Deana Ferreri, PhD

 study of the trastuzumab biosimilar CT-P6 (trastuzumab-pkrb, Herzuma) in Japan showed a disease control rate of 82%, progression-free survival of 7.4 months, and “no new safety concerns” in HER2-positive (HER2+) advanced gastric cancer. According to the authors, this post-marketing surveillance study is the first prospective cohort study evaluating real-world safety and effectiveness of CT-P6 in HER2+ advanced gastric cancer.

Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), inhibits proliferation of tumor cells overexpressing HER2, and is used to treat HER2+ breast cancer and metastatic gastric cancers. The reference product (Herceptin) was first approved by the US FDA in 1998. The authors noted that therapies targeting HER2 have “markedly improved” clinical outcomes for patients with HER2+ cancers. The biosimilar CT-P6 was approved in the European Union, US, and Japan in 2018 for all indications of the reference product, based on extrapolation from a clinical trial on HER2-positive 

, “highlighting the need for gastric cancer-specific evidence,” according to the authors. In Japan, the post-market surveillance study was required by the Ministry of Health, Labour, and Welfare (MHLW) as a condition for the approval of the biosimilar.

A total of 171 patients with HER2-positive unresectable advanced or recurrent gastric cancer were enrolled in the post-marketing surveillance study. CT-P6 was combined with chemotherapy, primarily fluoropyrimidine and platinum agents. In the majority of patients (59%), CT-P6 with chemotherapy was used as first-line therapy for inoperable tumors.

Adverse events (AEs) occurred in 151 patients (88%), 55 of whom (32%) experienced grade 3 or higher AEs. Infusion reactions occurred in 12% of patients, all of which were related to CT-P6, and none were serious. AEs related to CT-P6 occurred in 67% of patients. AEs occurring in more than 20% of patients included anemia, neutropenia, thrombocytopenia, diarrhea, nausea, anorexia, and peripheral neuropathy, most of which (90%) were related to CT-P6. Cardiac AEs and interstitial lung disease occurred in 4 patients each (2%), and were related to CT-P6.The authors commented that the safety profile of CT-P6 in this study was “consistent with that observed in the clinical trials.”

The objective response rate was 34%, the disease control rate was 82%, and three patients (2%) achieved a complete response. Regression analysis on data from 156 patients treated with CT-P6 in combination with fluoropyrimidine showed several prognostic factors that were significantly associated with shorter progression-free survival, including primary tumor site at the gastroesophageal junction, three or more metastases, no gastrectomy, prior chemotherapy, and no use of platinum agents.

During the one-year observation period, 123 patients (73%) discontinued treatment, 89 (53%) due to disease progression, and 16 patients (9.5%) due to AEs. Thirty patients (18%) continued CT-P6 therapy for the entire year, seven (4%) completed the planned treatment, and eight (5%) underwent conversion surgery following a good tumor response to CT-P6 therapy. The authors concluded that CT-P6 showed “sufficient efficacy and no new safety concerns” in HER2-positive advanced gastric cancer.

Taniguchi H, Nishikawa K, Haneji T, Izawa N, Imamura H, Yamaguchi H. Prospective cohort study of trastuzumab biosimilar CT-P6 in HER2-positive gastric cancer: Japanese real-world outcomes. 

. 2025;13(2):485-503. doi:10.1007/s40487-025-00341-7

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CT-P6 demonstrates strong efficacy and safety in HER2-positive advanced gastric cancer, achieving an 82% disease control rate in real-world settings.

Postmarketing Surveillance Data Reinforce Trastuzumab Biosimilar Safety in HER2+ Gastric Cancer

 of nonmedical switching from the infliximab reference product to biosimilar CT‐P13 (Inflectra; Celltrion) found long-term persistence was similar between patients in the switched and non-switched cohorts after 4 years of follow-up. The investigators said the results “provide further reassurance that nonmedical switching is safe and clinically comparable to ongoing originator infliximab in clinically stable patients with IBD.”

Image credit: Sandor Kacso - stock.adobe.com

 shown nonmedical switching to the infliximab biosimilar CT‐P13 from the originator was safe and noninferior compared to continuing the reference product in patients with inflammatory bowel disease (IBD).

Although several studies have reported cost savings associated with switching to infliximab, and several countries and regions require new prescriptions of anti-tumor necrosis factor biologics to be biosimilars, Australia does not mandate prescribing biosimilars, “and a significant portion of [IBD] patients may remain on originator infliximab owing to clinician and patient reluctance to switch.”

