Skylar Jeremias is the Managing Editor for The Center for Biosimilars and The American Journal of Managed Care (AJMC).

Skylar Jeremias

The launch of adalimumab biosimilars in the United States in 2023 marked a pivotal moment for health care cost savings and patient access, promising to disrupt the long-standing dominance of the originator biologic, Humira.

However, a recent analysis from Truveta, spanning data through April 2025 unveils a concerning trend: more than 13% of patients who initially switched to an adalimumab biosimilar ultimately reverted to the reference drug.

While the Truveta findings hint at patient dissatisfaction or adverse events, they leave crucial questions unanswered: Are the biosimilars themselves to blame? | Image Credit: Maksym - stock.adobe.com

While the Truveta findings hint at patient dissatisfaction or adverse events, they leave a crucial question unanswered: Are the biosimilars themselves to blame? Delving into these critical missing pieces can offer a more comprehensive understanding of the evolving adalimumab biosimilar landscape and the true implications of patient switching patterns.

The research analyzed switching patterns from bio-originator Humira to its biosimilars, finding a significant increase in biosimilar adoption, particularly peaking in April 2024 due to a major formulary change by CVS Health.

 Although biosimilar switching rates remained elevated compared to 2023, the study revealed that a notable proportion of patients—13.2% of those who initially switched—subsequently returned to reference drug Humira.

This "switching back" phenomenon was more prevalent among specific patient demographics: older adults (aged ≥ 65 years), women, and individuals with rheumatoid arthritis or ankylosing spondylitis. A key finding was the rapid nature of these switchbacks, with nearly 40% occurring within 30 days of initiating a biosimilar. Truveta researchers suggested potential early dissatisfaction, adverse events, or patient resistance and uncertainty regarding the new medication. Rural patients also showed higher rates of early switchbacks compared with urban patients.

The study highlighted that although biosimilar uptake is growing, sustained use faces challenges. Patient perceptions, clinical uncertainty, and factors like pharmacy stock or complex health conditions in older adults may contribute to patients reverting to the originator. Understanding these real-world experiences is crucial for promoting broader and more sustained biosimilar adoption, despite clinical trials showing no meaningful differences in safety or efficacy between biosimilars and the originator.

At first glance, the analysis provides a stark insight into the switching patterns of patients receiving adalimumab treatments but there is a significant lack of investigation into the possible reasons behind patients switching back. Although there are mentions of patient perceptions and adverse events after switching to a biosimilar, there is missing context for whether the biosimilars themselves are to blame for patients’ choosing to switch back to Humira. Without this context, it could be implied that biosimilars fail for more than 10% of patients who switch to them, calling into question the safety and efficacy of switching to biosimilars generally.

Overall, a major factor that can cause a patient to switch back from a biosimilar to the reference agent is the nocebo effect, a phenomenon where a patients’ negative opinions about a drug lead to perceived worsened clinical outcomes or adverse events.

Many studies, several of which concern switching between Humira and an adalimumab biosimilar,

 have looked at reference product to biosimilar switching and have found the nocebo effect to be the main cause for patients who switched back, suggesting that switching between biologic products of the same molecule is safe despite some patients still choosing to go back to Humira. Additionally, these studies are often conducted with patients undergoing multiple switches back and forth between products, which is an FDA data requirement to obtain interchangeability status.

Interchangeability is a regulatory designation that allows for pharmacies to exchange a reference product with an approved biosimilar version without waiting for a provider to approve the change first.

 The policy is intended to give patients easier access to their medications and provide pharmacies with better flexibility to deal with supply chain issues and drug shortages. Of the 10 adalimumab biosimilars currently on the market, 8 have interchangeability designations (Cyltezo, Hadlima, Hyrimoz, Simlandi, Yuflyma, Abrilada, Hulio, and Amjevita).

In addition, all states, as well as Puerto Rico, have individual laws regarding interchangeability, most of which concern requirements for patient and/or provider notification that a switch has occurred.

 Currently, 44 states either do not require patients to be notified or require patients to be notified but do not require them to give their consent for the switch, creating a breeding ground for the nocebo effect to occur in chronic patient populations who are typically unaware of what a biosimilar even is. These patients may also have taken many years and treatment failures to settle on a medication that works for them, and a new brand name or injector device could be jarring and anxiety-inducing.

Private labeling has also become popular in the ustekinumab space, another market in which a large number of biosimilars launched within the same year. | Image credit: New Africa - stock.adobe.com

Although Truveta did not look into how interchangeability played into their results,

 it could be worth investigating as the FDA and other governmental bodies consider whether the US should continue to allow interchangeability policy or to follow in the footsteps of the European Union and UK, where regulatory agencies have declared all biosimilars interchangeable.

