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.
OBJECTIVE
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.


BACKGROUND
NCT01451203.
Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tatsuya
T
Atsumi
The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Yoshiya
Y
Tanaka
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kazuhiko
K
Yamamoto
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Tsutomu
T
Takeuchi
Tokyo Women's Medical University, Tokyo, Japan.
Hisashi
H
Yamanaka
Nagoya University Graduate School and Faculty of Medicine, Nagoya, Japan.
Naoki
N
Ishiguro
Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan.
Katsumi
K
Eguchi
Tohoku University, Sendai, Japan.
Akira
A
Watanabe
Division of Biostatistics and Clinical Epidemiology, The University of Toyama Graduate School of Medicine, Toyama, Japan.
Hideki
H
Origasa
Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Shinsuke
S
Yasuda
Hiroshima Rheumatology Clinic, Hiroshima, Japan.
Yuji
Y
Yamanishi
Yokohama Rosai Hospital, Yokohama, Japan.
Yasuhiko
Y
Kita
Matsubara Mayflower Hospital, Kato, Japan.
Tsukasa
T
Matsubara
Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan.
Masahiro
M
Iwamoto
UCB Pharma, Tokyo, Japan.
Toshiharu
T
Shoji
UCB Pharma, Tokyo, Japan.
Osamu
O
Togo
Astellas Pharma Inc., Tokyo, Japan.
Toshiyuki
T
Okada
Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Désirée
http://orcid.org/0000-0002-5781-158X
D
van der Heijde
Department of Rheumatology, Tokyo Medical and Dental University, Tokyo, Japan.
Nobuyuki
N
Miyasaka
Hokkaido University Graduate School of Medicine, Sapporo, Japan.|Sapporo Medical Center NTT EC, Sapporo, Hokkaido, Japan.
Takao
T
Koike
D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068582:Certolizumab Pegol / Q000627:therapeutic use*; D000069340:Deprescriptions; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D061345:Early Medical Intervention; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D019233:Retreatment; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D000068582:Certolizumab Pegol; D008727:Methotrexate
Anti-TNF; DMARDs (biologic); Early Rheumatoid Arthritis; Methotrexate