論文 - 竹内　勤

Risk factors for abnormal hepatic enzyme elevation by methotrexate treatment in patients with rheumatoid arthritis: A hospital based-cohort study

Hakamata J., Hashiguchi M., Kaneko Y., Yamaoka K., Shimizu M., Maruyama J., Takeuchi T., Mochizuki M.

Modern Rheumatology （Modern Rheumatology）  28 （ 4 ） 611 - 620 2018年07月

研究論文（学術雑誌）, 査読有り,  ISSN  14397595

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© 2017, © 2017 Japan College of Rheumatology. Objectives: Methotrexate (MTX) is used as first-line treatment of rheumatoid arthritis (RA) worldwide. Large interindividual differences in MTX effectiveness and safety occur, and the most frequent adverse reaction is hepatotoxicity, although the main cause remains unknown. We investigated factors associated with MTX-induced hepatic enzyme elevation in a hospital-based cohort study. Methods: Study participants were 114 Japanese adult RA outpatients prescribed MTX. Sixteen types of single-nucleotide polymorphisms were investigated using real-time PCR. Patient characteristics were collected from the electronic medical records. The onset of MTX-induced abnormal hepatic enzyme elevation was defined according to deviation from normal liver enzyme reference values during treatment. The observation period was 1 year after beginning MTX. Associations between MTX-induced hepatic enzyme elevation and patient characteristics were evaluated using the multivariate logistic regression model. Results: Thirty-two patients experienced MTX-induced abnormal hepatic enzyme elevation. In multivariate analysis, MTX dosage, estimated glomerular filtration rate (eGFR), and genetic polymorphisms of ABCB1 3435C>T and ATIC 347C>G were associated with abnormal hepatic enzyme elevation. Conclusions: MTX-induced abnormal hepatic enzyme elevation in Japanese RA patients was associated with dosage and eGFR as nongenetic factors, and with ABCB1 3435C>T and ATIC 347C>G as genetic factors in this hospital-based cohort study.

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Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis

Dokoupilová E., Aelion J., Takeuchi T., Malavolta N., Sfikakis P., Wang Y., Rohrer S., Richards H.

Scandinavian Journal of Rheumatology （Scandinavian Journal of Rheumatology）  47 （ 4 ） 276 - 281 2018年07月

研究論文（学術雑誌）, 査読有り,  ISSN  03009742

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© 2018, © 2018 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation. Objective: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. Method: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. Results: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. Conclusions: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.

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Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials

Tanaka Y., Atsumi T., Amano K., Harigai M., Ishii T., Kawaguchi O., Rooney T., Akashi N., Takeuchi T.

Modern Rheumatology （Modern Rheumatology）  28 （ 4 ） 583 - 591 2018年07月

研究論文（学術雑誌）, 査読有り,  ISSN  14397595

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© 2017, © 2017 Japan College of Rheumatology. Published by Informa UK Limited, trading as Taylor & Francis Group. Objectives: To evaluate efficacy/safety of baricitinib for rheumatoid arthritis (RA) in Japanese subpopulations from four phase 3 studies, and assess whether results in these subpopulations are consistent with the overall study populations. Methods: Subgroup analyses (394 patients) of four phase 3 randomized controlled trials: RA-BEGIN [no or limited treatment with disease-modifying antirheumatic drugs (DMARDs)], RA-BEAM [inadequate response (IR) to methotrexate], RA-BUILD [IR to conventional synthetic DMARDs (csDMARDs)], and RA-BEACON (IR to tumor necrosis factor inhibitors receiving csDMARDs). Results: For American College of Rheumatology 20% improvement (ACR20) response rate, Japanese patients receiving baricitinib 4-mg showed similar improvement compared to methotrexate at Week 24 (72 versus 69%; RA-BEGIN), and greater improvement compared with placebo at Week 12 (67 versus 34%; RA-BEAM). Japanese patients receiving baricitinib 4-mg also showed greater improvement compared with placebo at Week 12 in RA-BUILD and RA-BEACON. Across all studies, baricitinib was well-tolerated, with no deaths and one malignancy. In RA-BEGIN and RA-BEAM, herpes zoster rates were higher for Japanese patients than for overall populations; all events were mild/moderate. Conclusion: Data for baricitinib, with/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy/safety profile in overall study populations. Baricitinib appears to be similarly effective in Japanese patients.

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Safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis up to 5.5 Years: An Updated Integrated Safety Analysis

Keystone Edward, Genovese Mark, Smolen Josef, Takeuchi Tsutomu, Hyslop David, Macias William, Rooney Terence, Chen Lei, Dickson Christina, Camp Jennifer, Cardillo Tracy, Ishii Taeko, Winthrop Kevin, Otawa Susan

JOURNAL OF RHEUMATOLOGY 45 （ 7 ） 1003 - 1003 2018年07月

研究論文（学術雑誌）, 査読有り,  ISSN  0315-162X

Dose Reduction of Baricitinib in Patients with Rheumatoid Arthritis Achieving Sustained Disease Control: Results of a Prospective Study

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

JOURNAL OF RHEUMATOLOGY 45 （ 7 ） 1054 - 1054 2018年07月

研究論文（学術雑誌）, 査読有り,  ISSN  0315-162X

IgG4-related fibrosing mediastinitis diagnosed with computed tomography-guided percutaneous needle biopsy

Takanashi S., Akiyama M., Suzuki K., Otomo K., Takeuchi T.

