We spoke with three world-renowned HSS rheumatologists whose research has led to major treatment advances for patients with autoimmune disease: Physician-in-Chief Mary K. Crow, MD, Benjamin M. Rosen Chair in Immunology and Inflammation Research; Jane E. Salmon, MD, Collette Kean Research Chair and director of the HSS Systemic Lupus Erythematosus and Antiphospholipid Syndrome Center of Excellence; and Associate Chief Scientific Officer Lionel B. Ivashkiv, MD, David H. Koch Chair for Arthritis and Tissue Degeneration Research.
To date they have practiced at HSS for a combined 85 years. They discussed their experiences in a rapidly evolving medical specialty and their vision for the future.
Dr. Crow: As a medical student and medical resident I found that patients with systemic autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA) were by far the most challenging and complex. Having a background in immunology research prior to starting medical school, rheumatology seemed like an ideal field that would combine the intellectual stimulation of unraveling diseases based in altered immune function with the rewards of helping people with very significant and often debilitating diseases.
Dr. Ivashkiv: At the time, people asked me why I wanted to go into a field with so little understanding of how the diseases worked, and with such imperfect treatments. I saw that as an opportunity to learn more about these diseases and find some answers.
Dr. Salmon: As a student and resident, I took care of young women with lupus. Women are much more likely to get this disease than men, and I was compelled to find better ways to help them.
Dr. Salmon: The most important advance is biologic therapy. Biologics are bioengineered molecules that target specific immune mediators and cells involved in an autoimmune disease. We’ve identified specific targets, specific inflammatory molecules that we can inhibit with biologics, to prevent joint destruction, skin rash, and kidney inflammation.
Because of biologic therapies, patients with rheumatoid arthritis rarely need joint replacements, they can work, they’re not tired. The ability of these drugs to change the natural history of RA has been extraordinary.
Dr. Crow: And what was exciting as a rheumatologist is that rheumatology led the medical community in the introduction of these biological and targeted therapies in the 1990s. RA was one of the first diseases in which they were successful. Rheumatologists’ success with biologics gave other disciplines confidence to use them to treat many other diseases.
Dr. Ivashkiv: Biologics really did change the field and practice. There is now another advance – the introduction of JAK-inhibitors – which just came onto the market this year. We think that these new medications will be just as effective as the biologics, and they can be taken by mouth, which will make it much easier. Patients receive biologics through infusion therapy or injection. JAK-inhibitors work in part by blocking signaling by the protein interleukin 6 and probably other cytokines that we have been studying for years at HSS.
We started investigating JAKSTAT in my HSS lab in 1992 as soon as it was discovered, and we were the first to link JAK-STAT signaling with RA. It was very gratifying as the science moved from the laboratory to pre-clinical studies and now patients are using it and everyone thinks it really works. In the first 20 years of my career I’ve been privileged to be part of the progression of an innovation from the laboratory bench to the patient’s bedside.
Dr. Crow: We’re on the cusp of making great strides in the area of genomics and figuring out how environmental factors, such as smoking, interact with an individual’s genes to make some people more likely to get sick. Improved understanding of the cell alterations that contribute to lupus have led to new concepts for drug development that are now being tested and should yield more effective therapies in the next five to ten years.
Dr. Salmon: We will ultimately be able to determine exactly which therapy will work best for which patient by understanding each individual’s genes and genetic regulators.
Dr. Ivashkiv: This is one of the goals of the new HSS Genomics Center. We hope to identify new targets and also personalize therapy to find the best way to treat a specific person. Right now, rheumatologists still try one thing and see if it works, and then try the next thing if the patient doesn’t respond well. We’d like to be able to select the best drug right from the get-go, and genomics will allow us to do this.
Dr. Salmon: Research here is always rooted in patient care, and patients are our partners in research – they are active participants. It is rewarding to see patients with lupus feel good, live normal lives, enjoy their families the way they couldn’t when I was in medical school.
Dr. Crow: Rheumatology at HSS is all about collaboration. Scientists and physicians work together to help patients, and patients inspire us to push towards new advances.
Read the full Discovery to Recovery Fall 2013 issue.