Discontinuation of Methotrexate in Rheumatoid Arthritis Patients Achieving Clinical Remission by Treatment With Upadacitinib Plus Methotrexate

NCT ID: NCT05121298

Last Updated: 2021-12-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-12
• Study Completion Date: 2024-09-30

Brief Summary

The administration of Janus kinase (JAK) inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved even the clinical outcomes in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX). Upadacitinib is a selective JAK1 inhibitor to be approved for use in RA. Nearly half of patients added JAK inhibitors including upadacitinib can achieve clinical remission in RA patients with inadequate response to MTX. As the next step, it is the great issue whether disease activity can be maintained in good condition even if MTX is discontinued after achieving clinical remission in patients treated with the combination of JAK inhibitors and MTX. Thus, it is desirable to investigate the maintenance of clinical non-relapse after discontinuation of MTX in RA patients with clinical remission during treatment with upadacitinib plus MTX. In this study, we will evaluate the proportion of patients who maintained nonclinical relapse after discontinuation of MTX in patients with RA who achieved clinical remission after treatment with upadacitinib plus MTX. We will also use musculoskeletal ultrasound (MSUS) assessments to determine whether discontinuation of MTX can be maintained nonclinical relapse in RA patients achieving clinical remission.

Conditions

Rheumatoid Arthritis; JAK Inhibitor; Musculoskeletal Ultrasound; Biomarker

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Upadacitinib

The administration of upadacitinib 15mg/day

Group Type: EXPERIMENTAL

upadacitinib 15mg/day

Intervention Type: DRUG

Patients will receive upadacitinib 15mg/day and continue to receive same doses of MTX until 24 weeks. If patients achieve a European League Against Rheumatism (EULAR) moderate response or a Disease Activity Score 28 (DAS28-CRP) ≤3.2 at 12 weeks, and a DAS28-CRP of \<2.6 at 24 weeks, they will discontinue MTX, and continue upadacitinib until 48 weeks.

Interventions

upadacitinib 15mg/day

Patients will receive upadacitinib 15mg/day and continue to receive same doses of MTX until 24 weeks. If patients achieve a European League Against Rheumatism (EULAR) moderate response or a Disease Activity Score 28 (DAS28-CRP) ≤3.2 at 12 weeks, and a DAS28-CRP of \<2.6 at 24 weeks, they will discontinue MTX, and continue upadacitinib until 48 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must meet all of the following requirements to be considered for entry into the study:

1. ≥20 years old

2. with the diagnosis of RA based on the American College of Rheumatology (ACR) /EULAR 2010 RA Classification Criteria

3. with at least moderate DAS28-CRP >3.2 at the eligibility evaluation

4. with at least one PD score positive joint of 22 joints examined MSUS at the eligibility evaluation

5. treated with MTX for ≥8 weeks prior to the providing consent, including 4 weeks or more at the same doses of 6 to 16 mg per week

6. ability and willingness to provide written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria

(1) concurrent use of a corticosteroid equivalent to >7.5 mg/day of prednisolone (2) applicable an item for the contraindication of upadacitinib (3) a previous use of a JAK inhibitor (4) treatment with a corticosteroid and change of dose within 4 weeks prior to the providing consent (5) treatment with a csDMARD except MTX within 2 weeks prior to the providing consent; (6) treatment with a biologic DMARD or a biosimilar DMARD (ie, infliximab, biosimilar of infliximab, adalimumab, golimumab, certolizumab pegol, tocilizumab, sarilumab or abatacept) within 8 weeks prior to the providing consent (7) treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent (8) use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent (9) a complication causing musculoskeletal disorders other than RA (ie, ankylosing spondyloarthritis, reactive arthritis, psoriatic arthritis, crystal-induced arthritis, systemic lupus erythematosus, systemic scleroderma, inflammatory myopathy, or mixed connective tissue disease) (10) current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period (11) inappropriateness for inclusion in this study as determined by the investigator

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Atsushi Kawakami

OTHER

Sponsor Role: lead

Responsible Party

Atsushi Kawakami

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Atsushi Kawakami, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nagasaki University

Locations

Nagasaki University Hospital

Nagasaki, , Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Atsushi Kawakami, MD, PhD

Role: CONTACT

Phone: +81-95-819-7260

Email: atsushik@nagasaki-u.ac.jp

Toshimasa Shimizu, MD, PhD

Role: CONTACT

Phone: +81-95-819-8527

Email: t.shimizu@nagasaki-u.ac.jp

Facility Contacts

Atsushi Kawakami, MD, PhD

Role: primary

Toshimasa Shimizu, MD, PhD

Role: backup

References

Shimizu T, Kawashiri SY, Sato S, Kawazoe Y, Kuroda S, Kawasaki R, Ito Y, Morimoto S, Yamamoto H, Kawakami A. Discontinuation of methotrexate in rheumatoid arthritis patients achieving clinical remission by treatment with upadacitinib plus methotrexate (DOPPLER study): A study protocol for an interventional, multicenter, open-label and single-arm clinical trial with clinical, ultrasound and biomarker assessments. Medicine (Baltimore). 2022 Jan 14;101(2):e28463. doi: 10.1097/MD.0000000000028463.

Reference Type: DERIVED

PMID: 35029189 (View on PubMed)

Other Identifiers

CRB20-024

Identifier Type: -

Identifier Source: org_study_id