Clinical trial NCT05121298: Discontinuation of Methotrexate in Rheumatoid Arthritis Patients Achieving Clinical Remission by Treatment With Upadacitinib Plus Methotrexate
Official title: Discontinuation of Methotrexate in Rheumatoid Arthritis Patients Achieving Clinical Remission by Treatment With Upadacitinib Plus Methotrexate: an Interventional, Multicenter, Prospective, Open-label, Single-arm Clinical Trial With Clinical, Ultrasound and Biomarker Assessments
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rheumatoid Arthritis
JAK Inhibitor
Musculoskeletal Ultrasound
Biomarker
Lead sponsor: Nagasaki University
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2021-11-16
Enrollment: 155
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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:

* The exclusion criteria are as follows:

  (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

Primary outcomes:
measure: maintenance of DAS28-CRP <=3.2 from week 24 to 48 in patients who achieve the DAS28-CRP <2.6 at week 24.
timeFrame: at week 48
Secondary outcomes:
measure: achievement of DAS28-CRP <=3.2
timeFrame: at weeks 12, 24 and 36
measure: achievement of DAS28-CRP <2.6
timeFrame: at weeks 12, 24, 36 and 48
measure: clinical relapse (DAS28-CRP >3.2) at week 48 in patients who achieve the DAS28-CRP <2.6 at week 24
timeFrame: at week 48
measure: achievement of EULAR moderate response
timeFrame: at week 12
measure: changes in the DAS28-CRP value
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the DAS28-ESR value
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the DAS28-CRP value
timeFrame: from week 24 to weeks 36 and 48
measure: changes in the DAS28-ESR value
timeFrame: from week 24 to weeks 36 and 48
measure: changes in the clinical disease activity index (CDAI) value
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the simplified disease activity index (SDAI) value
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the clinical disease activity index (CDAI) value
timeFrame: from week 24 to weeks 36 and 48
measure: changes in the simplified disease activity index (SDAI) value
timeFrame: from week 24 to weeks 36 and 48
measure: achievement of CDAI <=2.8
timeFrame: at weeks 12, 24, 36 and 48
measure: achievement of SDAI <=3.3
timeFrame: at weeks 12, 24, 36 and 48
measure: changes in the serum levels of biomarkers
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the serum levels of biomarkers
timeFrame: from week 24 to weeks 36 and 48
measure: changes in the total power Doppler (PD) score
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the total grayscale (GS) score
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the combined PD score
timeFrame: from baseline to weeks 12, 24, 36, and 48
measure: changes in the total PD score
timeFrame: from week 24 to weeks 36 and 48
measure: changes in the total GS score
timeFrame: from week 24 to weeks 36 and 48
measure: changes in the combined PD score
timeFrame: from week 24 to weeks 36 and 48
measure: change in van der Heijde-modified total Sharp score (vdH-mTSS)
timeFrame: from baseline to weeks 12, 24, 36 and 48
measure: change in vdH-mTSS
timeFrame: from week 24 to weeks 36 and 48
Other outcomes:
Locations:
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
Study officials:
affiliation: Nagasaki University
name: Atsushi Kawakami, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.