“If we want to make faster progress,” Dr. Parmar said, “if we want not just a series of negative results from lots of individual biomarker-defined stratified trials, we need to think more strategically.”
Window of Opportunity
In another talk, Bernard Combe, MD, PhD, professor of rheumatology at the University of Montpellier in France, said the holy grail of stratified medicine that’s tailored to the needs of a specific patient in daily practice has been elusive, but there are increasingly reliable factors that can be used to help make treatment decisions. He said the goal of treatment should be the “right drug for the right disease at the right time.”
“We currently have no valid predictive factors which have been identified to [guide] the choice of a specific treatment in daily practice,” he said. “However, we may select therapeutic strategies based on baseline predictive factors of outcome, autoantibodies, control of disease activity, patient profile and patient preferences.”
One fairly recent study—an analysis of the French ESPOIR cohort data of RA patients treated with disease-modifying anti-rheumatic drugs—showed how a single factor can drastically change the likelihood that an RA patient will respond to methotrexate, for instance. A patient with elevated CRP, a high swollen joint count and who is ACPA positive, but shows no erosion on X-ray, was found to have a 33% risk of radiographic progression. But that same patient with erosion was found to have a 64% risk.1
Other studies have shown the apparent importance of response at the start of treatment, suggesting that a “window of opportunity” exists in the early phase of disease, Dr. Combe said.
A different analysis of the ESPOIR data showed drastic differences between patients with sustained DAS28 remission after one year of treatment and those with persistent moderate disease activity after a year. More than 80% of those in remission after a year were in DAS28 remission after 5 years, compared to 39% in the other group. The real-life effects were striking: 45 days of work missed over five years in the group in remission after a year, compared with 272 in the other group.2
“Earlier response is a very good indicator of achieving a remission state at one year,” Dr. Combe said.
Gene Classifications
Michael Townsend, PhD, senior scientist at Genentech, discussed progress by researchers there in classifying gene sets and using those classifications to help predict treatment response.
Using samples in early RA from knee joint synovium, researchers have developed a scoring system to describe the samples as “lymphoid,” “myeloid” or “fibroid,” and have used those classifications to help predict treatment response.