Randomized controlled trials and real-world studies have found infliximab biosimilars are safe and effective in IBD, for both infliximab-naive and switched patients. However, longer-term outcomes “remain less well described,” the authors said. Furthermore, they added, since some studies have suggested switching may negatively affect long-term clinical outcomes due to the nocebo effect, there is a need for longer-term studies.

The prospective parallel cohort noninferiority study enrolled 345 patients with IBD in steroid-free clinical remission across multiple centers in Australia on the originator infliximab. Patients either continued treatment with the originator (n = 141) or switched to CT‐P13(n = 204). Independent of the study, 4 hospitals had decided to switch all stable patients to the biosimilar, while 3 had decided to continue to use the originator.

At 48 weeks, treatment persistence, the primary outcome, was 92% among patients in the biosimilar group, and 94% in the originator group. Among patients who did not change from their initial treatment (n = 297) during follow-up, there was no difference in the risk of disease worsening between groups (HR, 1.08; 95% CI, 0.68-1.72).

Trough drug levels were not different between switch and non-switch over time or at any single time period throughout the follow-up. However, the authors did find that patients who were receiving dose escalation prior to the start of the study had lower drug levels than those who weren’t. Also, dose escalation of more than 5 mg/kg every 8 weeks was significantly associated with disease worsening (HR, 1.89; 95% CI, 1.13-3.17).

Rates of antidrug antibodies (ADAs) were similar between groups. Develoment of ADAs occurred in 5 patients in the switch group and 4 who remained on the originator. Overall rates of ADAs were similar between groups, at 10% in the switch group and 11% in the reference product group. The authors added that all patients who developed “clinically significant” antibodies had a change in drug therapy sometime during follow-up.

At least 1 adverse event (AE) occurred in 49% of patients in the biosimilar group and 53% of the reference product group, with no significant difference between groups. The authors said most AEs were mild and did not affect treatment persistence. In the biosimilar group, 25 patients (12%) experienced an AE leading to discontinuation of infliximab treatment, as well as 15 (11%) of patients in the reference product group. AEs leading to discontinuation included infection, vasculitis, drug‐induced lupus, and one death, which was associated with a pre‐existing malignancy.

Rates of infliximab discontinuation were also not significantly different between groups, occurring 35% in the switched group and 38% of those who stayed on the reference product (HR, 0.87; 95% CI, 0.59-1.28). One patient switched back to the originator, after a change in symptoms without objective evidence of inflammation.

Reasons for discontinuation included disease worsening (22% of those who discontinued the biosimilar and 24% of those who discontinued the reference product), dose escalation (35% and 32%), antibody development (5% and 11%), and infliximab‐related adverse events (8% and 8%), and were comparable between groups. Regardless of group, patients with UC had a higher likelihood of treatment discontinuation than those with CD.

According to the authors, this is the longest real-world study to compare switched and non-switched groups of patients with IBD on infliximab. The authors concluded their findings “provide reassurance to clinicians, patients, and healthcare payers, alike, regarding the long‐term safety, clinical effectiveness, and pharmacokinetic profile of nonmedical switching.”

Suo P, Srinivasan A, Thin L, et al. Comparing long-term infliximab persistence following a switch to a biosimilar in patients with inflammatory bowel disease: no cause for concern. 

. 2025;40(5):1174-1181. doi:10.1111/jgh.16916

Long-term data from the SAME study confirm that switching to infliximab biosimilars is safe and effective for patients with inflammatory bowel disease (IBD).

Australian Patients With IBD Switched to Biosimilar Infliximab Maintain Long-Term Persistence

 assessed the safety of the infliximab biosimilar CT-P13 (Inflectra) after switching from the reference product (Remicade) in Japanese patients with Crohn disease (CD), ulcerative colitis (UC), and rheumatoid arthritis (RA). Among patients with CD, 39% experienced at least one uncommon adverse drug reaction (ADR), as well as 50% of patients with UC and 13% with RA. However, most ADRs (94%) were considered not related to CT-P13.

The tumor necrosis factor (TNF)-α inhibitor infliximab is used to treat a variety of immune-mediated inflammatory diseases, including IBD (CD and UC) and RA, in which the cytokine TNF plays a central role. 

 was the first infliximab biosimilar and first biosimilar monoclonal antibody approved in Japan in 2014. Clinical trials and real-world studies have established CT-P13 is similarly effective and safe as the originator, however, according to the authors, there are few studies on long-term CT-P13 treatment in Japan, where patient co-pays for biosimilars and originators are the same.

