Fractalkine (CX3CL1) is a chemokine that regulates chemotaxis and cell adhesion of leukocytes expressing the cognate receptor, CX3CR1, during their migration. The serum level of fractalkine is elevated in patients with RA and is linked to disease activity. Peripheral blood CD16+ monocytes and a subset of T cells express CX3CR1, while fractalkine is expressed on fibroblast-like synoviocytes and endothelial cells in the synovial tissue of patients with RA [1].
Dr Yoshiya Tanaka et al. (University of Occupational and Environmental Health, Japan) evaluated the efficacy and safety of E6011 in RA compared with placebo [2]. This 24-week phase 2 study was set up as a double-blind, placebo-controlled study with 4 treatment arms. A total of 190 patients were randomised to receive E6011 subcutaneously (100 mg/day, n=28; 200 mg/day, n=54; 400/200 mg/day, n=54), or placebo (n=54). In the E6011 lower-dose and placebo groups, subjects received treatment at weeks 0, 1, 2, and every 2 weeks thereafter. In the E6011 400/200 mg group, subjects received 400 mg at weeks 0, 1, 2, 4, 6, 8, 10 followed by 200 mg every 2 weeks subsequently.
At week 24, the ACR20 response rate was significantly higher in patients receiving the two higher doses E6011 compared with placebo (53.7% for 200 mg, 57.4% for 400/200 mg vs 35.2% for placebo). Differences in the ACR20 response rate at week 12 were statistically not significant between the 4 arms (37.0% in the placebo group, 39.3% in the 100 mg group, 48.1% in the 200 mg group, and 46.3% in the 400/200 mg group). A higher ACR20 response became apparent in a dose-dependent manner in patients who expressed higher CD16+ monocytes at week 24 (30.0% for placebo, 46.7% for 100 mg, 57.7% for 200 mg, and 69.6% for 400/200 mg). E6011 also demonstrated a favourable safety profile and was generally well-tolerated during the study period.
- Nanki T, et al. Mod Rheumatol. 2017 May;27(3):392-397.
- Tanaka Y, et al. Abstract OP0223. EULAR 2019
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Table of Contents: EULAR 2019
Featured articles
Efficacy and safety of ixekizumab versus adalimumab in patients with PsA
Rheumatoid Arthritis
Cohort study shows improvement during 25 years of RA treatment
Filgotinib in RA patients with inadequate response or naïve to methotrexate
Clinical effectiveness of fenebrutinib in RA patients with methotrexate or TNFi failure
Short methotrexate stop is safe in patients with RA
Tofacitinib is safe according to real-world data analysis
Tapering of prednisone in RA patients who achieved low disease activity or remission with tocilizumab
Efficacy and safety of E6011 in RA patients with inadequate response to methotrexate
Preliminary efficacy and safety data of RG6125 in RA patients with an inadequate response to TNF inhibitors
Integrated 10-year analysis confirms safety profile abatacept
Switching among multiple infliximab biosimilars does not cause immunogenicity
Switch to sarilumab from adalimumab is efficacious and safe
Axial Spondyloarthritis
Treat-to-target approach emerging in axial spondyloarthritis
NSAIDs consumption is linked to patient-assessed disease activity and decreases with use of TNF inhibitors
Psoriatic Arthritis
Efficacy and safety of ixekizumab versus adalimumab in patients with PsA
Efficacy and safety of bimekizumab in patients with active PsA
Filgotinib is efficacious and safe in PsA
Ixekizumab improves signs and symptoms in TNFi-naïve PsA patients
Etanercept and methotrexate as first-line treatment in PsA
Unacceptable pain is common in patients with psoriatic arthritis
Osteoarthritis and Osteoporosis
Miscellaneous
Interstitial lung disease in rheumatic diseases and systemic sclerosis
Emapalumab in patients with macrophage activation syndrome
Support for tocilizumab use in giant cell arteritis
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