Robert Zutaut, RPh, a clinical specialist from McKesson Provider Solutions

Robert Zutaut, RPh

This article was originally published on Pharmacy Times

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Rheumatoid arthritis (RA), an autoimmune inflammatory disease that attacks the synovial tissues in the joints, is the most common form of autoimmune arthritis, affecting 1.3 million people in the United States.

 Rheumatologists often employ disease-modifying anti-rheumatic drugs (DMARDs) to slow disease progression, but many patients have an incomplete response. For those people, biologic DMARDs are usually prescribed, but these drugs are too costly for many, putting optimal disease management out of reach for this population.

To meet the need for more affordable biologIcs, biosimilar DMARDs were developed, reducing costs to allow more patients to access these critical therapies. So far, 4 biosimilars for the RA reference product Remicade have received FDA approval, but only 3 are currently available on the US market: Inflectra, Renflexis, and Avolsa.

Although these medications have no clinically meaningful differences with their reference biologics and offer significant cost advantages, adoption of these products by rheumatologists has been slow.

 Educating providers and patients about the biosimilar approval process could decrease patient resistance and increase the likelihood of rheumatologists embracing biosimilars.

Several more RA biosimilars will be released soon, and stakeholders remain cautiously optimistic. The impact of these biosimilars could be massive, both in terms of cost savings and health outcomes, so it is worthwhile to examine how pharmacists can help overcome obstacles blocking the uptake of these life-changing therapies.

Both rheumatologists and patients have been slow to accept biosimilars due to the lack of awareness around the biosimilar streamlined approval process. Providers may not know that biosimilars have no clinically meaningful differences from the original product, which may lead to concerns that biosimilars might not be as effective or safe as brand products.

Patients also have concerns, especially if they switch to a biosimilar from a drug they have taken for a long time. Often when this happens, the nocebo effect comes into play. This is when adverse effects (AEs) or symptoms are experienced with a drug just because the patient believes they may occur.

These symptoms may not actually materialize because the treatment is not working, but the patient believes that is what is happening. In other specialties like oncology, this situation is not as big an issue because the provider can use scans and lab tests to verify what is actually happening, but rheumatologists usually rely on qualitative factors, such as asking the patient about pain level or range of motion.

This is discouraging to rheumatologists, as these patients strongly believe they have experienced treatment failure with the biosimilar. Some patients may also refuse to even try a biosimilar because they do not understand the drug is highly similar to the more expensive brand product with no clinically meaningful differences in the safety and efficacy.

The public has a high level of trust in pharmacists, as demonstrated by more than 30 years of polling from Gallup, which for decades has placed pharmacists among the most trusted professions.

 Consequently, pharmacists can play a key role with helping rheumatologists and patients understand and accept the new RA biosimilars entering the market.

Pharmacists will have the opportunity to use their knowledge of biosimilars to reinforce their benefits, safety, and efficacy. Rather than just telling patients they will be getting a product similar to what they had in the past, the pharmacist can explain in detail they will be receiving a product just as clinically safe and effective as the one they have been taking, and it will actually cost less than the brand product. Additionally, they will be able to answer any questions that may arise.

The pharmacist’s skill set is tailor-made for the roll out of products such as biosimilars, and there is little doubt they can do a fantastic job of getting providers and patients on board with these complex products. Pharmacists have been tackling problems like this for years and have a proven track record of affecting change.

For example, when generics were launched in the late 1990s, there was a high level of patient distrust around their use. Pharmacists were able to educate patients to the point where today when patients fill a prescription, many request a generic. If history is any indication, pharmacists will be able to achieve comparable results with biosimilars.

Editorial Staff. How common is rheumatoid arthritis? MedicalNews Today. Accessed online April 4, 2023. 

https://www.medicalnewstoday.com/articles/rheumatoid-arthritis-prevalence

Conran C, Moreland L. A review of biosimilars for rheumatoid arthritis. Current Opinion in Pharmacology. Volume 64, June 2022, 102234. Accessed online April 4, 2023. https://www.sciencedirect.com/science/article/abs/pii/S1471489222000613

White E, Billingsley A. Is there a biosimilar for remicade? GoodRXHealth. February 22, 2023. Accessed online July 1,2023. https://www.goodrx.com/remicade/biosimilar-list.

U.S. Food & Drug Administration. Biosimilars: Overview for health care professionals. December 13, 2022. Accessed online July 1, 2023. 

https://www.fda.gov/drugs/biosimilars/overview-health-care-professionals#What%20is%20a%20biosimilar%20product

National Cancer Institute. NCI Dictionary of Cancer Terms: nocebo effect. Accessed online April 5, 2023. 

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/nocebo-effect

Editorial Staff. Why trust in pharmacists remains high. CVS Health. June 03, 2022. Accessed online April 10, 2023. 

https://www.cvshealth.com/news/pharmacy/why-trust-in-pharmacists-remains-high.html#:~:text=Americans%20have%20a%20special%20confidence,health%20care%20needs%20monthly2.

Articles

Pharmacists will have the opportunity to use their knowledge of biosimilars to reinforce their benefits, safety, and efficacy.

Pharmacy Can Help Drive Adoption of Rheumatoid Arthritis Biosimilars

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.

 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.

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.

 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.

 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.

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.

 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 

 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.

 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.”

 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.

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.

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.

White E, Billingsley A. Is There a Biosimilar for Remicade? GoodRXHealth. February 22, 2023. Accessed July 1,2023. 

https://www.goodrx.com/remicade/biosimilar-list

FDA. Biosimilars: Overview for health care professionals. December 13, 2022. Accessed July 1, 2023. 

New Zealand Medicines and Medical Devices Safety Authority. The nocebo effect. Prescriber Update 40(1): 14-15. March 7, 2019. Accessed April 1, 2023. 

https://medsafe.govt.nz/profs/PUArticles/March2019/The%20nocebo%20effect.htm

U.S. Food & Drug Administration. Biosimilars: Overview for Health Care Professionals. December 13, 2022. Accessed July 1, 2023. 

National Cancer Institute. NCI dictionary of cancer terms: Biomarker. Accessed April 2, 2023. 

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biomarker

Subbiah V. The next generation of evidence-based medicine. 

. 2023;29:49-58. doi:10.1038/s41591-022-02160-z

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.

Robert Zutaut, RPh

Pharmacy Can Help Drive Adoption of Rheumatoid Arthritis Biosimilars

Contributor: The Promise of RA Biosimilars Could Be Realized, but Greater Adoption Rates Are Needed