Data on 220 patients was collected in routine clinical practice at multiple centers in Japan, 123 of whom had CD, 74 with UC, and 23 with RA. Patients were stable on the reference product prior to switching to CT-P13. The study is ongoing with patients continuing to complete annual follow-up visits.

After 2 years of CT-P13 therapy, 48 (39%), 37 (50%), and 3 (13%) patients with CD, UC, and RA reported at least 1 ADR. However, the vast majority (94%) were not related to CT-P13. Most ADRs (74%) were grade 1 or 2. The most frequent classes of ADRs reported were gastrointestinal disorders in 11% of patients with CD, infections and infestations in 20% of patients with UC, and injury, poisoning, and procedural implications in 9% of patients with RA.

Adverse events (AEs) and serious AEs (SAEs) were secondary endpoints of the study. AEs were reported by 59% of patients with CD, 70% of patients with UC, and 30% of patients with RA. Serious AEs were reported by 10%, 13.5%, and 9% of patients. Most AEs were grade 1 or 2 and most SAEs were grade 2 or 3. The most frequent AEs were gastrointestinal disorders in patients with CD (40%) and UC (40.5%), and infections and infestations in patients with RA (17%). Herpes zoster infection and pneumonia in patients with CD and UC and nasopharyngitis in patients with RA were considered to have a “plausible relationship to CT-P13 treatment.” One patient with CD and 4 patients with UC reported infusion-related reactions.

Nineteen patients (9%) discontinued CT-P13 for reasons related to the drug, 4 (9%) with CD, 11 (31%) with UC, and 4 (31%) with RA. The primary reason was loss of efficacy in patients with UC and RA, and AEs in patients with CD. Two patients with CD and 1 with UC experienced SAEs leading to discontinuation of treatment.

The authors concluded that CT-P13 was “well tolerated” over 2 years in this study, as most ADRs were not related to CT-P13, and few patients stopped treatment due to reasons related to the biosimilar. They added that the effectiveness of infliximab therapy was “well maintained,” and said their findings demonstrate long-term safety of CT-P13 in real-world practice. They plan to report 5-year data at the completion of the study.

Ishida T, Yokoe I, Obata H, Park S, Kim S, Nishimata N. A real-world, observational, prospective cohort study evaluating the safety and effectiveness of CT-P13 in inflammatory bowel disease and rheumatoid arthritis: the MEGA-J study. 

. 2025;41(4):601-606. doi:10.1080/03007995.2025.2492638

The MEGA-J study reveals CT-P13's long-term safety and effectiveness in treating inflammatory bowel disease and rheumatoid arthritis, with minimal adverse reactions.

Real-World Data Suggest Long-Term Safety of CT-P13 in IBD, RA

Pediatric patients with inflammatory bowel disease (IBD) treated with adalimumab biosimilars had “high durability and remission rates” at a lower cost of treatment, according to a 

 in 2 European centers. The authors said their findings confirm the cost-effectiveness of adalimumab biosimilars in pediatric IBD.

The authors said their findings confirm the cost-effectiveness of adalimumab biosimilars in pediatric IBD. | Image credit: zinkevych - stock.adobe.com

According to the authors, although real-world studies have reported similar safety and effectiveness of adalimumab biosimilars to the reference product in 

, there is very little data from pediatric populations. Their study assessed the long-term durability of adalimumab biosimilars in pediatric IBD centers in Scotland and Sicily over up to 72 months, as well as effectiveness, safety and cost savings.

Adalimumab, a monoclonal antibody targeting tumor necrosis factor (TNF)-α, is used to treat IBD in both adults and children. Following the expiration of the originator’s (Humira) patent in 2018, biosimilars have become available in Europe, including ABP 501 (Amgevita), GP2017 (Hyrimoz), and SB5 (Hadlima).

A total of 130 patients,115 (88%) with Crohn disease (CD), 7 (5%) with ulcerative colitis (UC), and 8 (6%) with IBD unclassified (IBDU) were included. The mean age was 12.3 years, and patients used biosimilars ABP 501 (85%), GP2017 (14%), and SB5 (1%). About one-third (32%) of patients switched from the originator to 1 of the biosimilars, 80% of whom were in clinical remission at the time.

The probabilities of durability at 6, 12, 24, 26, and 54 months were 93%, 86%, 75%, 62%, and 57%. After a median follow-up of 26 months (IQR, 12-50; maximum, 72 months), 87 (67%) patients remained on adalimumab biosimilar treatment.

