CHICAGO — Biosimilars to the infliximab originator are not significantly different in terms of drug levels, measures of clinical response, or safety, according to researchers from South Korea and Norway, who came to essentially the same conclusion.
These "well-done" studies, presented here at Digestive Disease Week 2017, "are giving us good comparative data in terms of drug levels and drug antibodies, and at least give us preliminary data that, indeed, the switch between the innovator agent and the biosimilar is actually possible," said session comoderator Ryan Stidham, MD, from the University of Michigan in Ann Arbor.
"We're starting to have some of our fears allayed about the introduction of biosimilars," he told Medscape Medical News.
In the double-blind, randomized, phase 3 study conducted in South Korea, infliximab (Remicade, Janssen) was compared with CT-P13, a biosimilar approved in 80 countries and marketed as Inflectra by Pfizer in the United States.
A decrease of at least 70 points on the Crohn's Disease Activity Index (CDAI-70) at 6 weeks was the main outcome. The participants came from 16 countries.
"The efficacy of CT-P13 was comparable to infliximab in terms of CDAI-70," reported investigator Young Ho Kim, MD, from Sungkyunkwan University School of Medicine in Seoul.
For the secondary end points of CDAI-100 scores at week 6 and week 30, steroid-free remission at week 30, and levels of calprotectin or C-reactive protein at any time, Dr Kim's team found no significant differences between infliximab and the biosimilar.
Differences in serum levels of medication and scores on the patient-reported Short Inflammatory Bowel Disease Questionnaire were also not significant.
Table. Six-Week Outcomes
| Outcome | Infliximab, % (n = 101) | Biosimilar, % (n = 105) | P Value |
| CDAI-70 response | 75 | 71 | .5613 |
| CDAI-100 response | 64 | 62 | .7744 |
| Clinical remission | 45 | 43 | .8329 |
In terms of immunogenicity, levels of anti-infliximab antibodies were not significantly different between the two treatment groups at week 14 or week 30.
In addition, "we did not identify any new safety signals," Dr Kim reported.
The proportion of patients reporting at least one treatment-emergent adverse event was similar in the infliximab and biosimilar groups (36% vs 31%), as were the proportion reporting at least one serious treatment-emergent adverse event (2% vs 2%), the rate of infusion-related reactions (6% vs 5%), and the rate of infections (2% vs 3%).
"CT-P13 was well tolerated, with safety comparable to that of infliximab up to week 30," Dr Kim said.
The Nor-Switch Trial
In the Norwegian randomized, double-blind, 52-week Nor-Switch Trial, the 500 participants had a variety of inflammatory conditions: Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, and psoriasis.
Overall, the study demonstrates the noninferiority of CT-P13. The rate of disease worsening — the primary outcome — was similar in the infliximab and the biosimilar groups (26% vs 30%).
"The switch from infliximab to CT-P13 was not inferior to continued treatment with infliximab in terms of efficacy, safety, and immunogenicity," said investigator Kristin Jørgensen, MD, from Akershus University Hospital in Lorenskog, Norway. "The results support switching from infliximab to the biosimilar for nonmedical reasons."
"We can conclude that CT-P13 is not inferior to infliximab, but Nor-Switch was not powered to prove noninferiority for each disease," she added. However, she did present findings from an exploratory subanalysis of the data specific to Crohn's disease and ulcerative colitis.
All patients were stable after at least 6 months of treatment with infliximab before the switch to the biosimilar.
For the 129 people with Crohn's disease and the 75 with ulcerative colitis, remission rates at baseline were not significantly different than those at the end of the study. Similarly, changes in drug trough levels, anti-drug antibodies, and levels of calprotectin and C-reactive protein were not significantly different between the infliximab and biosimilar groups.
As in the South Korean study, "we did not find anything unexpected here. As expected, infections were the most common adverse event," Dr Jørgensen reported.
But although the subanalysis showed similarities between the two treatment groups, she cautioned against extrapolating the findings to other biologic and biosimilar pairs.
"The audience brought up some very good questions," Dr Stidham told Medscape Medical News. For example, the participants in these trials were volunteers with stable disease in remission.
"We don't really know the dynamics of how these biosimilars will work if we introduce them in someone with active disease. That being said, if the levels are similar, the antibody immunogenicity is similar, and 16-week outcomes are similar, it's becoming increasingly reasonable to hypothesize that we would see similar behavior in terms of someone with active disease," he explained. "That trial has yet to be done, but needs to be done."
Dr Kim reports that he is a consultant and on the advisory board for Celltrion. Dr Stidham reports that he is a consultant for AbbVie and has received previous grant support from Pfizer. Dr Jørgensen disclosed no relevant financial relationships.
Digestive Disease Week (DDW) 2017: Abstracts 248 and 249. Presented May 7, 2017.
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Cite this: 'Fears Allayed' by Latest Infliximab Biosimilar Evidence - Medscape - May 08, 2017.
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