Additionally, although Truveta did point out that CVS announced that its pharmacy benefit manager Caremark chose to prioritize adalimumab biosimilars on formulary over Humira as a big reason for growing adalimumab biosimilar adoption,

 it left out the several other PBMs that followed suit, overlooking the full extent of how the industry has been bolstering adalimumab biosimilars for success. Notably, the report omitted information on how PBMs Express Scripts, Optum Rx, Prime Therapeutics, Smith Rx, as well as private label pharmacies such as CarePartners Specialty Pharmacy and the Mark Cuban Cost Plus Drug Company have all chosen at least 1 adalimumab biosimilar to embrace.

 In fact, private labeling has also become popular in the ustekinumab space, another market in which a large number of biosimilars launched within the same year.

Sustaining the Biosimilar Momentum: Addressing Perceptions and Policy

The Truveta analysis, although shedding light on the increasing uptake of adalimumab biosimilars, underscores the intricate challenges of maintaining patient adherence. The seemingly high rate of patients reverting to originator Humira, particularly those experiencing early switchbacks, could, at first glance, cast a shadow on biosimilar efficacy and safety.

 However, a deeper dive into the market dynamics reveals that these switchbacks are often less about inherent biosimilar failure and more about the powerful influence of patient perception and the nuances of policy implementation.

Ultimately, the real-world data on adalimumab switchbacks serves as a vital call to action.

 To truly unlock the full potential of biosimilars in the US health care system, stakeholders must move beyond simply encouraging the initial switch. A concerted effort is needed to educate both patients and providers about the robust science underpinning biosimilar safety and interchangeability, actively mitigating the nocebo effect through transparent communication.

Furthermore, ongoing evaluation of interchangeability policies, potentially aligning with the broader European approach of universal biosimilar interchangeability, could further streamline access and build sustained patient confidence. By addressing these challenges, the US adalimumab biosimilar market might be able to fulfill its promise of delivering high-quality, affordable care to the masses.

1. Jeremias S. US welcomes first adalimumab biosimilar, Amjevita. The Center for Biosimilars

. January 31, 2023. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/us-welcomes-first-adalimumab-biosimilar-amjevita

2. Truveta Research. Biosimilar use is on the rise – but 1 in 8 patients return to Humira. Truveta Research. June 23, 2025. Accessed June 29, 2025. 

https://www.truveta.com/blog/research/research-insights/biosimilar-use-humira/

3. CVS to remove Humira from some reimbursement lists in favor of biosimilar options. The Center for Biosimilars. January 6, 2024. Accessed June 29, 2025 . 

https://www.centerforbiosimilars.com/view/cvs-to-remove-humira-from-some-reimbursement-lists-in-favor-of-biosimilar-options

4. Jeremias S. 13 strategies to avoid the nocebo effect during biosimilar switching. The Center for Biosimilars. December 18, 2024. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/13-strategies-to-avoid-the-nocebo-effect-during-biosimilar-switching

5. Jeremias S. Etanercept biosimilar switch shows stable outcomes and disease control in RA. The Center for Biosimilars. May 13, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/etanercept-biosimilar-switch-shows-stable-outcomes-and-disease-control-in-ra

6. Ferreri D. Switching from Avastin to bevacizumab-bvzr in CRC, NSCLC can reduce Medicare costs. The Center for Biosimilars. May 10, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/switching-from-avastin-to-bevacizumab-bvzr-in-crc-nsclc-can-reduce-medicare-costs

7. Ferreri D. High acceptance levels after switching to an adalimumab biosimilar for IBD. The Center for Biosimilars. June 14, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/high-acceptance-levels-after-switching-to-an-adalimumab-biosimilar-for-ibd

8. Jeremias S. New data support Hulio as an interchangeable adalimumab option. The Center for Biosimilars. June 16, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/new-data-supports-hulio-as-an-interchangeable-adalimumab-option

9. Considerations in demonstrating interchangeability with a reference product. FDA. May 2019. Accessed June 29, 2025. 

https://www.fda.gov/media/124907/download

10. Interchangeable biological products. FDA. Accessed June 29, 2025. 

https://www.fda.gov/media/151094/download

11. Jeremias S. Happy Birthday adalimumab biosimilars: reflecting on the first year of US competition. The Center for Biosimilars. January 31, 2024. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/happy-birthday-adalimumab-biosimilars-reflecting-on-the-first-year-of-us-competition

12. Biosimilar interchangeability laws by state. Cardinal Health. Updated January 2024. Accessed June 29, 2025. 

https://www.cardinalhealth.com/en/product-solutions/pharmaceutical-products/biosimilars/state-regulations-for-biosimilar.html

13. Mazzoni D, Vener C, Mazzocco K, Monzani D, Pravettoni G. The psychological risks associated with the non-medical switch from biologics to biosimilars. 

14. Biosimilar medicines can be interchanged. EMA. September 19, 2022. Accessed June 29, 2025. 

https://www.ema.europa.eu/en/news/biosimilar-medicines-can-be-interchanged

15. Guidance on the licensing of biosimilar products. UK MHRA. Accessed June 29, 2025. 

https://www.gov.uk/government/publications/guidance-on-the-licensing-of-biosimilar-products/guidance-on-the-licensing-of-biosimilar-products

16. Jeremias S. The Age of adalimumab is upon us: how stakeholders can prepare. The Center for Biosimilars. June 28, 2023. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/the-age-of-adalimumab-is-upon-us-how-stakeholders-can-prepare

17. Jeremias S. Welcome Wezlana: the first Stelara biosimilar to launch in the US. The Center for Biosimilars. January 31, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/welcome-wezlana-the-first-stelara-biosimilar-to-launch-in-the-us

18. Jeremias S. Eye on pharma: interchangeability, private labels, and patent settlements for biosimilars. The Center for Biosimilars. May 9, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/eye-on-pharma-interchangeability-private-labels-and-patent-settlements-for-biosimilars

19. Jeremias S. European data confirm real-world benefits of adalimumab biosimilars. June 11, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/european-data-confirms-real-world-benefits-of-adalimumab-biosimilars

Articles

About 13% of patients who switch from Humira to an adalimumab biosimilar switch back to the originator, according to research from Truveta. However, the presented data may not tell the full story.

Adalimumab Double Take: The Unexpected Return to Reference Humira

Alvotech and Advanz Pharma have announced a positive Committee for Medicinal Products for Human Use (CHMP) opinion for their aflibercept biosimilar, AVT06, aiming for European approval. Concurrently, Amneal Pharmaceuticals shared positive clinical trial results for Kashiv BioSciences' omalizumab biosimilar, ADL-018, targeting the US market, while Bio-Thera Solutions and SteinCares have partnered to bring a dupilumab biosimilar to Latin America.

Alvotech and Advanz Pharma announced that the European Medicines Agency's CHMP has issued a positive opinion, recommending approval for AVT06, a proposed biosimilar to Eylea (aflibercept, 2 mg).

 The decision brings the companies closer to marketing the biosimilar in the European Economic Area for various eye conditions, including wet age-related macular degeneration and diabetic macular edema. Alvotech is responsible for development and supply, while Advanz Pharma handles registration and commercialization in Europe.

“CHMP’s positive opinion takes us a step closer to being able to market our proposed biosimilar in Europe, which is excellent news for patients and their caregivers,” commented Joseph McClellan, chief scientific officer of Alvotech. The recommendation follows positive results from a 2024 clinical study confirming AVT06's therapeutic equivalence to Eylea, a drug with global sales of approximately $9 billion in 2024.

AVT06 is a recombinant fusion protein designed to bind vascular endothelial growth factors, thereby inhibiting abnormal blood vessel growth and vascular permeability, which are key mechanisms in the progression of various eye disorders. Alvotech is also developing AVT29, a biosimilar candidate for Eylea HD (aflibercept, 8 mg), and Advanz Pharma holds the distribution rights for both biosimilar candidates in the same European territories. The European Commission will make the final decision on European approval for AVT06.

Amneal Shares Results for Omalizumab Biosimilar

Amneal Pharmaceuticals has announced positive topline results from a pivotal clinical trial for ADL-018, a proposed biosimilar to reference omalizumab (Xolair), developed by Kashiv BioSciences.

 The study, involving patients with chronic idiopathic or spontaneous urticaria, successfully met its primary and secondary end points, demonstrating therapeutic equivalence and comparable safety between ADL-018 and reference omalizumab. This represents a crucial step toward making an omalizumab biosimilar available in the US.

Amneal anticipates submitting a biologics license application to the FDA in Q4 2025 and holds exclusive US commercialization rights. With Xolair's US annual sales reaching approximately $3.9 billion, ADL-018 is poised to be a significant addition to Amneal's biosimilar portfolio, enhancing access to this vital treatment.

Omalizumab is a humanized monoclonal antibody targeting free IgE indicated for various allergic conditions, including severe allergic asthma, chronic rhinosinusitis with nasal polyps, food allergies, and chronic spontaneous urticaria. Expanded access to omalizumab could significantly benefit patients and health care systems by offering a more affordable treatment alternative for these conditions.

Bio-Thera and SteinCares Join Forces on Dupilumab

Bio-Thera Solutions and SteinCares have forged a new agreement to commercialize a proposed dupilumab biosimilar across Latin America. This marks their fourth collaboration, underscoring a shared commitment to enhancing access to affordable, high-quality therapies in the region. Bio-Thera will handle product development and supply, while SteinCares will manage registration and commercialization throughout Latin America.

