University of Maryland School of Medicine Researcher Reports on Clinical Trial Results for Experimental Drug that Increases Knee Cartilage Thickness
More than 10 percent of Americans over age 60 experience knee pain related to osteoarthritis, the most common disease of the knee joint. Osteoarthritis of the knee causes pain, activity limitation, physical disability, reduced health-related quality of life and excess mortality compared with the general population. The pain is usually treated with over-the-counter pain relievers, anti-inflammatory drugs, local steroid injections and sometimes surgery. There are currently no drugs approved to treat the underlying cause of the condition, which results from the breakdown of joint cartilage covering the long bones due to increasing age, injury/overuse, obesity, genetics and/or local inflammation. A new experimental growth factor therapy, however, appears to prevent a worsening of osteoarthritis by increasing the thickness of cartilage in the knee joint and preventing further loss, according to results from an early clinical trial that were published today in the Journal of the American Medical Association.
The study, led by researchers at the University of Maryland School of Medicine (UMSOM), involved 549 volunteers with knee osteoarthritis who were randomly assigned to get injections of the drug sprifermin, recombinant human fibroblast growth factor 18, either at a low dose of 30 micrograms (μg) or a high dose of 100 μg, either once or twice a year, or assigned to get placebo injections. The researchers found that those who received a 100 μg dose either twice or once yearly experienced a statistically significant but slight gain in joint cartilage thickness after two years as measured on quantitative magnetic resonance imaging (MRI), a gain of 0.03 or 0.02 millimeters (mm) compared to the placebo group that lost 0.02 mm of cartilage during the two-year period. Those given smaller doses had smaller gains in cartilage; indeed, the gains in the lower dose groups were not deemed to be statistically or clinically significant.
Patients treated with the higher dose of sprifermin, however, did not experience any significant improvement in their arthritis symptoms -- including pain, stiffness, and physical dysfunction like walking difficulties – compared to those given the lower dose or those given placebo injections.
“While the increase in cartilage thickness is a positive sign, we do not know at this point whether it has any clinical significance,” said study lead investigator Marc Hochberg, MD, MPH a Professor of Medicine at UMSOM. “It is not known whether those who experience increased cartilage thickness over time will be able to avoid or delay knee replacement surgery.”
While injections were stopped after 18 months, the analyses showed that the difference between groups that received the higher dose of sprifermin and placebo persisted out to three years. The study was designed to continue for a total of five years and future analyses of the entire trial dataset are planned.
In a more recent post-hoc analysis of the data, Dr. Hochberg and his colleagues evaluated a subgroup of osteoarthritis patients with severe pain and narrow joint space in their knee who were at higher risk of disease progression; they found that those in the group who received sprifermin 100µg every six months experienced significant improvements in their arthritis symptoms 18 months after their last injection compared to those who received placebo injections. “These results support further investigation of sprifermin as a potential osteoarthritis treatment for both structure modification and symptom relief for higher-risk patient populations,” Dr. Hochberg said. These results were presented in June at the European Congress of Rheumatology’s annual meeting,
“Finding an effective therapy that can treat the cause of common chronic pain conditions like osteoarthritis would be a ground-breaking achievement,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “I’m proud that our scientists are helping to move the knowledge forward on the effectiveness of new therapies to replace worn cartilage in the joints. This is very important work, and more answers are certainly needed.”
Side effects associated with the use of sprifermin were mostly mild or moderate and consisted mainly of acute inflammatory reactions (pain, redness, swelling) at the site of the injections. The study was funded by Merck KGaA, manufacturer of sprifermin, located in Darmstadt, Germany.
About the University of Maryland School of Medicine
Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 43 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished recipient of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for more than 1.2 million patients each year. The School has over 2,500 students, residents, and fellows, and more than $540 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total workforce of nearly 7,000 individuals. The combined School and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine faculty, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu