Newswise — SAN DIEGO — Starting with a combination of three traditional disease-modifying antirheumatic drugs (called DMARDs) for treating early rheumatoid arthritis is more cost-effective long term, with comparable benefits, than using either an immediate or step-up approach with anti-tumor necrosis factor (called Anti-TNFs) drugs and methotrexate, according to new research findings presented this week at the American College of Rheumatology Annual Meeting in San Diego.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Researchers at the University of Nebraska Medical Center, the University of Minnesota, the University of Alabama at Birmingham, the University of Pittsburgh, and the National Data Bank for Rheumatic Diseases compared the long-term cost-effectiveness of using a triple therapy approach to treating early RA with using a more aggressive approach with a newer, TNF-inhibitor agent plus methotrexate.

The researchers used patient data from the double-blind, randomized, two-year Treatment of Early Aggressive RA (TEAR) trial and the National Data Bank for Rheumatic Diseases to measure treatment outcomes and estimate long-term cost of these therapies. They evaluated four strategies: Immediate triple therapy of methotrexate, sulfasalazine and hydroxychloroquine; immediate therapy of etancercept, an anti-TNF agent, and methotrexate; a step-up triple therapy and a step-up etanercept therapy. The two step-up therapies involve switching a patient with persistent disease activity from methotrexate monotherapy to either triple therapy or methotrexate plus etanercept after six months. The researchers simulated an extension of the two years of TEAR results to lifetime use of the therapies to estimate the long-term cost.

“Randomized controlled trials between active therapies are rare and important in treating RA. We felt it was important to determine the quantitative differences between these four treatment arms of early RA,” says Kaleb Michaud, PhD; assistant professor, University of Nebraska Medical Center & co-director, National Data Bank for Rheumatic Diseases; and lead investigator in the study.

The researchers estimated Quality Adjusted Life Year (called QALY) measurements by analyzing various data from TEAR, including disease-activity scores in 28 joints and results of Health Assessment Questionnaires. They used a Markov simulation model to estimate QALY measurements and the costs associated with therapy approaches in the TEAR trial. QALY is a standard measurement to determine the effectiveness of various medical interventions in achieving quality and quantity of life over the long term.

Looking at the four therapy approaches, the researchers determined that the lifetime benefits of all four were comparable, or within 0.06 QALY scores. However, the two therapies using etanercept were almost twice as expensive due to the higher cost of the anti-TNF agent. The researchers estimated that the incremental cost-effectiveness ratio of using immediate etanercept therapy versus immediate triple therapy was $837,100 per QALY score over the long term. This increase in cost and the difference in incremental cost-effectiveness ratio may be too high for many health care settings to find acceptable, considering the comparable benefits, the researchers concluded.

“The current ACR treatment guidelines for early RA indicate initiating after methotrexate either a concomitant anti-TNF biologic or another non-biologic DMARD depending on the severity of the prognosis,” Dr. Michaud says. “While this study should not change those guidelines, our results suggest that physicians should consider use of triple therapy as a viable alternative to a biologic for patients where costs may be an impediment to care.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 9,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit or join the conversation on Twitter by using the official hashtag: #ACR13

Editor’s Notes: Dr. Michaud will present this research during the ACR Annual Meeting at the San Diego Convention Center at 11:30 AM on Tuesday, October 29 in Room 6A. Dr. Michaud will be available for media questions and briefing at 8:30 AM Tuesday, October 29 in the on-site press conference room, 27AB. Abstract Number: 2646

Cost-Effectiveness Analysis Of Triple Therapy Versus Etanercept Plus Methotrexate In Early Aggressive Rheumatoid Arthritis: Analysis Based On The TEAR Trial

Hawre Jalal1, Jeffrey R. Curtis2, Stacey Cofield2, Larry W. Moreland3, James R. O'Dell4 and Kaleb Michaud5, 1University of Minnesota, Minneapolis, MN, 2University of Alabama at Birmingham, Birmingham, AL, 3University of Pittsburgh, Pittsburgh, PA, 4Omaha VA and the University of Nebraska Medical Center, Omaha, NE, 5National Data Bank for Rheumatic Diseases & University of Nebraska Medical Center, Omaha, NE

Background/Purpose: The long-term cost-effectiveness of triple therapy (methotrexate [MTX], sulfasalazine [SSZ], hydroxychloroquine [HCQ]) disease modifying anti-rheumatic drugs (DMARDs) compared to a combination of MTX and anti-TNF therapy in patients with early rheumatoid arthritis (RA) is unknown. In this study, we used patient-level data from the Treatment of Early Aggressive RA (TEAR) trial and the National Data Bank for Rheumatic Diseases (NDB) to evaluate the cost-effectiveness of immediate combination therapy (with biologic or non-biologic DMARDs) versus stepping up to combination therapy at 6 months if disease activity persists despite MTX monotherapy.

Methods: We developed a Markov simulation model to estimate quality-adjusted life years (QALYs) and costs associated with the treatment strategies examined in the TEAR trial. We evaluated four strategies: immediate triple (IT), immediate etanercept (IE), step-up triple (ST), and step-up etanercept (SE). The step-up strategies involved switching those with persistent disease activity (DAS28 >= 3.2) from MTX monotherapy to MTX plus either etanercept or triple therapy at 6 months. The simulation model extends the 2-year trial to the life-time horizon, using parameters taken from longitudinal NDB data for therapy discontinuation rates, HAQ transitions, and DAS28-HAQ-QALY mappings as well as the published literature for direct and indirect cost estimates. Annual discontinuation rates of triple therapy and etanercept from the NDB were estimated to be 22% and 10%, respectively. Those who discontinued were assumed to continue to receive methotrexate. Markov health states were defined by DAS28. DAS28 score transitions were obtained directly from individual patients in the trial. Death was modeled as an additional state with background mortality estimated from the 2007 US Life Tables. HAQ scores were used as a secondary variable to estimate QALYs, RA-specific mortality, and direct and indirect costs (e.g., due to productivity loss). We assumed a 3-month cycle length, and discounted both costs and effectiveness by 3% annually.

Results: The etanercept strategies (SE and IE) were more costly than the triple strategies (ST and IT) mainly due to treatment costs [Table]. The lifetime benefits from IT, ST and SE were numerically similar (within 0.06 QALYs). Although IE was more effective than IT, the incremental cost-effectiveness ratio (ICER) of IE relative to IT was $837,100/QALY. These results were robust to parametric sensitivity analyses.

Conclusion: We used patient-level data from the TEAR trial, and then projected their lifetime costs and benefits using the NDB. The benefits from all strategies were comparable, but biologics strategies were almost twice more expensive than triple strategies, producing ICERs greater than what most healthcare settings find acceptable. Disclosures: H. Jalal, None.J. R. Curtis, Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, Abb Vie, 2, Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, Abb Vie, 5 S. Cofield, None.L. W. Moreland, None.J. R. O'Dell, None.K. Michaud, University of Nebraska Medical Center, 3, National Data Bank for Rheumatic Diseases, 3

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