Biologics for Rheumatoid Arthritis Continue to Thrive

Although the care of patients with rheumatoid arthritis who have high disease activity has improved substantially over the past 2 decades with the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs), data on population-level time trends in the use of bDMARDs have been relatively scarce. But a new study provides insight on the increasing use-and success-of these agents.

Researchers observed a steady increase in the proportion of patients initiating new bDMARDs, as well as switching between bDMARDs, in both public and private health insurance programs.

“Use of bDMARDs in recent years has contributed to the markedly increased remission rates of RA,” wrote the investigators, led by Rishi J. Desai, MS, PhD, of Brigham and Women’s Hospital and Harvard Medical School. “And sustained remission is known to result in economic benefits to the health care system in the form of reduced use of health services in addition to improved quality of life and patient productivity.”

They reported their findings in the August 2017 issue of the Journal of Managed Care & Specialty Pharmacy.

Unlike older nonspecific immunomodulatory agents, such as methotrexate and hydroxychloroquine, bDMARDs target specific components of the immune system involved in the pathogenesis of rheumatoid arthritis. Currently, 9 targeted bDMARDs are approved for the indication of rheumatoid arthritis: 5 tumor necrosis factor (TNF)-α inhibitors (infliximab, etanercept, adalimumab, certolizumab, and golimumab); 2 interleukin inhibitors (tocilizumab and anakinra); a T-cell activation inhibitor (abatacept); and a CD-20 activity blocker (rituximab). A tenth targeted DMARD approved for rheumatoid arthritis, a janus kinase inhibitor (tofacitinib), is a small molecule-targeted DMARD and not a biologic.

The study

Deriving data from more than 200,000 patients with a diagnosis of rheumatoid arthritis, this study is the largest currently available in the literature that describes time trends in the use of bDMARDs. Data were obtained from private (Optum Clinformatics, 2004-2015) and public (Medicaid Analytic eXtract, 2000-2010) insurance programs. This investigation also is the first detailed report that documents rates of use of bDMARDs in a nationwide population of Medicaid enrollees.

Patients with diagnosis codes for rheumatoid arthritis and continuous health plan enrollment for 1-year baseline and 1-year follow-up periods were identified in 2 separate cohorts. The first cohort included patients not yet using any bDMARD. This group was further stratified by “incident RA,” defined as only 1 RA visit and no DMARD use in the pre-index period, and “prevalent RA,” defined as more than 1 RA visit or the use of non-bDMARDs in the pre-index period. The second cohort included patients who used a single bDMARD during the baseline period.

The outcome of interest during the 1-year follow-up period was initiation of the first bDMARD from the first cohort and switch to a second bDMARD from the second cohort. There were 97,751 patients with private insurance and 113,031 patients with public insurance.

The data provided comprehensive records of medical diagnoses and prescription dispensing, which allowed the study to account for a large number of potential variables in the analysis that may distort time trends because of the changing case-mix of patients over the study period. The study also had high generalizability, as it included patients from all over the country with a broad range of socioeconomic backgrounds.

The findings

Using mixed-effects regression models, the researchers were able to calculate yearly rates of initiation and switch for bDMARDs, adjusted for case-mix. The rates of initiation of bDMARDs (per 100 patients) increased significantly over time in Medicaid data for incident RA patients (from 1.1 to 3.1) and prevalent RA patients (from 4.6 to 10.9). In Optum Clinformatics data, initiation rates were stable for both incident RA patients (7.7 to 8.3) and prevalent RA patients (11.0 to 11.5). The rates of switching (per 100 patients) increased over time in both Medicaid data (6.4 to 16.0) and Optum Clinformatics data (9.1 to 17.0).

The researchers also documented widespread adoption of more recently approved bDMARD agents, which now account for about 1 of 4 new initiations and 2 of 5 switches. Although etanercept remains the most frequently used agent, at about 50% of biologic initiations, use of newer agents-especially abatacept, golimumab, and certolizumab-has risen considerably in recent years. Conversely, use of adalimumab and infliximab is decreasing; anakinra, commonly used in the early 2000s, fell to near zero in 2005 in both cohorts.

Implications

Although this study focused on a large population over 15 years and has high generalizability, it has some limitations. Most important is a lack of disease activity data, which may have hampered researchers’ ability to completely account for the changing patient case-mix over the years. Also, because the data did not contain information on prescriptions that were written but never filled, the findings may not fully represent physician practice patterns.

Still, by documenting practice pattern changes after the availability of newer bDMARDs, this study contributes valuable data to the literature. The sustained preference for etanercept as the agent of choice for patients initiating new treatment with bDMARDs may reflect the availability of more complete safety information for this agent. Etanercept repeatedly has been shown to be associated with fewer adverse events compared with adalimumab and infliximab in numerous meta-analyses.

Although evidence from a small number of comparative randomized controlled trials suggest comparable efficacy of newer agents, there is a dearth of comparative safety evidence for the newer bDMARDs in a systematic review. “The observation of widespread uptake of these agents from this study further highlights the importance of continuing research to guide evidence-based decision making for patients with RA,” the authors concluded.

The authors also observed lower absolute rates of bDMARD initiation among patients with no previous use of these agents in Medicaid, as compared with equivalent patients with private insurance. This observation may reflect the possibility of more restrictions to access at a policy level. Additional research evaluating access and patient outcomes could be used to inform future policy.

As bDMARDs for rheumatoid arthritis account for a high proportion of specialty drug spending, a more complete understanding of the temporal changes in use patterns of these agents may have important policy implications when it comes to managed care in formulary planning, anticipating future need, and cost trajectories. Continuing to closely monitor patterns, pricing, and outcomes of bDMARD use could continue to provide important insights, particularly with the introduction of biosimilars to the market.

Disclosures:

This study was supported by an investigator-initiated research grant from Pfizer. The authors conducted the study independent of the sponsor.

References:

Desai RJ, Solomon DH, Jin Y, et al. “Temporal Trends in Use of Biologic DMARDs for Rheumatoid Arthritis in the United States: A Cohort Study of Publicly and Privately Insured Patients.” J Manag Care Spec Pharm. 2017;23:809-814. doi: 10.18553/jmcp.2017.23.8.809.