Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve 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

P Emery; C O Bingham; G R Burmester; V P Bykerk; D E Furst; X Mariette; D van der Heijde; R van Vollenhoven; C Arendt; I Mountian; O Purcaru; D Tatla; B VanLunen; M E Weinblatt

doi:https://doi.org/10.1136/annrheumdis-2015-209057

Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve 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

P Emery, C O Bingham, G R Burmester, V P Bykerk, D E Furst, X Mariette, D van der Heijde, R van Vollenhoven, C Arendt, I Mountian, O Purcaru, D Tatla, B VanLunen, M E Weinblatt

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.

METHODS: DMARD-naïve 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-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.

TRIAL REGISTRATION NUMBER: NCT01519791.

Original language	English
Pages (from-to)	96-104
Number of pages	9
Journal	Annals of the rheumatic diseases
Volume	76
Issue number	1
DOIs	https://doi.org/10.1136/annrheumdis-2015-209057
Publication status	Published - Jan 2017

Keywords

Adult
Antirheumatic Agents
Arthritis, Rheumatoid
Certolizumab Pegol
Clinical Trial, Phase III
Double-Blind Method
Drug Therapy, Combination
Female
Humans
Infection
Journal Article
Male
Methotrexate
Middle Aged
Multicenter Study
Prognosis
Radiography
Randomized Controlled Trial
Remission Induction

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Cite this

Emery, P., Bingham, C. O., Burmester, G. R., Bykerk, V. P., Furst, D. E., Mariette, X., van der Heijde, D., van Vollenhoven, R., Arendt, C., Mountian, I., Purcaru, O., Tatla, D., VanLunen, B., & Weinblatt, M. E. (2017). Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve 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. Annals of the rheumatic diseases, 76(1), 96-104. https://doi.org/10.1136/annrheumdis-2015-209057

Emery, P ; Bingham, C O ; Burmester, G R et al. / Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve 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. In: Annals of the rheumatic diseases. 2017 ; Vol. 76, No. 1. pp. 96-104.

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title = "Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-na{\"i}ve 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",

abstract = "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-na{\"i}ve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.METHODS: DMARD-na{\"i}ve 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-na{\"i}ve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.TRIAL REGISTRATION NUMBER: NCT01519791.",

keywords = "Adult, Antirheumatic Agents, Arthritis, Rheumatoid, Certolizumab Pegol, Clinical Trial, Phase III, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Infection, Journal Article, Male, Methotrexate, Middle Aged, Multicenter Study, Prognosis, Radiography, Randomized Controlled Trial, Remission Induction",

author = "P Emery and Bingham, {C O} and Burmester, {G R} and Bykerk, {V P} and Furst, {D E} and X Mariette and {van der Heijde}, D and {van Vollenhoven}, R and C Arendt and I Mountian and O Purcaru and D Tatla and B VanLunen and Weinblatt, {M E}",

year = "2017",

month = jan,

doi = "https://doi.org/10.1136/annrheumdis-2015-209057",

language = "English",

volume = "76",

pages = "96--104",

journal = "ANNALS OF THE RHEUMATIC DISEASES",

issn = "0003-4967",

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Emery, P, Bingham, CO, Burmester, GR, Bykerk, VP, Furst, DE, Mariette, X, van der Heijde, D, van Vollenhoven, R, Arendt, C, Mountian, I, Purcaru, O, Tatla, D, VanLunen, B & Weinblatt, ME 2017, 'Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve 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', Annals of the rheumatic diseases, vol. 76, no. 1, pp. 96-104. https://doi.org/10.1136/annrheumdis-2015-209057

Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve 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. / Emery, P; Bingham, C O; Burmester, G R et al.
In: Annals of the rheumatic diseases, Vol. 76, No. 1, 01.2017, p. 96-104.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors

T2 - 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study

AU - Emery, P

AU - Bingham, C O

AU - Burmester, G R

AU - Bykerk, V P

AU - Furst, D E

AU - Mariette, X

AU - van der Heijde, D

AU - van Vollenhoven, R

AU - Arendt, C

AU - Mountian, I

AU - Purcaru, O

AU - Tatla, D

AU - VanLunen, B

AU - Weinblatt, M E

PY - 2017/1

Y1 - 2017/1

N2 - 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-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.METHODS: DMARD-naïve 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-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.TRIAL REGISTRATION NUMBER: NCT01519791.

AB - 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-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.METHODS: DMARD-naïve 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-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.TRIAL REGISTRATION NUMBER: NCT01519791.

KW - Adult

KW - Antirheumatic Agents

KW - Arthritis, Rheumatoid

KW - Certolizumab Pegol

KW - Clinical Trial, Phase III

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Humans

KW - Infection

KW - Journal Article

KW - Male

KW - Methotrexate

KW - Middle Aged

KW - Multicenter Study

KW - Prognosis

KW - Radiography

KW - Randomized Controlled Trial

KW - Remission Induction

U2 - https://doi.org/10.1136/annrheumdis-2015-209057

DO - https://doi.org/10.1136/annrheumdis-2015-209057

M3 - Article

C2 - 27165179

SN - 0003-4967

VL - 76

SP - 96

EP - 104

JO - ANNALS OF THE RHEUMATIC DISEASES

JF - ANNALS OF THE RHEUMATIC DISEASES

IS - 1

ER -

Emery P, Bingham CO, Burmester GR, Bykerk VP, Furst DE, Mariette X et al. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve 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. Annals of the rheumatic diseases. 2017 Jan;76(1):96-104. doi: https://doi.org/10.1136/annrheumdis-2015-209057