This post is following on from my previous post: Biologics and IBD: Part 1, feel free to give that one a read to familiarise yourself with biologics as a treatment for IBD and how they work. By the end of this post I hope to help you understand why biologics don’t work for some people, and why they might stop working for others. Finding the right treatment for IBD can be a testing process, but knowing more about the treatments we’re taking is not only fascinating, but empowering.
My experience with biologic treatment failure
Just to inject some of my personal story here, I tried infliximab, which targets that pesky little cytokine TNF-a. It was just over 2 weeks into my hospital stay, I got to sample some of this expensive cuisine. Wheeled over to me on an IV stand, I thought this browny reddish liquid gold would be my ticket to finally leave hospital a healthy woman.
Initially, we saw signs of it working. I was making my way through the Bristol Stool Chart(1), feeling good, getting out of bed to do squats and building up my strength again to go home after being bedridden. But like a distracted college student I was dropping lower on the Bristol Stool Chart before long.
We gave the second dose of infliximab a chance, and this time there was no change. So why did this happen? Why didn’t infliximab work for me? Why do biologics work for some and not others? Well, we’re all different and unique, but it’s hard to celebrate that when 65 year old Diane* in the hospital bed across from me gets to go home after achieving an excellent Bristol Stool score and I’m stuck in hospital for another 4 weeks (good for you Diane, I genuinely hope you’re still happy and healthy).
But we are all different, and essentially, that’s the crux of it. Different disease mechanisms, different disease complexity, different immune responses. I may have had the same symptoms as Diane, but what’s going on inside may be a totally different ball game, needing a totally different therapeutic approach.
How common is it that biologics don’t work for some people?
To give you an overview of how many people benefit from infliximab, I’ll draw from the results of an observational study completed in 2011 that looked at infliximab for chronic IBD (2). Over 3000 patients were treated with infliximab at weeks 0, 2, 6 and every 4-8 weeks afterwards for 2 years. Patients were assessed by their physicians on a scale of not at all ill, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, or extreme severe illness.
In chart 1, I have plotted the percentage of patients at each illness severity against time. The response to infliximab was favourable, reducing the categories of markedly ill and severely ill by the 3rd dose at week 6. However, you can still see at each point some patients were severely ill and markedly ill. We don’t know if this is the same population each week who are severly ill or markedly ill, or if individuals dropped or increased illness severity level. But we can propose that perhaps the severely ill some some of the markedly ill population don’t respond well to infliximab treatment.
By week 102 there were 4.2% of the cohort in the severely ill category. I guess I’m with those guys. Remember, this isn’t a summary of all biologics, but specifically infliximab, and I’m using these Phase IV clinical trial results as an example to highlight why we need multiple biologics for inflammatory bowel disease. For the people that don’t respond so well to one treatment, and for the people that used to respond, but don’t any longer. This is another issue entirely. Let’s get into it.
Chart 1: Percentage of patient illness severity level over time with infliximab treatment.
This chart shows the percentage of patients at different illness severity categories assessed by patients physicians (Severely ill; Markedly ill; Moderately ill; Mildly ill; Borderline ill; not at all ill) over 24 months during treatment with infliximab at weeks 0, 2, 6 and every 4-8 weeks following (2).
Why do biologics stop working?
Remember that biologics are made from living cells, so to your body, the biologic treatment is a foreign body that it needs to get rid of. When patients are repeatedly exposed to the biologic, a common treatment plan for managing IBD, they may generate an immune response against the biological treatment, meaning it’s cleared from the body sooner than it can have a therapeutic effect.
Additionally the immune system can produce anti-drug antibodies (ADAs). Your own antibodies that target the biologic monoclonal antibodies. ADAs will bind to the biologic, preventing it from binding its target, reducing or stopping the biologic mechanism of action.
ADAs can develop in up to a third of patients treated with biologics (3). TNF inhibitors, like infliximab shown above or adalimumab have a higher risk of biologic treatment failure (4). While expecting the perfect treatment is a big ask, these 30% of patients really need additional therapies made available to them to manage their symptoms. Luckily, IL-23 biologics seem to demonstrate a lower incidence of failure due to ADAs (5).
A breakthrough treatment option for IBD, but far from perfect
Most drugs come with their flaws and side effects. It’s truly a devastating day to discover the miracle biologic you’ve been waiting for to fix all your symptoms doesn’t work at all or has stopped working. However, I hope I was able to describe to you how they work, why they may stop working and highlighting that there are more biologics to try if you or someone close to you is going through this.
While biologics have their limitations, the hunt is not over to find better treatments for IBD, and additional options for those who are unresponsive or developing immunity (without resorting to surgery). Leave a comment below with your experiences of biologics! I’d love to hear from you! If you have anything else you’d like me to write about in the technologies section of this blog let me know!
*Diane is a substitute name based on a real individual who did indeed get better and leave hospital thanks to infliximab
References:
- Heaton, K. W., & Lewis, S. J. (1997). Stool form scale as a useful guide to intestinal transit time. Scandinavian Journal of Gastroenterology, 32(9), 920–924.
- ClinicalTrials.gov. (2008). Post Marketing Surveillance Study of Remicade in Patients With Chronic Inflammatory Diseases (P04840) (REMission) (NCT00727298). U.S. National Library of Medicine. Retrieved July 2, 2025, from https://clinicaltrials.gov/study/NCT00727298
- Schaeverbeke, T., Truchetet, M.-E., Kostine, M., Barnetche, T., Bannwarth, B., & Richez, C. (2016). Immunogenicity of biologic agents in rheumatoid arthritis patients: Lessons for clinical practice. Rheumatology, 55(2), 210–220. https://doi.org/10.1093/rheumatology/kev277
- Lin, S., Chanchlani, N., Carbery, I., et al. (2022). Understanding anti-TNF treatment failure: Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease? Alimentary Pharmacology & Therapeutics, 56, 783–793. https://doi.org/10.1111/apt.17089
- Valenzuela, F., & Flores, R. (2021). Immunogenicity to biological drugs in psoriasis and psoriatic arthritis. Clinics (São Paulo), 76, e3015. https://doi.org/10.6061/clinics/2021/e3015
