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Certolizumab Pegol treatment with Reducing and stoppIng MEthotrexate in patients with Rheumatoid Arthritis in stable low disease activity-state (PRIMERA study)

Certolizumab Pegol treatment with Reducing and stoppIng MEthotrexate in patients with Rheumatoid Arthritis in stable low disease activity-state (PRIMERA study)

84

Patient characteristics (mean or %) for the CZP+MTX group (41 patients) vs. CZP group (43 patients) were: age 60.2 vs. 58.2 years, female 85 vs. 81%, disease duration 11.7 vs. 8.7 years, CDAI 2.9 vs. 2.3, and MTX dose 7.9 vs. 8.7 mg/week.

In the CZP+MTX group, 39 of 41 patients initiated protocol treatment; of these, 1 discontinued due to adverse events, and 38 completed 52 weeks. In the CZP group, all 43 patients initiated protocol treatment and completed 52 weeks.

In the CZP+MTX group, 8 adverse events occurred in 7 patients; in the CZP group, 7 adverse events occurred in 6 patients. No serious adverse events were observed.

Proportions (90% CI) of patients who maintained low disease activity (LDA) without a flare 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%. The present study met its primary endpoint by demonstrating non-inferiority of the CZP group compared with the CZP+MTX group. Comparison by the chi-square test showed no significant difference in the proportions (95% CI) of patients who maintained LDA without a flare between the CZP+MTX and CZP groups at week 12 (90.2% (76.9 to 97.3%) vs. 93.0% (80.9 to 98.5%), p = 0.645), week 24 (85.4% (70.8 to 94.4%) vs. 88.4% (74.9 to 96.1%), p = 0.683), week 36 (85.4% (70.8 to 94.4%) vs. 83.7% (69.3 to 93.2%), p = 0.835), and week 52 (82.9% (67.9 to 92.8%) vs. 81.4% (66.6 to 91.6%), p = 0.855). We also found no significant differences between the two groups in the estimated means and mean changes from baseline for CDAI, SDAI, DAS28-CRP, serum CRP and MMP-3 levels, HAQ-DI, and EQ-5D at all time points. In the CZP group, a total of eight patients had a flare by week 52. Of these, two patients with CDAI scores >10, and four patients who maintained CDAI scores <=10, received rescue treatment, whereas one patient with a CDAI score >10 requested not to (and did not) undergo rescue treatment. Both of the two patients with CDAI scores >10 who received rescue treatment (one patient restarted MTX and received intra-articular injection, and another restarted MTX) regained LDA by week 36. There were no significant differences between the two groups in the estimated means and mean changes from baseline for FSSG score at all time points. The proportion of patients with FSSG score =>8 was significantly lower in the CZP group than in the CZP+MTX group at week 36 (2.4% vs. 15.8%, P = 0.034), while there was no significant difference between the two groups at weeks 0, 12, 24 and 52.

Discontinuing concomitant MTX in RA patients on CZP is clinically feasible for maintaining low disease activity.

Dec. 31, 2025

April. 05, 2025

https://link.springer.com/article/10.1186/s13075-025-03548-1

No

NA

https://jrct.mhlw.go.jp/latest-detail/jRCTs041200048

Asai Shuji

Nagoya University Hospital

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

asai@med.nagoya-u.ac.jp

Suzuki Mochihito

Nagoya University Hospital

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

+81-52-744-1908

asai@med.nagoya-u.ac.jp

Not Recruiting

Oct. 02, 2020

Interventional

randomized controlled trial

open(masking not used)

no treatment control/standard of care control

parallel assignment

treatment purpose

1) Patients fulfilled the 1987 ACR classification criteria or the new ACR/EULAR diagnostic criteria for RA
2) RA patients with sustained low disease activity (CDAI <=10) for >=12 weeks while undergoing combination therapy with CZP plus MTX
3) RA patients receiving CZP, MTX, csDMARDs, and glucocorticoids at a stable dosage regimen for >=12 weeks prior to obtaining informed consent
4) RA patients aged >=20 years
5) Obtaining written informed consent

1) Patients with adherence problems
2) Patients judged as inadequate at the discretion of inevstigators

Both

Rheumatoid arthritis

1) MTX*
- Continued group:
Continued at a stable dose and interval throughout the cours of the study.
Folic acid is continued if concomitantly used.
- Withdrawn group:
Week 0 to 12
Reduced after registration.
The dose of MTX is reduced to half, regardless of the initial dose.
Folic acid is continued if concomitantly used.
Week 12 to 52
Discontinued if low disease activity was maintained.
Folic acid is discontinued if concomitantly used.
*The allowable range of adherence is -20% to +20%.

2) CZP and csDMARDs other than MTX
Continued at a stable dose and interval throughout the course of the study in both groups.

3) Glucocorticoids
Continued at a stable dose up to week 36, and allowedto taper after week 36 in both group.

4) Rescue treatment
One or more of the following rescue treatments are performed if the CDAI score was >10 and at the discretion of the investigator and/or upon patient request.
- Restoring, restarting, or increasing doses of MTX
- Increasing doses of or adding csDMARDs other than MTX.
- Increasing doses of or adding glucocorticoids
- Drainage of synovial fluid.
- Administering an intraarticular injection of corticosteroids, hyaluronic acid, or lidocaine.

Proportion of patients maintaining low disease activity without a flare* at week 36 (24 weeks after MTX discontinuation).
*Disease flare is defined as a CDAI score >10 or intervention with the rescue treatments for any reason.

1) Proportion of patients maintaining low disease activity evaluated with CDAI at week 12, 24, and 52
2) Proportion of patients maintaining clinical remission evaluated with CDAI at week 0, 12, 24, 36, and 52
3) Following parameters from week 0 to 52
- CDAI, SDAI, DAS28-CRP, J-HAQ
- CRP, MMP-3
- FSSG, EQ-5D
4) Changes of following parameters from week 0 to 52
- Total Sharp score
- Atlantodental interval
5) Proportion of patients with structural remission
and clinically relevant radiographic progression at week 52
6) Rate of regaining low disease activity in patients with CDAI>10
7) Predictors of maitaining low disease activity, structural remission, and clinically relevant radiographic progression
8) Adverse events

+81-52-744-2479

July. 27, 2020

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