At the Academy of Managed Care Pharmacy (AMCP) annual meeting last week, several posters bolstered existing real-world evidence that biosimilar adalimumab was associated with similar outcomes to those of Humira, and that may translate into the absence of any significant nocebo effect.
Only 2% Switched Back to Humira
Researchers from Employers Health, Columbus, Ohio,1 evaluated the results of switching from the reference product Humira to a biosimilar adalimumab. They analyzed pharmacy claims data from 284 self-insured employers over a 14-month period who excluded Humira from coverage. This research identified over 2,400 members with adalimumab prescriptions. The investigators found that 79% switched to the preferred biosimilar adalimumab, 9% instead began taking a different biologic (i.e., product hopped), 5% stepped through the preferred biosimilar to another branded biologic, and only 2% switched back to Humira after using the preferred biosimilar. Of the 56 patients who switched back to Humira, one-third had rheumatoid arthritis vs. 20% who had Crohn’s disease.
The researchers analyzed the prior authorization data for the most common reasons for switching back to the reference product. Inadequate efficacy (68%, 38 patients) or intolerable side effects (25%, 14 patients). Assuming at least a portion of these patients experienced non-nocebo-related side effects or treatment failure, it can be confidently said that fewer than 2% of those receiving biosimilar adalimumab experienced nocebo effects.
More Patients Discontinued Biologic Treatment Than Switched to Another Biologic
Another retrospective pharmacy claims study found similar switch-back results, this time from the PBM Navitus Health Solutions and the University of Kentucky. These investigators evaluated claims from three commercial plans, focusing on patients who had been receiving Humira for at least 6 months before a mandated transition to biosimilars in June 2024.2
Three months after the exclusion of the reference product, 94% of 504 eligible patients had switched; 21 discontinued biologic treatment, 9 switched to another biologic, and 2 continued to take Humira (assumedly by medical exception). Of the 472 switching to the biosimilar, 41 (8.7%) discontinued by 3 months, with 29 stopping any biologic therapy and 12 moving to another biologic treatment. In only 7 reported cases, treatment was discontinued by either patient or provider decision, and in only 1 case were side effects cited (however, no documentation was available in 26 cases). For those who switched therapy to another class, 71% chose an interleukin inhibitor. The researchers noted that 91% of these patients indicated they were satisfied with their new biosimilar treatment after the transition.
Low Side-Effect Rates for Biosimilar Adalimumab
In early 2023, Kaiser Permanente became one of the first major payers to exclude Humira from coverage and replace it with the available adalimumab biosimilar manufactured by Amgen (Amjevita). As reported previously, Kaiser’s conversion rate was rapid and nearly complete. In a poster presented by Kaiser Permanente National Clinical Pharmacy Services, they detailed patient efficacy and safety outcomes, pointing to the lack of a nocebo effect among more than 2,300 patients receiving adalimumab therapy for rheumatoid arthritis before or after the new policy was enacted.3
In one year of follow-up, they found that disease worsening occurred in 24.8% of patients taking the biosimilar versus 31.0% of those in the reference group who received Humira in the previous 7 years. (The study was not powered to determine superiority, only noninferiority). Furthermore, the incidence of composite side effects or complications was 5.6 events per 100 person-years for those taking the biosimilar compared with 7.2 events per 100 person-years for those receiving Humira.
These AMCP-presented findings would imply that patients taking the adalimumab biosimilar certainly did not experience a greater incidence of side effects or complications or lower efficacy, which would be hallmarks of a significant nocebo effect.
References
1. Brewster E, Berger C, Keefe C, et al. Preliminary real-world evidence on the pharmacy benefit uptake of biosimlar products for self-insured employers. Poster U56. Presented at the 2025 annual meeting of the Academy of Managed Care Pharmacy, Houston, Texas, April 1-3, 2025.
2. Arzt J, Siwak A, Wickizer M, et al. Real-world clinical outcomes of an adalimumab biosimilar transition program. Poster D20. Presented at the 2025 annual meeting of the Academy of Managed Care Pharmacy, Houston, Texas, April 1-3, 2025.
3. Pham C, Niu F, Delate T, et al. Clinical and out-of-pocket cost outcomes of patients with rheumatoid arthritis who switched to biosimilar adalimumab-atto from reference product adalimumab. Poster M3. Presented at the 2025 annual meeting of the Academy of Managed Care Pharmacy, Houston, Texas, April 1-3, 2025.
