TEAR Trial and Combination Therapy for RA

Derek van Amerongen, MD, MS: The TEAR trial is interesting because, I think, it validates a lot of the approaches that managed care has used traditionally, such as starting with less intensive therapy like methotrexate and building upon that once you identify patients who are not responding in an optimal way—or at least to the level that the clinician or the patient would hope. Methotrexate was added to a TNF or sulfasalazine was added to methotrexate in order to improve the outcomes that were seen. Certainly, that is a very logical clinical approach, and I think that the trial validates a lot of the messages that we’ve been sending out for managed care over the years: to start with a more conservative therapy and move to the more aggressive/intensive therapy, but make sure that we’re giving the patient an opportunity to respond at each step along the way.

I think the TEAR trial does validate the use of combination therapy—combination being methotrexate plus something like a TNF. It certainly substantiates the idea that, as we build on that conservative therapy to more intense levels, having 2 agents in place might well give us the kind of outcomes that we’re hoping to see. However, I think that it’s also important to recognize that the validation of the combination therapy with the TEAR trial also comes after they’ve been able to clearly demonstrate the importance of starting with monotherapy and making sure that we’ve given the patient an adequate time period to respond.

Rheumatoid arthritis is a lifelong condition, and the drugs that we use today have been able to demonstrate very impressive clinical improvements. At the same time, we all recognize that they’re very expensive and certainly have potential for adverse events and tolerability issues. One of the challenges that we have with drugs coming to market for rheumatoid arthritis is the paucity of head-to-head data, understanding how a new drug compares to the existing agents: Is it better in a way that is going to be clinically meaningfully, as opposed to something that’s simply statistically significant? How do we as an industry, as a profession, provide useful information for a clinician in the office to help him or her understand whether or not a new drug is one that he or she should be moving existing patients to, or one that should be reserved for either subgroups of patients or new starts? That’s a challenge, and I’m not sure today that we have an answer to that. Hopefully, over the next few years, we’ll see more and more head-to-head data come out.

Certainly, one of the things that a lot of third-party organizations are trying to develop are frameworks to understand the value of drugs—existing drugs as well as new drugs—with value being that combination of clinical benefit as well as cost, so that all of us can understand what the way is to get the optimal clinical result for a cost that is in line with that result. From a managed care perspective, our goal is to provide members with the optimal clinical care and provide access to all of the services that each member will need for their condition. And in this case, we’re talking about rheumatoid arthritis, and one of the challenges of rheumatoid arthritis is not only the lifelong progressive nature of the condition but also the cost, which has really driven it into the top category for most health plans, as well as most employers, in terms of drug cost.

From a managed care perspective, the lines of therapy that come together to provide not only the optimal outcome but also an outcome that’s in line with the cost of that therapy are really what we’re trying to achieve. Combination therapy, for example, with subcutaneous methotrexate certainly has a role. The role is really going to be defined by the clinical condition that we’re talking about: the aspects of the individual patient and the experience of that patient in terms of response to earlier lines, such as oral methotrexate, the addition of a TNF, and so on.

Ultimately, I think the challenge for all of us—managed care, clinicians, employers, pharmaceutical companies, as well as consumers—is: How do we identify the treatment options that are going to be best for individual patients—but also options that are not going to deliver the optimal clinical outcome—and do so at a cost that everyone believes and recognizes is in line with the clinical improvement?

The future of rheumatoid arthritis is going to evolve towards even more consumer-centric approaches. In other words, how do we make sure that the information that everyone is providing—all of the stakeholders—is aligned with what the individual patient/consumer needs to know in order to maximize his or her outcome? I think we’re certainly seeing a shift away from parenteral treatment as more oral treatments come out, and those are all treatments on a par with the clinical results we’ve seen with the parenterals: the subcutaneous treatment, the IVs. That’s going to drive a lot more focus on self-management by the individual—of course, with the guidance of the physician, but breaking away from the mind-set we had 20 or more years ago, where every single patient had to be treated in a doctor’s office frequently with an IV that he or she may or may not really have understood.

I think a lot of this is in line with that drive towards value. How do we identify the treatments that are going to give the optimal outcome and be in line—in terms of cost—with what consumers/patients, society, and employers recognize as having value? Certainly, we have a challenge with many chronic conditions such as rheumatoid arthritis in terms of the cost burden on society and the economy. As the population continues to age, we see that group of RA patients increase over time. It’s going to be a challenge for everyone in the medical profession to make sure that we’re providing the optimal care at a cost that is tolerable.

However, I think that with a lot of the information that’s being generated in terms of outcomes and how we align those outcomes with cost to create that value equation, we will have lots of opportunity in the future for driving towards the best outcomes we can, hopefully, achieve—and at a cost that everyone agrees is acceptable and reasonable.