Session Title: 3S109: RA – Treatments II: Novel Treatments for RA (927–932)
Session Type: ACR Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Fractalkine (CX3CL1, designated as FKN hereafter) is the sole member of the CX3C-chemokine which leads to dual actions, chemotaxis and cell adhesion for leukocytes expressing the cognate receptor, CX3CR1. We have conducted clinical trials of E6011, a novel humanized anti-FKN monoclonal antibody, for patients with rheumatoid arthritis (RA) in Japan1. This is the report of efficacy and safety results of E6011 from a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study in RA patients inadequately responding to MTX (NCT02960438)
Methods: During the 24-week double-blind period, patients with moderately to severely active RA of inadequate response to MTX were randomly assigned to E6011 100 mg, 200 mg, 400/200 mg, or placebo groups at a 1:2:2:2 ratio. In the E6011 100 mg, 200 mg, and placebo groups, subjects received 100 mg, 200 mg, or placebo at Weeks 0, 1, 2, and every 2 weeks subsequently. In the E6011 400/200 mg group, subjects received 400 mg at Weeks 0, 1, 2, 4, 6, 8, 10 and then 200 mg every 2 weeks subsequently.
Results: A total of 190 subjects (54 in the placebo group, 28 in the 100 mg group, 54 in the 200 mg group, 54 in the 400/200 mg group) received study drug. Of the 190 subjects, 169 completed and 21 discontinued study treatment prematurely during the 24-week double-blind period. The ACR20 response rate at Week 12 (non-responder imputation), the primary endpoint, was 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 (not statistically significant), and statistically significant difference from placebo in ACR20 response rate was found in the 200 mg and 400/200 mg groups at Week 24 (35.2% for placebo, 39.3% for 100 mg, 53.7% for 200 mg, 57.4% for 400/200 mg). In addition, we focused on CD16+ monocytes which highly expressing FKN receptor/CX3CR1 as a blood biomarker that linked to the clinical response to E6011. The whole patient population was divided into 2 groups according to the median value of baseline CD16+ monocyte percentage (Median: 10.35%). Much clearer ACR20 response was observed in a dose dependent manner in the subjects who showed higher baseline CD16+ monocytes over the median at Week 24 (NRI) (30.0% for placebo, 46.7% for 100 mg, 57.7% for 200 mg, and 69.6% for 400/200 mg) although such fashion was obscure in the subjects below the median value. This study explored the effect on progression of joint destruction by mTSS, a clear signal that E6011 suppressed the progression of joint destruction was not detected.
Adverse events that occurred in ≥5% of subjects in any E6011 group were nasopharyngitis, upper respiratory tract infection, stomatitis, bronchitis, back pain, pharyngitis, and dental caries. As a results, E6011 was well tolerated with no notable safety concerns at doses of 100, 200, and 400/200 mg when administered subcutaneously for 24 weeks.
Conclusion: E6011 provided clinical improvements with a good safety profile in RA patients with inadequately responding to MTX. Especially, a higher efficacy of E6011 was suggested in patients with higher baseline CD16+ monocytes (%). This is the world-first evidence suggesting that a novel approach to target FKN/CX3CR1 interaction could be beneficial for RA.
To cite this abstract in AMA style:Tanaka Y, Takeuchi T, Yamanaka H, Nanki T, Umehara H, Yasuda N, Tago F, Kitahara Y, Kawakubo M, Torii K, Hojo S, Kawano T, Imai T. Efficacy and Safety of E6011, an Anti-Fractalkine Monoclonal Antibody, in MTX-IR Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-e6011-an-anti-fractalkine-monoclonal-antibody-in-mtx-ir-patients-with-rheumatoid-arthritis/. Accessed January 19, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-e6011-an-anti-fractalkine-monoclonal-antibody-in-mtx-ir-patients-with-rheumatoid-arthritis/