Mitchell Waserstein, CEO of SteinCares, emphasized that the partnership reinforces their position as a leading biosimilar platform in the region, aiming to make advanced therapies more accessible and affordable. Given dupilumab's status as 1 of the top 5 medicines globally by annual sales, this biosimilar represents a significant milestone for SteinCares' expansion, potentially aiding in the treatment of chronic inflammatory conditions in both adults and children.

1. European Medicines Agency recommends market approval of AVT06, Alvotech’s proposed biosimilar to Eylea (aflibercept). Press release. Alvotech; June 23, 2025. Accessed June 26, 2025. 

https://www.globenewswire.com/news-release/2025/06/23/3103152/0/en/European-Medicines-Agency-Recommends-Market-Approval-of-AVT06-Alvotech-s-Proposed-Biosimilar-to-Eylea-aflibercept.html

2. Amneal highlights positive topline results from confirmatory clinical study of biosimilar candidate to Xolair (omalizumab), developed by Kashiv BioSciences. Press release. Amneal Pharmaceuticals; June 25, 2025. Accessed June 26, 2025. 

https://www.globenewswire.com/news-release/2025/06/25/3105002/0/en/Amneal-Highlights-Positive-Topline-Results-from-Confirmatory-Clinical-Study-of-Biosimilar-Candidate-to-XOLAIR-R-omalizumab-Developed-by-Kashiv-BioSciences.html

3. Bio-Thera Solutions and SteinCares expand partnership to commercialize biosimilars for treatment of inflammatory diseases across Latin America. Press release. Bio-Thera Solutions; June 25, 2025. Accessed June 26, 2025. 

https://www.prnewswire.com/news-releases/bio-thera-solutions-and-steincares-expand-partnership-to-commercialize-biosimilars-for-treatment-of-inflammatory-diseases-across-latin-america-302490693.html

Regulators and manufacturers advance biosimilars for aflibercept, omalizumab, and dupilumab, enhancing access to treatment in Europe and Latin America.

Eye on Pharma: CHMP Aflibercept Decision; Omalizumab Results; Dupilumab Biosimilar Deal

Infliximab biosimilar initiation among pediatric patients with inflammatory bowel disease (IBD) rose gradually from 1% in 2018 to nearly 42% in 2023, with no consistent differences by age, race, or ethnicity and notable regional variation, according to a retrospective study.

, incorporated data from the ImproveCareNow (ICN) Network, a multicenter pediatric IBD quality improvement collaborative.

Pediatric IBD is becoming increasingly common, with an incidence of about 10 cases per 100,000 children in the US and Canada and a rising trend | Image credit: Art_Photo - stock.adobe.com

Pediatric IBD is becoming increasingly common, with an incidence of about 10 cases per 100,000 children in the US and Canada and a rising trend.

 In the US alone, IBD prevalence ranges from 100 to 200 per 100,000 children—amounting to an estimated 70,000 affected children—meaning that most pediatricians are likely to encounter and care for patients with IBD in their practice.

Access to FDA-approved treatments for pediatric IBD remains limited, as tumor necrosis factor-α inhibitors are currently the only class of medications approved for use in children with Crohn disease and ulcerative colitis, despite the availability of multiple therapeutic options for adults.

 Additionally, a 2018 survey by the Crohn’s and Colitis Foundation found that pediatric IBD providers were less comfortable prescribing biosimilars than their adult-care counterparts, likely due to the limited experience with biosimilars in children and the scarcity of pediatric-specific safety and efficacy data.

Although infliximab biosimilars offer a promising opportunity to reduce drug costs and expand treatment access, their uptake in pediatric populations has been slow, in part because of provider hesitancy, limited pediatric-specific efficacy and safety data, and regulatory and educational barriers.

 This retrospective cohort study was conducted to assess patterns in the initiation of infliximab biosimilars among a large pediatric IBD cohort and to determine whether differences in use existed by age, race, ethnicity, or geographic region.

Researchers prospectively collected data from 2016 to 2023 within the ICN Network to evaluate patterns in the initiation of infliximab originator and biosimilars among children and young adults with IBD, using statistical tests to assess differences by age, race, ethnicity, IBD phenotype, region, and year, while excluding patients with prior infliximab use, incomplete data, or enrollment at centers with limited infliximab prescribing.

“A notable strength is that data in the ICN Network registry are collected prospectively by clinicians. The ICN Network represents one of the largest pediatric IBD registries in existence and includes both large academic medical centers as well as small hospital-based and private practices, truly reflective of the real-world nature of pediatric IBD care,” the authors wrote.

Out of 26,256 pediatric IBD patients in the ICN registry, 4602 patients from 73 US-based centers met the study criteria and were included in the analysis. The study population was 45% female, with a median age of infliximab initiation of 13.7 years. Most patients had Crohn disease (70%). Between 2016 and 2023, 3807 patients began treatment with the infliximab originator, while 795 patients started on a biosimilar. No meaningful clinical differences were observed between the 2 groups.