One-third of patients (33%) discontinued therapy, due to primary non-response (14%), secondary loss of response (37%), adverse events (AEs; 33%), IBD-related surgery (14%), and severe needle phobia (2%).

When analyzing potential factors associated with treatment failure, the investigators found patients who had previously been exposed to the adalimumab reference product had a lower risk of biosimilar treatment failure (HR, 0.51; 95% CI, 0.26-0.99; 

 = .047). Other factors, such as IBD subtype, perianal disease, or previous exposure to infliximab were not associated with treatment failure.

Clinical remission rate improved over time, from 39% at baseline, to 71% at 6 months and 72% at 12 months. The investigators also observed improvements in luminal remission, C-reactive protein (CRP) levels, and fecal calprotectin levels over time.

Based on therapeutic drug monitoring (TDM) data, patients who experienced treatment failure had lower drug concentrations at 6 months (10.7 μg/ml; IQR 7.6-12.0) than those who continued treatment (12.0 μg/ml; IQR, 10.4-15.9). Trough levels of at least 11.6 μg/ml at 6 months were associated with greater durability of adalimumab biosimilar therapy.

AEs occurred in 46 (36%) patients, which were mainly psoriasis (13%) and injection site reactions (13%), and 1 case of lymphoma. Of the 14 who discontinued due to AEs, 6 switched to the originator because of injection site reactions or difficulty with delivery. Of patients who experienced injection site pain, most (94%) were receiving ABP 501, and the rest were receiving GP2017.

The cost savings from using an adalimumab biosimilar in place of the reference product were estimated at 5,030 Euro per patient per year. According to the authors, this is the first real-world study assessing the long-term durability of adalimumab biosimilars in pediatric IBD. “Durability can be considered a general marker of treatment success, as it reflects overall effectiveness, AEs, and patient acceptance,” they wrote. They said the treatment persistence rate they observed is comparable to 

, with a larger sample size and extended follow-up period, adding that the treatment persistence results were also similar to those found in adult patients with IBD.

Ancona S, Armstrong K, Longo C, Rabone R, Merrick V, Henderson P, Gandullia P, Wilson DC, Arrigo S, Russell RK. Adalimumab biosimilars demonstrate long-term durability and cost-effectiveness in paediatric inflammatory bowel disease: a real-world two-centre European cohort study. Biologics. 2025;19:265-279. doi:10.2147/BTT.S511248

A real-world study reveals that pediatric patients with IBD achieve high remission rates and cost savings using adalimumab biosimilars over time.

Long-Term Durability and Cost-Effectiveness of Adalimumab Biosimilars in Pediatric IBD

 found “high acceptance levels” among patients with inflammatory bowel disease (IBD) offered a switch from the adalimumab reference product to 1 of 5 biosimilars when also given education and tailored guidance. The study found that 92% of patients accepted the switch, and 71% remained on a biosimilar at 12 months.

Image credit: Prostock-studio - stock.adobe.com

The most common reason for discontinuing biosimilar treatment was injection site pain. At 12 months, 85% of patients who switched were in clinical remission. The researchers concluded that most patients with IBD receiving the adalimumab originator are open to switching to a biosimilar and “achieve good outcomes.”

About 7 million people worldwide are afflicted with IBD, an immune-mediated inflammatory disease of the gastrointestinal tract which encompasses Crohn disease (CD) and ulcerative colitis (UC). IBD treatment is costly, primarily because of the cost of biologics, including adalimumab, a monoclonal antibody targeting tumor necrosis factor-α.

The study assessed 5 of the adalimumab biosimilars that are available in Europe: Amgevita, Hulio, Hyrimoz, Idacio, and Imraldi. Notably, adalimumab products differ in injection devices, excipients, and injection volumes.

The concerns of patients about biosimilars “remain poorly addressed,” according to the authors, despite recommendations of medical organizations such as the European Crohn’s and Colitis Organisation (ECCO) and accumulating clinical evidence supporting the safety and effectiveness of biosimilars. These concerns could limit patient acceptance and treatment adherence.

The prospective observational study evaluated the acceptance rate of biosimilar switching and factors associated with non-acceptance, as well as biosimilar persistence, clinical outcomes, and patient perceptions at 12 months. The study was conducted at a single hospital in France and included 97 adult patients with IBD who had been treated with the adalimumab reference product for at least 6 weeks. All patients received standardized verbal information about biosimilars from their regular gastroenterologist and a trained nurse assigned to guide their switch process. Patients were offered the option to switch from the reference product to their choice of 5 biosimilars, and were followed for 12 months.

