“Apparently the fact that a TNF inhibitor interferes with the pro-inflammatory cytokine shuts down some of the components in the body that are measured by the MBDA more than abatacept—even if it doesn’t mean anything clinically or radiologically,” he said.
Dr. Smolen added that patients with high disease activity should be expected to have the lowest rate of no radiographic progression. That has been shown to be the case using the Simplified Disease Activity Index (SDAI), but when using the MBDA, the results partially reverse, Dr. Smolen said.
“So is such a biomarker appropriate to inform us about disease activity and correlations?” he asked. “Disease activity assessment appears to be the far better way to go.”
The list of potential biomarkers that have produced similarly dashed hopes is a long one, among them the IL-2 receptor, CD4 cells, IL-12 & IL-23.
The Search Continues
He expects new biomarkers to emerge eventually, but they must be legitimate, he said.
“The search must go on,” he said. “We are running biomarker trials currently. And we will actually find markers. But we will have to find the right ones that really distinguish what we want to distinguish. And we need to ask the right questions.”
Dr. van Vollenhoven said he understands the frustration surrounding the slow progress in the search for biomarkers.
“You can always say, ‘Biomarkers are just around the corner,’ [but] people get tired of that,” he said. “What we were hoping for was that we could find biomarkers that could guide us more in terms of treatment.”
That doesn’t mean the field should give up the search.
The MBDA has its merits, he said. An analysis of data from the SWEFOT trial, which compared conventional with biological treatment in early RA, showed that those with a low or moderate MBDA score at baseline have hardly any radiographic progression after two years, while those with a higher score had what he called “a substantial risk,” with about one in five patients experiencing radiographic progression.
This information could help clinicians discuss patients’ prospects and potentially lead to more intense treatment in some cases, said Dr. van Vollenhoven, who reported working as a consultant for Crescendo Bioscience, the developer of the MBDA test.
Also, he said, the MBDA has been better than traditional measures at predicting which patients are more likely to respond to triple therapy as opposed to anti-TNF therapy. Those data are expected to be published in a forthcoming paper, he said.