1.5 vs. 2.6 ± 1.3, p = .27), BASFI (2.34 ± 1.3 vs. 2.17 ± 1.2, p = 0.051), ASDAS-CRP (1.35 ± 0.3 vs. 1.28 ± 0.2, p = 0.24), DAS28-CRP (2.66 ± 0.67 vs. 2.67 ± 0.35, p = 0.92), MASES (0.35 ± 0.7 vs. 0.17 ± 0.4, p = 0.08), or VAS pain scores (18 ± 14.7 vs. 16.7 ± 11.3, p = 0.55), whereas the median duration of morning stiffness had significantly decreased (7.2 ± 6.9 vs. 5.8 ± 6, p = 0.02). Furthermore, there was no change in circulating INX (4.22 ± 2.89 vs 4.84 ± 2.86 μg/mL, p = 0.80) or anti-INX antibody levels (27.76 ± 17.13 vs 27.27 ± 17.28 ng/mL, p = 0.98). The switch from innovator to biosimilar INX in this Italian multicentre SpA cohort was not associated with any statistically significance differences in efficacy, adverse events or anti-drug antibody level.
生物类似药英夫利昔单抗（INX）最近获得了欧洲药品管理局的批准，用于治疗类风湿性关节炎、强直性脊柱炎（AS）、克罗恩病、溃疡性结肠炎、银屑病关节炎（PsA）和银屑病，理由是其药代动力学、安全性和疗效与创新型INX相当。本研究的目的是调查脊柱关节炎（SpA）患者从创新型INX转换为生物类似药INX后的实际疗效、安全性和免疫原性。41名在三个意大利风湿病中心就诊的患者，此前诊断为SpA，临床处于非活动期或中度疾病活动期（ASDAS-CRP < 2.1；22例AS，5例肠病性关节炎，10例PsA，4例未分化SpA），根据ASAS/EULAR指南，他们接受创新型INX治疗超过6个月，出于药物经济学原因（2015年4月7日托斯卡纳第450号法律）转换为生物类似药INX，并随访6个月。记录他们的巴斯强直性脊柱炎疾病活动指数（BASDAI）、巴斯强直性脊柱炎功能指数（BASFI）、ASDAS-CRP、28关节疾病活动评分（DAS28-CRP，存在外周疾病时）、脊柱关节炎国际学会测量指数（MASES）、视觉模拟评分（VAS）疼痛评分、晨僵持续时间和不良事件（AE）。转换时，患者的中位年龄为50.9岁（范围23 - 80岁），中位病程为124.5个月（范围14 - 372个月），接受创新型INX治疗的中位持续时间为73.7个月（范围6 - 144个月）。生物类似药INX治疗6个月后，他们的中位BASDAI（2.73±1.5 vs. 2.6±1.3，p = 0.27）、BASFI（2.34±1.3 vs. 2.17±1.2，p = 0.051）、ASDAS-CRP（1.35±0.3 vs. 1.28±0.2，p = 0.24）、DAS28-CRP（2.66±0.67 vs. 2.67±0.35，p = 0.92）、MASES（0.35±0.7 vs. 0.17±0.4，p = 0.08）或VAS疼痛评分（18±14.7 vs. 16.7±11.3，p = 0.55）没有统计学差异，而晨僵的中位持续时间显著缩短（7.2±6.9 vs. 5.8±6，p = 0.02）。此外，循环中的INX（4.22±2.89 vs 4.84±2.86μg/mL，p = 0.80）或抗INX抗体水平（27.76±17.13 vs 27.27±17.28 ng/mL，p = 0.98）没有变化。在这个意大利多中心SpA队列中，从创新型INX转换为生物类似药INX与疗效、不良事件或抗药抗体水平的任何统计学显著差异均无关。
