Meta-analysis of the impact of patient characteristics on estimates of effectiveness and harms of recombinant human bone morphogenetic protein-2 in lumbar spinal fusion

Study Design. Meta-analysis of individual patient data from randomized controlled trials of recombinant human bone morphogenetic protein-2 (rhBMP-2) in lumbar spinal fusion. Objective. To determine how patient characteristics impact estimates of effectiveness and harms of rhBMP-2 versus iliac crest bone graft (ICBG) in lumbar spinal fusion. Summary of Background Data. Patient characteristics are thought to impact rates of fusion in spinal fusion surgery, but no analyses examining the effect of patient characteristics on efficacy and safety of rhBMP-2 as compared with ICBG have been conducted. Methods. Using individual patient data obtained from the Yale Open Data Access Project, the impact of patient characteristics on the effects of rhBMP-2 on fusion, overall success, and harms were assessed using linear and generalized linear mixed effects models. Results. Ten industry-sponsored randomized controlled trials of rhBMP-2 were included in the analysis. There is preliminary support for an association between rhBMP-2 and improved outcomes for smokers (P=0.01), individuals under the age of 60 years (P<0.01), and patients of normal weight (P=0.03), but not in patients who are nonsmokers, over the age of 60 years, obese or severely obese. RhBMP-2 usage was associated with decreased harms in individuals with no previous back surgeries but this was not seen in individuals with a previous back surgery (P<0.01). Conclusion. Effects of rhBMP-2 may vary according to patient characteristics. Future studies of rhBMP-2 should include planned subgroup analysis in patients over 60 years, smokers, patients that are obese and severely obese, and individuals with previous back surgeries to better identify those most likely to benefit.