論文 - 竹内　勤

Significant association between joint ultrasonographic parameters and synovial inflammatory factors in rheumatoid arthritis

Kondo Y., Suzuki K., Inoue Y., Sakata K., Takahashi C., Takeshita M., Kassai Y., Miyazaki T., Morita R., Niki Y., Kaneko Y., Yasuoka H., Yamaoka K., Yoshimura A., Takeuchi T.

Arthritis Research and Therapy （Arthritis Research and Therapy）  21 （ 1 ） 14 2019年10月

研究論文（学術雑誌）, 査読有り,  ISSN  14786354

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© 2019 The Author(s). Background: Ultrasonography (US) can directly demonstrate joint inflammation, including grayscale (GS) signs of synovial hypertrophy and power Doppler (PD) techniques to demonstrate increased blood flow and vascularization. Recently, echogenicity, especially hypoechoic synovium, has also been associated with local inflammatory activity. However, only a few studies have demonstrated correlation between histopathologic and immunopathologic evaluation and US findings. The aim of this study was to clarify whether joint US findings including synovial hypertrophy, vascularity, and echogenicity can accurately characterize synovial pathophysiology in patients with active rheumatoid arthritis (RA). Methods: A total of 44 patients with RA were included, both treated (n = 25) and untreated (n = 19) and scheduled for US examination of the knee joint with synovial fluid (SF) aspiration and two treated patients also underwent synovial biopsy. US images were quantitatively analyzed using grayscale assessment of synovial hypertrophy and PD for vascularity and echogenicity. Levels of nine SF cytokines and growth factors were also measured. Results: Both US synovial hypertrophy and PD vascularity significantly correlated with SF inflammatory cytokine levels such as IL-6, IL-8, IL-1β and IL-10 in untreated patients. Angiogenic factors, including vascular endothelial growth factor (VEGF), only correlated with PD vascularity. In the treated patients, the associations between synovial hypertrophy and any cytokines were diminished, although synovial vascularity and echogenicity correlated with IL-6 and VEGF (p < 0.05). Histopathologic analysis revealed that hypoechogenicity of the synovium correlated with marked infiltration of lymphocytes and hypervascularity. Conclusions: We demonstrated the pathophysiological origins of US findings in the joint. The degree of US vascularity of the synovium correlated with local inflammatory cytokine levels and angiogenetic factors in patients with active RA. Synovial echogenicity, and not hypertrophy, correlated with inflammation, especially in treated patients with RA.

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Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial.

Takeuchi T, Tanaka Y, Soen S, Yamanaka H, Yoneda T, Tanaka S, Nitta T, Okubo N, Genant HK, van der Heijde D

Annals of the rheumatic diseases 2019年04月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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Efficacy and safety of namilumab, a human monoclonal antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) ligand in patients with rheumatoid arthritis (RA) with either an inadequate response to background methotrexate therapy or an inadequate response or intolerance to an anti-TNF (tumour necrosis factor) biologic therapy: a randomized, controlled trial

Taylor Peter C., Saurigny Didier, Vencovsky Jiri, Takeuchi Tsutomu, Nakamura Tadashi, Matsievskaia Galina, Hunt Barbara, Wagner Thomas, Souberbielle Bernard

ARTHRITIS RESEARCH & THERAPY 21 （ 1 ） 101 2019年04月

研究論文（学術雑誌）, 査読有り,  ISSN  1478-6354

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Clinicopathological features of clinical methotrexate-related lymphoproliferative disorders.

