This article is more than 5 years old. Information may no longer be current.
Current, emerging treatment options improve outcomes for patients with RA
Eric M Ruderman, MD, is professor of medicine (rheumatology) at Northwestern Medicine’s Feinberg School of Medicine. He also conducts research about new treatment options for patients with rheumatoid arthritis. Ruderman spoke with Healio about his research, the current approach to treatment in patients with RA and the new options on the horizon for these patients.
What does your research focus on?
I’ve been involved in trials of new therapies for the last 25 years, since I started in rheumatology. I’ve participated in a number of very exciting multicenter trials, many of which have investigated novel therapies that address unmet needs and change the way we treat RA.
Northwestern University is also working on a large, ongoing project in personalized medicine. Specifically, we’re trying to determine whether biopsies from the joints of people with active disease can tell us, on a cellular level, which drugs are best for which patient. It’s a bit like the oncology model. You wouldn’t treat a patient with breast cancer or with lung cancer without a biopsy. We’re trying to determine, with a biopsy, what the individual cells are, what the markers on those cells are and what the genetics of those cells are. You can then tailor therapy to the patient based on the biology that you’ve identified in that patient.
People have tried to do this for years in rheumatology using blood-based markers without a tremendous amount of success. Harris R Perlman, PhD, chief of rheumatology in the department of medicine at Northwestern, has spearheaded a large project that works with a number of other institutions to obtain ultrasound-guided tissue biopsies of the joints, which is where RA begins in the body. This group is looking at what kind of cells are in the joints, what markers are there and what we can learn from that in regard to treatment decisions. It’s still early, but we’re hoping that biopsies done before treatment can help us determine who responds to therapy and who doesn’t; we also want to see what markers might indicate a response to drug A versus drug B. The hope is that, in the future, we can select therapies directed at the individual patient we intend to treat rather than by happenstance. The biopsies are done now with an ultrasound and a needle, which limits morbidity. It’s just a matter of getting the right tissue. It isn’t any more invasive than taking some fluid out of the joint, which is something we’ve done for years.
How does the treat-to-target approach work in RA?
Prior to the treat-to-target approach, rheumatologists often would not make medication changes if a patient reported that he or she was feeling better. If the patient wasn’t getting better, we would consider making changes. It was a very basic approach to therapy.
However, you wouldn’t change insulin therapy in a patient with diabetes based on whether or not the person felt like his blood sugar level was high, just like you wouldn’t adjust medication in a patient with high blood pressure based on a headache or blurry vision. You follow blood sugar and treat to a target HbA1C; you follow blood pressure and treat to a target.
The treat-to-target model is a common-sense approach that looks at the patient in a matter-of-fact way, but the challenge with RA is that we’ve never had an easily measurable target. We have markers of inflammation, such as the sedimentation rate, which is generally elevated in patients whose disease is active and does tend to improve in people whose disease gets better, but it’s an imperfect marker. There are certainly people with very active disease who have a pretty normal sedimentation rate; there are also people whose disease is pretty well-controlled with a persistently elevated sedimentation rate. We’ve struggled with how to handle this.
In the last 10 to 15 years, clinicians have begun to question whether our target should not be a single number, but rather a composite outcome measure. There are data points that measure the number of active joints, swollen joints and tender joints that a person has at a given time. This composite number might include sedimentation rate or C-reactive protein, which is another marker of inflammation. It should also include measures of function. There is a functional assessment that asks what patients are capable of: Can you wash your hair? Can you lift a glass? Could you mow the lawn if you had to? These are simple, straightforward factors that help clinicians understand how much the disease is impacting patients’ lives.
We can use all these factors to develop a composite scale. We can say whether the disease is well-controlled and if a patient is effectively in remission; we can say, in patients who score a little higher, that they have low disease activity. We can also identify moderate and high disease activity. We want to be able to measure where any patient is at any given time.
The premise behind the treat-to-target approach is achieving the best possible outcome, which – in the case of RA – is remission. If you haven’t achieved this in a given patient, you adjust the medication and check back in a defined period of time to evaluate the response to the adjustment you made. You have to give the medication time to take effect, but – if they still haven’t reached the point you want them to when you check again – you switch to a different drug or add a new agent.
