Molecular signature-assisted drug selection may improve results in rheumatoid arthritis
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Molecular signature response classifier-assisted rheumatoid arthritis treatment selection may improve real-world results in patients with rheumatoid arthritis, according to data published in Expert Opinion on Biological Therapy.
“This study reports the second interim analysis of the [Accelerate Information of Molecular Signatures (AIMS)] real-world study evaluating the clinical utility of the [molecular signature response classifier (MSRC)] test,” Vibeke Strand, MD, adjunct clinical professor at the division of immunology and rheumatology at the Stanford University School of Medicine, and colleagues wrote. “Change from baseline in disease activity according to CDAI scores in response to treatment selections based on MSRC test results was assessed and the resulting cost savings per patient were evaluated.”
To evaluate the impact of MSRC tests on RA therapy, Strand and colleagues conducted an interim analysis of data collected as part of the AIMS study, which included data from a network of 72 rheumatology practices in the United States. Data for this analysis were collected between September 2020 and November 2021. Patients were eligible for inclusion if they were aged 18 years or older, received their diagnosis and treatment from a rheumatologist, were disease-modifying antirheumatic drug-naive or received TNF inhibitors at the time of testing.
Study endpoints included changes from baseline in absolute clinical disease activity index (CDAI) scores at 12 and 24 weeks. Treatment responses were also assessed “within and between” patient subsets, including the molecular signature of non-response to TNF inhibitors among those treated with TNF inhibitors and those who received non-TNF inhibitor DMARDs. Other subsets included patients with no detected molecular signature of non-response among those treated with a TNF inhibitor, as well as those who received a non-TNF inhibitor DMARD.
Changes in CDAI scores were reported when patients presented for their 12- and 24-week follow-ups.
According to the researchers, patients who were predicted TNF inhibitor non-responders who received a DMARD with an alternative method of action demonstrated an “up to 1.8-fold greater improvement in CDAI scores,” compared with those who received a TNF inhibitor at 24 weeks — 14.2 vs. 7.8 (P = .009). At 12 weeks, the improvement was 12.8 in patients who received DMARDs and 8 in patients who received a TNF inhibitor (P = .083).
“Blood tests that reveal a person’s unique molecular disease signature and match it to the most effective existing therapy are clinically valuable and make a significant impact on patient treatment outcomes,” Sam Asgarian, MD, MBA, chief medical officer of Scipher Medicine, said in a press release.
Reference:
Scipher Medicine Publishes New Data Further Supporting Clinical Utility of PrismRA Blood Test. https://www.sciphermedicine.com/scipher-medicine-publishes-new-data-further-supporting-clinical-utility-of-prismra-blood-test%ef%bf%bc/. April 28, 2022. Accessed May 3, 2022.
Perspective
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The development of the VECTRA-DA measurement by Crescendo Biosciences marked the introduction of a commercially available, specific, validated and predictive biomarker for measuring disease activity in patients with rheumatoid arthritis. Now, the arrival of the MSRC test developed by Scipher Medicine Corporation heralds the dawn of precision medicine for medication selection when managing patients with RA.
Although we have made tremendous advances in the diagnosis and treatment of RA, current treatment paradigms are still guided by clinical habit and the formulary requirements of insurance companies and pharmacy benefit managers. As such, TNF inhibitors remain the typical first-line agents following methotrexate failure.
In the present study, Strand and colleagues successfully re-demonstrate significant improvements (i.e., up to 1.8-fold greater improvements in CDAI measurements) in patients whose RA medication choice (i.e., TNF vs. alternative mechanism of action) was informed by the MSRC test. Given that not all patients will respond to TNF inhibitors and many formularies mandate multiple TNF-inhibitor failures prior to using medications with alternative mechanisms of action, the MSRC test should prove useful in reducing time spent on ineffective treatments and yield cost savings for the health system as a whole.
The paper raises several potential questions as well as directions for future exploration. The immunobiology of RA can change in a given individual over the lifetime of their disease. Conceivably, this may impact one’s responsiveness to a particular medication.
Rheumatologists sometimes return to previously used therapies in a given patient only to find that they do “work” again even after a previous failure. It would be useful to see if the MSRC result similarly changes over the lifetime of a patient, and at what interval of time one could potentially retest and see a variant result, which could drive clinical decisions.
In the future, there will likely be new TNF inhibitors to the market, such as Ozoralizumab (Ablynx NV). Given that the structure of this drug features a unique non-IgG biochemical structure, and confers resistance to the development of anti-drug antibodies, it will be useful to see if the MSRC test results can be replicated in such newer generation TNF inhibitors when they are commercially available.
Finally, the test predicts a patient’s likelihood of nonresponse to a TNF inhibitor, but it does not specifically predict your patient’s response to the drug class. As an example, if the MSRC test predicts that your patient has a 5% or lower chance of responding and they have a moderately elevated Vectra DA score of 30 (lower end of moderate), and they are on a TNF inhibitor presently, and they have previously failed other MOA drugs, we are still left with clinical judgement to decide if the VECTRA score of 30 and their present clinical status represent a good outcome for that individual vs. time to move on to a different drug.
Just as the arrival of the biologic era transformed the practice of rheumatology and what we could do for our patients, the advent of more personalized medicine is a reason to be excited yet again for the future of rheumatology, where we will be able to make better clinical decisions for our patients and deliver better outcomes. The present study clearly reinforces the value of using the MSRC test to guide TNF vs. non-TNF drug choice.
Still, the true value of this test will only be fully realized when there are other tests that can define a patient’s likelihood of responsiveness to alternative MOA drugs. Hopefully Scipher can continue their work in this area and develop even more useful tools for rheumatologists in the future.
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