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Discontinuation of methotrexate in rheumatoid arthritis patients achieving clinical remission by treatment with upadacitinib plus methotrexate (DOPPLER study): Study protocol for an interventional, multicenter, open-label and single-arm clinical trial with clinical, ultrasound and biomarker assessments

Discontinuation of methotrexate in rheumatoid arthritis patients achieving clinical remission by treatment with upadacitinib plus methotrexate (DOPPLER study): Study protocol for an interventional, multicenter, open-label and single-arm clinical trial with clinical, ultrasound and biomarker assessments

Kawakami Atsushi

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki

atsushik@nagasaki-u.ac.jp

Kawashiri Shinya

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki

+81-95-819-7200

shin-ya@nagasaki-u.ac.jp

Recruiting

Jan. 12, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Patients with 18 years older at the time of obtaining informed consent.
2. Patients with rheumatoid arthritis (RA) fulfilled the ACR/EULAR classification criteria for RA (2010).
3. Patients with moderate or more disease activity (DAS28-CRP > 3.2) at the time of the eligibility evaluation.
4. Patients have >= 1 power Doppler (PD) positive joint (of 22 examined using musculoskeletal ultrasound (MSUS)) at the time of the eligibility evaluation.
5. Patients who have received MTX treatment .
6. Patients who can personally provide written consent at their own free will after being receiving a thorough explanation of the study and fully understanding their participation in the study.

1. Patients treated with more than 7.5 mg per day of prednisolone.
2. Patients with contraindications to upadacitinib
3. Patients treated with two or more JAK inhibitors previously.
4. Patients treated with upadacitinib previously.
5. Patients with concurrent illness causing musculoskeletal disorders other than RA (ie, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, crystal-induced arthritis, systemic lupus erythematosus, systemic scleroderma, inflammatory myopathy, and mixed connective tissue disease).
6. Women who are currently pregnant or will not be compliant with a medically approved contraceptive regimen during and 12 months after the study period and lactating women. Men who will not be compliant with a contraceptive regimen during and 12 months after the study period.
7. Patients who jugged unsuitable for this study by the investigator.Patients who jugged unsuitable for this study by the investigator .

Both

Rheumatoid arthritis

Starting at baseline (week 0), all patients will receive upadacitinib 15mg/day and continue to receive a stable pre-baseline dosage of MTX until week 24 (Stage I). In addition, if patients achieve a EULAR moderate response or a DAS28-CRP <= 3.2 a week 12, and a DAS28-CRP of < 2.6 at week 24, they will discontinue MTX, and continue upadacitinib monotherapy until week 48 (Stage II).
Patients not achieving a EULAR moderate response or a DAS28-CRP <= 3.2 at week 12 or a DAS28-CRP of < 2.6 at week 24 will be excluded from this study.

Proportion of subjects sustained therapeutic response (DAS28-CRP <= 3.2) after discontinuation of MTX in RA patients who achieve clinical remission (DAS28-CRP < 2.6) during treatment with upadacitinib plus MTX at week 48.

*Proportion of subjects who achieve a DAS28-CRP <= 3.2 at week 12, 24 and 36.
* Proportion of subjects who achieve a DAS28-CRP < 2.6 at week 12, 24, 36 and 48.
* Clinical non-relapse rate (DAS28-CRP <= 3.2) at week 48 in subjects who progressed to Stage II.
* Proportion of subjects who achieve an EULAR moderate response at week 12.
* Changes in DAS28-ESR/CRP at week 12, 24, 36 and 48.
* Changes in CDAI/SDAI at week 12, 24, 36 and 48.
* Proportion of subjects who achieve a CDAI <= 2.8/SDAI <= 3.3 at week 12, 24, 36 and 48.
* Changes in various cytokines and other biomarkers at week 12, 24, 36, and 48.
* Change in total PD score, total GS score and composite score at week 12, 24, 36 and 48.
* Change in mTSS at week 24 and 48.
* Change in HAQ-DI at week 12, 24, 36 and 48.

+81-95-819-7229

Jan. 06, 2021

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