Sequencing of Therapy for Rheumatoid Arthritis - Episode 6

Treatment Options for Rheumatoid Arthritis

Derek van Amerongen, MD, MS: Rheumatoid arthritis is similar to most chronic conditions in the sense that there is an algorithm—going back to the ACR guidelines that clearly identify that—that starts with more conservative, less invasive or expensive treatments, and goes stepwise to the ones that are more intense and have, hopefully, greater efficacy but also carry higher rates of potential adverse events and, of course, high costs.

Our guidelines, which are very similar to those you see across the managed care sector, urge physicians to start with the lower cost—simpler, if you will—interventions, up to and including methotrexate. When we get requests for a drug like a TNF inhibitor—say, Humira (adalimumab) or Enbrel (etanercept)—we would hope to find that there has been a meaningful trial of that drug for, say, 3 to 6 months to establish that, in fact, the patient has responded, or at least responded to the optimal level. At that point, it’s a lot easier for the role of a drug like Humira, Enbrel, or even Remicade (infliximab) to be identified and to say, “Yes, that’s the next logical step in the treatment pattern.”

One option for treating severe rheumatoid arthritis is subcutaneous methotrexate. Typically, that is for patients who have severe RA and have failed to respond to generic methotrexate. We don’t see a lot of it because of the efficacy and very high level of tolerability of the TNFs: Remicade, Enbrel, and Humira. Certainly, subcutaneous methotrexate is an option. We do allow it if the member meets the criteria, as I’ve outlined it. However, I think the trend seems to be more towards the TNFs. In fact, this trend has been going on for some years, and even as more oral drugs come out, I think they supplant a lot of the parenteral treatments, as well.

Subcutaneous methotrexate is typically covered for severe rheumatoid arthritis, usually in a scenario where the patient has failed to respond—or at least not responded to the level that either the patient or clinician would expect—to something like an oral methotrexate. It has a prior authorization that’s typically required, not so much for cost but mainly because of the potential for adverse events, and also because the subcutaneous version of methotrexate is primarily indicated for severe RA, as opposed to mild or moderate RA, or as a first-line treatment.

Certainly, what’s driven rheumatoid arthritis into the top-10 or, at most, top-15 category in terms of drug costs, nationally, has been the advent of the TNFs—Humira, Enbrel, Remicade—that really revolutionized the treatment of rheumatoid arthritis over the last 15-plus years. We cover those drugs that are universally covered for rheumatoid arthritis. There is universally a prior authorization required. Typically, that prior authorization reflects the expectation that patients will start with less intense treatments and build their way up to something like a TNF. We do want to see, at least, a meaningful trial of something like oral methotrexate, usually in the 3- to 6-month range. But certainly, if the clinician feels that the level of improvement has been suboptimal, that’s an appropriate time to request a drug like a TNF.

Combination treatment in rheumatoid arthritis—combination treatment being defined as, say, methotrexate plus a TNF—has been around for a long time. Certainly, one of the strategies that many rheumatologists use is to layer the TNF on top of the methotrexate, as opposed to stopping the methotrexate or NSAIDs, and then moving solely to monotherapy with the TNF.

The appropriateness of that is probably going to depend on each individual clinical situation. Our plan, as do many plans, will defer to the recommendation of the clinician as to whether or not the combination of methotrexate plus a TNF is most appropriate versus the TNF alone. Regardless, we’re, ideally, only talking about the use of a biologic like a TNF if the prior treatment with a methotrexate has not reached the clinical endpoints that the physician was hoping for.

Biologics are frequently used in rheumatoid arthritis, and that’s certainly the main driver for rheumatoid arthritis being a high-cost area today, despite the fact that it is not as common as conditions like diabetes, for example. Biologics are typically viewed as second-line treatments; i.e., after a meaningful course of methotrexate. Are there conditions or situations when we approve biologics as our first-line therapy? Potentially. I’m thinking, perhaps, of a situation where you had a brand-new diagnosis of rheumatoid arthritis with significant joint pain, anatomical distortion, and a patient whose condition was progressing very rapidly. If the clinician did not feel that this patient had the time to start on a course of methotrexate, moving straight to a TNF might be appropriate. However, I think the default, both clinically as well as from the managed care perspective, is that we’ll see progression from the less intense therapy to the more intense therapy in order to give each line of therapy an opportunity to work.