Kikuchi, Jun

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Rheumatology) (Shinanomachi)

Position

Instructor

 

Research Areas 【 Display / hide

  • Life Science / Connective tissue disease and allergy

Research Keywords 【 Display / hide

  • Systemic lupus erythematosus

  • Rheumatoid arthritis

 

Papers 【 Display / hide

  • Deep remission within 12 months prevents renal flare and damage accrual in lupus nephritis.

    Kikuchi J, Hanaoka H, Saito S, Oshige T, Hiramoto K, Takeuchi T, Kaneko Y

    Clinical and experimental rheumatology  2023.01

    ISSN  0392-856X

  • Differences in the strength of inhibition of interleukin-6 signalling by subcutaneous sarilumab and tocilizumab in rheumatoid arthritis patients.

    Saito S, Suzuki K, Yoshimoto K, Kondo Y, Kikuchi J, Hanaoka H, Kaneko Y, Takeuchi T

    Clinical and experimental rheumatology  2022.12

    ISSN  0392-856X

  • Clinical and immunological effects of hydroxychloroquine in patients with active rheumatoid arthritis despite antirheumatic treatment.

    Hiroshi Takei, Satoshi Takanashi, Kotaro Otomo, Hironari Hanaoka, Jun Kikuchi, Kunihiro Yamaoka, Keiko Yoshimoto, Takayuki Abe, Tsutomu Takeuchi, Yuko Kaneko

    Modern rheumatology  2022.12

    ISSN  1439-7595

     View Summary

    OBJECTIVE: To investigate the efficacy and safety of hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). METHODS: Patients with active RA, despite conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), were recruited. HCQ was administered for 24 weeks, in addition to prior treatment. The primary endpoint was the proportion of American College of Rheumatology (ACR) 20 achievement at week 24, compared to that of a propensity score matched historical control group. RESULTS: Sixty patients were enrolled and administered HCQ. We also identified 276 patients as candidates for the historical control group. Propensity score matching yielded 46 patients in each group. The proportion of ACR20 achievements at week 24 was significantly higher in the HCQ group than that in the control group (54.4% vs. 28.3%, P = 0.007). The proportion of ACR50 and ACR70 achievement at week 24 were also higher in the HCQ group than those in the control group (ACR50, 30.4% vs. 4.3%, P = 0.006; ACR70, 17.4% vs. 0%, P = 0.005). Neither hydroxychloroquine retinopathy nor any new safety signal was observed during the study. CONCLUSION: The addition of HCQ to csDMARDs was effective, with no new safety signal in patients with RA.

  • Lupus low disease activity state and remission and risk of mortality in patients with systemic lupus erythematosus: a prospective, multinational, longitudinal cohort study

    Kandane-Rathnayake R., Golder V., Louthrenoo W., Chen Y.H., Cho J., Lateef A., Hamijoyo L., Luo S.F., Wu Y.J.J., Navarra S.V., Zamora L., Li Z., Sockalingam S., Katsumata Y., Harigai M., Hao Y., Zhang Z., Basnayake B.M.D.B., Chan M., Kikuchi J., Takeuchi T., Bae S.C., Oon S., O'Neill S., Goldblatt F., Ng K.P.L., Law A., Tugnet N., Kumar S., Tee C., Tee M., Ohkubo N., Tanaka Y., Yu D.Y., Karyekar C.S., Sing Lau C., Monk J.A., Nikpour M., Hoi A., Morand E.F.

