Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate

Atsushi Kawakami400 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

400

Conditions

Rheumatoid Arthritis JAK Inhibitor IL-6 Inhibitor

Interventions

filgotinib 200mg/dayDRUG

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.

subcutaneous tocilizumab 162mg/biweeklyDRUG

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.

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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 exclusion criteria are as follows: 1. concurrent use of a corticosteroid equivalent to \>5 mg/day of prednisolone 2. applicable an item for the contraindication of filgotinib or tocilizumab 3. a previous use of a JAK inhibitor or IL-6 inhibitor 4. treatment with a corticosteroid and csDMARD and change of dose within 4 weeks prior to the providing consent 5. treatment with a biologic DMARD or a biosimilar DMARD (ie, infliximab, biosimilar of infliximab, adalimumab, biosimilar of adalimumab, golimumab, certolizumab pegol or abatacept) within 8 weeks prior to the providing consent 6. treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent 7. use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent 8. 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) 9. current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period 10. inappropriateness for inclusion in this study as determined by the investigator

Outcomes

Primary Outcomes

the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response

Time frame: at week 12

Secondary Outcomes

the proportion of patients who achieve an ACR20 response

Time frame: at weeks 2, 4, 8, 12, 24, 36 and 52

the proportion of patients who achieve an ACR50 response

Time frame: at weeks 2, 4, 8, 24, 36 and 52

the proportion of patients who achieve an ACR70 response

Time frame: at weeks 2, 4, 8, 12, 24, 36 and 52

changes in the clinical disease activity index (CDAI) value

Higher scores mean a more active of RA.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

changes in the simplified disease activity index (SDAI) value

Higher scores mean a more active RA.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

changes in the Disease Activity Score (DAS)28-ESR value

Higher scores mean a more active RA.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

changes in the DAS28-CRP value

Higher scores mean a more active RA.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

changes in the serum levels of biomarkers

We analyze the serum levels of multiple biomarkers such as cytokines and chemokines.

Time frame: from baseline to weeks 2, 4, 12, 24, 36, and 52

changes in the total power Doppler (PD) score

Higher scores mean a more active RA.

Time frame: from baseline to weeks 4, 12, 24, 36, and 52

changes in the total grayscale (GS) score

Higher scores mean a more active RA.

Time frame: from baseline to weeks 4, 12, 24, 36, and 52

changes in the combined PD score

Higher scores mean a more active RA.

Time frame: from baseline to weeks 4, 12, 24, 36, and 52

change in van der Heijde-modified total Sharp score (vdH-mTSS)

Higher scores mean a more joint destruction and deformity.

Time frame: from baseline to weeks 24 and 52

change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data

Higher scores mean a more active RA.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data

Higher scores mean a worse QOL.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data

Higher scores mean a worse fatigue.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

changes in the morning stiffness duration

Higher scores mean a more active RA.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

changes in the morning stiffness activity

We analyze the visual analog scale of morning stiffness activity. Higher scores mean a more active RA.

Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts