Cost-effectiveness of adalimumab, etanercept, and tocilizumab as first-line treatments for moderate-to-severe rheumatoid arthritis

Abstract

Objective:

The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland.

Research design and methods:

The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab + methotrexate, etanercept + methotrexate, or tocilizumab + methotrexate were used as first biologics followed by rituximab + methotrexate and infliximab + methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed.

Main outcome measures:

Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI).

Results:

bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab + methotrexate was more cost-effective than adalimumab + methotrexate or etanercept + methotrexate in comparison with methotrexate alone, and adalimumab + methotrexate was dominated by etanercept + methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab + methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab + methotrexate should be considered before rituximab + methotrexate, infliximab + methotrexate, and BSC. Based on the CEAF, tocilizumab + methotrexate had a 60–93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230–2182).

Conclusions:

Tocilizumab + methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values.

Limitations:

Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.

Keywords::

• Adalimumab
• Economic evaluation
• Etanercept
• Quality-of-life
• Rheumatoid arthritis
• Tocilizumab
• Value of information

Transparency

Declaration of funding and author contributions

This work was supported by Roche Oy, Espoo, Finland. EJS contributed to the concept, design, and modelling, acquired data, analysed and interpreted data, and drafted and revised the manuscript. TAH contributed to the design and interpretation of data, and helped to draft and revise the manuscript. VV acquired data, and helped to draft the manuscript. MJK and KP contributed to the concept and interpretation of data, and revised the manuscript. All authors read and approved the final manuscript.

Declaration of financial and other relevant relationships

EJS and TAH have disclosed that they are consultants and shareholders in ESiOR Oy, a company that was commissioned by Roche Oy to perform this study. VV has disclosed that he is an employee of Roche. KP and MJK have disclosed that they received consulting fees from Roche and other companies such as Abbott, Bristol Myers-Squibb, MSD, Pfizer, and UCB. The final manuscript has been read and approved by all the authors, and all authorship decisions were made on the basis of scientific consideration.

Acknowledgments

The authors wish to thank Juhana Heinonen, Kalevi Nikula, Anne Hautala, and Wolfgang Berger (Roche) for contacts and/or beneficial comments during the writing process. Parts of this study were presented during the 74th ACR Annual Meeting (ACR Notable Poster nomination) in Atlanta and the 13th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in Prague in November 2010.