ORBIT secondary analysis may aid clinicians in their choice of biologics for RA

WASHINGTON — A secondary analysis of the ORBIT study may provide clinicians with a tool for selecting first-line biologic therapies in patients with rheumatoid arthritis, according to a presentation at the American College of Rheumatology Annual Meeting.

Duncan Porter, MD, of the Institute of Infection, Immunity and Inflammation at the University of Glasgow in the United Kingdom, presented findings from the ORBIT study, in which it was reported that rituximab was non-inferior to a tumor necrosis factor (TNF) inhibitor as first-line therapy for patients with rheumatoid arthritis (RA). The researchers noted many patients failed to respond to the first biologic therapy, and that a tool for stratifying patients may be useful.

“Over the last 15 [years] or 20 years, management of RA has been revolutionized by the advent of biologic therapies,” Porter said. “As a generalization, the response rates to each of these drugs is said to be 60, 40, 20. Meaning that if 60 respond, 40 have a good response and 20 have an excellent response. The question we wanted to answer was how do you choose which drug to give at which time. Now, it is mostly a flip of a coin because there are not a lot of comparative data. Those that do exist are non-inferiority data sets.”

Investigators sequenced RNA from the peripheral blood of 241 patients. They used 169 of those samples to develop response prediction models and used 72 samples for validation.

Results showed eight genes suggested general responsiveness to rituximab and TNF inhibition, while 23 genes suggested a response to rituximab and 23 other genes suggested a response to TNF inhibition.

Follow up with the validation set yielded receiver operating characteristic plots with an area under the curve of 91.6% for general responsiveness, 85.7% for rituximab and 89.7% for TNF inhibitor response when using a 25-feature stratification model for predicting response.

The researchers combined the drug-specific models for response at 3 months. Results of this analysis indicated a sensitivity of 96%, a specificity of 91%, a positive predictive value of 96% and a negative predictive value of 92%.

Patients who were predicted to demonstrate a response at 3 months were more likely to have a strong DAS28 response at 12 months (43% vs. 23%). These patients also were more likely to have a DAS28 remission at 12 months (23% vs. 10%).

Porter said the results of ORBIT can help clinicians find the right drug for the right patient at the right time.

“We are opening up the possibilities for stratification of patients,” he said. – by Rob Volansky

Reference:

Porter D, et al. Abstract #1957. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016.

Disclosure: Porter reports associations with Bristol-Myers Squibb and Roche Pharmaceuticals.