Two leaders in the field of rheumatology discussed the most influential studies that have been done and issues that have come to the forefront this year: Apremilast, a new drug approved for psoriatic arthritis, the rise of biosimilar drugs, and a new way of thinking about immune dysfunction.
Apremilast was approved in 2014 for the treatment of psoriatic arthritis. It is the first biologic agent to be approved that works as a phosphodiesterase 4 (PDE4) inhibitor. The drug works by increasing PDE4, a molecule which helps inhibit the production of several different inflammatory cells. Other biologic agents on the market for psoriatic arthritis are mostly Tumor Necrosis Factor (TNF) inhibitors which also prevent inflammation.
A phase three trial including 504 patients compared a placebo to both low and high dose apremalast. Apremilast was shown to increase ARC20, a sign that it was able to decrease inflammation, as well as improve physical function and psoriasis. It is still unclear whether or not the drug can be used in conjunction with other biological agents.
Two biosimilars, modeled after Infliximab, have already been approved by the EMA in Europe, as the first monoclonal antibody biosimilars. Clinical trials compared the safety and efficacy of the drugs, marketed as Remsima and Inflectra, to the safety and efficacy to infliximab, and did not find significant differences between the drugs for rheumatoid arthritis or ankylosing spondylitis. While the biosimilars were tested for safety and efficacy for these two indications, they are marketed to treat all of the same diseases as Infliximab: Rheumatoid Arthritis, Ankylosing Spondylitis, Crohn’s Disease, Ulcerative Colitis, Psoriasis and Psoriatic Arthritis. In August, Remsima was submitted to the FDA for approval.
Using biosimilars in all diseases has the potential to save $1.1 trillion over the next 10 years. However, Dr. Louis Bridges jr, MD, PhD and director of clinical rheumatology and immunology at the University of Birmingham Alabama cautioned that “like 2 snowflakes are never alike, no two proteins are totally identical.” Generic drugs are considered to be identical and interchangeable. But since biosimilars are only similar to the original drug, there is some room for small differences in effects between patients. The protocol for substituting biosimilars will vary from country to country, and precise protocols have not yet been established for the United States.
Immune Function is Not a Spectrum
An autoimmune disease, such as rheumatoid arthritis is often described as a person having “too much immunity,” whereas diseases in which a person has a deficient immune system
are described as having “too little immunity.” Dr. Connie Weyland, professor of medicine- immunology and rheumatology at Stanford University called for action to change this thinking at the Year in Review discussion during the American College of Rheumatology Conference 2014. She definitively stated “That is not a concept that can carry us into the future.”
These two conditions do not occur on a spectrum with autoimmune disease on one end and immunodeficiency on the other. In fact, many individuals who suffer from autoimmune disease also suffer from types of immunodeficiency. A study of patients with mutations in CTLA4, a gene which helps regulate the immune system showed that the patients who should have been suffering primarily from autoimmune disease, also had recurrent infections. If they just had “too much immunity” their body would not struggle with infections. Citing several other studies recently exploring this concept, she discussed the possibility that immunosuppressive therapy may even induce autoimmune disease in some patients. “One wishes these patients would read the textbooks so they could make the right mistakes,” she lamented near the end of her speech.