Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial

Tatsuya Atsumi, Yoshiya Tanaka, Kazuhiko Yamamoto, Tsutomu Takeuchi, Hisashi Yamanaka, Naoki Ishiguro, Katsumi Eguchi, Akira Watanabe, Hideki Origasa, Shinsuke Yasuda, Yuji Yamanishi, Yasuhiko Kita, Tsukasa Matsubara, Masahiro Iwamoto, Toshiharu Shoji, Osamu Togo, Toshiyuki Okada, Désirée van der Heijde, Nobuyuki Miyasaka, Takao Koike

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Abstract

Objectives To investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone. Methods MTX-naïve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA), a multicentre, randomised, controlled study, which consisted of a 52-week double-blind (DB) period and subsequent 52-week post treatment (PT) period. Patients were randomised to optimised MTX+CZP (n=159) or optimised MTX +placebo (PBO; n=157). Following the DB period, patients entered the PT period, receiving MTX alone (CZP+MTX→MTX; n=108, PBO+MTX→MTX; n=71). Patients who flared could receive rescue treatment with open-label CZP. Results 34 CZP+MTX→MTX patients and 14 PBO +MTX?MTX patients discontinued during the PT period. From week 52 through week 104, significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO +MTX (week 104: 84.2% vs 67.5% (p<0.001)). Remission rates decreased after CZP discontinuation; however, higher rates were maintained through week 104 in CZP+MTX?MTX versus PBO+MTX?MTX (41.5% vs 29.3% (p=0.026), 34.6% vs 24.2% (p=0.049) and 41.5% vs 33.1% (p=0.132) at week 104 in SDAI, Boolean and DAS28(erythrocyte sedimentation rate) remission. CZP retreated patients due to flare (n=28) showed rapid clinical improvement. The incidence of overall adverse events was similar between groups. Conclusions In MTX-naïve patients with early RA with poor prognostic factors, an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years, even after stopping CZP.

Original languageEnglish
JournalAnnals of the Rheumatic Diseases
DOIs
Publication statusAccepted/In press - 2017 Feb 2

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Methotrexate
Rheumatoid Arthritis
Therapeutics
Certolizumab Pegol
Blood Sedimentation
Sedimentation
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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation : 2-year results of the C-OPERA study, a phase III randomised trial. / Atsumi, Tatsuya; Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Yasuda, Shinsuke; Yamanishi, Yuji; Kita, Yasuhiko; Matsubara, Tsukasa; Iwamoto, Masahiro; Shoji, Toshiharu; Togo, Osamu; Okada, Toshiyuki; van der Heijde, Désirée; Miyasaka, Nobuyuki; Koike, Takao.

In: Annals of the Rheumatic Diseases, 02.02.2017.

Research output: Contribution to journalArticle

Atsumi, T, Tanaka, Y, Yamamoto, K, Takeuchi, T, Yamanaka, H, Ishiguro, N, Eguchi, K, Watanabe, A, Origasa, H, Yasuda, S, Yamanishi, Y, Kita, Y, Matsubara, T, Iwamoto, M, Shoji, T, Togo, O, Okada, T, van der Heijde, D, Miyasaka, N & Koike, T 2017, 'Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial', Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2016-210246
Atsumi, Tatsuya ; Tanaka, Yoshiya ; Yamamoto, Kazuhiko ; Takeuchi, Tsutomu ; Yamanaka, Hisashi ; Ishiguro, Naoki ; Eguchi, Katsumi ; Watanabe, Akira ; Origasa, Hideki ; Yasuda, Shinsuke ; Yamanishi, Yuji ; Kita, Yasuhiko ; Matsubara, Tsukasa ; Iwamoto, Masahiro ; Shoji, Toshiharu ; Togo, Osamu ; Okada, Toshiyuki ; van der Heijde, Désirée ; Miyasaka, Nobuyuki ; Koike, Takao. / Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation : 2-year results of the C-OPERA study, a phase III randomised trial. In: Annals of the Rheumatic Diseases. 2017.
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title = "Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial",
abstract = "Objectives To investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone. Methods MTX-na{\"i}ve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA), a multicentre, randomised, controlled study, which consisted of a 52-week double-blind (DB) period and subsequent 52-week post treatment (PT) period. Patients were randomised to optimised MTX+CZP (n=159) or optimised MTX +placebo (PBO; n=157). Following the DB period, patients entered the PT period, receiving MTX alone (CZP+MTX→MTX; n=108, PBO+MTX→MTX; n=71). Patients who flared could receive rescue treatment with open-label CZP. Results 34 CZP+MTX→MTX patients and 14 PBO +MTX?MTX patients discontinued during the PT period. From week 52 through week 104, significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO +MTX (week 104: 84.2{\%} vs 67.5{\%} (p<0.001)). Remission rates decreased after CZP discontinuation; however, higher rates were maintained through week 104 in CZP+MTX?MTX versus PBO+MTX?MTX (41.5{\%} vs 29.3{\%} (p=0.026), 34.6{\%} vs 24.2{\%} (p=0.049) and 41.5{\%} vs 33.1{\%} (p=0.132) at week 104 in SDAI, Boolean and DAS28(erythrocyte sedimentation rate) remission. CZP retreated patients due to flare (n=28) showed rapid clinical improvement. The incidence of overall adverse events was similar between groups. Conclusions In MTX-na{\"i}ve patients with early RA with poor prognostic factors, an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years, even after stopping CZP.",
author = "Tatsuya Atsumi and Yoshiya Tanaka and Kazuhiko Yamamoto and Tsutomu Takeuchi and Hisashi Yamanaka and Naoki Ishiguro and Katsumi Eguchi and Akira Watanabe and Hideki Origasa and Shinsuke Yasuda and Yuji Yamanishi and Yasuhiko Kita and Tsukasa Matsubara and Masahiro Iwamoto and Toshiharu Shoji and Osamu Togo and Toshiyuki Okada and {van der Heijde}, D{\'e}sir{\'e}e and Nobuyuki Miyasaka and Takao Koike",
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month = "2",
day = "2",
doi = "10.1136/annrheumdis-2016-210246",
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TY - JOUR

