By Emil DeAndreis
Autoimmune conditions can be rife with contradiction. Take the nature of them: they take our body’s first line of defense and make it our worst enemy. To stay healthy, we must shut down the system that is supposed to keep us healthy.
In terms of treatment, the medical world has come so far, yet has so far to go. This is the confusing and frustrating Bermuda Triangle of chronic illness. But there is some solace in knowing that we are always learning more. There is momentum, improvement, and hope.
Here’s what’s coming around the bend in terms of innovative treatments for autoimmune conditions.
Homing in on how to block the immune system
There are upcoming developments worth noting within the three autoimmune drug families, according to Angela Crowley, MD, a rheumatologist at the Illinois Bone and Joint Institute. Crowley has an active practice in Chicago and also participates in clinical research.
The three types of immunosuppressants are distinguished by the parts of the immune system that they block. Methotrexate—which blocks chemicals that can cause inflammation—is the oldest and remains the gold standard in the industry, often the first drug prescribed for certain autoimmune conditions. Biologics and JAK inhibitors are newer, and most people likely recognize them by their brand names, like Humira, Enbrel, Xeljanz, or Rinvoq.
“More and more biologics are on the way,” Crowley says. “There are so many different cytokines [signaling molecules] involved in the inflammatory process. That’s what is constantly being studied. So Enbrel, Humira, Simponi work against the tumor necrosis factor cytokine; Actemra blocks something called IL6; Rituxan works against the B cells. The immune system is so complex; there’s so many different ways you can work to block it. In the coming years, I think we’re going to be constantly discovering better, different ways.”
Following biologics, JAK inhibitors—such as Xeljanz, Olumiant, and Rinvoq—are the most recent arrivals for autoimmune treatment. While they’ve enjoyed popularity for their immediate results, their newness also has meant more unknowns.
“We’re seeing some safety signals with them,” explains Crowley. “There was a recent report from the FDA about Xeljanz, so we’re doing more involved safety trials with the other two now about increased risk of cancer, blood clots, and cardiovascular events. That said, we still use a ton of JAK inhibitors with our patients. I’ve never seen something work as fast.”
So with this in mind, what pharmaceutical developments can we expect to see in the future?
“With all these different medications out, we have so many options and no guarantee of which will work or not,” shares Crowley. “It can be like flipping a coin picking which one to try. Then we can only cross our fingers. The next hurdle, and exciting development, will be: How do we predict the mechanism of action for each specific patient? Can we test your blood levels and say, ‘If your TNF, or your IL6, or your JAK is high, this is the medicine you need’? And we haven’t been able to show that that works yet. But we will get there.”
A device with promising implications
Another innovative treatment for rheumatoid arthritis under consideration is nerve stimulation. Recently, a study was conducted in Spain that involved stimulation of the vagus nerve in the neck from an implanted earpiece. The vagus nerve plays a large role in inflammatory reflex, immune responses, and inflammation, so it is speculated that stimulating it might disrupt and reduce the body’s inflammatory response, according to an article on the study in The Rheumatologist.
The 30 patients who participated in the study were predetermined to have “active” rheumatoid arthritis; one of the indicators used was elevated C-reactive protein levels, which is found in a number of autoimmune diseases.
The patients wore the device for 30 minutes each day and were prohibited from using other autoimmune medications. At the conclusion of the three-month study, there were encouraging results in the measurement of patients’ C-reactive protein. After a single week, the protein levels were reduced, and that pattern continued into the 12th week; 37% of patients reached a level that indicates low disease activity, and 23% reached a level indicating remission.
The soil and the seed
Atul Deodhar, MD, MRCP, rheumatologist and professor of medicine at Oregon Health and Science University, is hopeful that research in genetics and the gut microbiome might eventually lead to more specialized treatments and even preventative measures for certain autoimmune conditions.
“For anything to grow, you need a soil, and you need a seed,” he says. “This is true for all diseases as well. For diseases, environmental factors are the soil, and genetics are the seed. I am hoping soon that research should find more genetic material or markers that dictate our medication prescriptions.”
Deodhar says that insurance companies limit the medications that can be prescribed, and that currently, doctors do not have enough information to justify demands for specific drugs for individual patients. This leaves the all-too-common “see if this one works” approach to prescriptions. But he believes that with enough research and analysis on the role of genetics in autoimmune diseases, rheumatologists will have the necessary information for more targeted, individualized drug prescription.
“When we are further along with that information, I can then go to the insurance companies and say, ‘Based on my patient’s genetic assessment, he needs this drug, and the one you are allowing may actually increase their side effects,’” Deodhar says.
Genetics are one factor in autoimmune disease, but not the only one. In fact, in twin siblings (who have identical genes), if one sibling has rheumatoid arthritis, the odds of the second twin having the disease are only 15%. This is because their environments are different.
“We still don’t understand very well what the environmental triggers are,” Deodhar says. “But one of the triggers we’ve found is the gut microbiome. We have trillions of germs in our bodies, most in our gastrointestinal tract, and those have immense effects on how your immune system is shaped and which diseases you are vulnerable to. We are just scratching the surface on this front.”
Deodhar points out that patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis have different microbiomes than their healthy counterparts. “Will changing the gut microbiome make any changes?” he asks. “We don’t know. Studies so far are unsuccessful. And this is perhaps because the environment has already made changes by the time of diagnosis. The barn is broken and the horse is gone, so to speak. But, can gut information guide us to preventative measures? Can we change this environment before it’s too late? We don’t know this either, but that is a direction this field is going. It is one of the frontiers I’m very excited about.”
This is just a glimpse of autoimmune illness treatment in 2021: advancing, but unfinished. Yet amid this limbo, it gives our community hope to see the global effort to understand these enigmatic conditions—thanks to doctors and researchers across the world working to navigate our ship out of the Bermuda Triangle. •