Switching Between Reference Infliximab and CT-P13 Is Unlikely to Evoke Different ADAs

All monoclonal antibodies have the potential to evoke anti-drug antibodies (ADAs) in patients, and these products can have multiple quality attributes that can impact the immunogenicity, and therefore efficacy, of the drug product. While treatment with reference infliximab (Remicade) and its biosimilar, CT-P13 (Inflectra, Remsima), resulted in similar rates of ADAs in patients who received the drugs in 2 pivotal clinical trials, only limited data are available related to cross‐immunogenicity of reference infliximab and CT‐P13.

A new study, published in Alimentary Pharmacology and Therapeutics, sought to test antigenic comparability between the reference infliximab and the biosimilar. The researchers included the sera of patients with inflammatory bowel disease (IBD) who were treated with the biosimilar or the reference infliximab; they assessed 42 ADA-positive sera samples from patients with IBD who had been treated with the biosimilar for 9 months or more to determine whether the ADAs to CT-P13 would cross-react with 5 different batches of reference infliximab.

They found that all 42 ADA-positive samples of sera reacted to CT-P13 and also reacted to all 5 batches of the reference, and similar antibody cross-reactivity was present in sera from patients who had previous infliximab exposure and in those who were naïve to anti—tumor necrosis factor (anti-TNF) therapy.

Additionally, the researchers measured immunoglobulin G4 activity (IgG4) against 5 batches of the biosimilar and 5 batches of the reference drug. The results showed a similar response of IgG4 against all batches of both products.

“Our findings indicate that sera from IBD patients who developed anti‐CT‐P13 antibodies are cross‐reactive with infliximab,” conclude the authors, adding that, “Interestingly, we observed no difference in the concentration of IgG4 [ADAs] whether the patients were anti‐TNF naïve or infliximab‐experienced patients. Therefore, no specific long‐term immunity was developed to infliximab and exacerbated to CT‐P13 after the switch.”

They add that switching between these products is unlikely to elicit different ADAs, and say that “These data point toward a safe switching between the [2] drugs in ADA‐negative patients.”

Reference

Goncalves J, Santos M, Acurcio R, et al. Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition. [Published online June 5, 2018.] Aliment Pharmacol Ther. doi: 10.1111/apt.14808.