Exploratory research on therapeutic optimization parameters for upadacitinib by single-cell analysis of synovial tissue and peripheral blood from rheumatoid arthritis and psoriatic arthritis patients

JRCT ID: jRCTs031230485

Registered date:30/11/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Rheumatoid arthritis or Psoriatic arthritis
• Date of first enrollment: 25/12/2023
• Target sample size: 40
• Study type: Interventional
• Intervention(s): UPA 15mg is administered orally once a day. At the 12-week mark after initiation of administration, if there is no improvement of 20% or more in TJC and SJC from the start of administration, treatment optimization will be performed based on the "Rheumatoid Arthritis Treatment Guidelines 2020" in Japan, as determined by the treating physician. Regardless of the continuation of UPA, all patients will be tracked for a research treatment period from the start of UPA administration to 24 weeks.

Outcome(s)

• Primary Outcome: ACR50 achievement rate at 12 weeks of UPA administration based on the immunological phenotype (synovial tissue type) of the joint synovium.

Secondary Outcome

(1). ACR20/70 achievement rates at 12 weeks of UPA administration based on each synovial tissue type.
(2). ACR20/50/70 achievement rates at 4 weeks of UPA administration based on each synovial tissue type.
(3). Improvement rates of ACR components at 4 and 12 weeks of UPA administration based on each synovial tissue type.
(4). Improvement rates of MMP-3 components at 4 and 12 weeks of UPA administration based on each synovial tissue type.
(5). Immunological characteristics of peripheral blood mononuclear cells (cell subset balance, gene expression, etc.) based on each synovial tissue type.
(6). Treatment responsiveness to UPA at 4 and 12 weeks based on disease (RA or PsA) and synovial tissue type.
(7). Continuation rates of UPA at 24 weeks based on synovial tissue type.
(8). Treatment responsiveness at 24 weeks based on synovial tissue type for patients who changed treatment at 12 weeks of UPA administration.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1). Patients with RA or PsA (for RA, patients must fulfill the 2010 ACR/EULAR classification criteria, and for PsA, patients must fulfill the CASPAR classification criteria).
(2). Patients with disease activity (TJC>=3 and SJC>=3).
(3). Patients aged 18 years and above.
(4). Patients who have had inadequate efficacy or difficulty continuing with one or more csDMARDs and one or fewer bDMARDs due to insufficient effectiveness or adverse events.
(5). Gender: Not restricted.
(6). Patients who have received sufficient explanation regarding participation in this study, have understood it adequately, and have provided written consent based on their own free will.
(7). Patients who can attend outpatient visits in accordance with the study implementation schedule.
(8). Patients for whom residual samples of synovial tissue have been collected and stored for purposes other than this study within the 4 weeks prior to obtaining consent.

Exclude criteria

(1). Patients with a history of hypersensitivity to components of upadacitinib (UPA).
(2). Patients with active severe infections.
(3). Patients with active tuberculosis.
(4). Patients with severe liver dysfunction (Child-Pugh Score C).
(5). Patients who are carriers or have a history of hepatitis B virus (negative for HBsAg and positive for either HBcAb or HBsAb). However, if HBV DNA is negative, participation is possible with attention to signs and symptoms of hepatitis B virus reactivation while monitoring liver function test values and HBV DNA.
(6). Patients who are carriers of hepatitis C virus.
(7). Patients with neutrophil count < 1000 / mm3, lymphocyte count < 500 / mm3, or Hb < 8 g/dL.
(8). Patients who are pregnant or possibly pregnant.
(9). Other individuals deemed inappropriate for participation in this study by the principal investigator or participating physicians.

Related Information

• Primary Sponsor: Fujio Keishi
• Source(s) of Monetary Support: AbbVie GK