T1 - Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation

T2 - 2-year results of the C-OPERA study, a phase III randomised trial

AU - Atsumi, Tatsuya

AU - Tanaka, Yoshiya

AU - Yamamoto, Kazuhiko

AU - Takeuchi, Tsutomu

AU - Yamanaka, Hisashi

AU - Ishiguro, Naoki

AU - Eguchi, Katsumi

AU - Watanabe, Akira

AU - Origasa, Hideki

AU - Yasuda, Shinsuke

AU - Yamanishi, Yuji

AU - Kita, Yasuhiko

AU - Matsubara, Tsukasa

AU - Iwamoto, Masahiro

AU - Shoji, Toshiharu

AU - Togo, Osamu

AU - Okada, Toshiyuki

AU - van der Heijde, Désirée

AU - Miyasaka, Nobuyuki

AU - Koike, Takao

PY - 2017/2/2

Y1 - 2017/2/2

N2 - Objectives To investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone. Methods MTX-naïve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA), a multicentre, randomised, controlled study, which consisted of a 52-week double-blind (DB) period and subsequent 52-week post treatment (PT) period. Patients were randomised to optimised MTX+CZP (n=159) or optimised MTX +placebo (PBO; n=157). Following the DB period, patients entered the PT period, receiving MTX alone (CZP+MTX→MTX; n=108, PBO+MTX→MTX; n=71). Patients who flared could receive rescue treatment with open-label CZP. Results 34 CZP+MTX→MTX patients and 14 PBO +MTX?MTX patients discontinued during the PT period. From week 52 through week 104, significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO +MTX (week 104: 84.2% vs 67.5% (p<0.001)). Remission rates decreased after CZP discontinuation; however, higher rates were maintained through week 104 in CZP+MTX?MTX versus PBO+MTX?MTX (41.5% vs 29.3% (p=0.026), 34.6% vs 24.2% (p=0.049) and 41.5% vs 33.1% (p=0.132) at week 104 in SDAI, Boolean and DAS28(erythrocyte sedimentation rate) remission. CZP retreated patients due to flare (n=28) showed rapid clinical improvement. The incidence of overall adverse events was similar between groups. Conclusions In MTX-naïve patients with early RA with poor prognostic factors, an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years, even after stopping CZP.

AB - Objectives To investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone. Methods MTX-naïve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA), a multicentre, randomised, controlled study, which consisted of a 52-week double-blind (DB) period and subsequent 52-week post treatment (PT) period. Patients were randomised to optimised MTX+CZP (n=159) or optimised MTX +placebo (PBO; n=157). Following the DB period, patients entered the PT period, receiving MTX alone (CZP+MTX→MTX; n=108, PBO+MTX→MTX; n=71). Patients who flared could receive rescue treatment with open-label CZP. Results 34 CZP+MTX→MTX patients and 14 PBO +MTX?MTX patients discontinued during the PT period. From week 52 through week 104, significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO +MTX (week 104: 84.2% vs 67.5% (p<0.001)). Remission rates decreased after CZP discontinuation; however, higher rates were maintained through week 104 in CZP+MTX?MTX versus PBO+MTX?MTX (41.5% vs 29.3% (p=0.026), 34.6% vs 24.2% (p=0.049) and 41.5% vs 33.1% (p=0.132) at week 104 in SDAI, Boolean and DAS28(erythrocyte sedimentation rate) remission. CZP retreated patients due to flare (n=28) showed rapid clinical improvement. The incidence of overall adverse events was similar between groups. Conclusions In MTX-naïve patients with early RA with poor prognostic factors, an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years, even after stopping CZP.

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