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There are roughly 100 autoimmune diseases, plus about 40 more that are immune-based. Total annual direct healthcare costs for these debilitating conditions are nearly double that of cancer treatments, according to the American Autoimmune-Related Diseases Association. For this reason, the stakes in autoimmune disease research are high.
Read on to discover some of the newest innovations affecting common autoimmune diseases.
Much of the focus in lupus research is focused on interferons, which are signaling proteins made and released by cells in response to the presence of pathogens. Interferons have been found to be overproduced in many lupus patients.
"This observation has led to interferon itself being identified as a therapeutic target," says Mary Crow, MD, physician-scientist lupologist, co-chair of the Lupus Research Alliance Scientific Advisory Board, and physician-in-chief of Hospital for Special Surgery. Anifrolumab, in phase 3 clinical trials, is one medication showing promise in this area, she says, noting it's likely that at least one new medication could be approved for use in the next year.
More than 30 clinical trials are ongoing in various phases of lupus drug development, says Rosalind Ramsey-Goldman, MD, DrPH, Solovy Arthritis Research Society Professor of Medicine and medical director of the clinical research unit at Northwestern University in Chicago. In the last six months, several phase 2 trials showed positive results and are likely to move on to the next phase, she adds.
Ustekinumab, which blocks the IL12/23 pathway linked to the pathogenesis of lupus, and previously approved for psoriasis, psoriatic arthritis, and Crohn’s disease, has been evaluated in lupus in a phase 2 trial, Ramsey-Goldman says. One study showed efficacy in the treatment of active lupus and plans are in place for more studies.
Another study is evaluating sirolimus, which is already approved by the FDA for immunosuppression and to prevent rejection after organ transplantation. Ramsey-Goldman says this medication may be useful in lupus to restrict T cell activity.
Two phase 2 clinical trials in 2016 that are now in phase 3 could result in FDA approval for anifrolumab and voclosporin, a calcineurin inhibitor and immunosuppressant that blocks T cells.
Researchers are also working to identify biomarkers that can help clinicians improve diagnosis and better identify those at risk for developing the disease, Goldman says. Biomarkers may also help clinicians predict flares, as well as how patients will respond to different treatments.
The most effective intervention for celiac disease is to follow a strict gluten-free diet, but this can be difficult, says Peter H.R. Greene, MD, director of the Celiac Disease Center at Columbia University in New York, the Phyllis and Ivan Seidenberg Professor of Medicine at Columbia University Medical Center, and attending physician at New York Presbyterian Hospital.
Though a gluten-free diet is not easy, it is highly effective and safe. This means that all potential therapies and treatments have a high standard to meet to be considered appropriate alternatives. Some research is focusing on altering wheat to remove or detoxify gluten, but there is a general dislike for genetically altered foods, Greene says. There is also research looking at the use of anti-glutenase enzymes that could reduce the damage caused by gluten.
Larazotide, which is entering phase 3 trials, is helpful in reducing symptoms of celiac disease. Budesonide and prednisone, along with other steroids, have been used to reduce symptoms in celiac patients. Researchers are also working on a vaccine that involves the injection of peptides that may protect patients from some gluten contamination, Greene notes, adding that study is moving to phase 2 trials.
More than 20 different immunotherapy targets are also being investigated, one in particular for refractory celiac disease-a particularly bad form of the disease that does not respond to a gluten-free diet "There is a lot of interest, and some of the bigger pharma companies are getting involved," Greene says.
Next: Multiple sclerosis
Kathy Costello, adult nurse practitioner and associate vice president of clinical care for the National Multiple Sclerosis Society, says several genes have been identified as posing a risk for multiple sclerosis development, but there’s not enough definitive data yet to prevent the disease onset through gene therapy.
There are many new developments in treatment on the horizon, though, including an oral medication that was approved for relapsing forms of multiple sclerosis. Fingolimod, approved for adult MS patients since 2010, received a breakthrough therapy designation from the FDA for children and adolescents ages 10 years and older with relapsing MS.
Other medications are in development that restrict the activation and circulation of immune cells, therefore reducing the inflammatory process in multiple sclerosis.
Another medication to watch is ibudilast, used in Japan and Korea for a variety of issues like post-stroke and bronchial asthma since the 1980s. Researchers are looking into the medication's potential benefit for problems including multiple sclerosis, amyotrophic lateral sclerosis, substance abuse, and neuropathic pain, Costello says. In recent phase 2 clinical studies, patients experienced a significant reduction in the progression of whole brain atrophy. The research may move to phase 3 trials soon and ibudilast has been designated as a fast-track product in terms of its development as a possible treatment for progressive MS, says Costello.
