TNFI biosimilars for the treatment of RA have been on a tear lately, with more than a half dozen Humira biosimilars released in 2023 alone.
Although more research needs to be done, RA biosimilars are likely as safe and effective as reference products.
A mix of legal, regulatory, patient, and clinician issues have hindered the uptake of biosimilars in the US.
Rheumatoid arthritis (RA) is a debilitating inflammatory disease, which targets the joints and erodes quality of life. Across the world, there are about 20 million people with the disease. Although effective and safe in the treatment of RA, tumor necrosis factor-α inhibitors (TNFIs) are expensive, which limits patient access.
Biosimilar drugs have the potential to lower the costs of TNFIs and improve access to therapy. These drugs are recommended by international guidelines. Nevertheless, more research needs to be done, as recommendations to date primarily rely on single trials or expert consensus, with only a few recommendations relying on meta-analysis, according to the authors of a recent article published in JAMA Network Open.
In 2023, a spate of adalimumab (Humira) biosimilars hit the market, with seven TNFI biosimilars hitting the market in July alone.
These biosimilars are expected to stoke competition in the space, with the expectation to relieve the financial burden of those struggling with RA, psoriatic arthritis, ulcerative colitis, Crohn's disease, and similar.
According to an article published in Managed Healthcare Executive, the wholesale acquisition cost of Humira is nearly $7,000 for 4 weeks of treatment. Amgen and Biocon Biologics stated that they would sell Humira biosimilars at two prices. The first price is a small discount, and the other is an 85% discount, which results in a cost of about $12,500 per year. The higher price is ostensibly a before-rebate price for pharmacy-benefit managers, who will pay less after rebates/other discounts.
To date, only one of these biosimilars—or adalimumab-adbm (Cyltezo)—is designated as interchangeable.
According to the FDA, an interchangeable biosimilar can be swapped out for the original product without prescriber input, akin to how generic drugs are routinely substituted for brand name counterparts (ie, pharmacy-level substitution). Such substitution is governed by state pharmacy laws.
“Both biosimilars and interchangeable biosimilars are as safe and effective as the original biologic they were compared to, and they can both be used in its place. This means that health care professionals can prescribe either a biosimilar or interchangeable biosimilar product instead of the original biologic,” advises the FDA.
Although rheumatologists are generally accepting of biosimilars, uptake differs globally. In Europe, biosimilar usage is higher than the rest of the world, due to the EU’s established biosimilar market and liberal policies, according to an editorial published in The Lancet Rheumatology. Overall in 2020, 92% of EU clinicians said they prescribed biosimilars to at least 25% of RA patients. This percentage is up from 70% of EU clinicians in 2018 who prescribed biosimilars to at least 25% of RA patients.
In the US, the biosimilar milieu involves various regulatory complexities and patient/legal challenges.
Even though the FDA greenlighted biosimilars years ago, patient litigation stopped their introduction to the US market, thus undermining competition and limiting accessibility to Americans who need these medications.
Overall, 90% of Americans have health insurance, but 60% still have trouble paying for medications. Today, biosimilars represent only 2% to 3% of the market, with low uptake becoming the norm, according to the Lancet authors.Related: That's debatable! Doctors dissect 5 hot topics in rheumatology
The root of opposition to biosimilars involves mandatory switching in patients with stable disease (ie, mandatory switching). This opposition to interchangeability was lodged by the American College of Rheumatology (ACR) and rheumatologists alike. In contrast, the European Medicines Agency unilaterally allows biosimilars to be automatically interchanged. The rigamarole reflects the FDA practice of requiring multiple switching studies before serving up a biosimilar or interchangeable designation.
Unfortunately, such testing is expensive and uncommon. Today, only three biosimilars for any indication are considered interchangeable.
“The rheumatology community has raised valid concerns around non-medical switching, with many believing it will negatively impact quality of care, including effectiveness, side-effects and medication adherence,” the Lancet authors write. “Another concern is that it will compromise physicians' autonomy in clinical decision making. Lack of understanding and fear of the unknown have also triggered uncertainties for patients. In a 2019 survey, 79% of patients reported that they attempted to avoid non-medical switching.”
The authors advise education is necessary for both patients and rheumatologists to ease the transition into this “new phase of health care,” noting that the FDA has a plethora of resources on interchangeable biosimilars. The authors also note that relying on pharmacies can help ease the burden on the healthcare system overall, as it will allow patients to access necessary medications much more quickly.
What the research says
Analysis on the use of biologics in RA is limited, with only four systematic reviews in the literature including data from head-to-head trials of biosimilars vs reference products. One notable example is the meta-analysis and systematic review published in JAMA Network Open in May 2023. These researchers included 25 randomized clinical trials representing 10,642 RA patients taking biosimilars for adalimumab, etanercept, and infliximab vs their reference biologic drugs.
The JAMA Network Open authors wrote, “Our review shows up-to-date conclusive evidence on the equivalence between biosimilars and their reference biologics via bayesian meta-analysis using prespecified margins of equivalence and trial sequential analysis. Overall, our results are in line with the conclusions that both biosimilars and reference biologics are equally valuable for RA treatment.”
What this means for you
Although biosimilars for the treatment of RA are likely to be just as effective and safe as reference products, for various reasons, their uptake in the US has been slow. Many patients in the US (and worldwide) have trouble affording these medications, thus experts recommend that physicians consider biosimilars when prescribing.
There is also a dearth of biologics for RA that are interchangeable, so rheumatologists must still make specific requests for biosimilars. For specialists, it may be a good idea to continue to follow clinical research on emerging biosimilars in the treatment of RA and other rheumatic disease, as well as policy that impacts their use, to better appreciate movements in this rapidly changing field.