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Research ArticleArticle

Effect on Costs and Quality-adjusted Life-years of Treat-to-target Treatment Strategies Initiating Methotrexate, or Tocilizumab, or Their Combination in Early Rheumatoid Arthritis

Maxime M.A. Verhoeven, Janneke Tekstra, Jacob M. van Laar, Attila Pethö-Schramm, Michelle E.A. Borm, Johannes W.J. Bijlsma, Johannes W.G. Jacobs, Floris P.J.G. Lafeber and Paco M.J. Welsing
The Journal of Rheumatology August 2020, jrheum.200067; DOI: https://doi.org/10.3899/jrheum.200067
Maxime M.A. Verhoeven
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Janneke Tekstra
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Jacob M. van Laar
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Attila Pethö-Schramm
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Michelle E.A. Borm
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Johannes W.J. Bijlsma
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Johannes W.G. Jacobs
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Floris P.J.G. Lafeber
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Paco M.J. Welsing
The U-Act-Early trial and the U-Act-After study were funded by Roche Nederland B.V. M.M. Verhoeven, PhD student, J. Tekstra, MD, PhD, J.M. van Laar, MD, PhD, J.W. Bijlsma, MD, PhD, J.W. Jacobs, MD, PhD, F.P. Lafeber, PhD, P.M. Welsing, PhD, Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; A. Pethö-Schramm, MD, PhD, F. Hoffmann-La Roche, Basel, Switzerland; M.E. Borm, PhD, Roche Nederland BV, Woerden, the Netherlands. J.L. reports personal fees from Arxx Tx, personal fees from Gesyntha, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Sanofi-Genzyme, personal fees from Leadiant, personal fees from Roche, grants from Astra Zeneca, grants from MSD, and grants from Roche, outside the submitted work. A.P-S. reports personal fees from F. Hoffmann-La Roche, outside the submitted work; M.B. is an employee of Roche Nederland B.V. J.B. reports grants from Roche during the conduct of the study. Address correspondence to M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl. Accepted for publication July 15, 2020.
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Abstract

Objective Our study aimed to evaluate the cost effectiveness of initiating tocilizumab (TCZ) ± methotrexate (MTX) versus initiating MTX as treat-to-target treatment strategies over 5 years in early disease-modifying antirheumatic drug (DMARD)-naïve rheumatoid arthritis (RA).

Methods Data on resource use were collected with questionnaires at baseline, 3, 6, 12, and 24 months, and yearly thereafter, and were converted to costs using Dutch reference prices. Quality-adjusted life-years (QALY) were calculated using the EQ5D5L, with utility based on Dutch tariff or estimated by the Health Assessment Questionnaire. To account for missing cost data and QALY data and for sample uncertainty, first bootstraps (10,000 samples) were obtained. Second, single imputation using chained equations nested within these bootstrap samples was performed. An economic evaluation was performed for TCZ + MTX and TCZ, compared to MTX, as initial treatment in a treat-to-target strategy from a healthcare and societal perspective over 5 years. Several sensitivity analyses were performed.

Results Mean differences in QALY were small and not significant (TCZ + MTX vs MTX: 0.06, 95% CI –0.02 to 0.13; TCZ vs. MTX: –0.03, 95% CI –0.05 to 0.11). Limited savings in indirect nonhealthcare costs and productivity loss costs (for TCZ only) were observed, but these did not compensate for the higher medication costs. Sensitivity analyses did not materially change these findings, although lower-priced TCZ, or reserving TCZ as initial therapy for prognostically unfavorable RA patients, improved cost effectiveness considerably but did not individually lead to a strategy being cost effective.

Conclusion Based on our analyses, early initiation of TCZ + MTX is not cost effective compared to MTX initiation in a step-up treat-to-target treatment strategy over 5 years in early RA patients.

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The Journal of Rheumatology: 53 (10)
The Journal of Rheumatology
Vol. 53, Issue 10
1 Oct 2026
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Effect on Costs and Quality-adjusted Life-years of Treat-to-target Treatment Strategies Initiating Methotrexate, or Tocilizumab, or Their Combination in Early Rheumatoid Arthritis
Maxime M.A. Verhoeven, Janneke Tekstra, Jacob M. van Laar, Attila Pethö-Schramm, Michelle E.A. Borm, Johannes W.J. Bijlsma, Johannes W.G. Jacobs, Floris P.J.G. Lafeber, Paco M.J. Welsing
The Journal of Rheumatology Aug 2020, jrheum.200067; DOI: 10.3899/jrheum.200067

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Effect on Costs and Quality-adjusted Life-years of Treat-to-target Treatment Strategies Initiating Methotrexate, or Tocilizumab, or Their Combination in Early Rheumatoid Arthritis
Maxime M.A. Verhoeven, Janneke Tekstra, Jacob M. van Laar, Attila Pethö-Schramm, Michelle E.A. Borm, Johannes W.J. Bijlsma, Johannes W.G. Jacobs, Floris P.J.G. Lafeber, Paco M.J. Welsing
The Journal of Rheumatology Aug 2020, jrheum.200067; DOI: 10.3899/jrheum.200067
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