Infliximab biosimilar CT-P13 therapy in patients with Takayasu arteritis with low dose of glucocorticoids: a prospective single-arm study

Abstract

To evaluate the efficacy and safety of infliximab biosimilar CT-P13 in patients with active Takayasu arteritis (TAK). In this single-center open-label trial, patients with active TAK received CT-P13 at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks up to week 46. They were followed up until week 54. From week 14 to week 46, patients with inadequate response received increased dose of CT-P13 by 1.5 mg/kg. Concomitant prednisolone was allowed ≤ 10 mg/day. The primary efficacy end point was the achievement of partial or complete remission at week 30. All patients underwent positron emission tomography-computed tomography (PET-CT) at baseline and week 30. Twelve patients with TAK received CT-P13; one patient with protocol violation was excluded from analysis. Nine (81.8%) patients had taken concomitant prednisolone with median dose of 5.0 mg/day. At week 30, three (27.3%) patients achieved complete remission and six (54.5%) patients achieved partial remission. Statistically significant improvements in modified Indian Takayasu Clinical Activity Score (ITAS2010), ITAS-A, and serum levels of erythrocyte sedimentation rate and C-reactive protein were seen at week 30 from baseline. PET parameters were significantly reduced from baseline to week 30, including maximum standardized uptake value, target-to-vein ratio, target-to-liver ratio, and PET Vascular Activity Score. There were no serious adverse events. Treatment with CT-P13 may lead to improvement in clinical, radiographic, and serological activities with lower glucocorticoid requirement in TAK.Trial registration number NCT02457585.

Keywords: Infliximab; Positron emission tomography computed tomography; Takayasu arteritis; Treatment; Tumor necrosis factor-alpha.

Conflict of interest statement

Conflict of interest

The authors have declared no conflicts of interest.

Ethical standards

Ethical approvement was obtained from Institutional Review Board of Seoul National University Hospital (IRB No: 1312-079-541).

Figures

Fig. 1

Summary of the study design. a Patients whose ESR and CRP improved by ≥ 50% at week 14. b Patients whose ESR and CRP did not improve by ≥ 50% or increased. c Primary end point. ESR erythrocyte sedimentation rate, CRP C-reactive protein, PTX3 pentraxin-3, sHLA-E soluble human leukocyte antigen-E, TNFα tumor necrosis factor-α, IL-6 interleukin-6, ITAS-2010 Indian Takayasu Clinical Activity Score, PET–CT positron emission tomography–computed tomography

Fig. 2

Patient disposition through week 54 and outcome of treatment of patients with Takayasu arteritis

Fig. 3

Modified ITAS2010 (a), ITAS-A (ESR) (b), ESR (c), and CRP (d) in Takayasu arteritis (n = 11). Values are medians and IQRs. ITAS2010 Indian Takayasu Clinical Activity Score, ESR erythrocyte sedimentation rate, CRP C-reactive protein. *p ≤ 0.05, **p ≤ 0.01 vs. baseline (Wilcoxon signed-rank test)

Fig. 4

Measurement of 18F-FDG uptake on PET–CT before and after anti-TNF therapy in patients with Takayasu arteritis. Horizontal bars represent median and IQRs. a Changes from baseline in SUVmax values of 18F-FDG in arterial walls. b Changes from baseline in values of TVR defined as the ratio of SUVmax of a vascular ROI to the mean SUV of vein. c Changes from baseline in values of TLR defined as the ratio of SUVmax of a vascular ROI to the mean SUV of liver. d Changes from baseline in PETVAS, a summary score based on global arterial FDG uptake visually assessed in specified nine arterial territories (ascending, arch, descending thoracic and abdominal aorta, innominate, carotid, and subclavian arteries) using a 4-point scale. 18F-FDG18F-fluorodeoxyglucose, PET–CT positron emission tomography–computed tomography, SUVmax maximum standardized uptake value, TVR target-to-vein ratio, ROI region of interest, TLR target-to-liver ratio, PETVAS PET vascular activity score