Conventional and Biologic Rheumatoid Arthritis Therapies: Utilization and Cost Trends

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The American Journal of Pharmacy Benefits, November/December 2012, Volume 4, Issue 6

Based on American College of Rheumatology recommendations and novel emerging treatment options, the trend of increasing biologic use for rheumatoid arthritis is expected to continue.

Rheumatoid arthritis (RA) is an autoimmune disorder that poses a signifi cant public health burden because of its prevalence, direct and indirect costs, the debilitating nature of the disease, and the fact that there is no cure. It is a long-term disease that causes pain, stiffness, swelling, and limited motion and function of many joints, leading to substantial loss of functional mobility due to pain and joint destruction. The exact cause of RA is unknown, but genetic, hormonal, and environmental factors are believed to be involved.1

Although the incidence and prevalence of RA in populations have varied over time and noted fluctuations exist between geographic locations, a 2010 study by the American College of Rheumatology (ACR) found that an estimated 1.5 million Americans were affected by RA in 2005, with an overall incidence rate of 40.9 per 100,000 population.2 About 75% of those affected are women, and although RA most often appears in patients between age 40 and 60 years, its onset can occur at any age.3 With an aging population, we can expect continued growth in the prevalence of RA.

Estimates of the direct and indirect costs of RA vary and are partly dependent on the severity of the disease. Research evidence suggests the adjusted average annual total medical expenditure for RA in 2008 was approximately $13,000 per patient, including an average pharmacy expenditure of $5825. While these figures are significantly higher than what would be recorded in a non-RA control group, the authors indicated that the majority of patients with RA at that time were being treated with conventional (nonbiologic) disease-modifying antirheumatic drugs (DMARDs).4 The use of a biologic DMARD can more than double pharmacy costs; the annual cost of therapy for those patients using tumor necrosis factor (TNF) antagonists in 2008 ranged from roughly $10,000 to $14,000 annually,5 at which time the estimated total direct medical expenditures for RA were $73.4 billion. Indirect costs of the disease include lost productivity due to work-related disability, increased morbidity, and shortened survival. Between 25% and 50% of all patients with RA are unable to work within 20 years of being fi rst diagnosed.6

The treatment of RA has evolved dramatically over the past few decades. The main goal of treatment is to control pain and infl ammation, and ultimately slow the progression of joint destruction, on the basis of a stepped-care approach. Patients are initially treated with rest, exercise, physical and occupational therapy, and nonsteroidal anti-inflammatory drugs.1 This step is followed by more aggressive treatment; ACR recommends the use of conventional DMARDs and/or biologic DMARDs (biologics) depending on the stage/progression of the disease, efficacy of the current treatment, and presence of other comorbid conditions, among other factors.7

The ACR did not provide guidelines regarding the utilization of biologic agents until 2008. The 2008 guidelines and the subsequent 2012 update included recommendations for use of biologic agents in new and early cases. In patients with early RA (less than 6 months since disease onset), ACR recommends the use of a single-therapy DMARD for low disease activity or moderate/high disease activity without poor prognosis. In patients with early RA who have high disease activity with poor prognosis, ACR recommends the use of an anti-TNF biologic as monotherapy or in combination with methotrexate. For patients with moderate/high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy, ACR recommends switching to an anti-TNF or non-TNF biologic. If moderate/high disease activity persists after 3 months of anti-TNF biologic therapy due to lack of benefit, switching to another anti-TNF biologic or a non-TNF biologic is recommended. In the event of high disease activity due to lack of benefi t from an anti-TNF biologic and/or a serious adverse event, switching to a non-TNF biologic is recommended.8

The objective of our research was to quantify the impact of recommended and evolving RA treatment guidelines on cost and utilization trends over a 6-year period.


The study was designed as a retrospective longitudinal study of CVS Caremark de-identifi ed administrative claims data of therapy utilizers between January 1, 2006, and December 31, 2011. The study was limited to utilizers of the conventional and biologic therapies used to treat RA and other related conditions. Utilization and costs were measured on a per member per year (PMPY) and per utilizer per year basis.

The study focused on utilizers of conventional DMARDs, including auranofi n, azathioprine, gold sodium thiomalate, hydroxychloroquine, lefl unomide, and methotrexate. Biologics included in the study were the anti- TNFs adalimumab, anakinra, certolizumab, etanercept, golimumab, and infl iximab, and the non-TNFs abatacept, rituximab, and tocilizumab.


On average, 380,472 pharmacy benefit—eligible members used these medications each year. Over the study period, DMARDs accounted for 67% of overall utilization, based on days’ supply of therapy. As shown in the


, the relative utilization of conventional DMARD therapy has steadily declined compared with utilization of biologics. In 2006, DMARDs accounted for 77.6% of the total days’ supply of therapy; in 2011, DMARDs made up 56.4% of the utilization, representing a 27% decline in the relative utilization of these drugs. The relative utilization of biologic therapy nearly doubled over the same time period.