Despite the introduction of infliximab biosimilars in late 2016, their uptake was initially minimal—rising from just 1% of infliximab initiations in 2018 to nearly 42% by 2023. Infliximab-dyyb (Inflectra; Celltrion) was the most commonly used biosimilar. While biosimilar use was generally consistent across age groups, a statistically significant difference was observed in 2020, likely due to the small number of children under age 6 initiating therapy that year. Similarly, 2020 was the only year with a significant difference in biosimilar use by race, with higher usage among patients categorized as “other.” No consistent differences in biosimilar use by ethnicity were observed. However, regional variation was evident, with the Midwest, West, and Southwest regions consistently initiating biosimilars at higher rates than the Northeast and Southeast from 2020 onward.

Cumulatively, just 17.3% of patients initiating infliximab from 2016 to 2023 were started on a biosimilar, reflecting a gradual but uneven adoption. The number of ICN centers using biosimilars increased significantly—from just 1 center in 2016 to 59 centers (88.1%) by 2023. The percentage of centers with very low biosimilar use (fewer than 10% of patients) steadily declined, while the number of centers with moderate (25%-69%) or high (70%-100%) biosimilar adoption grew notably. By 2023, more than half of centers had at least 25% of infliximab initiators starting on a biosimilar, highlighting a clear trend toward broader, though still variable, uptake.

This study had several limitations, including potential biases stemming from differences in how ICN centers consented patients and recorded infliximab product use, which may have led to underreporting—particularly for biosimilars like infliximab-axxq that were not explicitly tracked in the registry. The accuracy of the real-world data could not be independently verified, and missing race (8%) and ethnicity (4.6%) data may have affected analyses of disparities. Additionally, insurance type was recorded only at diagnosis, not at the time of infliximab initiation, limiting the ability to assess its influence on biosimilar use.

1. Maltz RM, Saeed SA, Adler J. infliximab biosimilar utilization in a large pediatric learning health system. 

. 2025;12(5):656. doi:10.3390/children12050656

2. Rosen MJ, Dhawan A, Saeed SA. Inflammatory bowel disease in children and adolescents. 

2015;169(11):1053-1060. doi:10.1001/jamapediatrics.2015.1982

3. Malter L, Jain A, Cohen BL, et al. Identifying IBD providers' knowledge gaps using a prospective web-based survey. 

. 2020;26(9):1445-1450. doi:10.1093/ibd/izaa032

Pediatric infliximab biosimilar use has risen significantly, reflecting evolving treatment patterns in inflammatory bowel disease (IBD) among children and young adults.

Increasing Biosimilar Use Reflects Changing Practice in Pediatric IBD Care

CT-P39, an omalizumab biosimilar, and reference omalizumab demonstrated comparable efficacy, pharmacokinetics, pharmacodynamics, safety, and immunogenicity, as well as quality of life impact, in patients with chronic spontaneous urticaria, as confirmed by a 16-week follow-up of a phase 3 trial.

Omlyclo is approved in the European Union, Canada, and the US. | Image credit: NATALYA - stock.adobe.com

CT-P39, also known as Omlyclo, was approved by the European Medicines Agency in May 2025 as the first omalizumab biosimilar.

 The biosimilar was also approved by Health Canada in December 2024 and the FDA in March 2025.

The present international, multicenter, double-blind, randomized, active-controlled, parallel-group study, 

, sought to confirm that Omlyclo can perform with the same safety and efficacy as the original product.

 Access to omalizumab, an effective biologic for chronic spontaneous urticaria, can be limited by its high cost, prompting the development of biosimilars like CT-P39 to improve affordability and access. According to Novartis’ financial records, global sales for reference omalizumab (Xolair) in 2024 amounted to $4.4 billion, making it the seventh highest-grossing immunology product in the world.

The study involved 619 patients with chronic spontaneous urticaria across two 12-week treatment periods and a 16-week follow-up, in which patients received subcutaneous injections of either CT-P39 or reference omalizumab at 150-mg or 300-mg doses, with rerandomization or dose escalation in the second period. Throughout the study, efficacy, quality of life, pharmacokinetics, pharmacodynamics, safety, and immunogenicity were assessed using patient-reported outcomes, clinical monitoring, and blood analyses, with results summarized descriptively through week 40.

Of the 619 patients randomized, 554 (89.5%) entered the 16-week follow-up phase, and 518 (83.7%) completed the full study through week 40, with completion rates ranging from 80.6% to 88.7% across all treatment groups. Discontinuation rates and reasons were similar between groups, with the most common reason during follow-up being categorized as “other.”

