Infliximab Biosimilar Switching Study Yields Evidence of Safety, Efficacy

January 14, 2021
Deana Ferreri, PhD

A need for clinical evidence on the efficacy and safety of infliximab switching led the authors to pursue this investigation.

Switching patients with inflammatory bowel disease (IBD) from the CT-P13 infliximab biosimilar to the SB2 infliximab biosimilar appears to be safe and effective whether 1 or more switches between biosimilars and the originator product were involved, investigators concluded in a retrospective study.

In seeking to elucidate the safety and efficacy of switching, the investigators noted little clinical evidence is yet available on switching patients with IBD between infliximab products. Further, they cited a lack of evidence for SB2 in patients with IBD, saying most of the available evidence “derives from the rheumatologic field.”

They enrolled patients who had originally been treated with CT-P13 or the originator product, but all patients had been treated with CT-P13 before switching to SB2. Clinical activity and adverse events were evaluated; the investigators also compared loss of response (LOR) between the biosimilars.

Lower Cost Makes Switching Attractive

Originator infliximab (Remicade), a monoclonal antibody to tumor necrosis factor alpha, has been used to treat IBD for over 20 years. CT-P13 (Inflectra, Remsima; Celltrion) was the first approved infliximab biosimilar for IBD—Europe in 2013 and the United States in 2016)—and SB2 (Renflexis; Samsung Bioepis) was approved in Europe in 2016 and in the United States in 2017.

Multiple switches, from the reference product to CT-P13 and then to SB2 are likely to occur, the authors said, because of the lower cost of SB2 vs CT-P13. However, European guidelines do not advocate multiple switches because of a lack of clinical evidence.

Thirty-six patients, 14 with Crohn disease and 22 with ulcerative colitis, were followed for 6 months following a switch from CT-P13 to SB2. Twelve had previously switched from the infliximab reference product to CT-P13, and the rest were naïve to infliximab before treatment with CT-P13. Thirteen patients were treated with adalimumab or golimumab immunosuppressants prior to using an infliximab product.

Study Findings

Clinical activity was assessed 6 months before and 3 months after switching to SB2. The proportion of patients in clinical remission was 58.3% both before and after the switch, and rates of mild clinical activity were not significantly different before and after (27.8% vs 33.3%, respectively; P = 0.68). The percentages of patients with normal C-reactive protein levels were not significantly different 6 months before and 3 months after switching (94.4% vs 91.7%, respectively; P = 1).

The authors said SB2 treatment for 2 patients was suspended after they achieved clinical and endoscopic remission,” and 2 patients (5.5%) receiving SB2 experienced an adverse event (AE).

After switching from CT-P13 to SB2, 25 patients (69.4%) maintained clinical remission and 11 (30.5%) experienced LOR.

Comparing patients who experienced LOR with those who didn’t, the investigators found that 40% of those without LOR (n = 25) had undergone ≥2 switches (reference product to CT-P13 to SB2) compared with just 9.1% of patients who did experience LOR (n = 11), although the difference did not reach significance. Previous AEs during treatment with CT-P13 were more common among patients who experienced LOR on SB2 (27.3%) compared with those who did not (4%), although these findings also did not reach significance.

In univariate and multivariate analyses, the investigators evaluated the number of switches, AEs during CT-P13 treatment, previous LOR to CT-P13, endoscopic activity, clinical activity, clinical variables, and demographic variables, and did not find significant associations with LOR on SB2.

The authors recommended these factors be studied in a larger population to determine their potential influence on LOR, saying, “The low number of enrolled patients could explain why, at univariate, no significant variable was predictive.”

Author Conclusions

The nvestigators said it would have been “helpful to evaluate the value of infliximab trough levels and the detection of anti-infliximab antibodies,” to more precisely evaluate the potential association between previous AEs to CT-P13 and LOR to SB2. However, they were unable to perform this analysis due to the retrospective nature of the study and recommended future investigation into this potential predictive factor.

They concluded that switching from CT-P13 to SB2 is safe and effective in patients with a single switch or multiple switches among infliximab treatments. The authors described their efforts as “one of the initial studies investigating the efficacy and safety of the SB2 administration to IBD patients in a real-life setting.”

Reference

Lovero R, Losurdo G, La Fortezza RF, et al. Safety and efficacy of switching from infliximab biosimilar CT-P13 to infliximab biosimilar SB2 in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2021;32(2):201-207. doi:10.1097/MEG.0000000000001988