The Value of Monotherapies for RA

As with many treatments in modern medicine, the treatments for for rheumatoid arthritis (RA) have advanced significantly in the last 2 decades. It was not all that long ago, about 85 years or so, that the gold standard of treatment for RA was in fact intramuscular injections of gold. While there is some evidence that gold may help with symptoms, many with RA were left without relief from the pain and disability that comes with the disease. In the decades that followed, RA treatment moved from to corticosteroids and traditional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, leflunomide, and hydroxychloroquine.

Some patients considered the relief they experienced from these therapies to be miraculous but others found them less efficacious or had intolerable side effects. Most recently we have seen the development of multiple targeted therapies including biologics—a far cry from injections of gold.

Targeted Therapies

The first targeted therapy approved by the Food and Drug Administration (FDA) for the treatment of RA was the biologic Enbrel (etanercept; Amgen) in 1998. In the years that have followed, we have seen at least seven more biologics and a targeted DMARD, Xeljanz (tofacitinib; Pfizer), approved by the FDA for the treatment of RA. All of these targeted therapies have prices that put them comfortably in the specialty space and all except Remicade (infliximab; Janssen) remain brand-only therapies. While clinically effective, targeted therapies cost quite a bit more than the traditional DMARD. The difference in price of thousands of dollars per month for the targeted agents compared to tens of dollars per month for the generic DMARDs should give us pause to consider the value the targeted agents bring to the table.

With the ever-rising cost of the targeted agents, some more than doubling in price since 2012, and the earlier use of targeted therapies within the treatment course of RA by some providers, the medical community needs to remain aware of the values each of these bring.

With the extremely low cost and longer term track record, the value of the traditional DMARDs is apparent. There is generally consensus between guidelines, standard medical practice, clinical texts, and provider feedback that DMARDs should be the first-line therapy for the treatment of RA. If one DMARD provides some benefit, but not complete relief then often-times a second or third DMARD can be added. Unfortunately, there are a number of patients who still do not get relief or have intolerable side effects and therefore require a targeted therapy to get the treatment they need.

Cost-Effectiveness Analysis

In April of this year, the Institute for Clinical and Economic Review (ICER) released their latest report in RA. The report compares the value between the targeted agents and also calculates their values individually on a cost per quality adjusted life year (QALY) basis. One of the more interesting conclusions in the report relates the value between some of the newer targeted agents and Humira (adalimumab; AbbVie). Humira, along with Enbrel, has some of the highest utilization among the targeted therapies for many payers. The report notes that Humira also has one of the highest annual costs among the targeted therapies, and that when compared head to head with some of the newer agents, Humira is either comparable or inferior in clinical efficacy. This means that one of the highest utilized drugs in this space, Humira, may not offer the best value.

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This creates a bit of a chicken and egg problem for payers who may want to move members to a therapy with a higher overall value but cannot because they would take too big of a hit on rebates for Humira and Enbrel, while unable move members to the newly preferred therapy fast enough to overcome the decrease in rebate.

Another interesting finding in the ICER report is that the cost per QALY for every one of the targeted therapies exceeds $150,000 per QALY with most running over $200,000 per QALY. The threshold to consider a drug cost effect with the cost per QALY measure is debated, but it usually hovers somewhere between $50,000 to $150,000 per QALY. This means that none of the targeted therapies could be classified as cost-effective under the ICER calculations without significant discounts. Any discounts on these therapies would need to run anywhere from 29% to 69% for the drug to be considered cost effective.

Looking Forward

Does this lack of ability to label these targeted RA therapies as cost-effective mean that we should write them off? Of course not. For a patient with RA who has either failed a DMARD or had intolerable side effects while taking a DMARD, having another option for treatment represents a much brighter future.

Left under-treated or untreated, those with RA face debilitating pain and a decrease in function over time. This not only leaves the individual with a lower quality of life, but there are a number of direct and indirect costs to their health plan and society that can conceivably exceed the cost of a targeted therapy. It is predictable then that value of a targeted therapy in a patient who has no other options for treatment is likely quite high compared to the value in someone who could be successfully treated with a DMARD.

So what can we do to ensure the long-term financial viability of treating RA? We can bring together all of the stakeholders and each take part in maximizing the value of therapy. Continued use of low cost DMARDs, even in combinations of two or three agents, by providers and their patients will help keep initial costs low.

Payers and their representatives can continue to innovate in the areas of formulary strategy to encourage use of the therapies with the greatest value and improve their rebate/outcomes contracting to maximize the value they and their members are realizing on the targeted therapies. Manufacturers can provide cost-saving measures to payers and balanced education to providers to support appropriate use of their products. Bringing together each of the stakeholders with these and similar strategies will help us ensure the long-term value and financial viability of using targeted therapies in the treatment of RA.

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