How will surgeons use recombinant bone morphogenic protein-2 in the post-YODA era?
A panel at the 2014 North American Spine Society Annual Meeting titled "BMP Use in Spine Surgery: The Post-YODA Era" discussed just that.
Medtronic's rhBMP-2 product, Infuse, exploded from 2002, when it received FDA clearance and studies were released showing its efficacy, to 2009 when data showing increased cancer risk was higher than originally reported. The Yale University Open Data Access project examined whether there were issues with the original clinical trials reported. BMP use reached its zenith at 28 .1 percent of all fusions and then dropped significantly after the new data was published, hitting 7.8 percent of procedures.
Over the past six months, the number of procedures using BMP increased slightly again. "If you look at a technology of any sort, it's not surprising to see the technology trigger, followed by the peak of inflation and then a trough of disillusionment followed by a slope of enlightenment — which is where I think we are with BMP — and then a plateau of productivity," said Wellington Hsu, MD, of Northwestern Medicine in Chicago. "New technologies always have some kind of craze behind them followed by typical use, and this is what we see."
Cancer risk is an issue for patients and physicians. Dr. Hsu discussed how rhBMP contributes to the genesis of cancer. "I think all of those surgeons who do use BMP should have a judicious algorithm in which to use it," Dr. Hsu said. He uses BMP in ALIF, minimally invasive applications, nonunion risk, long deformity constructs and previous ICBG harvest. He does not use BMP in the cervical spine, one- and two-level open lumbar fusions, posterior interbody fusion, patients with a history of cancer and when patients have concerns.
Since surgeons are still split on use given current data, will better data come out in the future?
"Our current level of information, in my opinion is as good as it gets," he said. "You're not going to get a randomized controlled trial with these patients."
There are surgeons still using rhBMP-2. According to Dr. Hsu's research, around 7.8 percent of surgeons are using rhBMP-2 in open posterior lumbar fusions, 6.2 percent in open interbody surgery and 12.1 percent in minimally invasive interbody surgery for patients with degenerative spondylolisthesis.
Having surgery in the North America also significantly predicted whether patients received rhBMP-2. The data shows:
Posterolateral
• 10.81 percent in North America
• 6.62 percent not in North America
Open interbody
• 2.78 percent in North America
• 5.88 percent not in North America
MIS interbody
• 23.53 percent in North America
• 8.15 percent not in North America
The survey also asked why surgeons chose not to use BMP. The most common overall response was cost and risk of complications. "When you look at the cohort from North America, you see the opposite pattern. Clearly we are concerned about complications, and reports over the past few years of complications have led us away," said Scott Daffner, MD, of West Virginia University in Morgantown.
The impact of the FDA advisory shows BMP use in cervical fusion decreased around 5 percent after the advisory was released. However, overall the BMP use in fusions plateaued at around 28.3 percent. NASS surveyed membership before and after the YODA data was released, asking about their concerns.
Around 85 percent of respondents read one or both of the YODA articles. The concern for complications was relatively similar from 2013 before the YODA data was released to 2014:
High concern for cancer risk: 3 percent in 2013 vs. 4.7 percent in 2014
Moderate concern: 16 percent in 2013 vs. 14.8 percent in 2014
Mild concern: 58 percent in 2013 vs. 54.2 percent in 2014
None: 24 percent in 2013 vs. 26.4 percent in 2014
The numbers were similar for concern in retrograde ejaculation and cervical swelling. Most respondents had high concern for cervical swelling. Among other complications, there was a decreased high concern and relative increase in mild concerns. Finally, they looked at utilization. In ALIF, the respondents reported:
• Always — 40 percent in 2013 vs. 37.3 percent in 2014
• Occasionally — 17 percent in 2013 vs. 14.3 percent in 2014
• Rarely — 12 percent in 2013 vs. 13.7 percent in 2014
• Never — 15 percent in 2013 vs. 18.1 percent in 2014
"In TLIF, we see a shift away from using BMP, and again a relative shift from always and occasionally to rarely and never. Posterolateral fusions, we see the same trend. Folks that used it a lot to folks using it a little bit less," said Dr. Daffner. ACDF and PCF had very little change.
However, when asked whether the physicians significantly changed their use patterns for BMP, 41 percent said they decreased their dose and frequency in 2013, compared to 21.8 percent in 2014. Seventeen percent decreased frequency in 2013, compared with 12.3 percent in 2014. Twelve percent just decreased dosage in 2013, compared with 7.3 percent in 2014. The most interesting was those who didn't change; 55.7 percent reported no change in 2014, compared with just 30 percent in 2013.
"What we see in the 2014 data is not only did people decrease their usage, but they didn't change it after. That decrease was not just a short term reaction to highly publicized articles, but it was actually sort of sustained," said Dr. Daffner. The sales from Medtronic is also dropping; the biologics division reported $809 million in sales in the United States for BMP sales for 2010; in the first quarter of 2015 there was $96 million which projects out to less than half of the sales reported five years ago by the end of the year.
"I think what we'll see in the future is not a complete abandonment of this technology and device but more judicious use," said Dr. Daffner. "We have to weigh the risks and benefits as we go forward."