TY - JOUR
T1 - Discontinuation vs. continuation of concomitant methotrexate in patients with rheumatoid arthritis on certolizumab pegol
T2 - results from a randomised, controlled trial
AU - Asai, Shuji
AU - Kojima, Toshihisa
AU - Ishikawa, Hajime
AU - Miyake, Nobumasa
AU - Kodera, Masanari
AU - Hasegawa, Hisanori
AU - Sobue, Yasumori
AU - Kanayama, Yasuhide
AU - Shimada, Hiromi
AU - Hirano, Yuji
AU - Hidaka, Toshihiko
AU - Fujibayashi, Takayoshi
AU - Matsumoto, Takuya
AU - Kobayakawa, Tomonori
AU - Yasuoka, Hidekata
AU - Kato, Takefumi
AU - Hanabayashi, Masahiro
AU - Kaneko, Yuko
AU - Tada, Masahiro
AU - Murata, Koichi
AU - Misaki, Kenta
AU - Ando, Masahiko
AU - Kuwatsuka, Yachiyo
AU - Suzuki, Mochihito
AU - Terabe, Kenya
AU - Imagama, Shiro
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Objective: The present non-inferiority study was designed to compare the effect of discontinuing versus continuing methotrexate (MTX) alongside certolizumab pegol (CZP) on maintaining low disease activity (LDA) in rheumatoid arthritis (RA) patients already stable on combination therapy. Methods: This multicentre, open-label, randomised, controlled trial included RA patients with sustained LDA (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with CZP + MTX. Patients were randomised 1:1 by computer to either continue MTX (CZP + MTX group) or discontinue MTX after a 12-week reduction period (CZP group) using a dynamic allocation strategy with the minimisation method. The primary endpoint was the proportion of patients maintaining LDA without a flare (i.e., a CDAI score > 10 or intervention with rescue treatments for any reason) at week 36 (24 weeks after MTX discontinuation). Non-inferiority is verified if the lower limit of the 90% confidence interval (CI) using normal approximation for the difference in the proportion of cases that maintained LDA at week 36 between the intervention group and control group exceeds the non-inferiority margin. Results: All 84 screened patients were randomised to the CZP + MTX group (n = 41) and CZP group (n = 43), and were included in the efficacy analysis. Proportions (90% CI) of patients who maintained LDA at week 36 were 85.4% (76.3 to 94.4%) in the CZP + MTX group and 83.7% (74.5 to 93.0%) in the CZP group. The difference (90% CI) between the two groups was − 1.6% (-14.6 to 11.3%), with the lower limit of the 90% CI exceeding the non-inferiority margin of -18%. Reported adverse events were broadly similar between the two groups. The proportion of patients with gastrointestinal symptoms, as assessed by a self-administered questionnaire, was significantly lower in the CZP group than in the CZP + MTX group at week 36 (2.4% vs. 15.8%, P = 0.034). Conclusion: Discontinuing concomitant MTX in RA patients on CZP is clinically feasible for maintaining LDA. Trial registration: Japan Registry of Clinical Trials (jRCTs041200048).
AB - Objective: The present non-inferiority study was designed to compare the effect of discontinuing versus continuing methotrexate (MTX) alongside certolizumab pegol (CZP) on maintaining low disease activity (LDA) in rheumatoid arthritis (RA) patients already stable on combination therapy. Methods: This multicentre, open-label, randomised, controlled trial included RA patients with sustained LDA (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with CZP + MTX. Patients were randomised 1:1 by computer to either continue MTX (CZP + MTX group) or discontinue MTX after a 12-week reduction period (CZP group) using a dynamic allocation strategy with the minimisation method. The primary endpoint was the proportion of patients maintaining LDA without a flare (i.e., a CDAI score > 10 or intervention with rescue treatments for any reason) at week 36 (24 weeks after MTX discontinuation). Non-inferiority is verified if the lower limit of the 90% confidence interval (CI) using normal approximation for the difference in the proportion of cases that maintained LDA at week 36 between the intervention group and control group exceeds the non-inferiority margin. Results: All 84 screened patients were randomised to the CZP + MTX group (n = 41) and CZP group (n = 43), and were included in the efficacy analysis. Proportions (90% CI) of patients who maintained LDA at week 36 were 85.4% (76.3 to 94.4%) in the CZP + MTX group and 83.7% (74.5 to 93.0%) in the CZP group. The difference (90% CI) between the two groups was − 1.6% (-14.6 to 11.3%), with the lower limit of the 90% CI exceeding the non-inferiority margin of -18%. Reported adverse events were broadly similar between the two groups. The proportion of patients with gastrointestinal symptoms, as assessed by a self-administered questionnaire, was significantly lower in the CZP group than in the CZP + MTX group at week 36 (2.4% vs. 15.8%, P = 0.034). Conclusion: Discontinuing concomitant MTX in RA patients on CZP is clinically feasible for maintaining LDA. Trial registration: Japan Registry of Clinical Trials (jRCTs041200048).
KW - Certolizumab pegol
KW - Drug tapering
KW - Methotrexate
KW - Randomised controlled trial
KW - Rheumatoid arthritis
UR - https://www.scopus.com/pages/publications/105003088207
UR - https://www.scopus.com/pages/publications/105003088207#tab=citedBy
U2 - 10.1186/s13075-025-03548-1
DO - 10.1186/s13075-025-03548-1
M3 - Article
C2 - 40188084
AN - SCOPUS:105003088207
SN - 1478-6354
VL - 27
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 82
ER -