The Role of Biosimilars in Inflammatory Bowel Disease

Paulo G. Kotze, PhD


February 25, 2022

Dr Paulo G. Kotze has written extensively on the treatment of inflammatory bowel disease. He answered questions about the value of biosimilar drugs in ulcerative colitis and Crohn's disease.

From the perspective of a clinical gastroenterologist, what are biosimilars and what are generics? Is the relationship of biosimilars to biologics the same as the relationship of generics to proprietary drugs?

The answer is no. Generics are small molecules which are chemically synthesized and identical to the reference product. Whereas biosimilars are designed to reproduce the properties of complex monoclonal antibodies and have the same sequence of amino acids, they are not an exact copy of the original drug. They are based on a different cell line. There are other reasons why they are not identical as well. For example, the growth conditions, the purification process, and the precise formulation in the manufacturing process can all differ from the original. The biosimilars are comparable versions of the reference products but they are not generic. Yet, there should be no significant differences in regard to safety and efficacy. Owing to these processes, the concept of generics is totally different from the concept of biosimilars.

In the treatment of inflammatory bowel disease (IBD), is the role of biosimilars the same for ulcerative colitis and Crohn's disease?

This is a very important topic. Biosimilars should perform in the same way as the original drug regardless of indication. This not only means the same activity in ulcerative colitis and Crohn's, but the same activity as the originator drugs when used in other types of inflammatory diseases. If the originator drug has indications for treatment of rheumatoid arthritis, psoriasis, or IBD, the approval of a biosimilar can be extrapolated to all indications that are in the label. So far, all of the biosimilars that are used for IBD are anti-TNF agents. For the biosimilars, which have essentially identical chemical properties, the anti-inflammatory effect of the biosimilar will be the same as the original whether treatment is for Crohn's or ulcerative colitis.

With numerous biosimilars approved for many of the biologics (eg, five are approved for adalimumab), is there a process for selection? Can another biosimilar be tried if response to the first is inadequate?

These are also important questions. In my experience and I think in the experience of others, the initial selection of the biosimilar is generally made by the payer. This might not be true everywhere, but this is the case where I practice in Brazil. If the biosimilar does not provide adequate efficacy, there is not much evidence about whether a second biosimilar to the same originator is reasonable. However, I would not expect a second agent to be effective if the first was not. On that basis, we would expect a second adalimumab biosimilar to also be ineffective if a first adalimumab biosimilar failed in a patient. These are basically the same products.

What impact do cost considerations have in selecting a biosimilar vs the originator biologic?

The impact of cost is huge. In some countries a biosimilar can be acquired at 30%-40% of the cost of the reference product. The opportunity to pay so much less for a drug that is almost identical to the originator biologics has major implications for improving access to these agents. Certainly, it allows more patients to consider these highly targeted and efficacious agents if cost has been a limiting factor in the past, and it lowers the cost of the originator biologics because of price competition. In some healthcare systems, this might mean a redistribution of funds when budgets are limited. In our center, saving money on drug costs will leave more money to address other needs, such as money for research. There is, however, a risk for diminished benefit if patients are not educated about biosimilars so that they recognize that efficacy and safety is comparable to the brand-name products. When patients are switched to a biosimilar for a nonmedical reason, there is a risk they will lose confidence in the drug. Costs are very, very important, but it is important to address patient perceptions to avoid a nocebo effect, a phenomenon in which patients develop a belief that the drug is inferior.

Can you describe what is known about cross-reactivity of antidrug antibodies and whether that's a factor when deciding what biologic or biosimilar to try next when there is loss of response?

It is true that the manufacturing process of these biosimilars poses at least a theoretical risk for changes in immunogenicity due to differences in glycosylation, phosphorylation, sulfation, and other posttranslational drug modifications. In a published comparative analysis, antidrug antibody formation was similar when patients on one of two biosimilars or the reference originator product were followed. So to date, there has been no evidence that antidrug antibody formation is different for biosimilars relative to originator biologics. On this basis, we would also expect similar cross-reactivity, but this has not been fully evaluated across all biosimilars. More studies about this issue are needed, but we have to conclude on the available evidence that antidrug antibody formation is comparable among biologics and their biosimilars as well as among biosimilars for the same originator agent.


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