Tokuhira M, Saito S, Suzuki K, Higashi M, Momose S, Shimizu T, Mori T, Kimura Y, Amano K, Okamoto S, Takeuchi T, Tamaru JI, Kizaki M

Leukemia & lymphoma    1 - 8 2019年04月

研究論文（学術雑誌）, 査読有り,  ISSN  1042-8194

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Demographics and clinical characteristics associated with sustained remission and continuation of sustained remission in patients with rheumatoid arthritis treated with adalimumab

Kimura Noriko, Suzuki Katsuya, Takeuchi Tsutomu

INFLAMMATION AND REGENERATION 39   5 2019年03月

研究論文（学術雑誌）, 査読有り,  ISSN  1880-8190

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Histopathological classification of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in a nationwide Japanese prospective 2-year follow-up cohort study

Yamagata K., Usui J., Nagata M., Sugiyama H., Sada K., Muso E., Harigai M., Amano K., Atsumi T., Fujimoto S., Yuzawa Y., Kobayashi M., Saito T., Ito T., Hirawa N., Homma S., Dobashi H., Tsuboi N., Ishizu A., Arimura Y., Makino H., Matsuo S., Takasaki Y., Banno S., Sugihara T., Murakawa Y., Hasegawa H., Komatsuda A., Ito S., Fujii T., Kawakami A., Nakaya I., Yamamura M., Nakano M., Nitta K., Ogura M., Naniwa T., Ozaki S., Hirahashi J., Ogawa N., Hosoya T., Wada T., Horikoshi S., Kawaguchi Y., Hayashi T., Yoshida M., Watanabe T., Inaguma D., Tsuruya K., Homma N., Okada Y., Takeuchi T., Nakagawa N., Takeda S., Katabuchi R., Iwano M.

Clinical and Experimental Nephrology （Clinical and Experimental Nephrology）  23 （ 3 ） 387 - 394 2019年03月

研究論文（学術雑誌）, 査読有り,  ISSN  13421751

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© 2018, Japanese Society of Nephrology. Background: The prognostic value of the EUVAS-proposed histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis has been evaluated throughout the world. Here, we performed a Japanese nationwide biopsy survey to assess the association between this histopathological classification and renal prognosis after 2-year follow-up in ANCA-associated glomerulonephritis. Methods: We collected 67 renal biopsy materials of the 321 entries in the RemIT-JAV-RPGN cohort study, and assessed their histologies. Based on the EUVAS-proposed histopathological classification and some histological parameters, we statistically evaluated renal survival and the comparison of renal function for 2 years. Results: Based on the histopathological classification, the largest number of biopsy samples belonged to the Focal class, followed by the Mixed, Crescentic, and Sclerotic classes (n = 30, 19, 10, 8, respectively). Although the number of events might be too low (four patients with renal death) to make this conclusion, the Focal and Mixed classes had higher renal-survival rates compared to the others in the renal-survival curve. Comparing renal function among all classes, the estimated glomerular filtration rate (eGFR) throughout 2-year follow-up period was significantly higher in the Focal class compared to the other 3 classes. The eGFR-values in the Crescentic, Mixed, and Sclerotic classes increased with time. Based on both combined results, the Focal class could be the best prognosis. Conclusion: This histopathological classification was valuable for both the stratification of renal function and the estimation of partial renal survival during 2-year follow-up in ANCA-associated glomerulonephritis.

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Radiographic and clinical outcomes following etanercept monotherapy in Japanese methotrexate-naïve patients with active rheumatoid arthritis.

Takeuchi T, Miyasaka N, Pedersen R, Sugiyama N, Hirose T

Modern rheumatology    1 - 10 2019年03月

研究論文（学術雑誌）, 査読有り,  ISSN  1439-7595

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Efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis who were refractory or intolerant to anti-tumor necrosis factor therapy: Subgroup analysis of a randomized, double-blind, multicenter, phase 3 study (SIRROUND-T)

Tanaka Y., Takeuchi T., Harigai M., Yamanaka H., Nakano T., Akagi K., Ukyo Y., Hsu B.