Of the 97 patients, 84 had CD and 13 had UC. The median disease duration was 13 years, and 92 patients (95%) were in clinical remission, defined by Harvey Bradshaw Index of 4 or lower for CD or a Partial Mayo Score of 1 or lower for UC. Seventy-four patients (82%) were in biochemical remission, defined as C-reactive protein (CRP) of 5 mg/L or lower.

While 89 patients (92%) accepted a switch to a biosimilar, only 45% reported having no concerns about biosimilars. The factors potentially associated with patient acceptance of biosimilars considered by researchers included sex, education level, flu vaccine adherence, previous biologic therapy, disease duration, and duration of originator therapy. The only factor significantly associated with non-acceptance of a biosimilar was a poor opinion of generic drugs.

Persistence with the initial biosimilar was 69% at 6 months and 60% at 12 months, and the overall persistence rates (non-discontinuation of biosimilar therapy) were 77% and 71%. Thirty-seven of the 89 patients who switched discontinued their first biosimilar: 22 switched back to the reference product, 3 discontinued adalimumab therapy, 12 switched to another biosimilar, and 2 were lost to follow-up. The most frequent causes of discontinuation were injection site pain (25%), loss of efficacy (7%), and difficulties with a new injection device (4.5%). Four patients (13%) discontinued due to abdominal pain, which was considered a nocebo effect because of the lack of objective disease activity.

At baseline, 84 (94%) of the 89 patients who accepted the switch were in clinical remission, 79 (89%) were in remission at 6 months, and 76 (85%) at 12 months. Sixty eight of 82 (83%) switched patients with CRP data were in biochemical remission at baseline, 48 (83%) of 58 at 6 months, and 42 (86%) of 49 at 12 months. One of the 8 patients who declined to switch was lost to follow-up, and the other seven remained on the originator at 12 months and remained in clinical and biochemical remission.

Of the 38 patients who completed the questionnaire at the end of the study, 66% reported a positive experience with switching to a biosimilar, 2.6% reported a positive impact on their disease, and 16% reported a negative impact.

The results suggest having a poor opinion of generics could lead to not accepting a switch to a biosimilar. The authors said the high rates of clinical and biochemical remission they observed at 12 months suggest that switching did not have a negative impact on disease control. Additionally, the majority of patients who switched and were surveyed reported a positive experience. They commented that continuous patient education and healthcare providers addressing patients’ individual concerns, “is crucial for improving overall satisfaction with biosimilars and maximizing their benefits.”

D’Abbundo G, Nachury M, Wartski A, et al. Switch acceptance and persistence of adalimumab biosimilars in IBD patients: a prospective observational study. 

Patients with inflammatory bowel disease (IBD) show high acceptance of adalimumab biosimilars, achieving positive outcomes and clinical remission after switching.

High Acceptance Levels After Switching to an Adalimumab Biosimilar for IBD

 of patients with metastatic colorectal cancer (mCRC) suggested similar effectiveness between bevacizumab biosimilars and the reference product. The investigators said their results will help to build confidence in biosimilars for health care professionals using bevacizumab.

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), is “one of the mainstays” for managing mCRC, alongside chemotherapy. The reference product (Avastin) lost patent protection in India in 2016. Biosimilars have since become available, however, according to the authors, real-world evidence comparing outcomes to the originator remains “limited.”

The retrospective analysis included patients diagnosed with mCRC between 2017 and 2022 who received chemotherapy and bevacizumab at a single hospital in India. The primary endpoint was median progression-free survival (mPFS) of patients receiving bevacizumab during first-line treatment. Bevacizumab biosimilars included Bevacirel (Reliance Life Sciences), Bryxta (Zydus Cadila), and Versavo (Dr. Reddy's Laboratories).

Of the total 944 patients, 652 (69%) received bevacizumab during first-line therapy, 449 (48%) during second-line therapy, and 74 (8%) beyond second-line therapy. Most patients (810; 86%) were treated with biosimilars, and 132 (14%) were treated with the reference bevacizumab.

After a median follow-up of 18 months, mPFS was 10 months in patients receiving the originator and 9.3 months in those receiving biosimilars during first-line therapy, with no significant difference between groups (

 = .62). There was also no difference between groups in median overall survival (mOS), which was 17.8 and 18 months (

 = .85) for the originator and biosimilars. Similarly, among patients who received bevacizumab during second-line therapy, there was no significant difference between the reference product and biosimilars in mPFS (5.5 vs 5.8 month; 

The incidence of complications related to bevacizumab, such as hypertension, fistula, and stroke, was not different between groups. Although there were more perforations among patients treated with biosimilars, the authors commented that this included tumor perforations.

