Rheumatoid Arthritis, JAK Inhibitor, IL-6 Inhibitor, Musculoskeletal Ultrasound, Biomarker
Conditions
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). The dysregulation of JAK-signal transducer and activator of transcription (STAT) pathways via overproduction of cytokines, such as interleukin-6 (IL-6) is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor to be approved for use in RA. Filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction due to inhibition of the JAK-STAT pathway. IL-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways due to inhibition of IL-6 signaling. We will evaluate whether the effectiveness and safety of filgotinib monotherapy is non-inferior to those of tocilizumab monotherapy in RA patients with inadequate response to MTX.
Interventions
Patients will be randomized in a 1:1 ratio to the administration of filgotinib 200mg/day or subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.
DRUGsubcutaneous tocilizumab 162mg/biweekly
Patients will be randomized in a 1:1 ratio to the administration of filgotinib 200mg/day or subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.
Sponsors
Gilead Sciences
Atsushi Kawakami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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 ACR/EULAR 2010 RA Classification Criteria 3. with at least moderate disease activity defined as a DAS28-ESR ≥3.2 at the eligibility evaluation 4. treated with MTX for ≥8 weeks prior to the providing consent, including 4 weeks or more at the same doses of 8 to 16 mg per week (stable doses of \<8 mg per week are allowed only in the presence of intolerance to higher doses) 5. ability and willingness to provide written informed consent and comply with the requirements of the study protocol
Exclusion criteria
* The
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response | at week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the proportion of patients who achieve an ACR50 response | at weeks 2, 4, 8, 24, 36 and 52 | — |
| the proportion of patients who achieve an ACR70 response | at weeks 2, 4, 8, 12, 24, 36 and 52 | — |
| changes in the clinical disease activity index (CDAI) value | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a more active of RA. |
| changes in the simplified disease activity index (SDAI) value | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
| changes in the Disease Activity Score (DAS)28-ESR value | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
| changes in the DAS28-CRP value | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
| changes in the serum levels of biomarkers | from baseline to weeks 2, 4, 12, 24, 36, and 52 | We analyze the serum levels of multiple biomarkers such as cytokines and chemokines. |
| changes in the total power Doppler (PD) score | from baseline to weeks 4, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
| the proportion of patients who achieve an ACR20 response | at weeks 2, 4, 8, 12, 24, 36 and 52 | — |
| changes in the combined PD score | from baseline to weeks 4, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
| change in van der Heijde-modified total Sharp score (vdH-mTSS) | from baseline to weeks 24 and 52 | Higher scores mean a more joint destruction and deformity. |
| change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
| change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a worse QOL. |
| change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a worse fatigue. |
| changes in the morning stiffness duration | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
| changes in the morning stiffness activity | from baseline to weeks 2, 4, 8, 12, 24, 36, and 52 | We analyze the visual analog scale of morning stiffness activity. Higher scores mean a more active RA. |
| changes in the total grayscale (GS) score | from baseline to weeks 4, 12, 24, 36, and 52 | Higher scores mean a more active RA. |
Countries
Japan
Contacts
Primary ContactAtsushi Kawakami, MD, PhD
Backup ContactToshimasa Shimizu, MD, PhD
Outcome results
None listed