Additional treatments in the research pipeline have a similar focus, by reducing activation of the immune system, reducing the activation of immune cells, or blocking the entry of those cells into the central nervous system.
"They're each coming at the immune system problems from various directions. This is good news for people with multiple sclerosis who may need to switch to a different medication due to a suboptimal response or side effects. Having medications with differing mechanisms of action will allow greater chance to impact the disease process,” says Costello.
There is also interest in how gut microbiota and exercise can impact multiple sclerosis, particularly regarding what exercises are best for stimulating different parts of the brain and improving mobility.
Stem cells transplants may also be an option. "Interim results from a study of hematopoietic stem cell transplant showed the procedure was well-tolerated and there may be benefit to rebooting the immune system," Costello says. "You are essentially suppressing the immune system and then reintroducing the patient's own stem cells, and in multiple sclerosis the hope is they will regenerate in a less harmful way.
Type 1 diabetes
Jessica L. Dunne, PhD, research director at the Juvenile Diabetes Research Foundation, says development of treatments for type 1 diabetes has been slow, partly because insulin works so well in treating it.
"While insulin may seem on the surface like a great therapy, and it is, there's still a burden of maintaining adequate blood sugars," Dunne says.
Technology may help, with insulin pumps, implantable monitors, and other devices easing the burden of the disease for some patients. Continuous glucose monitors are becoming more readily available, with a 20% uptake in use over recent years, and studies show they lead to improved outcomes, Dunne says.
There is also some progress in medication development, with researchers looking into new immunotherapies like SGLT 1 and 2 inhibitors. These inhibitors affect glucose absorption in the kidneys, providing glycemic control in a new way outside of simply increasing insulin levels. Researchers are also looking into encapsulating and implanting beta or islet cells into patients that could potentially reduce or eliminate the need for insulin therapy for the life of those implanted cells.
Increased interest in adjunct therapies like this for type 1 diabetes will improve access for patients, Dunne says. "It will make them easier to prescribe and improve insurance coverage," she says. "It's a huge step. I hope this opens the door for more adjunct therapies."
There are also studies investigating the role of cytokine inhibitors and antigen-specific therapies, a viral vaccine that may prevent the development of type 1 diabetes, and how the gut microbiome affects disease development and progress, she says.
"There has been some evidence showing the microbiome is changed in diabetes, but the big question now is, what do we do about it?" Dunne says.
Christopher Morris, MD, a Tennessee board-certified rheumatologist who serves on the government affairs committee for the American College of Rheumatology and on the board of directors for the Southern Medical Association, says biologics, such as adalimumab (the top-selling medication in the world) have shown tremendous progress in treating RA. Still, the cost of these new treatments can be prohibitive, Morris says, and the problem is compounded in rheumatology because there are so few FDA-approved medications and treatments are often used off-label. Patients have trouble getting medications approved for coverage by insurance companies, and can rarely afford them on their own, he says.
“This is something we are frustrated with in medicine. My first consideration when I write a patient a medication is, are they able to afford it?" Morris says. "We want a medicine that works and we want a medicine they can afford."
Biosimilars could be a more cost-effective alternative to biologics, he says, but there is hesitation over fears that cost savings could come at the expense of efficacy.
He says Janus kinase (JAK) inhibitors are likely the next big thing in treating RA, and future treatments are becoming increasingly selective to improve efficacy while reducing negative effects.
There has also been some research into vagal nerve stimulation-which usually involves either manual or electrical stimulation of the vagal nerve, Morris says, highlighting the idea that there is a neurologic component to some autoimmune diseases. "Maybe by modifying how the body is reacting neurologically, it can have an effect on rheumatoid arthritis.”
Next: Skin diseases
New medications being investigated for psoriasis and psoriatic arthritis include JAK inhibitors. Upadacitinib, for example, is being studied for use in psoriasis, psoriatic arthritis, atopic dermatitis, and other autoimmune diseases like Crohn's, says Morris. The once-a-day medication is now in phase 3 trials, he says. "It's an interesting medicine. We want to see what pro-inflammation markers are there and direct against that."
The issue with the psoriasis family of diseases and other autoimmune conditions, he says, is finding balance between toning down the immune system response to pathogens that trigger the conditions, without damaging the immune system too much. "Every one of these medicines is playing with your immune system."
Rheumatologists need to look at a patient's individual symptoms and condition to determine the best medications for them. For example, ustekinumab works well for psoriasis, but is not the first choice for patients with joint problems. Adalimumab, on the other hand, is approved for both, says Morris. “The more different approaches we have, the better.”
Rachael Zimlich, RN, is a writer in Columbia Station, Ohio.