Over the study period, PMPY gross cost of conventional DMARDs decreased 36%, from $0.61 to $0.39 (

Table 1

). Although a decrease in PMPY gross cost was experienced between 2007 and 2008, the PMPY gross cost of biologics increased nearly 24%, from $10.91 to $13.48. At the same time, per utilizer costs of both types of therapy have been growing (

Table 2

), by 9% for biologics and more than 41% for DMARDs.


The objective of our study was to quantify the impact of treatment guideline changes on cost and utilization trends over a 6-year period. Earlier research in this area (1) assessed dosing patterns and annual costs associated with the use of only a few biologics,9,10 (2) examined the effects of expansions in insurance coverage for nonbiologic and biologic DMARDs on access, costs, and health status of older patients,11 (3) examined the incremental direct medical expenditure associated with RA from a payer’s perspective using survey data,4 or (4) assessed the prevalence of RA and the utilization and costs of medical services and prescription medications among recipients of a state Medicaid or Medicare program.12,13

Our analysis examined utilization and costs of both conventional and biologic therapies in a large population drawn from commercial and government-sponsored prescription drug plans, including Medicaid and Medicare programs. Our results show that changes in PMPY costs of these therapies are not fully explained by changes in per utilizer costs. We observed a signifi cant shift to biologics as a percentage of overall utilization, as well as an increase in the overall PMPY costs of 24%, while per utilizer costs grew only 9%. The findings suggest that more patients utilized biologics in 2011 than in 2006.

Some of the drug classes identifi ed in the analysis are also used in the treatment of other medical conditions. Therefore, a limitation of this study is lack of International Classification of Disease, 9th edition codes in the data for determination of the actual condition(s) for which a specific drug/therapy was used, so the costs and utilization estimates presented are not limited to those with RA.


The treatment of RA is being changed not only by revised treatment guidelines, but by several innovative agents in the emerging RA treatment pipeline that could reach the market in the near term. Two of these agents offer the convenience of oral administration coupled with a novel mechanism of action: Pfizer’s Janus-associated kinase (JAK) inhibitor tofacitinib and AstraZeneca’s spleen tyrosine kinase (SyK) inhibitor fostamatinib disodium (FosD). Introduction of these novel therapies may further affect the treatment of RA.


Tofacitinib could revolutionize RA treatment due to its position as the first-in-class oral agent, with twice-daily dosing, impressive efficacy, and an acceptable safety profile.14 In a phase III active comparator clinical trial, tofacitinib demonstrated effi cacy in line with the current RA market leaders etanercept (Enbrel) and adalimumab (Humira). A US Food and Drug Administration (FDA) advisory panel recommended that tofacitinib be approved as a second-line indication for patients with moderately to severely active RA who have an inadequate response to 1 or more DMARDs. Questions remain over its exact positioning in the treatment algorithm and its eventual pricing relative to the market-driving biologic therapies. An FDA action date has been set for November 21, 2012, with a projected launch date in early 2013.15

Fostamatinib Disodium

Fostamatinib disodium (FosD) is another first-in-class oral treatment for RA with a novel mechanism of action. FosD has shown mixed efficacy results, with a phase II trial failing to meet its primary end point of ACR20 at 3 months. Safety has also been a concern, with increased risk of serious infections and hypertension. Based on clinical data, key opinion leaders in the industry believe that Syk inhibitors are not as effi cacious as JAK inhibitors. If approved, FosD is projected to launch in the third quarter of 2013.16

Market Impact

Recently reported results from a survey of rheumatologists suggest that 20% or more of patients eligible to take biologics are “easy” targets for oral RA drugs. Respondents indicated that 59% of their patients with RA are eligible for treatment with a biologic, and of these patients, 12% had failed or were intolerant of biologic therapy and 11% refused to initiate or continue their injections or infusions.17 Anti-TNFs appear to be most vulnerable to tofacitinib market entry; survey respondents estimated that anywhere from 24% to 35% of their patients with RA who are eligible to take biologics would be treated with tofacitinib in 3 years, with anti-TNF use declining from about 65% of all patients on a biologic to about 40% to 45% of patients in 3 years.

Surprisingly, the impact of tofacitinib on market shares of abatacept (Orencia) and tocilizumab (Actemra) is expected to be modest—a possible refl ection of their primary existing uses in patients who have failed anti-TNF therapy. In addition, survey results suggest that preferred reimbursement would have the biggest impact on the initial uptake of tofacitinib, provided it gains approval as a potential front-line agent after methotrexate.17


Increased use of biologics in the treatment of RA, as illustrated by this study, is in line with the 2008 ACR clinical treatment guidelines. The ACR’s recommendations addressed the rising use of biologics by incorporating the agents into the treatment guidelines. Furthermore, the 2012 updates to the ACR guidelines, which were made after the claims data period used in this study, continue to reinforce the important role biologics play in the treatment of RA. Based on the most recent ACR recommendations and the novel emerging treatment options, the trend of increasing biologic use is expected to continue. Study findings support the idea that as therapies evolve, practice guidelines are refi ned and real world practice follows.