Biosimilar multi-switching is a go

4 minute read

A new RCT looking at adalimumab multi-switching shows no problems.

Multiple switching between reference adalimumab and a biosimilar had similar outcomes to using the reference biologic alone, according to an international study in rheumatoid arthritis patients.

In the first such multi-switching study for adalimumab reference vs a biosimilar in RA patients, a research team led by Professor Roy Fleischmann of the University of Texas Southwestern Medical Center confirmed that the Pfizer Abrilada biosimilar “can be expected to produce the same clinical results as reference adalimumab in any given patient”.

“Our findings indicate that the risk of diminished efficacy (using pharmacokinetics as a surrogate) or safety when making multiple switches between reference adalimumab and [the biosimilar] adalimumab-afzb was not greater than the risk when using reference adalimumab alone,” wrote the authors in the Lancet Rheumatology.

“The efficacy, safety, tolerability, and immunogenicity of adalimumab-afzb are shown to be clinically equivalent to reference adalimumab, suggesting that adalimumab afzb provides an effective biosimilar alternative for patients requiring adalimumab therapy.”

The 32-week open-label study took place in 10 countries and included patients who’d had moderate to severe RA for at least four months and were on a stable dose of methotrexate.

The study was conducted according to FDA requirements for interchangeable designation. It comprised a lead-in period where all patients were treated with the reference biologic, after which they were then randomly assigned to either continue with the reference biologic or switch between the reference biologic and biosimilar three times.

Around 400 patients finished the lead-in period with the reference adalimumab (Humira, AbbVie) and were allocated 1:1 to the switching group or non-switching group. The switching group changed to the biosimilar (Abrilada, Pfizer) after 10 weeks, back to the reference at 16 weeks, and finally to the biosimilar at 22 weeks until the end of the study treatment period (32 weeks).

The primary pharmacokinetic endpoints were maximum observed serum concentration and area under the plasma concentration–time curve over the dosing interval.

These measures were a presumptive surrogate for efficacy and could determine the risk of diminished efficacy in the switching group relative to the non-switching group.

Secondary endpoints included time of maximum observed serum concentration, average serum concentration, apparent clearance over a two-week intensive sampling period and immunogenicity, with safety and tolerability also measured. There was no validated clinical efficacy endpoint.

Researchers found that there was essentially no difference in any of the outcomes, with the 90% confidence intervals of the geometric mean ratios of the primary pharmacokinetic endpoints within the standard prespecified equivalence margin of 80–125%. Rates of adverse events and dropouts were similar for both groups.

“With the increasing availability of biosimilars, the key question for clinicians and patients is whether repetitive switching between biosimilar and reference product is safe and effective. This study shows that multiple switches between adalimumab-afzb and reference adalimumab did not increase adverse events or affect the pharmacokinetics of either molecule adversely,” wrote the authors.

However, the authors made clear that their findings only applied to the investigational biosimilar and broader applications were unknown.

“This study did not address whether switching between multiple biosimilar products and the reference molecule also fits within these parameters. Additional data are needed to explore the effect of multiple switching in various scenarios.”

In Australia, there are eight adalimumab biosimilars listed on the ARTG, with five (plus the reference product) currently available on the PBS.

Biosimilars offer cost-saving benefits to the healthcare system, allowing greater access to the drugs and potentially lower out-of-pocket costs to patients in some countries.

Modelling based on volume sales data and PBS pricing data for the Australian healthcare system for seven calendar years, from 2015 to 2021, suggested there was $1 billion in savings generated by the use of biosimilars instead of reference drugs across seven different products, which included adalimumab.

The main benefit for Australian RA patients is that biosimilars have lower authority requirements – after the first two written applications you can get them on Streamline. Upcoming changes will see patients on biosimilars able to get their initial script via phone or online approval, rather than written, with all continuing scripts good to go with a streamline code.

An Australian Rheumatology Association Database (ARAD) patient survey found that while most patients (up to 82%) weren’t aware of biosimilars, they were generally willing to consider using them if recommended by their rheumatologist.

Lancet Rheumatology 2023, September

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