If you or someone you know has Inflammatory Bowel Disease (IBD), then you may already be familiar with biologics. But they don’t just treat IBD. Biologics are a promising therapeutic avenue for different auto-immune diseases. This will be a 2 part post where I’ll be exploring what they are and how they work in part 1, then in part 2, we’ll look into why they fail. To increase the relevance to my readers and simplify this post, I’ll discuss biologics in the context of treating IBD.
To put it simply, biologics are a type of drug that are produced by living organisms. Cells are grown in a laboratory, and edited so they produce a specific product (the biologic) that can be purified and used as a therapy. The difference here is that conventional drugs, sometimes called small molecule drugs- for example aspirin or paracetamol- are typically synthesised in a chemical laboratory without the use of organisms.
Why use organisms?
Biologics can be composed of proteins, sugars, nucleic acids and other molecules, depending on the biologics target – what it binds to- and mechanism of action – how it works.
These molecules are often large, complex structures, with folds and intra-interactions, that is why they need to be synthesised by living cells. Cells do the job way better than a human or machine could and already contain the machinery to make these products.
How do they work? Do they always work? Why do some people have to try multiple? And why are they so expensive? Let’s get into it, looking at them in the context of IBD.
Inflammatory Bowel Disease
IBD is an immune-mediated inflammatory disease, meaning the body’s immune system is attacking its own cells, considered ‘self’. Immune cells should be more specific, only attacking foreign pathogens. During development, the immune system is ‘taught’ what is ‘self’, and what isn’t. At some stage in adolescence or adulthood, something occurs that causes these cells to ‘forget’ what they’ve learned, and begin to damage ‘self’.
For this reason, biologics target specific parts of the immune system, disrupting specific inflammatory pathways to stop or reduce the damage against the digestive tract. For IBD, colonic cells (in Ulcerative colitis) or other cells within the digestive tract (Crohn’s disease) are the victims.
Suffering with IBD sometimes means spending a significant amount of time seeking out the correct treatment to control the inflammation. Or in my case, getting surgery before finding the right treatment.
Biologics are often offered after exhausting the list of other drugs in an attempt to calm down the angry inflammation. This is because biologics are a very expensive option, individual biologicals can cost upwards of £10,000 per patient, per year (1). However, prices of biosimilars are reducing the cost. They are very similar to the original biologic, but typically a different brand.
How do biologics work in IBD?
How do biologics work in IBD?
Monoclonal antibodies
Biologics produced to treat IBD are often monoclonal antibodies. Our cells also produce antibodies as part of our secondary immune response. To break down the nomenclature, ‘monoclonal’ means exactly what you might think, one clone.
Essentially, the IV bag or injection containing a monoclonal antibody biologic should have antibodies that are all identical to each other. Of course the clone changes depending on the biologic, see Table 1 for different biologics with different targets.
You might notice all the biologics listed in Table 1 end in -mab, this is shorthand for monoclonal antibodies. Typically each biologic also has a brand name which tends to omit the -mab ending.
These monoclonal antibodies have been edited to target specific proteins in order to block a pathway of the immune system, with the aim of reducing or preventing inflammation. The target of a biologic is what it is going to bind to and reduce the effect of, i.e. Adalimumab targets Tumour Necrosis Factor-alpha (TNF-a), a cytokine that causes inflammation.Once Adalimumab is in the body, it circulates until it comes across TNF-a where it binds and begins its therapeutic effect.
Table 1: Approved biologics for treatment of inflammatory bowel disease, the biologic target and type of target (2).
| Biologic name | Indication | Taregt | Type of target |
| Adalimumab | Crohn’s Disease or Ulcerative Colitis in adults and children over 6 | TNF-alpha | Cytokine |
| Golimumab | Ulcerative Colitis in adults | TNF-alpha | Cytokine |
| Infliximab | Crohn’s Disease (including fistulas) or Ulcerative Colitis in adults and children over 6 | TNF-alpha | Cytokine |
| Mirikizumab | Ulcerative Colitis in adults | IL-23 | Cytokine |
| Risankizumab | Crohn’s Disease in people over 16 | IL-23 | Cytokine |
| Ustekinumab | Crohn’s Disease or Ulcerative Colitis in adults | IL-23 and IL-12 | Cytokine |
| Vedolizumab | Crohn’s Disease or Ulcerative Colitis in adults | Integrin (on the surface of white blood cells) | Transmembrane receptor |
The complementary binding region
Different biologics can have the same target, i.e. Golimumab also targets TNF-a, but it will bind to a different part of the TNF-a. This is possible because antibodies have a region that can vary the target, called the complementary binding region (CBR).
The CBR results in precision and specificity of the monoclonal antibody. When using biologics as a treatment, the idea is to have a very specific treatment with precisely one target. If a biologic is less specific, the result is a higher dosage for the desired effect, more side effects and an increase in manufacturing costs.
The CBR makes the biologic specific to its target. By changing the CBR, you can change the target, whether that’s a different part of the same protein, or a different protein altogether.
Going back to Table 1 we have different biologics used to treat ulcerative colitis or Crohn’s disease. As you can see three different biologics target TNF-a. That is because they will have different sites on TNF-a where the CBR binds.
Once in the body the biologic monoclonal antibodies come across their target, bind to their target and effectively neutralise it, blocking it from interacting with other cells and stopping the downstream pathway that leads to inflammation.
In summary
Biologics are a real breakthrough in treating inflammatory bowel disease, but they do have their pitfalls, watch out for Biologics and IBD: Part 2. To end on a positive, biologics are only becoming smarter, giving us a good dose of hope for the future of treating debilitating inflammatory diseases.
Here’s to empowering yourself with knowledge about IBD! Make sure you share this amongst your interested loved ones! I’d love to hear from you in the comments, did you learn something new? Have you tried biologics before? Is there anything else you’d like me to feature on the blog? Let me know!
References
- Russell, M. D., Lim, W. S., & Moore, L. S. P. (2024). Driving down the cost of biologics: Lessons from a nationalised health-care system. The Lancet, 404(10464), 1723–1724. https://doi.org/10.1016/S0140-6736(24)01812-1
- Crohn’s & Colitis UK. (2023). Biologic medicines: What they are and how they work (3rd ed.). https://crohnsandcolitis.org.uk/media/byqpaebt/biologic-medicines-ed-3c-2023_final.pdf
