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.
AMCP Posters Tackle Interchangeability and Medicaid, Factors Driving Biosimilar Access
April 24th 2024Two posters from the Academy of Managed Care Pharmacy (AMCP) annual meeting explore how an interchangeable insulin glargine biosimilar plays into Medicaid budgets and the top factors driving access to biosimilars.
Decoding the Patent Puzzle: Navigating the Legal Landscape of Biosimilars
March 17th 2024On this episode of Not So Different, Ha Kung Wong, JD, an intellectual patent attorney and partner at Venable LLP, details the confusing landscape that is the US patent system and how it can be improved to help companies overcome barriers to biosimilar competition.
Julie Reed: Why 2024 Is Important for Biosimilars
April 17th 2024Julie Reed, executive director of the Biosimilars Forum, showcases how the biosimilar industry is expected to develop throughout 2024, including major policy changes and hope for continued improvement in market share for adalimumab biosimilars.
Biosimilars Gastroenterology Roundup for January 2024—Podcast Edition
February 4th 2024On this episode of Not So Different, we reminisce on all the major gastroenterology news from January, which brought several reports quantifying how the gastroenterology biosimilar market is progressing and marked the 1-year anniversary of adalimumab biosimilar competition in the US.
What Clinicians Need to Know About Using Biosimilars to Treat IBD
April 13th 2024A review article, intended to act as a guide for clinicians, summarizes the available infliximab and adalimumab biosimilars for treating inflammatory bowel disease (IBD) as well as others that are coming down the pipeline.
Global Biosimilar Market Projected to Reach $1.3 Trillion by 2032
April 11th 2024The global biosimilar market is projected to surge from $25.1 billion in 2022 to approximately $1.3 trillion by 2032, with a compound annual growth rate of 17.6%, driven mainly by the increasing prevalence of cancer and the cost-effectiveness of biosimilars, as outlined in a report by Towards Healthcare.