Lauret Ambre, Moltó Anna, Abitbol Vered, Gutermann Loriane, Conort Ornella, Chast François, Goulvestre Claire, Le Jeunne Claire, Chaussade Stanislas, Roux Christian, Batteux Frédéric, Dougados Maxime, Allanore Yannick, Avouac Jérôme
Department of Rheumatology - Hôpital Cochin. Assistance Publique - Hôpitaux de Paris, Paris Descartes University, France.
Gastroenterology Department, Paris Descartes University, Sorbonne Paris Cité, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
Semin Arthritis Rheum. 2020 Dec;50(6):1449-1456. doi: 10.1016/j.semarthrit.2020.02.007. Epub 2020 Feb 19.
To evaluatre the risk of immunogenicity in patients with chronic inflammatory diseases who experienced successive non-medical swiches to different biosimilars infliximab.
Observational study over a 3-year observation period assessing the risk of immunogenicity in i) patients in maintenance therapy with innovator infliximab who were successively switched to CT-P13, then to SB2 (cohort-1) and ii) biologic-naive patients initiated with CT-P13 before being switched to SB2 (cohort-2). A propotion meta-analysis was also performed, integrating our results to 16 additional studies.
Cohort-1 included 265 patients who switched to CT-P13, and 140 patients were subsequently switched to SB2. Among the 235 anti-drug antibody (ADA)-free patients at baseline, 20 patients (8.5%) developed ADA over the 3-year observation period (rate of 3 for 100 patient years). Cohort-2 included 44 patients, of whom 29 subsequently switched to SB2. A total of 11 patients (25%) developed ADA within 3 years (rate of 14 for 100 patients years). We found no influence of the number of biosimilars infliximab received on ADA deveopment in both cohorts. The risk of treatment discontinuation was significantly higher in patients with positive ADA in both cohorts. The meta-analysis including our data exposed an incidence of immunogenicity of 4.7% (95% CI 3.5-6.1%) after the switch from innovator infliximab to biosimilar infliximab and 21.1% (95% CI 13.1-30.3%) in patients initiating biosimilar infliximab.
Immunogenicity was not favored by successive non-medical switches to biosimilars infliximab in our study, but was associated with treatment discontinuation.
评估慢性炎症性疾病患者连续非医学转换使用不同英夫利昔单抗生物类似药时的免疫原性风险。
一项为期3年的观察性研究，评估免疫原性风险，其中包括：i）接受原研英夫利昔单抗维持治疗后先后转换为CT-P13、然后转换为SB2的患者（队列1）；ii）初治患者先使用CT-P13，然后转换为SB2（队列2）。还进行了一项比例荟萃分析，将我们的结果与另外16项研究的数据进行整合。
队列1包括265例转换为CT-P13的患者，随后有140例患者转换为SB2。在基线时235例无抗药抗体（ADA）的患者中，有20例患者（8.5%）在3年观察期内产生了ADA（每100患者年发生率为3例）。队列2包括44例患者，其中29例随后转换为SB2。共有11例患者（25%）在3年内产生了ADA（每100患者年发生率为14例）。我们发现，在两个队列中，接受英夫利昔单抗生物类似药的数量对ADA产生没有影响。两个队列中ADA阳性患者的治疗中断风险显著更高。纳入我们数据的荟萃分析显示，从原研英夫利昔单抗转换为生物类似药英夫利昔单抗后，免疫原性发生率为4.7%（95%CI 3.5-6.1%），而初用生物类似药英夫利昔单抗的患者中这一发生率为21.1%（95%CI 13.1-30.3%）。
在我们的研究中，连续非医学转换使用英夫利昔单抗生物类似药并不利于免疫原性的产生，但与治疗中断相关。
