Disability outcomes and dose escalation with etanercept, adalimumab, and infliximab in rheumatoid arthritis patients: a US-based retrospective comparative effectiveness study

Abstract

Introduction:

Rheumatoid arthritis (RA) is a chronic disease that if left untreated may substantially impair physical functioning. Etanercept, infliximab, and adalimumab are tumor necrosis factor (TNF) blockers whose FDA-approved indications in the US include moderate to severe RA. TNF-blocker dose escalation has been well documented in the literature; however, the comparative effectiveness of these agents remains uncertain.

Objective:

To compare the effectiveness and dose escalation rates of etanercept, adalimumab, and infliximab in US community settings. We hypothesized that etanercept would be equivalent to infliximab and adalimumab in patient-reported disability 9–15 months after therapy initiation, and that fewer etanercept patients would experience dose escalation.

Methods:

This is a retrospective analysis of the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). Adult patients with no biologic use 6 months before TNF-blocker initiation (index) and with Health Assessment Questionnaire Disability Index (HAQ-DI) scores at index and 9–15 months after index were analyzed (218 etanercept, 93 infliximab, and 40 adalimumab).

Results:

HAQ-DI change scores at 9–15 months did not differ by treatment (−0.12, −0.10, and −0.08 points for etanercept, infliximab, and adalimumab, respectively; p = 0.52). Dose increases were observed in 1.4% of etanercept, 10.8% of infliximab (p < 0.001), and 12.5% of adalimumab patients (p = 0.004). HAQ-DI change was associated with pre-index HAQ-DI score (p < 0.0001) and disease duration (p = 0.001).

Conclusions:

Fewer etanercept patients escalated dose than infliximab or adalimumab patients, but improvements in functional disability were similar. These differences may have been influenced by package labeling, mode of administration, or other factors. RA treatment with infliximab and adalimumab in community settings, characterized by dose escalation, did not yield greater disability improvements compared to etanercept, which remained at a relatively stable dose. Uncontrolled treatment selection in this observational design may have influenced outcomes, and prior methotrexate treatment may partly explain disability improvements smaller than typically observed in clinical trials.

Keywords::

• Adalimumab
• Arthritis, rheumatoid
• Comparative effectiveness research
• Etanercept
• Infliximab
• Receptors, tumor necrosis factor

Transparency

Declaration of funding

This study was financially supported by Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth, which was acquired by Pfizer Inc. in October 2009.

Declaration of financial/other relationships

D.R.G. and D.J.H. were employed by Amgen and owned Amgen stock during the conduct of the study. D.R.G. contributed to the study design and interpretation of the results. V.F.S., B.B., C.F.F., B.L. and J.F.F. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. D.J.H. contributed to the study design, oversaw study execution, and contributed to interpretation of the results. V.F.S. contributed to the study design, oversaw study execution, contributed to interpretation of the results, and drafted the manuscript. B.B. contributed to the study design, oversaw data validation, contributed to interpretation of the results. C.F.F. contributed to the study design, performed some of the statistical analysis and contributed to the interpretation of the results. B.L. performed the majority of statistical analysis and contributed to the interpretation of the results. J.F.F. contributed to the study design, oversaw study execution, and contributed to interpretation of the results. All authors read and approved the final manuscript.

The peer reviewers on this manuscript have disclosed any relevant financial relationships.

Acknowledgments

The authors acknowledge Eswar Krishnan MD for his contributions to the study design and interpretation of results.

Previous presentation: this study was presented in poster format at the 13th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in Prague, Czech Republic, November 6–9, 2010.

Notes

*Enbrel is a registered trade name of Amgen Inc. and Pfizer Inc. Manufactured by Immunex Corporation, Thousand Oaks, CA, USA.

†Remicade is a registered trade name of Centocor, Inc., Malvern, PA, USA.

‡Humira is a registered trade name of Abbott Laboratories, North Chicago, IL, USA.