An independent review of clinical trial data from Medtronic's bone graft substitute, Infuse, indicates that the product is no better than the more traditional gold standard, iliac crest bone graft (ICBG) method, for inducing spinal fusion.
Read more about ICBG: Bone Graft for Spine Fusion
The most recent studies carry a mixed message that needs to be carefully explained so patients "can make informed choices about the type of surgery they would prefer," the researchers wrote.
Responding to growing criticism that the company had under-reported safety concerns and overstated product benefits, Medtronic allowed Yale University Open Data Access (YODA) unprecedented access to all its data. In turn, YODA asked two groups, the University of York Group and the Oregon Health & Science University, to independently review the data.
The Annals of Internal Medicine published the two research teams' independent analysis June 17, 2013.
The University of York group
Researchers from the University of York analyzed data from a total of 1408 individual participants in 12 Infuse studies which included anterior lumbar interbody fusion (ALIF) (5 studies) anterior cervical interbody fusion (1 study), posterior lumbar fusion (5 studies), and posterior lumbar interbody fusion (1 study). These researchers focused on studying the primary end results of successful fusion and decreases in pain level.
The clinical trials they reviewed measured pain using the the Oswestry Disability Index (ODI) at 24 months post-surgery. ODI measures pain on a scale from 0% (no pain) to 100% (extreme pain). Radiographic evidence of bone bridging along with no evidence of motion was required to consider the fusion a success in the trials.
Meta-analysis results of reviewed studies
- Among Infuse recipients, the ODI score measuring pain was approximately 3.5 percentage points better than the ICBG group at 24 months past surgery, which was not considered clinically significant
- Successful fusion rates at 24 months were increased by 12% in the Infuse group versus the ICBG group
- No difference in hospital stay was noted between the two groups
- There was no evidence that using Infuse decreased the number of days before going back to work
- Using Infuse was associated with a shortened surgery time by 27 minutes
- Analgesic use was the same in both groups
- Infuse may be associated with an increased risk for cancer, but the rates of cancer were so low no definitive conclusion could be drawn
- Infuse may be associated with additional possible risks, but as with the risk of cancer, the reviewers concluded that because there were few events in these trials the findings were inconclusive at this time.
The group concluded, "The use of rhBMP-2 (Infuse) in spinal fusion surgery increases the likelihood of successful fusion at up to 24 months, but this does not seem to translate into a clinically significant reduction in pain. The small improvements in fusion and in the level of pain reduction, which manifest after 6 months, also seem to come at the expense of more frequent pain, in the immediate postoperative period and possibly an increased number of cancer cases."1
Oregon Health & Science University group
This review included data from 1981 patients from the Medtronic trials. All the trials compared the use of Infuse to the gold standard, iliac crest bone graft (ICBG). Researchers focused on benefits and harms associated with Infuse compared to ICBG.
Meta-analysis results of reviewed studies
- Fusion rates were similar among ICBG groups and Infuse groups
- Both techniques resulted in similar rates of adverse events when used for lumbar spine fusions
Overall lumbar spine fusion
Researchers reached a broad conclusion for all lumbar spine fusions:
The results of the individual techniques for both lumbar and cervical fusions are further broken down:
- Infuse was associated with an overall success rate for fusion of 61% versus ICBG success rate of 53% at 24 months
- Infuse was associated with non-significantly increased risk for retrograde ejaculation and urogenital problems at 24 months post-surgery
- No difference in fusion rates between the Infuse group and the ICBG group
- Infuse was associated with increased risk for wound complications and dysphagia (difficult or painful swallowing)
- Moderate-strength evidence of no consistent difference between Infuse and ICBG in effectiveness outcomes through 24 months
- No significant difference among the two groups in adverse events
Anterior lumbar interbody fusion (ALIF)
Data from five randomized controlled trials using ALIF technique on 465 patients total were compiled and showed:
Anterior cervical spine fusion
Data from one study with 33 patients showed:
Due to the small sample size for anterior cervical spine fusion, more study is needed before any firm conclusions can be drawn. Infuse has not been FDA-approved for use in the cervical spine and more evaluation is needed to understand the potential risks in this part of the spine.
Posterolateral lumbar fusion in lumbar spine
Data from five clinical trials using posterolateral lumbar fusion technique on 722 patients showed:
Posterior lumbar Interbody fusion (PLIF)
Researchers commented that there was not enough data to draw any conclusions about PLIF.
The researchers' conclusion for all the trials they analyzed states "…We found no evidence that rhBMP-2 (Infuse) is more effective than ICBG in spinal fusions, with some evidence of an association with important harms."
In an editorial on the subject, published in the Annals of Internal Medicine, two spine physicians comment that despite this news, Infuse may be a good choice for its only FDA-approved procedure (anterior lumbar interbody fusion - ALIF) in cases when bone cannot be taken from the hip (due to osteoporosis for example) or as an alternative for patients who don't want to have the bone harvesting surgical procedure.
If you are considering a spine fusion procedure, talk about this meta-analysis report with your surgeon so you can work together to develop the best surgical plan for your individual needs. Comment on this by going to our, Facebook page.
- Mark C. Simmonds, Jennifer V.E. Brown, Morag K. Heirs, Julian P.T. Higgins, Richard J. Mannion, Mark A. Rodgers, Lesley A. Stewart; Safety and Effectiveness of Recombinant Human Bone Morphogenetic Protein-2 for Spinal Fusion: A Meta-analysis of Individual-Participant Data. Annals of Internal Medicine. 2013 Jun;158(12):877-889.
- Rongwei Fu, Shelley Selph, Marian McDonagh, Kimberly Peterson, Arpita Tiwari, Roger Chou, Mark Helfand; Effectiveness and Harms of Recombinant Human Bone Morphogenetic Protein-2 in Spine Fusion A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2013 Jun;158(12):890-902.