Economic Burden and Treatment Patterns of Cycling between Conventional Synthetic Disease-modifying Antirheumatic Drugs Among Biologic-treated Patients with Rheumatoid Arthritis
Introduction
Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory disorder that affects multiple joints, such as the wrist, knuckles, knees, and ankles.1 It is estimated to affect 0.72% of adults in the United States and is more common in women and elderly populations.2 Recent evidence shows that RA imposes a significant economic burden on patients and society. The estimated annual excess direct health care costs of RA are more than $2000 per patient compared with a control cohort without RA, resulting in a total incremental expenditure of $22.3 billion (in 2008 US$) among all patients with RA in the United States.3
Medications are the mainstay of treatment for active RA and should start as early as possible. Conventional medication options include NSAIDs, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate), corticosteroids, and pain medications.4 In addition, biologic DMARDs (eg, adalimumab, etanercept, infliximab) that target specific parts of the immune system have been developed and approved for the treatment of RA.5, 6, 7, 8, 9, 10, 11
The 2015 American College of Rheumatology (ACR) guidelines recommend using a treat-to-target strategy regardless of disease activity to achieve remission and prevent damage of the joints and loss of function.12, 13 Evidence from clinical trials suggests that the more strict the treatment aim and the more tight the control, the better the clinical outcomes and that RA patients who achieved remission, normal physical function, and radiographic inhibition have improved short-term and long-term health-related quality of life, pain, fatigue, and work-related outcomes compared with patients who did not.14, 15 The European League against Rheumatism (EULAR) guidelines emphasize tight control by recommending frequent and strict monitoring every 1 to 3 months to achieve a target of remission or low disease activity for every patient.16
The ACR treatment guidelines further recommend switching to a biologic DMARD, for patients with moderate or high RA disease activity after using 1 or multiple conventional synthetic DMARDs.13 Similarly, the EULAR guidelines recommend using a biologic DMARD for patients with poor prognosis factors if the treatment goal is not achieved with the first conventional DMARD therapy.16 A previous study17 has shown that patients with RA who switched to a different conventional synthetic DMARD, as opposed to a biologic DMARD, after initial failure of a conventional synthetic DMARD had significantly smaller improvement in clinical outcomes measured by clinical disease activity index scores at 5, 9, and 24 months since treatment switch. In addition, patients who achieved sustained remission were found to incur less health care resource use and costs.18 However, many patients with moderate or high RA disease activity are not treated consistently with the ACR recommendations.19 The Consortium of Rheumatology Researchers of North America, Inc, registry20 study recently showed that the median time between first conventional synthetic DMARD and first biologic was more than 4 years, which suggests the delay in moving patients to appropriate therapy and gaps in real-world clinical practice compared with the treat-to-target principles. Delays in receiving appropriate treatment have been shown to have significant effects on long-term patient outcomes.21, 22
To date, no study has evaluated the real-world burden of cycling between conventional synthetic DMARDs among patients with RA. The real-world treatment patterns of biologic DMARD use after cycling between conventional synthetic DMARDs also remains unknown. The objective of the present study was to address this important knowledge gap by comparing health care costs and treatment patterns among patients with RA who cycled between different numbers of conventional synthetic DMARDs before initiating a biologic DMARD.
Section snippets
Data Source
The data for our study was obtained from the Truven Health MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental Database, available from January 1, 2000, to December 31, 2013. These databases contain private sector health care data from approximately 100 different insurance companies representing about 93 million covered lives. They consist of the medical claims of insured employees and their dependents, as well as Medicare-eligible retirees with employer-provided
Baseline Characteristics
Patient characteristics were measured during the 6-month baseline period and included patient demographic characteristics reported on the index date, including age, gender, region, insurance type, and index year; clinical information, including the claims-based index for RA severity,23 the Charlson comorbidity index,24 and common comorbidities of RA, including chronic obstructive pulmonary disease, congestive heart failure, deficiency anemia, diabetes, dyslipidemia, hypertension,
Patient Characteristics
A total of 10,418 patients were included in this study, with 6215 (59.7%), 3227 (31.0%), and 976 (9.4%) patients included in the 1, 2, and 3 or more conventional synthetic DMARD cohorts, respectively (Figure 2). At baseline, the 3 cohorts had similar demographic characteristics (Table I). Across all 3 cohorts, the average age was about 49 years and approximately 20% to 25% of the patients were men. Patients who cycled 3 or more conventional synthetic DMARDs had less severe RA, as indicated by
Discussion
Compared with conventional RA treatments such as NSAIDs and conventional synthetic DMARDs, biologic DMARDs are more effective in achieving and maintaining remission, and patients who achieve sustained remission incur less health care resource use and costs.6, 10, 11, 18 The ACR guidelines recommend adding a biologic DMARD for patients with moderate or high disease activity despite treatment with an initial conventional synthetic DMARD, and EULAR guidelines emphasize use of biologic combination
Conclusions
In this retrospective analysis of health insurance claims data, patients with RA who initiated a biologic DMARD after using a higher number of conventional synthetic DMARDs had increased economic burden in the 12 months following biologic DMARD initiation and were more likely to switch therapy. These results highlight the importance of timely switching to biologic DMARDs for the treatment of RA.
Conflicts of Interest
This study was funded by AbbVie, Inc. The design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication. Keith A. Betts, Nanxin Li, and Eric Q. Wu are employees of Analysis Group, a paid consultant of AbbVie. Jenny Griffith, Arijit Ganguli, and Kevin Douglas are AbbVie employees and own AbbVie stock. The authors have indicated that they have no other conflicts of interest regarding
Acknowledgments
The authors thank Ljubica Ristovska for providing analytic and writing support for this manuscript. All authors were involved in the study design and data interpretation. Keith A. Betts, Nanxin Li, and Eric Q. Wu were involved in data collection and analysis. All authors were involved in writing this manuscript.
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