    The Lancet Rheumatology (The Lancet Rheumatology)  4 ( 12 ) e822 - e830 2022.12

     View Summary

    Background: Treat-to-target goals for patients with systemic lupus erythematosus (SLE) have been validated to protect against organ damage and to improve quality of life. We aimed to investigate the association between lupus low disease activity state (LLDAS) and remission and risk of mortality in patients with SLE. We hypothesised that LLDAS has a protective association with mortality risk. Methods: In this prospective, multinational, longitudinal cohort study, we used data from patients with SLE in the Asia Pacific Lupus Collaboration cohort collected between May 1, 2013, and Dec 31, 2020. Eligible patients were adults (aged ≥18 years) who met either the 1997 American College of Rheumatology modified classification criteria for SLE or the 2012 Systemic Lupus International Collaborating Clinics classification criteria. The primary outcome was all-cause mortality, and LLDAS, remission, and variations of remission with lower glucocorticoid thresholds were the primary exposure variables. Survival analyses were used to examine longitudinal associations between these endpoints and risk of mortality. This study is registered with ClinicalTrials.gov, NCT03138941. Findings: Among a total of 4106 patients in the cohort, 3811 (92·8%) patients were included in the final analysis (median follow-up 2·8 years [IQR 1·0–5·3]; 3509 [92·1%] women and 302 [7·9%] men), of whom 80 died during the observation period (crude mortality rate 6·4 deaths per 1000 person-years). LLDAS was attained at least once in 43 (53·8%) of 80 participants who died and in 3035 (81·3%) of 3731 participants who were alive at the end of the study (p<0·0001); 22 (27·5%) participants who died versus 1966 (52·7%) who were alive at the end of the study attained LLDAS for at least 50% of observed time (p<0·0001). Remission was attained by 32 (40·0%) of 80 who died and in 2403 (64·4%) of 3731 participants who were alive at the end of the study (p<0·0001); 14 (17·5%) participants who died versus 1389 (37·2%) who were alive at the end of the study attained remission for at least 50% of observed time (p<0·0001). LLDAS for at least 50% of observed time (adjusted hazard ratio 0·51 [95% CI 0·31–0·85]; p=0·010) and remission for at least 50% of observed time (0·52 [0·29–0·93]; p=0·027) were associated with reduced risk of mortality. Modifying the remission glucocorticoid threshold (<5·0 mg/day prednisolone) was more protective against mortality than current remission definitions (0·31 [0·12–0·77]; p=0·012), and glucocorticoid-free remission was the most protective (0·13 [0·02–0·96]; p=0·046). Interpretation: LLDAS significantly reduced the risk of mortality in patients with SLE. Remission did not further reduce the risk of mortality compared with LLDAS, unless lower glucocorticoid thresholds were used. Funding: The Asia-Pacific Lupus Collaboration received funding from Janssen, Bristol Myers Squibb, Eli Lilly, and UCB for this study.

  • Patterns of Medication Use in Systemic Lupus Erythematosus - A Multi-Centre Cohort Study.

    Rangi Kandane-Rathnayake, Worawit Louthrenoo, Shue-Fen Luo, Yeong-Jian J Wu, Yi-Hsing Chen, Vera Golder, Aisha Lateef, Jiacai Cho, Sandra V Navarra, Leonid Zamora, Laniyati Hamijoyo, Sargunan Sockalingam, Yuan An, Zhanguo Li, Ricardo Montes, Shereen Oon, Yasuhiro Katsumata, Masayoshi Harigai, Yanjie Hao, Zhuoli Zhang, Madelynn Chan, Jun Kikuchi, Tsutomu Takeuchi, Fiona Goldblatt, Sean O'Neill, Sang-Cheol Bae, Chak S Lau, Alberta Hoi, Chetan S Karyekar, Mandana Nikpour, Eric F Morand

    Arthritis care & research (Arthritis Care and Research)  74 ( 12 ) 2033 - 2041 2022.12

    ISSN  2151464X

     View Summary

    OBJECTIVES: Evidence for the utility of medications in settings lacking randomised trial data can come from studies of treatment persistence. We examined patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicentre longitudinal cohort. METHODS: Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLEDAI-2K) and medication details, captured at every visit from 2013-18, were used. Medications were categorised as glucocorticoids (GC), anti-malarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time-to-discontinuation of medications, stratified by SLE disease activity. RESULTS: Data from 19,804 visits of 2,860 patients were analysed. Eight medication categories were observed: no treatment; GC, AM or IS only; GC+AM; GC+IS; AM+IS and GC+AM+IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits and biologicals in only 3%. Time-to-discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with time-adjusted mean SLEDAI-2K≥10 had lower discontinuation of GC and higher discontinuation of IS. CONCLUSION: Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.

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Reviews, Commentaries, etc. 【 Display / hide

