Interchangeability, Adverse Event Considerations for Adalimumab Biosimilars in IBD

Eduardo Redondo-Cerezo

Credit: LinkedIn

A real-world study comparing adalimumab biosimilars to the reference drug in patients with inflammatory bowel disease (IBD) is highlighting greater persistence among those taking a biosimilar but similar clinical response rates and biomarker reductions.¹

Findings support the cost-effective use of biosimilars but also emphasize the importance of monitoring interchangeability and adverse event risks, calling attention to an increased frequency of severe adverse events among patients who switched from the reference drug to a biosimilar.¹

Initially earning FDA approval for Crohn disease in 2007 and ulcerative colitis in 2012, adalimumab biosimilars have recently hit the market and gained traction as cost-effective alternatives to the originator. However, biosimilar drugs are not identical replicas of their reference drug and require extensive research to determine potential differences in safety, clinical response, and biomarker changes.²

“The evaluation of drug persistence has not been a primary focus in most biosimilar studies conducted thus far. The majority of current research focuses on assessing the clinical efficacy and safety of switching from an originator drug to a biosimilar,” wrote Eduardo Redondo-Cerezo, teaching director and faculty of medicine at the University of Grenada in Spain, and colleagues.¹ “Limited research exists specifically on adalimumab biosimilars used exclusively for inflammatory bowel disease.”

To address this gap in research, investigators conducted a retrospective observational study at Virgen de las Nieves University Hospital between June 2018 - June 2020. Patients with moderate-to-severe IBD who were enrolled in the adalimumab local registry and received treatment with adalimumab were included. Investigators collected clinical, demographic, and serum parameters from participants’ digital clinical records.¹

Among the cohort (n = 104), the average age at treatment initiation was 41.9 (95% CI, 39.13-44.79) years and there was an even proportion of male and female participants. Crohn disease accounted for 73.1% of cases and ulcerative colitis comprised 26.9%. The average disease duration before commencing adalimumab treatment was 94.73 (95% CI, 76.62-112.83) months.¹

Patients were divided into 3 groups based on their use of abalimumab originator or biosimilar. Group A (n = 50) included patients treated exclusively with the biosimilar form of adalimumab, Group B (n = 29) included patients who only received the original adalimumab, and Group C (n = 25) included patients who initially received the reference adalimumab and switched to the biosimilar.¹

The total follow-up period extended for 48 weeks from the initiation of therapy. The primary outcome measure was persistence, but investigators secondarily assessed security, efficacy, and biomarkers.¹

At week 10, a total of 44.23% (n = 46) of patients displayed clinical response, while 33.65% (n = 36) exhibited clinical response at week 20. Additionally, global loss of response to adalimumab was 10.58% at week 20, most prevalent among Group C (50.5%).¹

Adequate or above-upper-limit serum adalimumab levels were observed in 72.2% (n = 39) of patients with available measurements, while 27.8% (n = 15) had infra-therapeutic levels. Anti-adalimumab antibodies were present in 5.5% (n = 3) patients.¹

In Group A, 28% of patients experienced treatment-emergent adverse events, most of which were mild. Group B exhibited a similar proportion of treatment-emergent adverse events (27.58%), although more were considered severe than Group A.¹

Investigators pointed out Group C, however, demonstrated the greatest overall percentage of patients experiencing a treatment-emergent adverse event (60%), with more than half of this proportion suffering from a severe adverse effect (36%). Of note, the difference in the occurrence of treatment-emergent adverse events was statistically significant between the groups (P = .009).¹

Investigators assessed drug persistence by calculating the discontinuation rate and the duration of treatment until discontinuation during the 48-week follow-up period. The overall survival rate of adalimumab treatment after 48 weeks was 80.2% in Group A, 62.1% in Group B, and 61.3% in Group C. Throughout the entire duration of the follow-up, 8% of patients from Group A, 38% of patients from Group B, and 36% of patients from Group C discontinued treatment, primarily due to loss of response or the development of severe adverse effects.¹

Notably, patients in Group A, demonstrated higher and more consistent persistence compared with the other groups, with investigators pointing out significant differences in the survival functions among these groups (P = .04).¹

“Our real-world observations indicate that when transitioning from an original to a biosimilar or when using multiple biosimilars interchangeably, there may be an increased risk of adverse effects, ultimately impacting treatment outcomes,” investigators concluded.¹

References:

1. ^{Fernández-Cano MC, Fernández-Cano AJ, Martín-Rodríguez MM, et al. Adalimumab Persistence and Its Biosimilar in Inflammatory Bowel Disease: A Real-World Study. Journal of Clinical Medicine. 2024; 13(2):556. https://doi.org/10.3390/jcm13020556}
2. ^{Drugs.com. Humira FDA Approval History. August 25, 2022. Accessed February 9, 2024. https://www.drugs.com/history/humira.html}