In this study, similar progression-free and overall survival outcomes between the reference product and biosimilars were observed, “providing oncologists with greater confidence to use these molecules in their clinical practice,” the authors wrote.

Vaidyanathan A, Vana P, Joshi N, Sourav B, Bhargava P, John G, Ramaswamy A, Ostwal V. Real-world evidence for comparative outcomes between innovator and biosimilar bevacizumab in advanced colorectal cancers. 

. 2025;13(4):296-299. doi:10.1055/s-0045-1804535

Real-world study reveals comparable effectiveness of bevacizumab biosimilars and Avastin in metastatic colorectal cancer (CRC), boosting clinician confidence.

Indian Study Finds Comparable Outcomes Between Reference, Biosimilar Bevacizumab in CRC

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 

 by an expert panel of gastroenterologists.

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.

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.

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.”

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. 

. 2025;14(5):1561. doi:10.3390/jcm14051561

There's a need for early anti-tumor necrosis factor (TNF) therapy in inflammatory bowel disease (IBD), with new data showing that biosimilars can address cost barriers and enhance patient access and outcomes.

Biosimilars Can Help Expand Early Access Anti-TNF Therapy in IBD

The monthly savings from a 100% conversion of Medicare patients with metastatic colorectal cancer (mCRC) and non-squamous metastatic non-small cell lung cancer (mNSCLC) from the reference bevacizumab (Avastin) to bevacizumab-bvzr (Zirabev; Pfizer) could fund 13,887 additional patient-months of treatment in mCRC and 8,959 in mNSCLC, concluded the authors of a cost-effectiveness 

Originator bevacizumab, a vascular endothelial growth factor inhibitor, is approved by the FDA for multiple solid tumor indications, including first-line treatment of mCRC in combination with fluorouracil-based chemotherapy, and first-line treatment of unresectable, locally advanced, recurrent, or mNSCLC in combination with carboplatin and paclitaxel. According to the authors, although bevacizumab has improved outcomes in mCRC and mNSCLC, treatment costs may exceed $11,000 per patient per month.

After the reference product lost exclusivity in the US in 2019, Zirabev was the first biosimilar to be approved by the FDA and enter the US market. Additional biosimilars have since been approved, including bevacizumab-adcd, bevacizumab-awwb, and bevacizumab-maly.

Medicare is one of the largest payers for bevacizumab therapy in the US, the authors said, spending approximately $700 million in 2022. Thus, the authors aimed to estimate cost savings and potential for expanded access to therapy associated with substituting a biosimilar for the originator.

The simulation model estimated cost savings from using bevacizumab-bvzr or alternative biosimilars (bevacizumab-awwb, -maly, or -abcd) in place of the originator. They used Medicare enrollment data, SEER cancer incidence data, and the 2024 average sales price (ASP) to estimate numbers of patients expected to be treated and costs.

Assuming a 100% market shift from the originator to bevacizumab-bvzr, the per-patient per-month (PPPM) cost savings compared to the originator were $4,205 in mCRC. For the full mCRC cohort, the monthly savings were estimated at $27,664,432, a 68% reduction in cost. The number needed to convert (NNC) was 47 to treat an additional 100 patients with bevacizumab-bvzr + FOLFOX.

In mNSCLC, the mean PPPM savings were $8,410, and monthly savings in the full cohort were $32,319,323, a 70% reduction in cost compared to the reference product. The NNC to treat an additional 100 patients with bevacizumab-bvzr + paclitaxel + carboplatin was 43.

Bevacizumab-bvzr had the lowest ASP of the bevacizumab biosimilars. The cost savings associated with converting to bevacizumab-bvzr exceeded those for the alternative biosimilars in both indications. NNCs in mCRC for alternative biosimilars ranged from 60 to 4,564 and 55 to 4,422 in mNSCLC. “Medicare can potentially achieve the greatest degree of budget-neutral expanded access to bevacizumab through increased use of bevacizumab-bvzr,” the authors wrote.

Overall, bevacizumab biosimilars were more cost-effective than the reference product in all scenarios the authors modeled, and bevacizumab-bvzr was the most cost-effective for treating both mCRC and mNSCLC. The authors said the substantial cost savings to Medicare from converting from the reference product to bevacizumab-bvzr could be reinvested to treat more patients or fund other costs in Medicare on a budget-neutral basis, and that the cost savings could be passed on to patients to improve the affordability of treatment.

