Humira Biosimilar Uptake Surges After CVS Formulary Change, Then Declines Amid Nocebo Effect Concerns
核心洞察
Adalimumab biosimilar prescriptions among commercially insured patients rose from near 0% to over 25% in the month following the CVS Caremark (搜索) formulary change in early 2024, then fell by 12.3 percentage points the next month.
Among new biosimilar users, adalimumab-adaz (Hyrimoz) prescriptions increased to 24% after the formulary change but subsequently dropped by nearly 14 percentage points, suggesting a nocebo effect driving patients back to the originator.
Researchers from UCSF analyzed data from 22,079 patients in the RISE registry and found slow, linear increases for other adalimumab biosimilars, with even smaller uptake among Medicare-insured individuals.
The first meaningful increase in adalimumab biosimilar uptake in the United States occurred after CVS Caremark (搜索) announced its national formulary change in January 2024—but the initial surge was not sustained, according to new research published in Arthritis Care & Research.
Prescriptions for adalimumab-adaz (Hyrimoz, Sandoz) among commercially insured patients jumped from close to 0% to more than 25% in the month immediately following the formulary change. However, the following month saw a decrease of 12.3 percentage points for that same medication, indicating that many patients switched back to the originator product.
"Adalimumab is the highest-grossing drug in history, and legal battles delayed the market launch of biosimilar competition by about 6 years," said Eric T. Roberts, PhD, MPH, of the University of California San Francisco. "Understandably, the community was extremely excited about the potential for cost savings when biosimilars finally did launch in 2023. However, that excitement quickly gave way to confusion when there was nearly no uptake in the first year of availability."
Study Design and Population
Roberts and colleagues examined data for 22,079 patients drawn from the Rheumatology Informatics System for Effectiveness (RISE) registry of electronic health records. The analysis assessed the proportion of patients prescribed adalimumab-adaz or other adalimumab biosimilars each month between January 2023 and September 2024, with findings stratified by payor and use among new users.
Divergent Trends by Payor and User Type
The researchers observed a slow and linear increase in prescriptions for other adalimumab biosimilars over the study period. A "similarly timed" trend was noted among individuals insured by Medicare, though the increase in prescriptions for both adalimumab-adaz and other biosimilars was even smaller in this population.
For new biosimilar users, close to 0% were prescribed adalimumab-adaz at the outset of the study period. This figure increased to 24% in the first month after the CVS formulary change, but then decreased by nearly 14 percentage points in the following month. Prescriptions for other biosimilars increased 0.6 percentage points per month throughout the study duration.
The Nocebo Effect and Patient Trust
Roberts pointed to the nocebo effect—a phenomenon whereby negative expectations regarding a treatment lead to the perception or experience of worsened symptoms—as a likely driver of the reversal.
"Importantly, the biosimilar version CVS covered had similar product characteristics, being citrate-free, offered with a smaller gauge needle, and offered as a high concentration formula, which are all known to influence patient satisfaction, suggesting product features are not causing the switch back to originator adalimumab," Roberts said.
He emphasized that multiple studies document equivalent safety and effectiveness of biosimilars. "This information needs to be properly conveyed to patients to help smooth future biosimilar rollouts. Clinician and patient trust in biosimilars is necessary to ensure robust marketplace competition."
Broader Implications for Biosimilar Policy
Vibeke Strand, MD, FACP, MACR, of Stanford University, who was not involved with the study, noted that the impact of the 2024 CVS formulary change has not developed as the rheumatology community expected. "We had hoped for changes based on demonstrated use in the Kaiser and VA systems," she said. "Finding out what really happened is fascinating."
Strand highlighted the contribution of the nocebo effect, particularly among those who return to the originator adalimumab. "I see this among some colleagues at the Veterans Health Administration, where they personally are skeptical of biosimilar benefits," she said. "I also am very struck, as I have lectured, on the huge effect pharmacy benefit managers have on this process."
She added: "We are not likely to benefit from biosimilar use until we can fix the PBM situation, not to mention the co-pay issues, and administrative burdens to practices."
Roberts urged rheumatologists to engage with elected representatives about barriers to open market competition, including National Drug Code blocks, interchangeability designations, and prior authorization requirements.