In November 2019, the European Medicines Agency (EMA) approved subcutaneous (SC) CT-P13 for the treatment of rheumatoid arthritis. Several months later, the EMA approved SC CT-P13 as an extension for all indications of its IV form, including Crohn’s disease and ulcerative colitis. Patients treated with SC CT-P13 will save time spent in transport and in hospitals or infusion centres. The follow-up of these patients will be more distant, but not necessarily looser. Beyond these gains in quality of life, are there additional benefits associated with the use of the SC vs IV form of infliximab?

A randomised trial has compared SC and IV CT-P13 in 131 IBD patients naive to biologics.1 The primary endpoint for non-inferiority of trough level at week 22 was met; pre-dose levels were approximately 10-times higher with SC than IV administration. Clinical remission and endoscopic improvement rates were comparable in both arms. Therefore, higher trough levels were not associated with clinical improvement of the same magnitude, if any. Thus, thresholds of pre-dose levels of infliximab associated with favourable outcomes cannot be extrapolated from the IV to SC form. Indeed, an exposure-response analysis based on this trial showed that, within the SC arm, favourable outcomes were observed with trough concentrations above 20-27 mg/L.2

Hanzel et al recently provided further information on the pharmacokinetics of SC CT-P13.3 They showed that clearance increased with body weight and anti-drug antibodies, and decreased with serum albumin concentrations. Other variables such as serum CRP, faecal calprotectin or prescription of immunosuppressives did not inform CT-P13 clearance. However, the role of immunosuppressives could be indirect, in that they reduce the rate of immunisation. The area under the curve was higher with SC than IV dosing in patients weighing 50 kg; comparable in those weighing 70 kg and lower in those weighing 120 kg. However, fixed dosing (120 mg every 14 days) appeared appropriate for most patients apart from heavy patients in whom it may result in under-exposure. The model based on body weight, anti-drug antibodies and serum albumin concentration only explained 11.2% of inter-individual variability for clearance, leaving 27.7% unexplained. Future studies of Bayesian prediction will further specify dosing. In addition, for the same area under the curve, trough concentrations with SC dosing were higher than with IV dosing. Whether this offers a clinical advantage remains to be determined.

Several questions remain unanswered. Is CT-P13 by SC route less immunogenic than the IV route? Are there severe allergic reactions with SC CT-P13? Anaphylactic shock sometimes occurs in patients treated with IV infliximab. If it also occurs in patients treated at home, this could be a serious limitation of SC CT-P13.

Phase 3 studies of CT-P13 SC in the treatment of Crohn's disease (NCT03945019) and ulcerative colitis (NCT04205643), are ongoing in the US. These trials and large-scale, observational studies will answer these and other important questions.

Declaration of personal interests: Franck Carbonnel has served as a speaker for: Biogen, Ferring, Janssen, Takeda, Tillotts. He has served as an advisory board member for : Amgen, Celltrion, Janssen, Pharmacosmos, Roche, Tillotts and has received research funding from Mayoly Spindler and Alfa sigma. Antoine Meyer has no conflict of interest.