One Step Closer to Precision Medicine in RA


In rheumatoid arthritis, physician scientists are beginning to zero in on personalized medicine. In this interview, Dr. Leslie R. Harrold, chief scientific officer of Corrona, and a University of Massachusetts associate professor, summarizes a study she recently presented at ACR 2020 in which she describes biomarkers and patient characteristics she and her team have identified as taking us one step closer to precision medicine.


"So why is this study important? For me it's important because it lays the foundation for personalized medicine. We known that patients have a window of opportunity where we can maximally improve their disease and get it under control. But once they have long standing disease, it gets much harder to bring the disease under control. Ideally, we would like to identify what drugs patients should be getting as soon as possible based on their clinical profile and this is a much better approach than a trial and error approach to this selection of medications.

So the shared epitope, or SE, is a major risk factor for rheumatoid arthritis. It is associated with the production of anti-citrullinated protein autoantibodies (ACPAs) in patients with RA. In the early AMPLE trial, among ACPA plus patients with early RA, efficacy responses with abatacept (ABA) but not adalimumab were numerically higher in patients who were SE positive versus those who were SE negative.

The goal of this study was to explore that same topic in a real world cohort, in particular, we used data from patients enrolled in the Corrona CERTAIN study and looked at their improvement in disease activity. In this study, we used the CDAI index as a measure of disease activity and looked at change from baseline to six months among moderate to severe RA patients who were both ACPA and SE positive and initiated abatacept or TNF inhibitors.

Leslie R. Harrold, M,D., MPH

We found numerical improvement in ABA versus TNF inhibitors in most of the efficacy outcomes over six months. In these patients with long-standing rheumatoid arthritis who were both SE and ACPA positive. We did the analyses a couple of ways and saw these similar trends. So we did propensity score (PS) trimmed cohorts to maximize the sample size and we also did propensity score matched to do a more select group.

When we adjusted for covariates that remained imbalanced between the groups, in the biologic-experienced propensity scored trimmed cohorts, the improvement is CDAI score with ABA versus TNF inhibitors was significant meaning we saw more improvement with ABA than the TNFs.

Based on these results, it suggests there may be a benefit to using abatacept rather than cycling through a subsequent TNF in the management of biologic-experienced patients who are post SE and ACPA positive.

Now, of course there are some caveats. As with any research in an emerging topic we would suggest that the study be replicated in other patient populations. In addition, there are still some unanswered questions and we hope that there is further research exploring this further. For example, it's not clear what the relationship between the shared epitope and ACPA is. For example, could ACPA just be a marker of the shared epitope. Or, do they both work to impact response to medications or could their be a synergistic relationship. It's not clear. We also don't know if the number of copies of the shared epitope make a difference.

And, we do hope there is further exploration into this are by our group and others."

"At the end of the day, what I think is most impactful about it, is that it's starting to help us identify that there could be biomarkers or patient characteristics that help us make better decisions about what drugs people should be on. At the end of the day, as I said before, giving the right drug at the right time for patients is really the key. I think this abstract really gives that glimmer of hope that we will be getting there and are able to provide more personalized treatments to patients."


ABSTRACT NUMBER: 0801. Leslie Harrold. "The Comparative Effectiveness of Abatacept versus TNF Inhibitors in Patients Who Are ACPA Positive and Have the Shared Epitope: Results from a US National Observational Study." ACR Convergence 2020. Saturday, November 7, 2020

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