This is half of a two-part debate — read the opposing argument.
The safety and effectiveness of anti–tumor necrosis factor (TNF) therapy for the treatment of inflammatory bowel disease (IBD) has been well established for decades. Therefore, introducing anti-TNF biosimilars to the marketplace does not represent a new mode of treatment for patients with IBD, which is an important concept to emphasize to health care professionals (HCPs) and patients. In addition, it is important to educate patients and HCPs that biosimilars are not generic drugs; in fact, the process for a biosimilar to receive FDA approval is more rigorous than generic medications.
The FDA Biologics Price Competition and Innovation (BPCI) Act defines a biosimilar as a “biological product highly similar to the reference product notwithstanding minor differences in clinically inactive components” and one in which “there are no clinically meaningful differences between the biologic and reference products in terms of the safety, purity, and potency.”1 Per the BPCI Act, biosimilars must demonstrate similar protein structure of the active agent, pharmacokinetics/pharmacodynamics, immunogenicity profiles, and efficacy/safety in a condition where the originator product is used.1
For infliximab, randomized controlled trials were initiated to study rheumatoid arthritis and ankylosing spondylitis in order to compare the biosimilar and its originator products. These trials were able to demonstrate the “highly similar” nature of the biosimilars, thus leading to the extrapolation of efficacy and safety to the infliximab-treated conditions such as moderate to severe Crohn’s disease and ulcerative colitis. The key point is, unlike generic medications, anti-TNF biosimilars have accumulated clinical evidence that has demonstrated noninferiority to the original agent prior to their introduction into the marketplace.
Since the first FDA approval of a biosimilar in 2016, multiple studies have investigated the bioequivalence of biosimilars in patients with IBD, one of which was a randomized controlled trial of patients with Crohn disease. These published reports provide additional support that biosimilars should be positioned next to the originator agents when discussing treatment plans for patients with moderate to severe IBD.
Remembering that the goals of treatment in IBD are to induce and maintain steroid-free remission with mucosal healing, anti-TNF agents play an instrumental role in implementing a “treat-to- target” approach. Viewing the cumulative evidence, scenarios in which an HCP should feel comfortable discussing the use of biosimilars in IBD include patients naïve to treatment with the active agent or patients who are in sustained remission on the originator drug. Patients who were primary anti-TNF nonresponders or lost response due to immunogenicity should not be given the biosimilar, because doing so would essentially be treating the disease with the same active component but in a slightly different formulation.
Interchangeability still remains somewhat controversial. Although studies such as NOR- SWITCH suggest that switching from an originator agent to its biosimilar is feasible, the important feature to remember is that these patients were in stable remission, thereby representing a nonmedical switch.2 It is still unknown if patients with active disease or with multiple switches across different biosimilars and originator agents will experience the same efficacy, safety, and immunogenicity findings.
The primary benefit of biosimilars in the marketplace is for decreased costs of drug acquisition, because biologics represent a substantial percentage of treatment-associated costs for patients with IBD. They may also provide a means for greater access to anti-TNF agents due to lower prices for payors and organizations. With adjustments in pricing schedules and accessibility throughout the country, the potential for overall costs savings can be substantial. Yet, there is the sense of uncertainty and unfamiliarity that must be considered prior to the acceptance of biosimilars by HCPs and patients, and this is particularly true when making a switch from an originator agent to a biosimilar. Introducing a new IBD product that is targeting a different mechanism of action is fairly easy to accept and apply in clinical practice because there are still many patients whose disease will not respond or whose disease will lose response to anti-TNF agents and, thus, will need another option. However, the recently approved anti-TNF biosimilars are not that different from the other anti-TNFs gastroenterologists have used for years for IBD treatment.
It is the shared responsibility of the insurers, the pharmaceutical industry, pharmacies, and HCPs to be transparent about the utilization of biosimilars and to educate patients regarding the rationale, safety, and effectiveness of the biosimilar product, particularly when it comes to issues of interchangeability. The transition must be seamless with similar financial-assistance programs, dosing schedules, escalations of treatment, and therapeutic drug monitoring strategies based on the clinical response, loss of response or nonresponse. There also must be acknowledgment by leading gastroenterologic societies and providers of the similar efficacy and safety of biosimilars for IBD relative to the originator drug.
There are some excellent resources publicly available through AGA and the Crohn’s and Colitis Foundation, to increase awareness and acceptance of biosimilars for our patients with IBD. Patients and HCPs need to have reassurance that the quality of care and safety will not be compromised by using a biosimilar based on the currently available evidence. The cost savings should ultimately translate to higher quality and more cost-effective patient care.
Although the data for biosimilars in IBD may not be as robust as for a new mechanism of action, the available literature suggests that biosimilars are noninferior to the originators, particularly for patients starting treatment or in those with sustained remission on the originator product. It is up to all parties of the health care team to recognize and accept the role that biosimilars have in the IBD armamentarium for the same indications as any anti-TNF agent and remove the stigma of perceived inferiority that may be present among patients and colleagues. We must remember the same strategies remain to monitor for response and adverse events. We will need continued pharmacovigilance from the FDA and the pharmaceutical industry via postmarketing studies to ensure stringent quality standards during the manufacturing process are met and that surveillance is occurring for new safety or efficacy signals.
Dr. Ha is on the speaker’s bureau for Abbvie. She is also on the advisory board for Pfizer, Takeda and Janssen.
1. Biologics Price Competition and Innovation Act of 2009. § 7001 U.S.C. (2010).
2. Jørgensen, K.K., Olsen, I.C., Goll, G.L., et al, for the NOR-SWITCH study group. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2016;389:2304-2316.