Efficacy outcomes such as weekly itch severity scores, urticaria activity scores, and hives severity scores improved significantly during the 24-week treatment periods, which gradually declined during follow-up but remained better than baseline values, with no clinically meaningful differences between CT-P39 and reference omalizumab groups. At week 40, the number of antihistamine tablets used as rescue therapy remained lower than baseline in all groups, and fewer than 10% of patients in any group required an additional nonsedating H1-antihistamine as background therapy. Improvements in quality-of-life measures, including Dermatology Life Quality Index and Chronic Urticaria QoL Questionnaire, followed a similar pattern—peaking during treatment and partially declining by week 40, yet not returning to baseline levels.

Pharmacokinetic data showed a dose-related increase in omalizumab serum trough concentrations during treatment, followed by a gradual decrease after treatment cessation, with end-of-study mean concentrations ranging from 2.74 µg/mL (initial reference product 300-mg maintenance group) to 4.11 µg/mL (reference omalizumab 150-mg group). Pharmacodynamic results demonstrated a 2- to 3-fold increase in total immunoglobulin E (IgE) during treatment, with levels gradually decreasing during follow-up, while free IgE, which decreased during treatment, began to return to baseline after week 24 in all groups.

Safety profiles were consistent across groups during the follow-up period, with similar proportions of patients experiencing at least 1 treatment-emergent adverse event (TEAE). The most frequently reported TEAEs (≥ 2%) were COVID-19, headache, nasopharyngitis, tonsillitis, and upper respiratory tract infection. Serious TEAEs occurred in up to 3.1% of patients in any group and were considered unrelated to the study drug. No deaths, anaphylactic reactions, serum sickness, or parasitic infections were linked to the study treatment. One patient died by suicide, previously reported and determined unrelated to the drug. Injection-site reactions, the most common related TEAE, occurred only during the treatment period.

Immunogenicity analysis showed that the majority of patients tested negative for antidrug antibodies at week 40. Antidrug antibody positivity rates were 6.9% in the CT-P39 300-mg group, 1.5% in the reference omalizumab 300-mg group, 3.1% in the switched group (ref-OMA to CT-P39), 0% in the reference omalizumab maintenance group, 6.5% in the CT-P39 150-mg group, and 1.9% in the reference omalizumab 150-mg group.

The authors stated, “The overall safety profile of CT-P39 continues to be consistent with the known safety profile of omalizumab, with no new or unexpected concerns during the whole study period and no new safety findings, including after switching to CT-P39 from [reference omalizumab].”

1. Grattan C, Dytyatkovska Y, Springer M, et al. Efficacy and safety of CT-P39, an omalizumab biosimilar, in chronic spontaneous urticaria: 16-week follow-up study. 

. June 2, 2025. Accessed June 24, 2025. doi:10.1002/clt2.70069

2. Celltrion receives European Commission approval of Omlyclo (CT-P39), the first and only omalizumab biosimilar approved in Europe. Press release; Celltrion. May 24, 2025. Accessed June 23, 2025. 

https://celltrion.com/en-us/company/media-center/press-release/3246

3. Jeremias S. Health Canada approves first omalizumab biosimilar. The Center for Biosimilars®. December 16, 2024. Accessed March 7, 2025. 

https://www.centerforbiosimilars.com/view/health-canada-approves-first-omalizumab-biosimilar

4. Jeremias S. FDA approves first omalizumab biosimilar. The Center for Biosimilars. March 7, 2025. Accessed June 24, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-first-omalizumab-biosimilar

5. Novartis annual report 2024. Novartis. January 30, 2025. Accessed June 23, 2025. 

https://www.novartis.com/sites/novartiscom/files/novartis-annual-report-2024.pdf

6. Rashid A, Shashikumar S, Xie V, Kovacevic V. Top 10 best-selling immunology drugs by recent sales data. Xtalks. January 2, 2025. Accessed June 23, 2025. 

https://xtalks.com/top-10-best-selling-immunology-drugs-by-recent-sales-data-4025/

CT-P39, an omalizumab biosimilar, shows comparable efficacy and safety to the original in treating chronic spontaneous urticaria, enhancing patient access.

Omalizumab Biosimilar Matches Reference Product in Chronic Spontaneous Urticaria

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

Overcoming barriers to insulin access and adherence—particularly with biosimilar insulins—requires robust real-world evidence (RWE) and purpose-built data systems to improve diabetes outcomes and inform health policy, according to a review.

As of June 2025, there are 3 insulin biosimilars approved in the US: 2 insulin glargine (Semglee and Rezvoglar) and 1 insulin aspart (Merilog). | Image credit: Antto-AI - stock.adobe.com

, was conducted to address persistent challenges in realizing the full benefits of insulin therapy and to emphasize the importance of RWE in evaluating the safety, efficacy, and cost-effectiveness of biosimilar insulins. By highlighting current usage patterns, identifying critical data gaps, and proposing the development of purpose-built diabetes registers supported by trained clinical teams, the authors aim to strengthen real-world data infrastructure that can guide more equitable, timely, and effective diabetes care and policy.