Medicine (United States) （Medicine (United States)）  97 （ 22 ） e10935 2018年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0025-7974

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© 2018 the Author(s). Published by Wolters Kluwer Health, Inc. Rationale: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disease characterized by elevated serum IgG4 levels with infiltration of IgG4+ plasma cells and severe fibrosis in affected tissues. Recently, idiopathic fibrosing mediastinitis (FM), an extremely rare fibroinflammatory disorder, has been recognized as a form of IgG4-RD. As IgG4-RD can be treated by glucocorticoids, identification of the etiology of FM by surgical biopsy is essential; however, mediastinal biopsy is often difficult. We report 2 cases of IgG4-related FM successfully diagnosed with computed tomography (CT)-guided percutaneous needle biopsy. Patient concerns: Case 1 was a 66-year-old woman with elevated serum C-reactive protein without any symptoms and case 2 was 78-year-old woman with abnormal mediastinal contour on chest x-ray. By further work-up, both cases were found to have mediastinitis accompanied by elevated serum IgG4. CT-guided percutaneous needle biopsy revealed massive infiltration of IgG4+plasma cells along with storiform fibrosis. Diagnosis: IgG4-related FM. Interventions: Glucocorticoid therapy. Outcome: The treatment resulted in significant improvement of the lesions after 3 months. Lessons: Early recognition and diagnosis of IgG4-related FM is essential because a delay in appropriate treatment initiation leads to progressive fibrosis with irreversible organ damage and poor prognosis. Our cases highlight CT-guided percutaneous needle biopsy as a promising option for histological examination in patients with IgG4-related FM.

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POSSIBLE INVOLVEMENT OF BAFF AND MATRIXMETALLOPROTEINASE-9 IN THE ACTIVATION OF MONOCYTES OF PATIENTS WITH PRIMARY SJOGREN'S SYNDROME

Yoshimoto K., Suzuki K., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   882 - 882 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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RISK FACTORS FOR CYTOMEGALOVIRUS REACTIVATION IN PATIENTS WITH CONNECTIVE-TISSUE DISEASE; SINGLE-CENTREPROSPECTIVE COHORT STUDY

Ota Y., Kaneko Y., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   1766 - 1766 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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RHEUMATOID FACTOR POSITIVITY IS RELATED TO CLINICAL AND IMMUNOLOGICAL CHARACTERISTICS IN PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

Inamo J., Kaneko Y., Ohta Y., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   1481 - 1481 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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RESIDUAL SYNOVITIS IN ANKLES AND FEET DETECTED BY ULTRASONOGRAPHY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Inamo J., Kaneko Y., Sakata K., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   300 - 300 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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SERUM KL-6 IS A STRONG PREDICTOR FOR RELAPSE OF MYOSITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

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

ANNALS OF THE RHEUMATIC DISEASES 77   760 - 760 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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INFLAMMATORY FINDINGS ON ULTRASOUND AND MRI CAN PREDICT FUTURE DEVELOPMENT OF RHEUMATOID ARTHRITIS IN PATIENTS WITH SERONEGATIVE, UNDIFFERENCIATED ARTHRITIS

Kondo Y., Kaneko Y., Inoue Y., Takahashi C., Sakata K., Yamaoka K., Sato S., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   1711 - 1711 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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IMPAIRED ACTIVATION OF ATAXIA-TELANGIECTASIA MUTATED PROTEIN KINASE IN IMMUNE CELLS IS ASSOCIATED WITH CLINICAL FEATURES IN PATIENTS WITH SYSTEMIC SCLEROSIS

Sakata K., Yasuoka H., Yoshimoto K., Yamaoka K., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   1281 - 1282 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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HEPATITIS B VIRUS REACTIVATION IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH BARICITINIB: POST-HOC ANALYSIS FROM CLINICAL TRIALS

Harigai M., Winthrop K., Takeuchi T., Hsieh T. -Y., Chen Y. -M., Smolen J. S., Burmester G. R., Walls C., Wu W. -S., Dickson C., Liao R., Genovese M. C.

ANNALS OF THE RHEUMATIC DISEASES 77   584 - 585 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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EFFECTS OF DENOSUMAB, A SUBCUTANEOUS RANKL INHIBITOR, ON THE PROGRESSION OF STRUCTURAL DAMAGE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH CSDMARDS: RESULT FROM THE LONG-TERM TREATMENT OF PHASE 3, DESIRABLE STUDY

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

ANNALS OF THE RHEUMATIC DISEASES 77   947 - 948 2018年06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 M. C., Haraoui B., Li Z., Xie L., Klar R., Correia A. P., Otawa S., Lopez-Romero P., De la Torre I., Rooney T., Smolen J. S.

ANNALS OF THE RHEUMATIC DISEASES 77   988 - 989 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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CLINICAL AND FUNCTIONAL RESPONSE TO TOFACITINIB AND ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: PROBABILITY PLOT ANALYSIS OF RESULTS FROM THE ORAL STRATEGY TRIAL

Takeuchi T., Smolen J. S., Fleischmann R., Iikuni N., Fan H., Soma K., Akylbekova E., Hirose T.

ANNALS OF THE RHEUMATIC DISEASES 77   987 - 988 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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CHARACTERISTICS OF RECENT ELDERLY-ONSET RHEUMATOID ARTHRITIS PATIENTS

Oshige T., Kaneko Y., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   566 - 566 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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BIOMARKERS FOR RELAPSE IN PATIENTS WITH ADULT ONSET STILL'S DISEASE TREATED WITH IL-6 INHIBITOR

Yamada H., