Although the totality of the evidence is reassuring, the jury is still out on nonmedical switching to biosimilars, according to new study results.
Gastroenterologists generally are accepting of biosimilars for initiating therapy in patients who are biologics-naïve. However, they remain skeptical of switching patients to biosimilars if their disease is successfully managed with an originator biologic.This practice is called nonmedical switching, and it may be done to get patients on a less expensive form of the same therapy.
A systematic review of nonmedical-switching studies of patients with inflammatory bowel disease (IBD) has detailed the knowledge gaps and study limitations responsible for this hesitation by gastroenterologists.
The majority of studies thus far have suggested nonmedical switching from infliximab to its biosimilar CT-P13 (Inflectra; Remsima) is safe. Previous reviews have reported similar findings and recommended more widespread use of biosimilars in IBD.
A Systematic Study
The systematic review identified 44 studies on switching patients from infliximab (Remicade), the first biologic marketed for use in IBD, to the biosimilar CT-P13; however, only 3 were randomized controlled trials (RCTs), only 1 of which has been published. Approximately half of the studies reviewed by the authors, most of which were observational and not intended to change treatment patterns, were not yet published.
The authors of the current review concede that “safety and efficacy of biosimilar use in infliximab-naïve patients is generally accepted,” but they advise caution on nonmedical switching because of study limitations that include the small number of RCTs compared with observational studies, lack of controls in observational studies, lack of long-term data, and a reliance on studies published at conferences for which key study design details are missing.
An accompanying editorial by Frank I. Scott of the Crohn’s and Colitis Center at the University of Colorado Anschutz Medical Campus agrees that more research is needed before nonmedical switching can be widely adopted.
The review authors found shortcomings with the single published RCT, the NOR-SWITCH trial, which studied a switch from originator infliximab to the biosimilar in 6 inflammatory diseases, including IBD. The study included the use of a composite measure of disease worsening across the same 6 heterogeneous inflammatory diseases, with different dosing regimens and concomitant therapies.
The authors also criticized the inclusion criteria for the trial as having “ill-defined disease-specific criteria,” which they said “introduces the potential for bias and limits the inferences that can be extrapolated to IBD.” Furthermore, they criticized the noninferiority margin, which they say could have demonstrated noninferiority even if up to 50% of the patients switched to CT-P13 experienced disease worsening, based on enrollment numbers.
Although the NOR-SWITCH trial demonstrated noninferiority and included patients with IBD, the data presented on ulcerative colitis and Crohn disease (CD) “did not allay” the concerns of gastroenterologists regarding switching their patients on infliximab to a biosimilar, according to the editorial. The review authors noted “the trend toward increased disease worsening in CD patients has caused some concern in the gastrointestinal community and a desire for more robust data in IBD patients.”
In an IBD subgroup open-label extension of NOR-SWITCH, stable switched patients stayed on CT-P13, and stable patients on infliximab switched to CT-P13. Efficacy, safety, and immunogenicity were similar between the groups; however, the authors of the systematic review said that “low enrollment numbers precluded conclusive implications to be drawn.”
The other 2 RCTs on nonmedical switching were conducted wholly on patients with IBD. In these trials, similar efficacy, safety, and immunogenicity were reported between groups. However, the authors of the systematic review caution that our understanding of the details of these studies is incomplete because they were presented at conferences and have yet to be published, a concern Scott echoes in his editorial.
Studies Lacked Control Arms
The authors of the review acknowledge that, overall, the 21 published observational studies suggest that nonmedical switching from the infliximab originator to the biosimilar is safe, but they also note that study designs were heterogeneous and many lacked a control group. Loss of response and discontinuation rates also varied widely between studies. This variability in observational study design and results make it “difficult for broad generalizations regarding the safety and effectiveness of nonmedical [switching] to be made,” the authors noted, adding that observational studies have not had robust assessments for antidrug antibodies, leading to knowledge gaps regarding immunogenicity.
Mandatory switching to biosimilars to reduce health care costs and expand access to biologic therapies has been criticized by gastroenterologists, “who cite a lack of high-quality controlled trials to support such decisions in stable patients,” according to the review article. Several countries have instituted some measure of mandated switching to biosimilars, such as Denmark and Canada, and these policies have drawn criticism from physicians and patient advocacy groups. According to the editorial, “While nonmedical switching policies have been enacted, there has been incomplete pharmacovigilance reporting.”
Both the systematic review and accompanying editorial stress the need to ensure patient safety before cost reduction, as well as that future studies should address the knowledge gaps regarding long-term effectiveness and immunogenicity. They also recommend a greater reliance on published RCTs as opposed to those only available as conference abstracts.
Biosimilars Gastroenterology Roundup: March 2025
April 1st 2025As the biosimilar industry celebrates a decade of growth, the market continues to evolve with expanded treatment options, cost savings, and a flurry of new competitors—yet regulatory challenges, market dynamics, and patient accessibility remain key hurdles to unlocking its full potential.
How AI Can Help Address Cost-Related Nonadherence to Biologic, Biosimilar Treatment
March 9th 2025Despite saving billions, biosimilars still account for only a small share of the biologics market—what's standing in the way of broader adoption and how can artificial intelligence (AI) help change that?
Patients With IBD Maintain Therapy 2 Years Post Switching to Infliximab Biosimilar
March 23rd 2025People with inflammatory bowel disease (IBD) who switched to the infliximab biosimilar CT-P13 had higher treatment persistence (84% and 91%) than those new to infliximab (66% and 53%), with no new safety concerns.
Will the FTC Be More PBM-Friendly Under a Second Trump Administration?
February 23rd 2025On this episode of Not So Different, we explore the Federal Trade Commission’s (FTC) second interim report on pharmacy benefit managers (PBMs) with Joe Wisniewski from Turquoise Health, discussing key issues like preferential reimbursement, drug pricing transparency, biosimilars, shifting regulations, and how a second Trump administration could reshape PBM practices.
Comparable Pregnancy and Infant Milestones With Infliximab Biosimilars vs Originator in IBD
March 15th 2025A study evaluating pregnancy outcomes and infant developmental milestones found similar outcomes between pregnant women with inflammatory bowel disease (IBD) who received reference infliximab and those who received a biosimilar.