Since treat-to-target first came to the forefront, some papers have shown that this strategy results in better outcomes. These findings looked at two groups of patients. One group came in every three months. These patients might have their medications changed, or they might not, but, regardless, we see how they’re doing after a couple of years. The second group comes in every three months, but they’re mandated to change their treatment if they haven’t reached their specified target unless there’s an explicit reason that they can’t. Those patients did better; the percentage of patients who achieved remission at any point in time was much higher in the group that was treated to a target. There are also data showing that people in remission do better in the long run. Treating to target achieves therapeutic goals in a more effective manner and also leads to better long-term outcomes.
The challenge with this approach is that it’s not black and white. There are many questions you have to ask, including what’s appropriate, what’s the right target for the patient, is the benefit worth the potential risks of adding another medication, and so on. The treat-to-target approach may tell you when it would be appropriate to adjust or increase medication, but you also have to ask, for that individual patient, whether the change makes sense. This is part of the art of medicine; it’s not just about a computer algorithm.
This is, objectively, how rheumatologists like to practice these days; it’s how we teach fellows and trainees. Not everybody uses this approach, however. There is no question that not all providers measure specific outcomes every time they see a patient and, certainly, not everyone will make changes when a measurement suggests that might be appropriate. There are a lot of reasons for that. It remains an issue, but, increasingly, we’re using the treat-to-target approach as a way to manage RA.
What role do biosimilars have in the treatment of RA?
Biosimilars aren’t necessarily going to change the treatment paradigm in RA, but they do have a potential role in reducing the cost of therapy. In certain cases, if the price were different enough and there were several options available to the patient, the reduced cost would drive us toward using the biosimilar. This practice has certainly been true in Europe and Asia, where biosimilars have been available for several years at a much lower price point. In these regions, more widespread use of these agents has both reduced the cost of biosimilars and driven down the cost of the originator products.
Unfortunately, in the U.S., this hasn’t happened, and I’m not sure when it’s going to happen. In the U.S., the cost of therapy to a patient and to a health care plan bears only a passing resemblance to the actual wholesale cost of the drug. Even a biosimilar that is 50% less expensive than a branded TNF inhibitor may not cost the insurer any less because of rebates and other structural issues that allow the branded manufacturer to discount their drug. It certainly doesn’t change anything for patients, because none of those factors, such as the rebates, get passed on to the patient. As a result, there isn’t a large force that’s driving us to use biosimilars. In addition, ongoing patent litigation aims to keep these agents off the market in favor of the originator product. Four biosimilar TNF inhibitors have been approved in the U.S., but two of them aren’t even on the market because of this litigation, and we don’t know when they’ll be available. In short, in the U.S., biosimilars are generally not available to the extent that they are in other parts of the world.
The exception in the U.S. is infusion products. Most biologics are now given as a self-administered injection, though there are still some infusion products. In particular, infliximab (Remicade, Janssen) – the first biosimilar approved in the U.S. for rheumatology – is more likely to reduce costs, because the cost of this agent relates to how the hospital, office or the infusion center purchases the drugs.
In the U.S., Medicare is the largest insurer that pays for these drugs. Medicare will pay a specified amount for a particular drug, regardless of whether it’s a reference product or a biosimilar. The reimbursement is the same either way if you have Medicare. Infusion centers and hospitals have the ability to purchase the biosimilar at a significant discount. It wouldn’t make sense for them to purchase the reference product.
We saw this scenario play out several years ago with zoledronic acid (Reclast, Novartis). Providers transitioned to the generic version of this drug virtually overnight because Medicare said, “This is what we’ll pay for this drug. This is the single code.” That price covered the cost of the generic as well as acquisition and infusion, but it was frequently lower than the acquisition cost for the branded version of zoledronic acid. As a result, few infusion centers purchased the branded version of the drug anymore. I think the same thing is likely to happen with biosimilar infusions.
However, I don’t know when this will change for self-injectable agents. We’ve been watching this for a while. There isn’t a lot of resistance on the part of rheumatologists and other physicians to using biosimilars, if the opportunity were to arrive or if the insurer said it was necessary. A change in the approach insurers take with these agents is what will change things. No provider will go out of their way to write a prescription for a biosimilar right now because there’s no upside or advantage. There’s no reason for me to say, “Mrs. Smith, you need adalimumab (Humira, AbbVie). I’m going to write a prescription for a biosimilar to adalimumab because that’s what I think you should get.” There is no incentive for clinicians to prescribe biosimilars. At a certain point, if the insurer tells me that the cost to the patient will decrease if I prescribe the biosimilar, then that’s what we’ll do. But we’re not there yet.
Collapse
Read more about