Study Supports Switch From Remicade to SB2 in IBD

A real-world, multicenter study in Italy demonstrated equivalent safety, efficacy, and tolerability for patients with inflammatory bowel disease (IBD) who switched from reference infliximab (Remicade) to the biosimilar Renflexis (SB2, Flixabi), investigators concluded.

They said this was the largest study (N = 85) to date investigating crossover from Remicade to SB2.

“Our patients maintained clinical response to therapy after switching and did not develop serious adverse events (AEs). In addition, we did not find differences in immunogenicity between infliximab originator and SB2,” investigators said.

IBD includes ulcerative colitis (UC) and Crohn disease (CD), relapsing and remitting inflammatory diseases of the intestinal tract, for which anti–tumor necrosis factor (TNF) biologics including infliximab may be prescribed. TNF inhibitors have “greatly improved” outcomes for patients with refractory IBD and those who are intolerant to standard treatments, according to the researchers.

The authors explained that, in the context of IBD, there is “substantial and robust literature” on the biosimilar CT-P13 (Inflectra, Remsima) and only a “paucity of data” on SB2. CT-P13 was approved by the European Medicines Agency in 2013 and FDA in 2016, and SB2 was approved in 2016 by the EMA and 2017 by the FDA.

This study was conducted between 2018 and 2020 at 3 IBD treatment centers in Italy. The patient population included 28 (32.9%) with UC and 57 (67.1%) with CD. This was the first switch between infliximab products for this patient cohort. Data were collected at the time of switch and then at the first 2 follow-up visits to the IBD clinic, on average 135 days and 329 days later.

The proportion of patients in clinical remission was 82% at baseline and 69% at the second visit

At baseline, 70 (82.3%) patients were in remission, 12 (14.1%) had mild disease activity, 3 (3.5%) had moderate disease activity, and none of the patients had severe disease activity. At the first visit, 60 (70.6%) were in remission, 17 (20%) had mild disease, 8 (9.4%) had moderate disease, and none had severe disease.

Data for the second visit was available for 76 of the original 85 participants. By the second visit, 59 (69.4%) patients were in remission, 15 (17.6%) had mild disease, and 2 (2.4%) had severe disease. The authors noted there was a statistically significant difference in these proportions from baseline to visit one, but not from baseline to the second visit.

The authors said that over the duration of the study, 52 of the 70 patients in remission at baseline stayed in remission, and 11 developed mild disease. Five of the 12 patients with mild disease at baseline maintained mild disease, and 2 developed severe disease. One patient with moderate disease at baseline had mild disease at the second visit, and another was in remission.

Neither median fecal calprotectin, an indicator of inflammation in the gastrointestinal tract, nor the systemic inflammation indicator C-reactive protein (CRP) showed significant differences between baseline and the second visit.

The clinics used therapeutic drug monitoring to optimize drug administration rates. The researchers identified a significant increase in the need for therapeutic drug optimization; at baseline, 29 patients required treatment optimization compared with 37 patients at the first visit.

Four adverse events (AE) were recorded at the first visit and 5 at the second visit; no serious adverse events were reported. Overall, 16 patients (18.8%) discontinued treatment, 4 by visit 1 and 12 by visit 2: 5 patients due to adverse reactions, 8 due to lack of efficacy, 2 due to remission, and 1 due to pregnancy. One patient who discontinued treatment after the first visit due to lack of efficacy resumed therapy with the reference product and regained remission.

No New Antidrug Antibodies

The authors noted that a loss of response to anti-TNF therapy may occur due to low serum drug levels or high levels of anti-drug antibodies (ADAs), and that 10% to 50% of patients treated with TNF inhibitors experience a loss of response.

They measured serum trough levels (TLs) and ADAs in a subgroup of 55 patients at baseline and the first visit. At baseline, 20 patients (36.3%) demonstrated subtherapeutic TLs; 5 returned to therapeutic TLs, and 5 lost therapeutic TLs at the first visit. At both visits the same 2 patients (3.7%) showed ADAs; no new ADAs were identified after the switch to SB2. The authors said these data on TLs and ADAs suggest “no significant implication of these pharmacological features in therapeutic failure.”

The authors concluded, “overall, our data show that most of the patients switching from infliximab originator to SB2 maintain the clinical and biochemical remission for at least 1 year,” further noting they detected no serious AEs and no evidence of differences in immunogenicity between the originator and the biosimilar. However, they also acknowledged that 2 patients with mild disease developed severe disease, 8 patients required drug optimization, 16 patients discontinued therapy, and 10 patients required the addition of steroid therapy during the study.

They recommended more real-world, multi-center studies with larger sample sizes and longer follow-up times “to obtain more consistent data and further support the use of biosimilar drugs in clinical practice.”

Reference

Massimi D, Barberio B, Bertani L, et al. Switching from infliximab originator to SB2 biosimilar in inflammatory bowel diseases: a multicentric prospective real-life study. Therap Adv Gastroenterol. Published online June 27, 2021. doi:10.1177/17562848211023384