  • SLE患者末梢血単球におけるフラクタルカイン受容体CX3CR1発現と病態との関連に関する検討

    吉本 桂子, 鈴木 勝也, 池田 由美, 関 則靖, 平本 和音, 齋藤 俊太郎, 菊池 潤, 花岡 洋成, 菅原 邦夫, 千葉 健治, 竹内 勤, 金子 祐子

    日本臨床免疫学会総会プログラム・抄録集 ((一社)日本臨床免疫学会)  50回   97 - 97 2022.10

  • 活動性ループス腎炎における深い寛解(Deep remission)の臨床的意義と免疫学的関連因子の検討

    菊池 潤, 花岡 洋成, 齋藤 俊太郎, 平本 和音, 関 則靖, 竹内 勤, 金子 祐子

    日本臨床免疫学会総会プログラム・抄録集 ((一社)日本臨床免疫学会)  50回   97 - 97 2022.10

  • 膠原病患者におけるステロイド性骨粗鬆症に対するデノスマブの有効性を予測する因子の探索

    花岡 洋成, 菊池 潤, 近藤 泰, 齋藤 俊太郎, 金子 祐子

    日本臨床免疫学会総会プログラム・抄録集 ((一社)日本臨床免疫学会)  50回   109 - 109 2022.10

  • mRNA-1273ワクチンは、リウマチ性疾患患者においても高力価のSARS-CoV-2中和抗体、T細胞反応性を誘導する

    近藤 泰, 竹下 勝, 齋藤 俊太郎, 菊池 潤, 花岡 洋成, 鈴木 勝也, 金子 祐子

    日本臨床免疫学会総会プログラム・抄録集 ((一社)日本臨床免疫学会)  50回   112 - 112 2022.10

  • リウマチ性疾患の基礎研究 BAFFシグナル阻害活性作用を有する低分子化合物の自己免疫疾患病態モデルでの経口投与によるB細胞活性化抑制作用の検証

    吉本 桂子, 鈴木 勝也, 池田 由美, 齋藤 俊太郎, 菊池 潤, 竹内 勤, 金子 祐子

    日本リウマチ学会総会・学術集会プログラム・抄録集 ((一社)日本リウマチ学会)  66回   343 - 343 2022.03

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 全身性エリテマトーデスのマルチオミックス解析による新規バイオマーカーの開発

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

     View Summary

    全身性エリテマトーデスは、繰り返す再燃や臓器障害の蓄積が課題である。現在、ステロイドに代わる適切な治療薬の選択や予後予測のバイオマーカー、個別化医療の方法が模索されている。研究代表者は末梢血および尿中プロテオミクス解析からSLEの疾患活動性と相関する分子を多数見出している。本研究では、ELISAでのバリデーション、エクソーム解析、経時的な臨床特徴(障害臓器別、治療前後比較)と統計解析、末梢血免疫フェノタイピングおよびソーティング単球・リンパ球を用いたin vitro機能解析などを組み合わせることで、新規の病態関連分子の同定を行う。
    初めに、活動性全身性エリテマトーデス(SLE)の予後を規定する指標の構築を目的として、低疾患活動性状態(LLDAS; Lupus Low Disease Activity Score)達成の時期を検討した。活動性SLEにおいて寛解導入療法開始後12ヶ月以内のLLDASを達成することが、臨床的アウトカム(重症再燃低下、ステロイド積算量低値、期間中のLLDAS達割合高値)と関連することを示した。次に活動性SLEにおける寛解導入療法開始後の末梢血免疫細胞の変動を特定した。特にシクロホスファミド治療群ではCD4陽性T細胞全体、主にナイーブCD4陽性T細胞が有意に減少し、B細胞全体及びナイーブB細胞が有意に低下した一方、ミコフェノール酸モフェチル治療群ではナイーブCD4陽性T細胞とナイーブB細胞の変動は見出せず、活性化CD4陽性T細胞、活性化CD8陽性T細胞、plasmablast、plasma細胞、樹状細胞割合の低下が見出された。すなわち、寛解導入療法として主に用いられる2剤で変動する末梢血免疫細胞の種類が異なることを示した。さらに、臨床的アウトカムとの関連因子として、末梢血Plasmablastの変動が治療予後と関連することを見出し、12ヶ月以内LLDAS達成と関連する細胞分画の変動を免疫抑制剤ごと見出すことができた。臓器特異的な検討としてループス腎炎に着目した。臨床的に深い寛解状態と関連する末梢血免疫細胞としてT細胞、単球、樹状細胞、形質細胞分画が見出された。さらに、腎生検で得た組織学的な検討を行い、尿中タンパク質の解析を行い、活動性所見および間質病変所見と関連する病態として種々のパスウェイが関連することを示した。

  • Optimization of the treatment of systemic lupus erythematosus by immunological classifications

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Principal investigator

Awards 【 Display / hide

  • 優秀ポスター賞

    2012.09, 日本臨床免疫学会, IL-6阻害剤とTNF阻害剤はRA患者末梢血中のCD4+CD45RO+CCR6+CD161+細胞に異なった影響を及ぼす

 

Courses Taught 【 Display / hide

  • CASE STUDIES OF INTERNAL MEDICINE

    2022

  • CASE STUDIES OF INTERNAL MEDICINE

    2021

  • CASE STUDIES OF INTERNAL MEDICINE

    2020

  • CASE STUDIES OF INTERNAL MEDICINE

    2019

 

Memberships in Academic Societies 【 Display / hide

  • 日本内科学会

     
  • 日本リウマチ学会

     
  • 日本臨床免疫学会