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Treatment of Very Early Rheumatoid Arthritis With Symptomatic Therapy, Disease-Modifying Antirheumatic Drugs, or Biologic Agents: A Cost-Effectiveness Analysis

Axel Finckh, MD, MS; Nick Bansback, MS; Carlo A. Marra, PharmD, PhD; Aslam H. Anis, PhD; Kaleb Michaud, PhD; Stanley Lubin, MD; Marc White, PhD; Sonia Sizto, BA; and Matthew H. Liang, MD, MPH
[+] Article, Author, and Disclosure Information

From the University of Geneva, Geneva, Switzerland; University of British Columbia, Vancouver, British Columbia, Canada; University of Nebraska Medical Center, Omaha, Nebraska; National Data Bank for Rheumatic Diseases, Wichita, Kansas; and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Note: Dr. Finckh and Mr. Bansback contributed equally to this study.

Acknowledgment: The authors thank Allan Wailoo, University of Sheffield, for giving us access to the initial model code.

Grant Support: By an unrestricted research grant from the Arthritis Foundation and an anonymous donor.

Potential Conflicts of Interest:Consultancies: A. Finckh (Wyeth, Essex, Sanofi-Aventis), A.H. Anis (Abbott, Wyeth). Honoraria: A.H. Anis (Wyeth). Grants pending: A.H. Anis (Abbott, Schering-Plough, Wyeth). Other: N. Bansback (OMERACT).

Reproducible Research Statement:Study protocol: Not applicable. Statistical code: Available from Mr. Bansback (nbansback@cheos.ubc.ca). Data set: Certain portions of the analytic data set are available to approved persons through written agreements with the author or research sponsor; contact Mr. Bansback (e-mail, nbansback@cheos.ubc.ca).

Requests for Single Reprints: Axel Finckh, MD, MS, Division of Rheumatology, Department of Internal Medicine, University Hospital of Geneva, 26 Avenue Beau-Séjour, CH-1211 Geneva 14, Switzerland.

Current Author Addresses: Dr. Finckh: Division of Rheumatology, University Hospital of Geneva, 26 Avenue Beau-Séjour, CH-1211 Geneva 14, Switzerland.

Mr. Bansback, Dr. Anis, and Ms. Sizto: Centre for Health Evaluation and Outcome Sciences, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada.

Dr. Marra: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

Dr. Michaud: 986270 Nebraska Medical Center, Omaha, NE 68198-6270.

Dr. Lubin: General Practice, 101-777 Broadway West, Vancouver, British Columbia V5Z 4J7, Canada.

Dr. White: Canadian Institute for the Relief of Pain and Disability, 204–916 West Broadway Avenue, Vancouver, British Columbia V5Z 1K7, Canada.

Dr. Liang: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Francis Street, PBB-3, Boston, MA 02115.

Author Contributions: Conception and design: A. Finckh, N. Bansback, C.A. Marra, A.H. Anis, S. Lubin, M. White, M.H. Liang.

Analysis and interpretation of the data: N. Bansback, C.A. Marra, K. Michaud, M. White, S. Sizto, M.H. Liang.

Drafting of the article: A. Finckh, N. Bansback, A.H. Anis, K. Michaud, S. Sizto, M.H. Liang.

Critical revision of the article for important intellectual content: A. Finckh, N. Bansback, C.A. Marra, A.H. Anis, M. White, M.H. Liang.

Final approval of the article: A. Finckh, N. Bansback, C.A. Marra, A.H. Anis, S. Lubin, M. White, M.H. Liang.

Statistical expertise: A. Finckh, N. Bansback, A.H. Anis.

Obtaining of funding: A.H. Anis, M.H. Liang.

Administrative, technical, or logistic support: A. Finckh, A.H. Anis, M. White, M.H. Liang.

Collection and assembly of data: A. Finckh, N. Bansback, A.H. Anis, K. Michaud, M. White, S. Sizto, M.H. Liang.

Ann Intern Med. 2009;151(9):612-621. doi:10.7326/0003-4819-151-9-200911030-00006
Text Size: A A A

Background: Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined.

Objective: To assess the potential cost-effectiveness of major therapeutic strategies for very early RA.

Design: Decision analytic model with probabilistic sensitivity analyses.

Data Sources: Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs.

Target Population: U.S. adults with very early RA (symptom duration ≤3 months).

Time Horizon: Lifetime.

Perspective: Health care provider and societal.

Intervention: 3 management strategies were compared: a symptomatic or “pyramid” strategy with initial nonsteroidal anti-inflammatory drugs, patient education, pain management, and low-dose glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs) at 1 year for nonresponders; early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate.

Outcome Measures: Cost per quality-adjusted life-year (QALY) gained.

Results of Base-Case Analysis: By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater.

Results of Sensitivity Analysis: The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for patients for whom several biologics have failed.

Limitations: Data on the long-term effect of very early therapeutic interventions on the natural progression in disability and joint erosions are limited. The study considered only tumor necrosis factor inhibitors and not the newer biologics.

Conclusion: According to the most objective measures of RA progression, very early intervention with conventional DMARDs is cost-effective. The cost-effectiveness of very early intervention with biologics remains uncertain.


Grahic Jump Location
Figure 1.
Model schematic.

Patients can change disease state every 6 months, depending on the underlying disease type and the treatment strategy received. The time spent in a particular disease state determines the probability of transition and the ultimate outcome. DMARD = disease-modifying antirheumatic drug; HAQ = Health Assessment Questionnaire; RA = rheumatoid arthritis.

* See Appendix for discussion of this strategy.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Estimated progression of functional disability and radiographic joint damage over time for each strategy.

The evolution of functional disability and radiographic joint damage (erosion) after disease onset are displayed. The HAQ score ranges from 0 to 3 (maximum functional disability). Radiographic damage ranges from 0% (no joint damage) to 100% (total joint damage). DMARD = disease-modifying antirheumatic drug; HAQ = Health Assessment Questionnaire.

Grahic Jump Location




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