Roth JA, Kratochvil D, Dorman S, Bernauer M. Cost-efficiency and expanded access modeling of conversion to biosimilar bevacizumab in metastatic colorectal and non-squamous non-small cell lung cancer in Medicare. 

. 2025;28(1):378-386. doi:10.1080/13696998.2025.2474884

Monthly savings from fully converting Medicare patients with metastatic colorectal cancer (CRC) and non-squamous metastatic non-small cell lung cancer (NSCLC) from reference bevacizumab to bevacizumab-bvzr could fund 13,887 and 8,959 additional patient-months of treatment, respectively, according to a cost-effectiveness study.

Switching From Avastin to Bevacizumab-bvzr in CRC, NSCLC Can Reduce Medicare Costs

 on the future of ustekinumab biosimilars for treating Crohn disease (CD) discussed key challenges, including a lack of data in CD and opportunities to improve access to treatment.

The authors of a review article on the future of ustekinumab biosimilars for treating Crohn disease (CD) discussed key challenges, including a lack of data in CD and opportunities to improve access to treatment. | Image credit: sdecoret - stock.adobe.com

CD, under the category of inflammatory bowel disease (IBD), is a chronic inflammatory condition of the gastrointestinal tract. The advanced therapeutic options for moderate to severe CD, biologics targeting tumor necrosis factor (TNF)-α (infliximab, adalimumab, and certolizumab), integrins (vedolizumab and natalizumab), and interleukins (ustekinumab), have become “the primary financial burden associated with IBD management,” the authors said.

Ustekinumab is a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23. The reference product (Stelara) was first approved by the FDA and European Medicines Agency (EMA) in 2009. Both agencies approved ustekinumab for treating CD in 2016.

Ustekinumab can be used in biologic-naive patients and those who have had treatment failure on another biologic. However, the authors said that due to high costs, ustekinumab is usually reserved for situations in which a patient has had treatment failure on 1 or more anti-TNF biologics. The originator’s patent is nearing expiration, which opens the possibility of ustekinumab biosimilars that could reduce costs, increase access to therapy, and allow for earlier use of ustekinumab in the course of CD treatment.

“Robust evidence” shows that anti-TNF biosimilars are clinically equivalent to the reference product (Humira), the reviewers said. For ustekinumab biosimilars, comparable efficacy, safety, immunogenicity, and pharmacokinetics to the reference product have been demonstrated; however, their approval for CD is based on extrapolation, “and there is no real-world data available yet for this indication.”

The first ustekinumab biosimilar, ABP 654 (Wezlana), was approved by the FDA in November 2023. AVT04 (Uzpruvo) was approved by the EMA and FDA in 2024, making it the first ustekinumab biosimilar approved in Europe. Additional 

 are in development. For example, Celltrion’s 

is supported by a phase 3 randomized controlled trial (RCT) showing comparable efficacy to the originator in moderate-to-severe plaque psoriasis. Marketing authorization applications for Dong-A ST's DMB-311535 and Fresenius Kabi and Formycon's FYB20236 have been accepted by the EMA and will soon be entering the market.

Overall, according to the reviewers, ustekinumab biosimilars have shown similar pharmacokinetic features, safety profiles, efficacy, and immunogenicity compared to the reference product in studies on healthy subjects and those on patients with psoriasis. Real-world studies could “increase the confidence of gastroenterologists when adopting ustekinumab biosimilars to treat CD patients.”

The authors commented that although there are several biologics available, there is no “globally validated therapeutic algorithm” for treating patients with moderate to severe CD. TNF inhibitors are “generally considered the first-line therapy as they are safe and effective drugs and biosimilars are available which make them accessible.” However, a trial comparing ustekinumab and adalimumab found they were equally effective in patients with CD, and a better safety profile, tolerability, and persistence were observed for ustekinumab. “Based on these data, ustekinumab could emerge as a leading choice in CD,” the reviewers said.

Additional recently approved treatment options for CD therapy include the IL-23 inhibitor risankizumab. One trial found risankizumab superior to ustekinumab for achieving endoscopic remission in patients with CD who were previously treated with anti-TNF biologics, but another found no differences between mirikizumab and ustekinumab effectiveness in CD. The reviewers said more head-to-head trials will be necessary “to define the positioning of selective IL-23 inhibitors” in CD treatment. Since 

 biosimilars are not yet available, among IL-23 inhibitors, ustekinumab biosimilars have a cost advantage.

