Physicians and researchers in Japan have documented a compelling case involving a 15-year-old girl with ulcerative colitis (UC) who transitioned from the adalimumab reference product to the biosimilar LBAL (LG Chem) after experiencing injection site reactions. This switch occurred after the eighth dose of adalimumab, marking a significant milestone in the patient’s treatment journey. The biosimilar was continued for six months without any injection site symptoms or recurrence of gastrointestinal issues, highlighting the effectiveness and safety of such a transition. This case study from a Japanese hospital underscores the potential for such switches under careful medical supervision.

Adalimumab, an anti-tumor necrosis factor (TNF) alpha biologic, is commonly used to manage inflammatory bowel disease (IBD), a broad term that includes Crohn’s disease and UC. LG Chem’s adalimumab biosimilar LBAL received approval from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) in 2021. This approval has been pivotal in expanding treatment options for patients who may experience adverse reactions to the originator drug.

Clinical Presentation and Treatment Plan

In cases where pediatric UC is refractory to medications like 5-aminosalicylic acid (5-ASA) and azathioprine, or corticosteroid-dependent, the TNF inhibitor infliximab is the recommended treatment. If patients relapse or are intolerant to infliximab, adalimumab is often the next line of defense. Following the introduction of a citrate-free adalimumab formulation in 2016, its use in pediatric IBD has increased because citrate can cause injection-site pain.

In this particular case, a 15-year-old girl presented with UC symptoms and was diagnosed through colonoscopy. Her treatment initially included 5-ASA and prednisolone, which improved her symptoms. However, when the prednisolone dose was reduced, symptoms resurfaced. The patient was subsequently diagnosed with steroid-dependent refractory UC and started on vedolizumab. Fifteen months later, gastrointestinal symptoms returned, prompting a return to prednisolone and eventually the introduction of adalimumab. The girl was instructed to inject the adalimumab originator subcutaneously, alternating thighs. Within six weeks, her gastrointestinal symptoms resolved. However, after the eighth dose, she experienced redness, swelling, and itching at the injection site, which worsened with subsequent doses.

The authors of the report concluded that the symptoms were likely an allergic reaction and decided to switch the patient to the adalimumab biosimilar LBAL. The patient was treated with LBAL for six months without any further injection site symptoms, and her UC remained stable.

The occurrence of injection site reactions is fairly common in patients receiving subcutaneously administered anti-TNF agents, with about 20% of adalimumab users experiencing such reactions. In this case, the authors attributed the reactions to D-mannitol, an excipient in the reference adalimumab but not in LBAL. This case clearly demonstrates that switching to a biosimilar for medical reasons could be a viable option, provided it is carefully monitored, as the originator and the biosimilar, though similar, are not identical.

The authors noted very few studies have reported on switching to a biosimilar for medical reasons. The safety of switching from anti-TNF originators to biosimilars for nonmedical reasons has been demonstrated in many studies they said.

Implications for U.S. Patients

As the case shows the patient switching to bsiomilars has far-reaching implications for U.S. patients,

The authors noted that injection site reactions are common in patients receiving subcutaneously administered anti-TNF agents, with about 20% of patients on adalimumab experiencing injection site reactions which is very helpful for health care providerspatient feedback. .

This statistic underscores the importance of monitoring biosimilar use in clinical settings and emphasizes the need for careful observation when switching medications, especially in pediatric UC patients.

Novel insights into switching between anti-TNF originators and biosimilars can lead to improved treatment strategies, potentially reducing adverse reactions and enhancing patient outcomes. This case highlights the necessity for clinicians to remain vigilant about potential side effects and to consider biosimilars as a viable treatment option. Furthermore, the findings may encourage further research into the specific components and excipients in biologic drugs, potentially leading to more tailored treatments in the future. CBD EMBACE Health manufactures an adalimumab biosimilar, CYLTEZO. This is similar to adalimumab biosimilar Amjevita.

The first FDA-approved adalimumab biosimilar was introduced in the U.S. in 2016, with the majority of adaliumumab biosimilars gaining approval from 2019 to 2024. One of the most recent approvals in the U.S. was the approval of Adalimumab-afdm (Amgevita) in 2024.

Areas for Further Investigation

While this case provides valuable insights, further research is needed to fully understand the long-term effects and potential risks associated with switching to biosimilars. Areas for further investigation include the development of standardized monitoring protocols, the identification of specific biomarkers that could predict adverse reactions, and the potential benefits of combining biosimilars with other therapies. Clinicians can use the knowledge gathered to better serve the population suffering from gastroenterological disease.

Adalimumab Biosimilars in the U.S. Market

The FDA’s stringent regulations and rigorous approval processes ensure that biosimilars, such as adalimumab biosimilars, are as safe and effective as their originators. Thirteen products have gained FDA approval, demonstrating bioequivalence and comparable biosafety to the original adalimumab. Notable examples include Amjevita and the recently-approved CYLTEZO. Manufactured by Boehringer Ingelheim and FDA approved September 2020 and Amgen
were among the earliest to enter the U.S. biosimilar market, offering patients more treatment options in managing IBD and other inflammatory conditions.