- Rheumatoid arthritis is a painful, progressive joint disease characterized by particularly acute flare-ups.
- Biologics, used to treat autoimmune diseases such as rheumatoid arthritis, target symptom mechanisms without compromising the entire immune system.
- A new test may take the guesswork out of finding the right biological therapy for people with rheumatoid arthritis.
Scientists at Queen Mary, University of London, have announced a new machine-learning-based method for predicting the biological therapy, or biologic, most likely to successfully relieve symptoms for an individual with rheumatoid arthritis.
The scientists say that their system successfully predicted the optimal biologic for 79–85% of patients on its first try in validation tests.
Over the last 20 years, biologics have revolutionized the treatment of rheumatoid arthritis (RA) due to their potential to focus on the underlying cellular cause of a patient’s illness.
Since RA is an immune disorder, conventional treatments suppress the function of the entire immune system to reduce symptoms of the condition. Absent a robust immune system, the patient is left vulnerable to infections.
The idea behind biologics is that a more precise approach can be effective at reducing RA symptoms without significantly compromising the immune system.
According to its inventors, prior to the newly announced technique, identifying the correct biologic for each patient was somewhat of a hit-or-miss procedure — 40% of biological therapies fail due to inaccurate targeting.
The new prediction technique pinpoints which of the three main types of biologics shows the most promise for a patient.
“This innovation could have major benefits for patients and healthcare providers alike. Prescribing the right treatment the first time would reduce patient suffering,” Professor Constantino Pitzalis, study author, tells Medical News Express.
The scientists announced their new method of identifying the best biologic for an individual RA patient in
Rheumatoid arthritis is an autoimmune disease that causes pain and inflammation in and around the joints.
“The persistent inflammation can impair mobility and dexterity, making daily tasks difficult or impossible,” explained Syeda S. Nasrin, MSc, graduate of the Center for Regenerative Sciences in Dresden, Germany, who was not involved in the study.
Liz Bowen, PhD, bioethicist at SUNY Upstate Medical University, who was also not involved in the study, is someone who has personal experience with RA.
“When I developed RA, the pain was shocking. I’d wake up in tears in the middle of the night and no amount of NSAIDs, ice, heat, movement, rest — any of the usual things you’d try for joint pain — even began to offer relief. It spreads all over the body and makes basic life tasks, like putting on a shirt or opening a car door, agonizing,” she said.
RA is a chronic and progressive condition, and may also involve other parts of the body.
Aside from biologics, people with RA may be treated with immune suppressors such as methotrexate and Janus kinase (JAK) inhibitors, which target the overactive immune system. For pain, doctors prescribe NSAIDs, which are notoriously hard on the stomach and GI tract with long-term use, and corticosteroids to control flare-ups.
“Biologics,” said Nasrin, “target specific cellular pathways in the immune system that play key roles in the inflammatory process of RA.”
The idea is to address the mechanism causing an individual patient’s RA-related joint inflammation without attacking the immune system itself.
“For instance,” she explained, “Interleukin-6 (IL-6) is a cytokine that is involved in immune cell modulation and inflammation. Tocilizumab (Actemra), a monoclonal antibody, can inhibit this IL-6 cytokine and reduce inflammation.”
Nasrin made clear, however, that “as far as I know, these molecular targeted therapies are able to reduce inflammation, slow joint damage, and improve physical function, but they do not cure the disease.”
Since it currently takes time to identify a biologic that can address a specific patient’s RA, there is an extended period during which no symptom relief occurs.
There are also risks associated with this period of experimentation, pointed out Nasrin. “As these approaches often include altering the immune system at a molecular level, that means there is a suppression of the immune system in the body. This could increase infection susceptibility.”
Bowen pointed out as well that even the right biologic takes time to have a positive effect on symptoms. Extended periods of trial and error may be accompanied by uncertainty in addition to the ongoing physical pain.
As Bowen described it, “What works for one person may not work for another. So it can be really demoralizing and isolating if, say, you’re looking around and seeing all these people who are doing great on [one biologic], but it’s doing nothing for you.”
“It’s grueling,” she said, “not just on a physical level but also a psychological one, where you might be dealing with huge amounts of fear, hopelessness, and doubt that you will ever find something that works.”
The new method identifies which of three biologics — etanercept, tocilizumab, or rituximab — is most likely to work for a patient.
In a recent clinical trial that involved deep molecular phenotyping, the scientists developed a database of gene differences in RA patients who had responded well to biologics, compared to others who did not.
They were also able to ascertain the response of specific groups of RA-related cells to each of the drugs. From there, they built three predictive models for the three biologics to test how well a patient would do with a given biologic.
To predict the correct biologic for a specific patient, they extract a tissue sample from a joint affected by RA, and score the levels of activity in 524 genes they have identified as relevant. They can then match those scores to the most promising biologic.
Queen Mary, University of London, is seeking commercial partners to help develop the predictive system for real-world use. No timetable for when this may occur has yet been announced.
While the validation results are promising, Nasrin, struck a note of caution:
“Personalized medicine is still at a very early stage of development. So the approach should be taken with caution and only proceed with having solid clinical trial data.”
Clinical trials are reportedly underway.