As of June 2025, there are 3 insulin biosimilars approved in the US: 2 insulin glargine (Semglee and Rezvoglar)

According to the review, well-designed diabetes registers are essential for generating reliable RWE to guide clinical decisions, improve care quality, and inform health policies, especially in the use of cost-effective treatments like biosimilar insulins.

 Unlike unstructured electronic health records (EHRs), purpose-built registers ensure consistent data collection, enabling the assessment of treatment effectiveness, safety, adherence, and health care costs. When linked with EHRs and claims data, registers can track disease progression, identify care gaps, and evaluate interventions at both patient and population levels. With regulatory bodies increasingly recognizing RWE as critical for approval and policy decisions, robust diabetes registers are key to advancing data-driven, personalized diabetes care.

Recent RWE highlights key trends in insulin use, particularly among people with type 2 diabetes (T2D). Over the past 2 decades, there has been a clear shift from insulin monotherapy to combination therapy with oral glucose-lowering drugs across multiple regions, including Japan, the US, and Italy. Although insulin use as a first-line treatment has remained stable, its use as a second-line therapy is rising. Patterns vary regionally: Japan and the US show declines or stable use, while Hong Kong and Denmark report modest increases. There’s also been a notable global shift from human insulin to long-acting and fast-acting insulin analogues, especially in high-income countries. Basal-bolus regimens are increasingly common in people with T2D, while basal-only regimens are the most common treatment option for people with T2D. Concentrated insulin formulations are also gaining traction, especially in insulin-resistant populations.

Biosimilar insulin use is rising, especially in the US and Canada, where policy mandates have driven uptake. In contrast, adoption remains modest in Europe and many parts of Asia, reflecting variability in regulation, physician preference, and market access. Despite their cost benefits, biosimilars are still underused globally. These shifts underscore the need for better data from low- and middle-income countries, where most people with diabetes live, to understand global insulin use patterns and improve equitable access.

Insulin biosimilars match originators in efficacy and safety, including in insulin pumps, but real-world use remains low due to limited awareness and uptake. Despite being up to 64% cheaper, underutilization—seen even in countries like England and Spain—has prevented full cost savings. Therapeutic inertia, fear, stigma, and system-level barriers contribute to delays in insulin initiation and poor adherence, especially in lower-income regions. Nurse-led care and tech-based support improve outcomes, but provider education and trust in biosimilars remain essential. Compatibility with smart pens and novel delivery systems is still limited, hindering broader adoption.

Insulin needs vary across diabetes subtypes. People with type 1 diabetes require lifelong insulin due to absolute insulin deficiency, and incidence is rising globally, especially in low- and middle-income countries where access remains limited. Slowly progressing autoimmune diabetes (often misclassified as T2D) also leads to insulin dependence. Type 3c diabetes, linked to pancreatic disease, typically involves insulin deficiency and complex glucose regulation. Monogenic diabetes may require insulin, depending on the mutation, while around one-third of people with T2D will eventually need insulin due to progressive beta cell loss. Insulin use in T2D varies by age, duration, and region, with young-onset and older adults particularly affected.

Despite insulin’s century-old discovery, full benefits remain unrealized due to access, cost, and care quality barriers. The authors said that optimizing insulin use will require comprehensive phenotyping, timely initiation, and individualized management supported by education, monitoring tools, and emerging biosimilar options that may improve affordability and access.

The authors concluded, “Scientific evaluation with regulatory approval is critical in ensuring the quality of these technologies; it is here where diabetes registers implemented by a trained doctor–nurse team with system support can become an invaluable tool to assess the impacts of these technologies on clinical outcomes, quality of life and health care costs to inform practice and policies.”

1. Yang A, Yu J, Cheung JTK, Chan JCN, Chow E. Real world evidence of insulin and biosimilar insulin therapy—opportunities to improve adherence, outcomes and cost-effectiveness. 

. Published online April 15, 2025. doi:10.1111/dom.16386.

2. Hagen T. FDA approves Semglee insulin glargine as first interchangeable biosimilar. The Center for Biosimilars

. July 28, 2021. Accessed June 17, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-semglee-insulin-glargine-as-first-interchangeable-biosimilar

3. Rezvoglar broadens insulin glargine biosimilar options. The Center for Biosimilars. December 30, 2021. Accessed June 17, 2025. 

https://www.centerforbiosimilars.com/view/rezvoglar-broadens-insulin-glargine-biosimilar-options

4. Jeremias S. FDA approves first insulin aspart biosimilar. The Center for Biosimilars. February 17, 2025. Accessed June 17, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-first-insulin-aspart-biosimilar

Explore how real-world evidence and biosimilars enhance insulin access and adherence, improving diabetes care and outcomes for patients who have type 2 diabetes.

