Robert Zutaut, RPh, a clinical specialist from McKesson Provider Solutions, quantifies the major barriers to adoption for biosimilars used to treat rheumatoid arthritis (RA) and some major considerations for health systems looking to address them.
The utilization of biosimilars for rheumatoid arthritis (RA) vs what was anticipated has been less than expected. To date, 4 biosimilars for the reference product Remicade(infliximab) have received FDA approval, but only 3 are available on the US market.1 Although these medications have no clinically meaningful differences with their reference biologics and cost significantly less, biosimilar adoption by rheumatologists has been slow due to factors such as a lack of comfort with the product, patient concerns, and misinformation around biosimilars.2
However, there is new opportunity on the horizon with the introduction of adalimumab biosimilars referencing Humira, the newest RA biosimilars to enter the market. Hopefully, there will be more acceptance of the biosimilar product than seen in the past, and the comfort level of rheumatologists will grow as more biosimilars enter the market. Only time will tell, and while there are no easy solutions, taking a closer look at some of the challenges to RA biosimilar uptake may shed some light on how progress can be made.
A major obstacle: The nocebo effect
A phenomenon in medicine called the nocebo effect may play a role when it comes to biosimilar resistance, creating challenges for rheumatologists because of possible negative patient outcomes associated with brand changes. The nocebo effect describes a situation where a real adverse reaction actually happens due to the patient’s belief the intervention will cause harm.3 It arises oftentimes when a patient is switched from one product to another product with equivalent efficacy and safety. Changing to something different after a patient has been on a certain product for a long period of time creates a mindset that causes the patient to think the new medication does not work as well as the original, even though the products are essentially identical.
In oncology, this situation may not be a big problem because the physician can use scans and lab tests to verify what is actually happening and whether the medication is shrinking or stabilizing a tumor. With rheumatologists, however, much of what they do revolves around qualitative factors, such as asking the patient about their range of motion or pain level. Patients who have had their medication changed may respond negatively, indicating they are not doing as well with the new product. While these outcomes may not be caused by the actual impact of the disease, in the patient's mind that is what is happening. This may cause patients to be reluctant to even try a biosimilar because they fear it will not work as well as their original medicine.
Education is key
Part of this misunderstanding and fear may be curable with the proper education targeting both physicians and patients. All FDA-approved biosimilars may have minor differences from the reference product, but they must be highly similar to the original drug and also have no clinically meaningful differences from the reference product in terms of safety and effectiveness.4 Explaining this to patients should help alleviate anxiety and increase trust in the treatment.
The second part of the solution involves directing more education to rheumatologists and the entire care team, especially concerning the biosimilar approval process. Some mistakenly believe biosimilars do not undergo all the necessary safety and efficacy trials, leaving them thinking these drugs may not be as safe or effective as the original medicines.
More pharmacist involvement would be beneficial in educating both the care team and patients, highlighting the rigorous approval process biosimilars undergo. This would be especially helpful to patients, as adding the voice of these very credible pharmacists into the discussion may lessen some of the anxiety patients have.
Biomarkers could drive targeted treatments and biosimilars
The National Cancer Institute defines a biomarker “as a biological molecule present in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.”5 Biomarkers can be diagnostic and predictive, and they are often used to determine how well a patient may respond to a specific treatment, enabling a more personalized therapy. Biomarkers have informed clinical trial designs, leading to great progress resulting in numerous biomarker-based targeted therapies and immunotherapies during the last decade.6
Biomarkers are now playing a critical role in the treatment of many diseases, especially cancer, but unfortunately, not RA. To date, there are only a few blood tests that even indicate the RA disease state, and there is nothing that could be called biomarker-specific that guides using one medication over another. The primary test today for RA is built around identifying the rheumatoid factor, which is used to diagnosis arthritis. Two other tests can then be employed to determine if the disease is progressing or if it is responding to treatment. Basically, the tests give an indication the patient has the disease and then help measure how much inflammation is present.
As strides are made in advancing biomarkers for RA—something that is obviously still years away—more effective targeted therapies will hopefully emerge that will eventually also drive the development of biosimilars. For the time being, however, manufacturers are continuing to focus on tissue necrosis factor products such as infliximab and adalimumab. As long as these products are working effectively, other manufacturers will most likely look very closely at whether there is a sufficient return on investment to search for a breakthrough.
Acceptance will take time
The acceptance of biosimilars will be reliant on the same thing everything new relies on, namely common experience. As biosimilars are used more and more often over a longer period of time, the acceptance level will increase. There must always be pioneers and innovators—the ones who step forward and start doing something first. Biosimilars will most likely follow a path similar to generics years ago. Initially there was a lot of patient distrust around the use of generic products, but pharmacists were able to stem that tide through patient education. Today when patients get a prescription filled, one of the first things they ask is whether a generic is available. Hopefully, time and experience will eventually bring biosimilars to the point where they will just be another acceptable part of the patient’s treatment plan.