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Patient REported, Clinical, and Imaging OUtcomes of tapering methotrexate in patients with rheumatoid arthritis in Stable low disease activity with Baricitinib (PRECIOUS-B study)

PRECIOUS-B study (PRECIOUS-B study)

29

The patient background (mean or percentage) of the 28 patients after excluding withdrawn consent from the total enrolment was as follows: age 60 years, 68% female, disease duration 12 years, methotrexate dose 8.3 mg/week, CDAI 2.5.

The pace of enrolment was slower than initially anticipated and the target number of patients could not be achieved within the enrolment period. The number of patients enrolled was 29. Of these, one withdrew consent and 28 patients were included in the analysis.

Seven patients had nine adverse events, of which three had four serious adverse events. The serious adverse events included leg cellulitis, ischaemic enteritis, cerebral infarction and metacarpal fracture in one case each. All were adverse events expected during baricitinib treatment.

Primary endpoint: 27 patients were included in the efficacy analysis population after excluding one patient who was found to be ineligible after enrolment. The proportion of patients maintaining low disease activity by CDAI assessment at 24 weeks after MTX discontinuation was 77.8% (95% CI: 57.7-91.4%). A threshold response rate of 60% was set, but the lower limit of the two-sided 95% CI for the low disease activity maintenance rate was not above the threshold response rate. Secondary endpoints: Percentage of maintenance of low disease activity as assessed by CDAI at 12, 24 and 52 weeks was 88.9%, 81.5% and 77.8%, respectively. The values [mean (SD)] for each item at 0, 12, 24, 36 and 52 weeks are as follows. CDAI: 2.49 (2.42), 2.6 (2.36), 4.97 (6.13), 3.22 (3.00), 3.53 (3.83) SDAI: 2.60 (2.42), 2.79 (2.41), 5.32 (6.57), 3.41 (3.08), 3.81 (4.20) DAS28-CRP: 1.54 (0.43), 1.59 (0.47), 1.94 (0.98), 1.73 (0.60), 1.70 (0.64) DAS28-ESR: 2.24 (0.86), 2.36 (0.79), 2.57 (0.85), 2.42 (0.76), 2.43 (0.84) CRP), mg/dL: 0.11 (0.12), 0.16 (0.22), 0.35 (0.82), 0.19 (0.25), 0.28 (0.87) ESR), mm/h: 20.6 (18.1), 24.1 (19.6), 23.2 (16.1), 22.9 (18.4), 22.4 (19.3) MMP-3), ng/mL: 62.2 (44.8), 68.8 (53.7), 78.5 (57.0), 67.9 (43.9), 70.0 (46.8) HAQ-DI: 0.409 (0.566), 0.395 (0.610), 0.559 (0.693), 0.394 (0.580), 0.505 (0.744) EQ-5D: 0.83 (0.18), 0.82 (0.17), 0.81 (0.18), 0.79 (0.27), 0.80 (0.19) FACIT fatigue: 3.1 (0.7), 3.1 (0.7), 3.0 (0.7), 3.1 (0.8), 3.0 (0.7) FSSG: 7.4 (8.5), 8.2 (8.1), 7.1 (7.7), 5.9 (5.6), 5.7 (5.9)

Among RA patients maintaining low disease activity with combination BAR and MTX, 77.8% maintained low disease activity up to 24 weeks after MTX discontinuation.

Mar. 31, 2025

No

NA

https://jrct.mhlw.go.jp/latest-detail/jRCT1041190125

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

+81-52-744-1957

mochihito0511@yahoo.co.jp

Complete

Mar. 09, 2020

Interventional

single arm study

open(masking not used)

uncontrolled control

single 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 BAR plus MTX
3) RA patients receiving BAR, 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*
Week 0 to 12
- Reduced after registration.
- The dosing frequency of MTX is decreased from weekly to biweekly without a change in dose, regardless of the initial dose.
- The dosing frequency of folic acid is decreased from weekly to biweekly without a change in dose 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) BAR
- Continued at a stable dose and interval throughout the course of the study.

3) csDMARDs other than MTX
- Continued at a stable dose and interval throughout the course of the study.

4) Glucocorticoids
- Continued at a stable dose up to week 36, and allowed to taper after week 36.

5) Rescue treatments
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
- Changing the dosing frequency back to weekly administration, 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 low disease activity evaluated with SDAI, DAS28-CRP, and DAS28-ESR at week 0, 12, 24, 36, and 52
3) Proportion of patients maintaining remission evaluated with CDAI, SDAI, DAS28-CRP, and DAS28-ESR at week 0, 12, 24, 36, and 52
4) Following parameters from week 0 to 52
- CDAI, SDAI, DAS28-CRP, DAS28-ESR, J-HAQ
- CRP, ESR, MMP-3
- FSSG, EQ-5D, SF-36, FACIT fatigue
5) Change from week 0 to 52 in total Sharp score
6) Proportion of patients with structural remission and clinically relevant radiographic progression at week 52
7) Rate of regaining low disease activity in patients with CDAI>10
8) Predictors of maitaining low disease activity, structural remission, and clinically relevant radiographic progression
9) Adverse events

none