Strengthening Diabetes Care With Purpose-Built Data Infrastructure

Celltrion announced the FDA had approved a new formulation of Steqeyma (ustekinumab-stba), a biosimilar to Stelara (ustekinumab). The approval, for a 45 mg/0.5 mL solution in a single-dose vial for subcutaneous injection, significantly broadened dosing flexibility for pediatric patients aged 6 to 17 years who weigh less than 60 kg and live with plaque psoriasis (PsO) or psoriatic arthritis (PsA). 

"Managing inflammatory diseases in pediatric patients can be particularly complex due to varying body weights and specific developmental needs," stated Hetal Patel, PharmD, MBA, vice president of medical affairs at Celltrion USA. | Image credit: WESTOCK - stock.adobe.com

The company stated that the strategic expansion ensures that Steqeyma now aligns with all existing dosage forms and strengths of its reference product, providing enhanced options for health care providers and individuals managing these chronic inflammatory conditions.

The FDA's decision marked a pivotal moment for pediatric dermatology and rheumatology, offering a precise dosing solution for a vulnerable patient population. Prior to this latest approval, in December 2024, the FDA had already granted approval for Steqeyma in 45 mg/0.5 mL and 90 mg/mL solutions in single-dose prefilled syringes for subcutaneous injection and a 130 mg/26 mL solution in a single-dose vial for intravenous infusion.

These initial approvals covered adult and pediatric patients aged 6 years and older with PsO and PsA, as well as adult patients with Crohn disease and ulcerative colitis. The addition of the new 45 mg/0.5 mL single-dose vial specifically addresses the nuanced requirements for precise weight-based dosing in smaller pediatric patients.

"Managing inflammatory diseases in pediatric patients can be particularly complex due to varying body weights and specific developmental needs," stated Hetal Patel, PharmD, MBA, vice president of medical affairs at Celltrion USA.

 "This new dosage form and strength of Steqeyma allows us to better meet the specific needs of young patients, giving physicians a valuable treatment option with flexibility, supported by a well-established safety and efficacy profile." This sentiment underscored the commitment to patient-centered care, a priority for managed care organizations focused on optimizing health outcomes and treatment adherence.

Thomas Nusbickel, chief commercial officer at Celltrion USA, emphasized the broader impact of the approval. "We are proud to offer a new presentation of Steqeyma that aligns with the indications of the reference product. This approval reinforces our commitment to broadening access for all patient populations, including children aged 6 years and older living with chronic inflammatory conditions."

The FDA’s approval of Steqeyma was built upon a comprehensive body of evidence, including the results from a phase 3 study conducted in adults with moderate to severe PsO. This study demonstrated that Steqeyma and the reference product exhibited high similarity, confirming no clinically meaningful differences in terms of safety and efficacy among adult individuals.

A key development for formulary decision-makers was the FDA’s decision to grant Steqeyma full interchangeability with Stelara across all its indications.

 Interchangeability status allows for direct pharmacy-level substitution, further simplifying access and potentially reducing health care costs.

The expanded approval of Steqeyma for pediatric patients represents a significant advancement in the treatment landscape for individuals living with PsO and PsA. By providing a full complement of dosage forms and strengths, Celltrion aims to enhance treatment continuity and improve access to a crucial therapeutic option, aligning with the core objectives of managed care to deliver high-quality, cost-effective care.

1. Celltrion announces U.S. FDA approval of additional presentation of Steqeyma (ustekinumab-stba), expanding dosing options for pediatric patients. Press release. Celltrion; June 15, 2025. Accessed June 17, 2025. 

https://www.prnewswire.com/news-releases/celltrion-announces-us-fda-approval-of-additional-presentation-of-steqeyma-ustekinumab-stba-expanding-dosing-options-for-pediatric-patients-302481004.html

2. Jeremias S. FDA approves Steqeyma: the seventh Stelara biosimilar. The Center for Biosimilars

. December 18, 2024. Accessed June 17, 2024. 

Celltrion's FDA approval of Steqeyma enhances pediatric psoriasis treatment, offering flexible dosing options for children with chronic inflammatory conditions.

Skylar Jeremias

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Increasing Biosimilar Use Reflects Changing Practice in Pediatric IBD Care

Omalizumab Biosimilar Matches Reference Product in Chronic Spontaneous Urticaria

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

Strengthening Diabetes Care With Purpose-Built Data Infrastructure

FDA Approves Steqeyma for Children With Plaque Psoriasis, Psoriatic Arthritis

Eye on Pharma: Keytruda Biosimilar Deal; German Court Bans Imraldi; New Biosimilars for Japan

New Data Support Hulio as an Interchangeable Adalimumab Option

European Data Confirm Real-World Benefits of Adalimumab Biosimilars