Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naive patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study

被引：90

作者：

Emery, P. ^{[1
,2
]}

Bingham, C. O., III ^{[3
]}

Burmester, G. R. ^{[4
]}

Bykerk, V. P. ^{[5
]}

Furst, D. E. ^{[6
]}

Mariette, X. ^{[7
]}

van der Heijde, D. ^{[8
]}

van Vollenhoven, R. ^{[9
]}

Arendt, C. ^{[10
]}

Mountian, I. ^{[10
]}

Purcaru, O. ^{[10
]}

Tatla, D. ^{[11
]}

VanLunen, B.

Weinblatt, M. E. ^{[11
,12
]}

机构：

[1] Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds LS7 4SA, W Yorkshire, England

[2] Leeds Teaching Hosp NHS Trust, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds LS7 4SA, W Yorkshire, England

[3] Johns Hopkins Univ, Baltimore, MD USA

[4] Charite, Rheumatol & Clin Immunol, Berlin, Germany

[5] Hosp Special Surg, Weill Cornell Med Coll, Div Rheumatol, 535 E 70th St, New York, NY 10021 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA

[7] Univ Paris Sud, Hop Univ Paris Sud, AP HP, Le Kremlin Bicetre, France

[8] Leiden Univ, Dept Rheumatol, Med Ctr, Leiden, Netherlands

[9] Karolinska Inst, Unit Clin Therapy Res, Inflammatory Dis, Stockholm, Sweden

[10] UCB Pharma, Brussels, Belgium

[11] UCB Pharma, Raleigh, NC USA

[12] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2017年 / 76卷 / 01期

关键词：

AMERICAN-COLLEGE; RHEUMATOLOGY/EUROPEAN LEAGUE; CLASSIFICATION CRITERIA; PLUS METHOTREXATE; PARALLEL-GROUP; MULTICENTER; ETANERCEPT; REMISSION; TRIAL; RECOMMENDATIONS;

D O I：

10.1136/annrheumdis-2015-209057

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naive patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks. Methods DMARD-naive patients with <= 1 year of active RA were randomised (3: 1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)<= 3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints. Results Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): -1.00 vs -0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY). Conclusions CZP+dose-optimised MTX treatment of DMARD-naive early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.

引用

页码：96 / 104

页数：9

共 22 条

[1]

Aletaha D, 2010, ANN RHEUM DIS, V69, P1580, DOI [10.1136/ard.2010.138461, 10.1002/art.27584]

[2] THE FIRST EARLY RHEUMATOID ARTHRITIS, CERTOLIZUMAB PEGOL, MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PARALLEL-GROUP STUDY: C-OPERA, IN PATIENTS FULFILLING THE 2010 ACR/EULAR CLASSIFICATION CRITERIA, DEMONSTRATES INHIBITION OF JOINT DAMAGE PROGRESSION [J].

Atsumi, T. ;

Yamamoto, K. ;

Takeuchi, T. ;

Yamanaka, H. ;

Ishiguro, N. ;

Tanaka, Y. ;

Eguchi, K. ;

Watanabe, A. ;

Origasa, H. ;

Shoji, T. ;

Okada, T. ;

van der Heijde, D. ;

Miyasaka, N. ;

Koike, T. .

ANNALS OF THE RHEUMATIC DISEASES, 2014, 73 :484-484

[3] 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

[4] Combination of infliximab and methotrexate therapy for early rheumatoid arthritis - A randomized, controlled trial [J].

Clair, EWS ;

van der Heijde, DMFM ;

Smolen, JS ;

Maini, RN ;

Bathon, JM ;

Emery, P ;

Keystone, E ;

Schiff, M ;

Kalden, JR ;

Wang, B ;

DeWoody, K ;

Weiss, R ;

Baker, D .

ARTHRITIS AND RHEUMATISM, 2004, 50 (11) :3432-3443

[5]

Cush JJ, 2007, J RHEUMATOL, V34, P1

[6] 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

[7] Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period [J].

Emery, Paul ;

Burmester, Gerd R. ;

Bykerk, Vivian P. ;

Combe, Bernard G. ;

Furst, Daniel E. ;

Barre, Emilie ;

Karyekar, Chetan S. ;

Wong, Dennis A. ;

Huizinga, Tom W. J. .

ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (01) :19-26

[8] Sustained Remission with Etanercept Tapering in Early Rheumatoid Arthritis [J].

Emery, Paul ;

Hammoudeh, Mohammed ;

FitzGerald, Oliver ;

Combe, Bernard ;

Martin-Mola, Emilio ;

Buch, Maya H. ;

Krogulec, Marek ;

Williams, Theresa ;

Gaylord, Stefanie ;

Pedersen, Ronald ;

Bukowski, Jack ;

Vlahos, Bonnie .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (19) :1781-1792

[9] Combination etanercept and methotrexate provides better disease control in very early (≤4 months) versus early rheumatoid arthritis (>4 months and <2 years): post hoc analyses from the COMET study [J].

Emery, Paul ;

Kvien, Tore K. ;

Combe, Bernard ;

Freundlich, Bruce ;

Robertson, Deborah ;

Ferdousi, Tahmina ;

Bananis, Eustratios ;

Pedersen, Ronald ;

Koenig, Andrew S. .

ANNALS OF THE RHEUMATIC DISEASES, 2012, 71 (06) :989-992

[10] The Effects of Golimumab on Radiographic Progression in Rheumatoid Arthritis Results of Randomized Controlled Studies of Golimumab Before Methotrexate Therapy and Golimumab After Methotrexate Therapy [J].

Emery, Paul ;

Fleischmann, Roy ;

van der Heijde, Desiree ;

Keystone, Edward C. ;

Genovese, Mark C. ;

Conaghan, Philip G. ;

Hsia, Elizabeth C. ;

Xu, Weichun ;

Baratelle, Anna ;

Beutler, Anna ;

Rahman, Mahboob U. .

ARTHRITIS AND RHEUMATISM, 2011, 63 (05) :1200-1210

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