Validation of the Methotrexate-First Strategy in Patients With Early, Poor-Prognosis Rheumatoid Arthritis: Results From a Two-Year Randomized, Double-Blind Trial

被引：60

作者：

O'Dell, James R. ^{[1
,2
]}

Curtis, Jeffrey R. ^{[3
]}

Mikuls, Ted R. ^{[1
,2
]}

Cofield, Stacey S. ^{[3
]}

Bridges, S. Louis, Jr. ^{[3
]}

Ranganath, Veena K. ^{[4
]}

Moreland, Larry W. ^{[5
]}

机构：

[1] Univ Nebraska, Omaha, NE 68182 USA

[2] Omaha VA Med Ctr, Omaha, NE USA

[3] Univ Alabama Birmingham, Birmingham, AL USA

[4] Univ Calif Los Angeles, Los Angeles, CA USA

[5] Univ Pittsburgh, Pittsburgh, PA USA

来源：

ARTHRITIS AND RHEUMATISM | 2013年 / 65卷 / 08期

基金：

美国医疗保健研究与质量局;

关键词：

MODIFYING ANTIRHEUMATIC DRUGS; DISEASE-ACTIVITY; PLUS METHOTREXATE; AMERICAN-COLLEGE; RADIOGRAPHIC PROGRESSION; COMBINATION THERAPY; INADEQUATE RESPONSE; TIGHT CONTROL; SULFASALAZINE; ETANERCEPT;

D O I：

10.1002/art.38012

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objective. Methotrexate (MTX) taken as monotherapy is recommended as the initial disease-modifying antirheumatic drug for rheumatoid arthritis (RA). The purpose of this study was to examine outcomes of a blinded trial of initial MTX monotherapy with the option to step-up to combination therapy as compared to immediate combination therapy in patients with early, poor-prognosis RA. Methods. In the Treatment of Early Rheumatoid Arthritis (TEAR) trial, 755 participants with early, poor-prognosis RA were randomized to receive MTX monotherapy or combination therapy (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine). Participants randomized to receive MTX monotherapy stepped-up to combination therapy at 24 weeks if the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was >= 3.2. Results. Attrition at 24 weeks was similar in the MTX monotherapy and combination groups. Of the 370 evaluable participants in the initial MTX group, 28% achieved low levels of disease activity and did not step-up to combination therapy (MTX monotherapy group). The mean +/- SD DAS28-ESR in participants continuing to take MTX monotherapy at week 102 was 2.7 +/- 1.2, which is similar to that in participants who were randomized to immediate combination therapy (2.9 +/- 1.2). Participants who received MTX monotherapy had less radiographic progression at week 102 as compared to those who received immediate combination therapy (mean +/- SD change in modified Sharp score 0.2 +/- 1.1 versus 1.1 +/- 6.4). Participants assigned to initial MTX who required step-up to combination therapy at 24 weeks (72%) demonstrated similar DAS28-ESR values (3.5 +/- 1.3 versus 3.2 +/- 1.3 at week 48) and radiographic progression (change in modified Sharp score 1.2 +/- 4.1 versus 1.1 +/- 6.4 at week 102) as those assigned to immediate combination therapy. The results for either of the immediate combination approaches, whether triple therapy or MTX plus etanercept, were similar. Conclusion. These results in patients with early, poor prognosis RA validate the strategy of starting with MTX monotherapy. This study is the first to demonstrate in a blinded trial that initial MTX monotherapy with the option to step-up to combination therapy results in similar outcomes to immediate combination therapy. Approximately 30% of patients will not need combination therapy, and the 70% who will need it are clinically and radiographically indistinguishable from those who were randomized to receive immediate combination therapy.

引用

页码：1985 / 1994

页数：10

共 36 条

[1]

Reporting Disease Activity in Clinical Trials of Patients With Rheumatoid Arthritis: EULAR/ACR Collaborative Recommendations [J].

Aletaha, D. ;

Landewe, R. ;

Karonitsch, T. ;

Bathon, J. ;

Boers, M. ;

Bombardier, C. ;

Bombardieri, S. ;

Choi, H. ;

Combe, B. ;

Dougados, M. ;

Emery, P. ;

Gomez-Reino, J. ;

Keystone, E. ;

Koch, G. ;

Kvien, T. K. ;

Martin-Mola, E. ;

Matucci-Cerinic, M. ;

Michaud, K. ;

O'Dell, J. ;

Paulus, H. ;

Pincus, T. ;

Richards, P. ;

Simon, L. ;

Siegel, J. ;

Smolen, J. S. ;

Sokka, T. ;

Strand, V. ;

Tugwell, P. ;

van der Heijde, D. ;

van Riel, P. ;

Vlad, S. ;

van Vollenhoven, R. ;

Ward, M. ;

Weinblatt, M. ;

Wells, G. ;

White, B. ;

Wolfe, F. ;

Zhang, B. ;

Zink, A. ;

Felson, D. .

ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH, 2008, 59 (10) :1371-1377

[2]

Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice [J].

Anderson, Jaclyn ;

Caplan, Liron ;

Yazdany, Jinoos ;

Robbins, Mark L. ;

Neogi, Tuhina ;

Michaud, Kaleb ;

Saag, Kenneth G. ;

O'Dell, James R. ;

Kazi, Salahuddin .

ARTHRITIS CARE & RESEARCH, 2012, 64 (05) :640-647

[3]

THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[4]

Low-Dose Prednisone Inclusion in a Methotrexate-Based, Tight Control Strategy for Early Rheumatoid Arthritis A Randomized Trial [J].

Bakker, Marije F. ;

Jacobs, Johannes W. G. ;

Welsing, Paco M. J. ;

Verstappen, Suzanne M. M. ;

Tekstra, Janneke ;

Ton, Evelien ;

Geurts, Monique A. W. ;

van der Werf, Jacobine H. ;

van Albada-Kuipers, Grietje A. ;

Jahangier-de Veen, Zalima N. ;

van der Veen, Maaike J. ;

Verhoef, Catharina M. ;

Lafeber, Floris P. J. G. ;

Bijlsma, Johannes W. J. .

ANNALS OF INTERNAL MEDICINE, 2012, 156 (05) :329-U138

[5]

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis [J].

Boers, M ;

Verhoeven, AC ;

Markusse, HM ;

vandeLaar, MAFJ ;

Westhovens, R ;

vanDenderen, JC ;

vanZeben, D ;

Dijkmans, BAC ;

Peeters, AJ ;

Jacobs, P ;

vandenBrink, HR ;

Schouten, HJA ;

vanderHeijde, DMFM ;

Boonen, A ;

vanderLinden, S .

LANCET, 1997, 350 (9074) :309-318

[6]

The PREMIER study - A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment [J].

Breedveld, FC ;

Weisman, MH ;

Kavanaugh, AF ;

Cohen, SB ;

Pavelka, K ;

van Vollenhoven, R ;

Sharp, J ;

Perez, JL ;

Spencer-Green, GT .

ARTHRITIS AND RHEUMATISM, 2006, 54 (01) :26-37

[7]

Curtis JR, 2011, ARTHRITIS RHEUM-US, V63, pS155

[8]

The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment - Results of a phase IIb randomized, double-blind, placebo-controlled, dose-ranging trial [J].

Emery, P ;

Fleischmann, R ;

Filipowicz-Sosnowska, A ;

Schechtman, J ;

Szczepanski, L ;

Kavanaugh, A ;

Racewicz, AJ ;

Van Vollenhoven, RF ;

Li, NF ;

Agarwal, S ;

Hessey, EW ;

Shaw, TM .

ARTHRITIS AND RHEUMATISM, 2006, 54 (05) :1390-1400

[9]

Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial [J].

Emery, Paul ;

Breedveld, Ferdinand C. ;

Hall, Stephen ;

Durez, Patrick ;

Chang, David J. ;

Robertson, Deborah ;

Singh, Amitabh ;

Pedersen, Ronald D. ;

Koenig, Andrew S. ;

Freundlich, Bruce .

LANCET, 2008, 372 (9636) :375-382

[10]

American College of Rheumatology/European League Against Rheumatism Provisional Definition of Remission in Rheumatoid Arthritis for Clinical Trials [J].

Felson, David T. ;

Smolen, Josef S. ;

Wells, George ;

Zhang, Bin ;

van Tuyl, Lilian H. D. ;

Funovits, Julia ;

Aletaha, Daniel ;

Allaart, Cornelia F. ;

Bathon, Joan ;

Bombardieri, Stefano ;

Brooks, Peter ;

Brown, Andrew ;

Matucci-Cerinic, Marco ;

Choi, Hyon ;

Combe, Bernard ;

de Wit, Maarten ;

Dougados, Maxime ;

Emery, Paul ;

Furst, Daniel ;

Gomez-Reino, Juan ;

Hawker, Gillian ;

Keystone, Edward ;

Khanna, Dinesh ;

Kirwan, John ;

Kvien, Tore K. ;

Landewe, Robert ;

Listing, Joachim ;

Michaud, Kaleb ;

Martin-Mola, Emilio ;

Montie, Pamela ;

Pincus, Theodore ;

Richards, Pamela ;

Siegel, Jeffrey N. ;

Simon, Lee S. ;

Sokka, Tuulikki ;

Strand, Vibeke ;

Tugwell, Peter ;

Tyndall, Alan ;

van der Heijde, Desiree ;

Verstappen, Suzan ;

White, Barbara ;

Wolfe, Frederick ;

Zink, Angela ;

Boers, Maarten .

ARTHRITIS AND RHEUMATISM, 2011, 63 (03) :573-586

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