Patients with moderate-to-severe inflammatory bowel disease (IBD) “at high risk of disease progression and bowel damage, or those who do not respond to conventional therapies within a reasonable time," should receive anti-tumor necrosis factor (TNF)-α therapy as early as possible to prevent disease progression, but the high cost of anti-TNF therapy is a major barrier to timely treatment, according to a review by an expert panel of gastroenterologists.

Image credit: sebra - stock.adobe.com

The panel discussed strategies to increase biosimilar use in IBD with the goal of improving patient access to early initiation of anti-TNF therapy.

IBD, including Crohn disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases of the gastrointestinal system. TNF inhibitors, such as infliximab and adalimumab, are effective for treating moderate to severe IBD, but biologics are associated with high costs. The authors noted that the economic burden of IBD is driven mainly by the cost of anti-TNF biologics, which negatively affects patient access to treatment and, therefore, outcomes.

As of 2024, 17 biosimilars were approved for treating IBD in the US and European Union, and 15 in Canada, and biosimilars had been used in IBD for more than 10 years. However, the panel wrote, the use of biosimilars in clinical practice remains “suboptimal.”

Early Treatment With Anti-TNF Biologics Could Delay Disease Progression

Research suggests that initiation of anti-TNF therapy earlier in the disease course could improve outcomes and delay disease progression, especially in CD. With evidence for a “top-down” approach to IBD treatment accumulating, the authors said, treatment guidelines are shifting, but standard treatment for IBD in many regions still follows a “step-up” approach, in which non-biologic therapies, such as aminosalicylates, corticosteroids, or immunomodulators, must be failed before biologics can be initiated.

Barriers to Anti-TNF Biosimilar Use

According to the panel, the major barrier to anti-TNF use overall is cost, and biosimilars could address the cost barrier. Research has confirmed the effectiveness and safety of biosimilars, and the authors noted that many professional societies, including the American Gastroenterological Association (AGA) and the European Crohn’s and Colitis Organisation (ECCO), support the use of biosimilars in IBD, including switching patients from an originator to a biosimilar. Furthermore, surveys suggest that physician confidence in biosimilars is growing.

However, they said a disconnect exists between guidance and clinical practice. They continued by discussing barriers that may be limiting the use of anti-TNF biosimilars in IBD, and potential solutions.

Barrier 1: Complex Reimbursement/Insurance Policies

According to the expert panel, this barrier is “particularly true” in the US, with many insurance companies requiring prior authorization which may delay treatment and charging high co-pays for biologics as “specialty drugs” which increases out-of-pocket spending. They cited a study that reported over 90% of US-based insurance companies required failure of at least 1 conventional therapy before permitting biologic treatment. Additionally, several countries with single-payer systems require failure of one or even 2 non-biologic treatments before biologic treatment becomes reimbursable.

Exacerbating the issue in the US, there are financial incentives for pharmacy benefit managers to place higher-cost reference biologics on formularies, which favors those reference products over biosimilars and leaves many healthcare professionals unable to choose a biosimilar for their patients.

The panel recommended the removal of payer requirements for the patient to fail on conventional therapies before initiating biologics to allow for earlier initiation of anti-TNF therapy and bring the ‘top-down’ treatment guidance into clinical practice. They added that the improved outcomes from earlier initiation of biologics could “potentially support a reduction in the cumulative costs of sustained disease.”

Barrier 2: Concerns of Health Care Professionals

Although attitudes of health care professionals are trending toward acceptance of biosimilars, “some resistance” persists,” the authors wrote, citing a US study from 2020 that found 73% of physicians surveyed refrained from prescribing biosimilars. The panel explained that physician skepticism and lack of confidence in biosimilars may stem from the differences in the development and approval pathways between originators and biosimilars, and a lack of understanding of extrapolation to additional indications or biosimilar switching data. Importantly, patients are likely to lack confidence in biosimilars if their physician does.

As a solution to address this barrier, the expert panel proposed continued education on the robustness of the biosimilar development process and safety of switching between originator and biosimilar products, as well as encouraging peer-to-peer education for physicians to share their experiences with biosimilars. They also recommended conducting more randomized controlled trials and real-world studies to address physician concerns, development of tailored educational materials on biosimilars that address specific needs and concerns of subpopulations of health care professionals, and integrating biosimilar education into medical and pharmacy school curricula.

Barrier #3: Patient Concerns

A patient’s concerns around biosimilars could lead to reluctance to begin treatment, as well as poorer outcomes due to the nocebo effect. The panel cited research showing that people with IBD frequently share negative experiences around biologics on social media, including concerns about safety and side effects. A lack of understanding of biosimilars can lead to a lack of confidence. The panel cited surveys finding large proportions of patients had not heard of biosimilars, and many of those who had were not confident in their effectiveness and safety, or viewed them as of lesser quality than reference biologics.

That anti-TNF biologics are delivered via intravenous or subcutaneous injection is another source of hesitation for some patients, due to fear of needles or previous injection site reactions or pain.

The panel recommended leveraging the educational materials of nonprofits and IBD patient support groups, such as the European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA), and discussed essential aspects of communication with patients, such as providing understandable, consistent, and up-to-date information, communicating transparently and positively to reduce the likelihood of a nocebo effect, and tailoring the materials to individual patient needs. They recommended physicians, nurses, and pharmacists adopt these strategies to ensure that information is accurate and explain how biosimilars can support the patient’s treatment goals.

Although there are structural barriers to the use of anti-TNF biosimilars, the expert panel emphasized that healthcare professionals can take action now to increase confidence in anti-TNF biosimilars in IBD, supporting the “top-down” approach to IBD treatment, “ultimately improving long-term disease management and patient outcomes, as well as paving the way for the future biosimilar landscape in IBD.”

Reference

Fiorino G, Ananthakrishnan A, Cohen RD, Cross RK, Deepak P, Farraye FA, Halfvarson J, Steinhart AH. Accelerating earlier access to anti-TNF-α agents with biosimilar medicines in the management of inflammatory bowel disease. J Clin Med. 2025;14(5):1561. doi:10.3390/jcm14051561