Subcutaneously-Administered Infliximab in the Management of Rheumatoid Arthritis: A Short Narrative Review of Current Clinical Evidence

Florenzo Iannone, Fabrizio Conti, Alberto Cauli, Alberto Farina, Roberto Caporali, Florenzo Iannone, Fabrizio Conti, Alberto Cauli, Alberto Farina, Roberto Caporali

Abstract

The first subcutaneous (SC) formulation of infliximab CT-P13 has been authorized for the treatment of rheumatoid arthritis (RA) in Europe in 2019. Later, in 2020, approved indications were extended also to ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn's disease (CD) and ulcerative colitis (UC). The present review provides summary of the key features of SC infliximab, with particular focus on pharmacokinetic profile, clinical development program in comparison with the intravenous (IV) formulation, and the latest evidence in the literature. We conclude that SC infliximab represents a new and promising approach in the treatment of patients with RA, offering an optimized clinical profile and a more practical option in comparison to the IV formulation. Nevertheless, SC formulation can improve the use of national health systems resources (e.g., through the time of healthcare workers not having to supervise infusions) and facilitate social distancing measures during the COVID-19 pandemic, as the patient can self-inject the medicine at home without going to the hospital. The limitations of the SC infliximab are mainly due to the limited experience of use in clinical practice and the absence of long-term drug retention data.

Keywords: IV; RA; SC; TNF inhibitors; infliximab; intravenous; rheumatoid arthritis; subcutaneous.

Conflict of interest statement

AF is an employee of Celltrion Healthcare Italy srl. Professor Fabrizio Conti reports personal fees from Lilly, personal fees from BMS, personal fees from Galapagos, personal fees from AbbVie, personal fees from Pfizer, outside the submitted work. Professor Roberto Caporali reports personal fees from pfizer, personal fees from AbbVie, personal fees from amgen, personal fees from celltrion, personal fees from BMS, personal fees from Lilly, personal fees from MSD, personal fees from Fresenius-Kabi, personal fees from Galapagos, during the conduct of the study. The other authors report no conflicts of interest in this work.

© 2022 Iannone et al.

Figures

Figure 1
Figure 1
Simulation of blood concentrations in comparison vs. IV infliximab 3 mg/kg expressed as trough concentration, or Ctrough, broken down by body weight bands. Summary Forest Plots of log transformed Ctrough GMRs (90% CIs) for the Simulated CT-P13 SC 120 mg Q2W Maintenance Dosing Regimen vs. CT-P13 IV 3 mg/kg Q8W Maintenance Reference Treatment by weight bands.
Figure 2
Figure 2
Simulation of blood concentrations in comparison vs. IV infliximab 5 mg/kg expressed as trough concentration, or Ctrough, broken down by body weight bands. Boxplot of Ctrough,ss Obtained Following 120 mg Q2W SC and 5 mg/kg Q8W IV Maintenance Dosing Regimens for NAB- subjects.
Figure 3
Figure 3
Design of part 2 of study CT-P13 3.5, a randomized, active-controlled, double-dummy, parallel groups, non-inferiority trial. The primary endpoint was measured during the double-blind and double-dummy phase at week 22, after which all patients switched to open-label SC formulation.
Figure 4
Figure 4
Primary endpoint results of part 2 of study CT-P13 3.5, analysis of change from baseline of DAS28 (CRP) at Week 22 (ANCOVA).

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