People with rheumatoid arthritis (RA) are treated in much the same way – their doctor prescribes a medication, and if that doesn’t work, they’re switched to another one until they find one that does. That’s not an ideal way to treat disease as the burden of uncertainty can add additional strain to a patient. As Dr. Kramer points out in his article on heterogeneity, RA is a disease that can have multiple causes and manifest in different ways, so we need diverse approaches.

One Patient’s Joints Are Not Like Another’s

We’re working to better understand exactly what is happening in each RA patient’s joints at the cellular level to help define the different types of RA. That research is supporting our efforts to identify biomarkers, which can help determine whether patients will respond well to one drug versus another. Specifically, we’re looking at what’s happening in the linings of the joints themselves. This yields a surprising amount of information about each patient’s RA, such as the state of their disease as well as their clinical manifestations.

The identification of different types of RA based on patients’ joint pathophysiology—the way a disease affects a body’s functions—in turn allows us to study what happens when we try different therapies in these patients. For instance, patients with one type of RA may respond well to an anti-TNF drug, while those with a different type of RA may not. Our knowledge of the different types of RA based on joint pathophysiology could help us to identify biomarkers for individual RA patients.

The Power of Uncertainty

Though our work is based in hard science, sometimes we have to take a leap of faith based on our accumulated knowledge. There are currently no biomarkers for RA, but we’re going to keep looking because we believe they have the potential to change the future of treatment.

Genentech is leading the field in looking at fundamental disease mechanisms and the biomarkers associated with various disease types. We are leveraging the work we’re doing in biomarkers across our entire portfolio to see how it applies to many diseases. For instance, we’ve stratified clinical trials in asthma, inflammatory bowel disease and lupus based on which patients respond to specific medications. Uncovering RA biomarkers would allow us to have diagnostic tools available alongside our medicines. This could, in turn, help us determine which patients will get the most clinical benefit from which drug. We’re also currently involved in a collaborative effort with other pharmaceutical companies to find biomarkers that identify which RA patients are likely to have no response to anti-TNF drugs.

Identification of a biomarker in RA is crucial, as there are currently no “personalized” RA treatments as there are in cancer. This work is much more complicated in RA than in cancer because there’s no precedent for biomarkers in inflammatory diseases. But we’re up to the challenge; we know that sometimes the days where you don’t have the answers are the kinds of days where those unexpected breakthroughs come to light.