Modern Rheumatology （Modern Rheumatology）  29 （ 2 ） 306 - 313 2019年03月

研究論文（学術雑誌）, 査読有り,  ISSN  14397595

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© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Objective: To evaluate the efficacy and safety of sirukumab, a human anti-interleukin six monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy. Methods: This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed. Results 116/878 patients received sirukumab 50 mg/4 weeks (q4w, n = 35), 100 mg/2 weeks (q2w, n = 44) or placebo (n = 37) subcutaneously. Significantly more patients achieved ACR 20 response at week 16 with sirukumab (50 mg q4w:20 [57.1%]; p <.001, 100 mg q2w:24 [54.5%]; p =.001) versus placebo (7 [18.9%]); consistent significant improvement in secondary endpoints at week 24 and 52 was observed. At week 24, incidence of treatment-emergent adverse events (TEAEs) was numerically higher with sirukumab groups (50 mg q4w:29 [82.9%]; 100 mg q2w:38 [86.4%] versus placebo (28 [75.7%]); however, at week 52, sirukumab combined groups had comparable incidence of TEAEs. Conclusion: Efficacy findings through 52 weeks were comparable between sirukumab doses in Japanese patients and consistent with primary SIRROUND-T study results. No new safety signals were observed.

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Pulmonary Vein Vasculitis Presenting as Multiple Pulmonary Nodules in a Patient with Systemic Lupus Erythematosus

Tamai Hiroya, Nishina Naoshi, Takeuchi Tsutomu

JOURNAL OF RHEUMATOLOGY 46 （ 3 ） 323 - 324 2019年03月

研究論文（学術雑誌）, 査読有り,  ISSN  0315-162X

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Development of the Asia Pacific Lupus Collaboration cohort

Kandane-Rathnayake R., Golder V., Louthrenoo W., Luo S., Jan Wu Y., Li Z., An Y., Lateef A., Sockalingam S., Navarra S., Zamora L., Hamijoyo L., Katsumata Y., Harigai M., Chan M., O’Neill S., Goldblatt F., Hao Y., Zhang Z., Al-Saleh J., Khamashta M., Takeuchi T., Tanaka Y., Bae S., Lau C., Hoi A., Nikpour M., Morand E.

International Journal of Rheumatic Diseases （International Journal of Rheumatic Diseases）  22 （ 3 ） 425 - 433 2019年03月

研究論文（学術雑誌）, 査読有り,  ISSN  17561841

　概要を見る

© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd Aim: The aim of this manuscript is to describe the development of the Asia Pacific Lupus Collaboration (APLC) cohort. Method: The APLC cohort is an ongoing, prospective longitudinal cohort. Adult patients who meet either the American College of Rheumatology (ACR) Modified Classification Criteria for systemic lupus erythematosus (SLE), or the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria, and provide informed consent are recruited into the cohort. Patients are routinely followed up at 3- to 6-monthly intervals. Information on demographics, clinical manifestations, treatment, pathology results, outcomes, and patient-reported quality of life (Short-form 36 version 2) are collected using a standardized case report form. Each site is responsible for obtaining local ethics and governance approval, patient recruitment, data collection, and data transfer into a centralized APLC database. Results: The latest APLC cohort comprises 2160 patients with >12 000 visits from Australia, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. The APLC has proposed the Lupus Low Disease Activity State (LLDAS) as a treat-to-target (T2T) endpoint, and reported several retrospective and cross-sectional analyses consistent with the validity of LLDAS. Longitudinal validation of LLDAS as a T2T endpoint is currently underway. Conclusion: The APLC cohort is one of the largest contemporary SLE patient cohorts in the world. It is the only cohort with substantial representation of Asian patients. This cohort represents a unique resource for future clinical research including evaluation of other endpoints and quality of care.

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Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus: A multicenter, phase 2, open-label study.

Tanaka Y, Takeuchi T, Okada M, Ishii T, Nakajima H, Kawai S, Nagashima T, Hayashi N, Wang L, Tummala R

Modern rheumatology    1 - 8 2019年02月

研究論文（学術雑誌）, 査読有り,  ISSN  1439-7595

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Does microbiome contribute to HLA-B52-positive Takayasu arteritis?

