Prometheus Laboratories has commercially launched Respondr TNF, a novel blood test that predicts inflammatory bowel disease (IBD) patients' likelihood to respond to anti-TNF biologics before initiating treatment. This first-of-its-kind diagnostic tool aims to improve treatment outcomes for patients with moderate to severe IBD by identifying potential non-responders before costly therapy begins.
Anti-TNF biologics, including infliximab, adalimumab, and their biosimilars, are standard first-line treatments for moderate to severe IBD. However, these medications come with significant limitations—approximately 40% of patients fail to respond initially, and up to 50% of initial responders experience secondary loss of response within the first year of treatment. With each treatment cycle potentially costing thousands of dollars, this represents a substantial financial burden on healthcare systems and patients.
"Our validated technology analyzes a patient's unique pre-therapy clearance profile along with a specific genetic marker to predict the likelihood of a patient's response to anti-TNF biologic therapy before initiation," explained Thierry Dervieux, PharmD, PhD, Chief Scientific Officer at Prometheus Laboratories. "Respondr TNF results support providers' therapy selection and management approaches."
How the Technology Works
The Respondr TNF test utilizes a serogenomic approach that examines two critical prognostic factors: pre-therapy drug clearance rates and genetic markers. This combination provides clinicians with objective data to guide treatment decisions before initiating biologics.
A study published in Frontiers in Immunology evaluated the combined effect of accelerated pre-therapy clearance and genetic risk factors in IBD patients considered for anti-TNF therapy. The research, co-authored by Dr. Marla Dubinsky, Chief of Pediatric Gastroenterology and Nutrition at Icahn School of Medicine at Mount Sinai, found that patients with accelerated clearance (>0.326 L/day) who also carried the HLA DQA1*05 risk allele were twice as likely to develop antibodies against the medication.
"We found that patients with accelerated clearance who were also genetic carriers of the HLA DQA1*05 risk allele were two-fold more likely to develop antibodies and each of these risk factors associated with incremental risk and lower likelihood of endoscopic remission," Dr. Dubinsky noted.
Clinical Impact on Treatment Decisions
For clinicians treating IBD, the test provides unprecedented insights into potential treatment outcomes. Dr. Audra Rouster, Division Chief of Pediatrics Gastroenterology at West Virginia University Health Sciences, highlighted the test's value in clinical practice.
"My patients look to me for advice, and before Respondr TNF, we never had objective insights into how patients may respond to these first-line biologics," Dr. Rouster said. "In pediatric IBD care, biologic options are extremely limited, and we can use the data from Respondr to identify patients where response needs to be more closely monitored."
The test enables clinicians to make more informed decisions about treatment strategies. For patients identified as likely non-responders, physicians can consider alternative therapies or implement more aggressive monitoring protocols. For those predicted to respond, clinicians can proceed with greater confidence in the treatment plan.
Complementary Precision Medicine Approach
Respondr TNF is part of Prometheus Laboratories' broader suite of precision medicine tools for IBD management. The company also offers PredictrPK tests, which help optimize dosing for patients already on biologic therapy.
When used together, these diagnostic tools create a comprehensive approach to personalized IBD treatment. If a patient is deemed suitable for anti-TNF therapy based on Respondr TNF results, PredictrPK can then be employed to determine optimal dosing regimens, potentially improving long-term outcomes.
"If an anti-TNF is selected, providers can consider the benefit of active therapeutic management utilizing precision-guided dosing, enabled by our PredictrPK tests, to optimize dosing and further improve the likelihood of achieving sustained remission for patients suffering from IBD," Dervieux explained.
Economic and Quality of Life Implications
The economic implications of improved treatment selection are substantial. Anti-TNF biologics represent a significant portion of IBD treatment costs, with annual expenses potentially exceeding $40,000 per patient. By reducing the number of non-responders who undergo ineffective treatment, healthcare systems could realize significant cost savings.
More importantly, patients benefit from reduced exposure to ineffective medications and their potential side effects. Faster identification of effective treatment approaches can help prevent disease progression, reduce complications, and improve quality of life.
Uncontrolled IBD can lead to serious complications including intestinal strictures, fistulas, and increased risk of colorectal cancer. It also significantly impacts patients' quality of life, affecting their ability to work, socialize, and perform daily activities. By improving treatment selection, Respondr TNF has the potential to reduce these negative outcomes.
Future Directions
The launch of Respondr TNF represents a significant advancement in precision medicine for IBD treatment. As more data becomes available on its clinical utility, the test could potentially become a standard component of IBD treatment protocols.
Prometheus Laboratories has been a leader in IBD patient care solutions for 30 years, with a continuum of tests that support providers throughout the patient care journey—from diagnosis to achieving and maintaining long-term remission. The addition of Respondr TNF further strengthens the company's position in the precision medicine landscape for IBD management.
As precision medicine continues to evolve, similar approaches may be developed for other biologic therapies used in IBD treatment, potentially expanding the range of predictive tests available to clinicians and patients.
