No Cost Advantage for Transplant-Rejection Blood Test vs Routine Biopsy, But Patients Prefer It

September 14, 2010

September 14, 2010 (San Diego, California) — Heart-transplant patients prefer the AlloMap (XDx, Brisbane, CA) gene-expression profiling test over routine endomyocardial biopsy, probably because it cuts the need for such biopsies in allograft rejection surveillance, but it doesn't save the healthcare system money and in some cases may even add to costs, according to a follow-up economic analysis [1] of a previously published randomized trial [2].

The cost-effectiveness of an AlloMap-based surveillance strategy, which calls for only provisional biopsies, can be high, depending on the cost of the more invasive, higher-risk biopsy-based strategy--which varies widely among centers, Dr Paul A Heidenreich (Veterans Affairs Palo Alto Heart Care System, CA) observed when presenting the analysis here at the Heart Failure Society of America 2010 Scientific Meeting.

"If the cost of biopsy is very low, then gene-expression profiling will be more expensive," he observed. Still, in such cases, "even a minimal improvement in quality of life would probably make the increased costs worth it."

As it happened in the cost-effectiveness analysis of the Invasive Monitoring Attenuation Through Gene Expression (IMAGE) trial, heart-transplant recipients randomized to the AlloMap-based and biopsy-based surveillance strategies used healthcare resources to about the same degree: they spent about the same time in intensive care, had about the same number of in-hospital days, visited the emergency department and needed angiography and right- or left-heart catheterization about as often, and required a similar amount of medication. But AlloMap-monitored patients underwent echocardiography significantly more often.

Allomap Tends to Be a Costly Strategy

As the featured discussant for Heidenreich's presentation, Dr Mandeep R Mehra (University of Maryland School of Medicine, Baltimore) contended not only that the cost of endomyocardial biopsy varies widely (while the AlloMap test's cost is relatively fixed), but also that surveillance protocols at some centers call for more frequent biopsy than other centers. But, "in no scenario does the gene-expression profiling test come out as cost-effective or cost-minimizing. It does tend to be a costly strategy," he said. "The cost assessment must be weighted using not only the variable cost of biopsy, but also the variable frequency of performing biopsies in general practice, and I don't believe that analysis was undertaken."

As previously covered by heartwire , the AlloMap test assesses expression levels of 11 genes related to the biochemical processes of acute transplant rejection and can determine high or low likelihood that those processes are indeed occurring. Higher scores on the test correlate with greater risk of acute rejection by histology. The test was FDA-approved in 2008.

IMAGE had randomized 297 transplant recipients to AlloMap-based surveillance and 305 to a strategy of scheduled endomyocardial biopsies; patients had to be at least six months posttransplantation and free of any signs of rejection at baseline.

An AlloMap score >34 led to endomyocardial biopsy, as did any clinical or echocardiographic evidence of graft dysfunction; lower scores allowed patients to avoid biopsy. As reported before, after a median of 19 months, the two groups showed no difference in the composite primary end point of hemodynamically significant rejection, graft dysfunction not due to rejection, death, or retransplantation. Mortality alone was also similar. And AlloMap-monitored patients had fewer biopsies, 409 vs 1249 for the other group (p<0.05).

But according to the current analysis, echocardiography was performed at a prevalence of 4.1 studies per patient for AlloMap patients and 3.6 per patient for biopsy patients (p<0.05).

The overall per-patient cost of care averaged $26 700 and $26 100 in the two respective groups and so was "pretty much identical," Heidenreich said. Over time, however, patients reported significantly greater satisfaction following the AlloMap-based strategy.

Mean Patient-Satisfaction Scores* in IMAGE

Time point AlloMap-based surveillance Biopsy-based surveillance P
Baseline 6.86 6.74  
1 y 8.14 6.64 <0.001
2 y 8.74 6.66 <0.001

*Patients were asked to rate their answer to the question "how satisfied are you with the current method of detecting rejection?" on a scale of 1 ("very unhappy") to 10 ("very happy")

In his presentation, Mehra referred to data from about five years ago suggesting that the cost of endomyocardial biopsy can range from about $640 to almost $5600, depending on a number of factors, such as, for example, whether a center does it in a cath lab or surgical suite.

Moreover, he noted, "There are some centers that stop protocol biopsies for rejection at the one-year time point; there are some centers that continue biopsies at three-month intervals for the second year and then stop. There are some centers that biopsy every six months for the next two years and then continue annually thereafter. And what's interesting about these centers is that they all have the same outcomes in the patients--questioning, in fact, the very strategy of performing surveillance biopsies beyond the phase of [early posttransplant] vulnerability in these patients."

Neither Biopsy Nor Gene-Expression Profiling Useful in Improving Clinical Outcomes

The primary IMAGE results, Mehra continued, suggested that "likely neither biopsy nor gene-expression profiling is useful in improving clinical outcomes in late low-risk survivors after heart transplantation. In fact, perhaps the strongest clinical message to emerge from this very important study is that we should question ourselves on whether it's time to do away with excessive and protocol-driven biopsies in low-risk [cardiac-transplant] survivors, particularly after the first year of transplantation. And in fact, it may not be necessary to replace that strategy with anything other than better standard clinical and functional allograft vigilance."

In the question-and-answer period following Mehra's presentation, session comoderator Dr Carl V Leier (Ohio State University, Columbus) observed that one of the questions yet to be addressed in AlloMap studies is whether it provides enough confidence to "ratchet down" the immunosuppression regimen, often one of the objectives of rejection surveillance.

In general, Mehra replied, immunosuppression is most often "aggressively adjusted" in the high-risk first six months after transplantation. "Maybe tests like AlloMap are suited to that early phase of transplantation," he said. "There's a fundamental difference between their molecular signals and endomyocardial biopsy."

The latter, even if it's completely normal, he said, "carries no predictive value for, say, the subsequent endomyocardial biopsy four weeks down the road. On the other hand, molecular signals may predate allograft events. And therein may lie the benefit of doing gene-expression profiling. But all that needs to be assessed, it's hypothetical."

The main IMAGE trial and the current economic analysis were funded by XDx, from which Heidenreich reports receiving research grants; he further reports no other relevant conflicts of interest. Mehra reports he has no current disclosures but that he had previously received research grants or consulting fees from XDx. Leier had nothing to disclose.

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