Akiyama M, Kaneko Y, Takeuchi T

Modern rheumatology    1 - 5 2019年02月

研究論文（学術雑誌）, 査読有り,  ISSN  1439-7595

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Safety and tolerability of sifalimumab, an anti-interferon-α monoclonal antibody, in Japanese patients with systemic lupus erythematosus: A multicenter, phase 2, open-label study.

Takeuchi T, Tanaka Y, Matsumura R, Saito K, Yoshimura M, Amano K, Atsumi T, Suematsu E, Hayashi N, Wang L, Tummala R

Modern rheumatology    1 - 8 2019年02月

研究論文（学術雑誌）, 査読有り,  ISSN  1439-7595

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Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: An integrated analysis of Phases 2 and 3 trials.

Harigai M, Takeuchi T, Smolen JS, Winthrop KL, Nishikawa A, Rooney TP, Saifan CG, Issa M, Isaka Y, Akashi N, Ishii T, Tanaka Y

Modern rheumatology    1 - 8 2019年02月

研究論文（学術雑誌）, 査読有り,  ISSN  1439-7595

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Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: Results of a prospective study

Takeuchi T., Genovese M., Haraoui B., Li Z., Xie L., Klar R., Pinto-Correia A., Otawa S., Lopez-Romero P., De La Torre I., Macias W., Rooney T., Smolen J.

Annals of the Rheumatic Diseases （Annals of the Rheumatic Diseases）  78 （ 2 ） 171 - 178 2019年02月

研究論文（学術雑誌）, 査読有り,  ISSN  00034967

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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives This study investigated the effects of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4 mg once a day. Methods Patients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4 mg for ≥15 months and maintained CDAI low disease activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety were assessed through 48 weeks. Results Patients in both groups maintained LDA (80% 4 mg; 67% 2 mg) or REM (40% 4 mg; 33% 2 mg) over 48 weeks. However, dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23% 4 mg vs 37% 2 mg, p=0.001). Rescue rates were 10% for baricitinib 4 mg and 18% for baricitinib 2 mg. Dose reduction was associated with a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar across groups. Conclusions In a large randomised, blinded phase 3 study, maintenance of RA control following induction of sustained LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to 2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or recapture with return to 4 mg if needed.

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Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study

Takeuchi Tsutomu, Genovese Mark C., Haraoui Boulos, Li Zhanguo, Xie Li, Klar Rena, Pinto-Correia Ana, Otawa Susan, Lopez-Romero Pedro, de la Torre Inmaculada, Macias William, Rooney Terence P., Smolen Josef S.

ANNALS OF THE RHEUMATIC DISEASES 78 （ 2 ） 171 - 178 2019年02月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study.

Takeuchi T, Genovese MC, Haraoui B, Li Z, Xie L, Klar R, Pinto-Correia A, Otawa S, Lopez-Romero P, de la Torre I, Macias W, Rooney TP, Smolen JS

Annals of the rheumatic diseases 78 （ 2 ） 171 - 178 2019年02月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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Cardiovascular Safety During Treatment with Baricitinib in Rheumatoid Arthritis.

Taylor PC, Weinblatt ME, Burmester GR, Rooney TP, Witt S, Walls CD, Issa M, Salinas CA, Saifan C, Zhang X, Cardoso A, González-Gay MA, Takeuchi T

Arthritis & rheumatology (Hoboken, N.J.) 2019年01月

研究論文（学術雑誌）, 査読有り,  ISSN  2326-5191

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Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data.

Takeuchi T, Yamanaka H, Yamaoka K, Arai S, Toyoizumi S, DeMasi R, Fukuma Y, Hirose T, Sugiyama N, Zwillich SH, Tanaka Y

Modern rheumatology    1 - 11 2019年01月

研究論文（学術雑誌）, 査読有り,  ISSN  1439-7595

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Usefulness of serum Krebs von den Lungen-6 for the management of myositis-associated interstitial lung disease.

Takanashi S, Nishina N, Nakazawa M, Kaneko Y, Takeuchi T

Rheumatology (Oxford, England) 2019年01月

研究論文（学術雑誌）, 査読有り,  ISSN  1462-0324

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