Use of Biologics in Rheumatoid Arthritis

Stanley B. Cohen, MD: We generally will initiate a biologic somewhere between 12 and 24 weeks in patients on a conventional synthetic DMARD, who still have evidence for active synovitis, symptoms, and an active disease as measured by one of our disease activity measurements. That’s when we’ll start a biologic. And unfortunately, there are no good data to say which biologic to start; it’s purely empirical. We, who have been around for a long time, are comfortable with what we know.

So, historically, most rheumatologists will start with a TNF inhibitor, and this has generally been Enbrel (etanercept) or Humira (adalimumab). Although now, speaking of the insurance companies, they control which TNF inhibitors we can actually use by their contracts. It really doesn’t matter. They’re all effective and have the same safety profile, and generally we’ll start with those.

In a patient who does not have a response, we would like them to have a response with the biologic. Generally, we will look again in 8 to 12 weeks, and by 12 weeks, patients will have a good response or no response. So, we know from multiple studies with TNF inhibitors, if they’ve not responding by 8 weeks, they’re not going to respond. At that point, we’ll move on to another biologic. Historically, it has been a second TNF inhibitor, but that’s changing.

There have been a number of observational registry studies and so forth, which have suggested that patients who switched to a different mechanism of action—whether it be abatacept, which blocks T-cell activation; tocilizumab or now sarilumab, which is on the market, that both block the IL6 receptor; or rituximab, which depletes B cells—might do better than going to a second TNF inhibitor.

Biologics have revolutionized the treatment of rheumatoid arthritis. When we had methotrexate, we could help a third of patients. Now with the biologics, we have good clinical responses—depending on however you measure it—in about 60% to 70% of our patients. The issue with our therapies is that we’re cycling through them to maintain low disease activity or remission. We know from observational registries, that if we start a TNF inhibitor in an RA patient, 42% of patients are no longer on that after 2 years.

So, why are they going off of the medication? They’re having toxicity, they’re losing efficacy, or they lost their coverage. My point is, a lot of people in drug development are concerned that it’s a very crowded market with RA therapies, but we need new therapies. We need new drug development. We prefer novel development. We don’t want any more “me-too” drugs. We are cycling through these various therapies to achieve these outcomes, and for some patients, we are running out of drugs. So, it’s very important that people continue to focus on rheumatoid arthritis and develop new therapies that we can use in the clinic.