The reviewers concluded that ustekinumab biosimilars “could be considered as first-line therapy for patients with IBD requiring advanced treatment,” increasing access and changing the drug’s positioning in the CD treatment algorithm. They added that real-world studies of ustekinumab biosimilars in IBD are needed to confirm long-term safety data.

D'Amico F, Bencardino S, Gonçalves A, Allocca M, Furfaro F, Zilli A, Parigi TL, Fiorino G, Peyrin-Biroulet L, Danese S. Unlocking hope: The future of ustekinumab biosimilars in Crohn's disease treatment. 

 2025;13(2):186-200. doi:10.1002/ueg2.12682

Future Directions for Ustekinumab Biosimilars in Crohn Disease

 of safety results from the VOLTAIRE clinical trials described the results of a recent 

 of safety data in patients with rheumatoid arthritis (RA), Crohn disease (CD), and chronic plaque psoriasis, which found no differences in safety outcomes between adalimumab-adbm (Cyltezo) and the reference product (Humira).

Image credit: New Africa - stock.adobe.com

The purpose of the summary, according to authors from Boehringer Ingelheim, is to help patients understand the findings and help health care professionals make treatment decisions. The summary included concise explanations of the results and their meaning, the conditions included, study designs, and definitions of biologics, biosimilars, interchangeability, and adverse events. It also provided links to external resources, including the original pooled safety publication and plain language summaries of the individual VOLTAIRE trials.

Biosimilars referencing adalimumab, a monoclonal antibody targeting tumor necrosis factor-α, first entered the US market in 2023, and Cyltezo was the first adalimumab biosimilar to gain the 

The 5 VOLTAIRE clinical trials compared effectiveness and safety of continually receiving the adalimumab originator to switching one or more times between the originator and Cyltezo in patients with RA (VOLTAIRE-RA, VOLTAIRE-RAext), Crohn disease (VOLTAIRE-CD), and chronic plaque psoriasis (VOLTAIRE-X, VOLTAIRE-PsO). Pooled safety results of all five trials were 

 in November 2024. The authors of the summary explained that the data was pooled “to provide a better understanding of the overall safety” of adalimumab-adbm.

Across all VOLTAIRE clinical trials, there were 1368 participants, 645 in VOLTAIRE-RA, 147 in VOLTAIRE-CD, 317 in VOLTAIRE-PsO, and 259 in VOLTAIRE-X. The pooled analysis evaluated total and serious adverse events (AEs), discontinuation of treatment due to AEs, deaths, and AEs of special interest, which included serious infections, cancers, and major adverse cardiac-related events. The researchers also investigated whether there were any differences in safety based on sex or age group.

In the pooled analysis, rates of AEs, serious AEs, and discontinuations were similar in patients with RA and chronic plaque psoriasis, regardless of whether they were treated with Cyltezo or the originator. Patients with CD had “slightly higher” rates of AEs, serious AEs, and discontinuations than the other two conditions in both biosimilar and reference product groups. There were no significant differences in deaths between conditions or between biosimilar and reference product groups. There were also no significant differences in safety outcomes between treatments in patients who were 65 or older, or those who were under 65.

Cancers and major adverse cardiac-related events were only reported in patients with RA and were not significantly different between treatment groups. Serious infections were reported in patients with RA and chronic plaque psoriasis, and there were no significant differences between groups. There were no AEs of special interest observed in patients with CD.

Limitations of the VOLTAIRE trials discussed by the authors included that the participants were predominantly white, thus the results may not be representative of all patients, and that the findings may not be applicable to patients with autoimmune conditions other than those included in the trials. When explaining the meaning of the results, the authors said since there were no differences in safety outcomes between biosimilar and reference product groups across the VOLTAIRE trials, patients with RA, CD, and chronic plaque psoriasis who take Cyltezo can expect similar side effects to those of the reference product.

Cohen S, Bender S, Shaberman A, Vinisko R, McCabe D. A plain language summary of the pooled safety results of adalimumab-adbm from the VOLTAIRE clinical trials in people with rheumatoid arthritis, Crohn's disease, and chronic plaque psoriasis. 

. 2025;25(4):323-329. doi:10.1080/14712598.2025.2476033

A plain language summary for patients explains there were no differences in safety outcomes between adalimumab-adbm and the originator in a pooled analysis of the VOLTAIRE clinical trials.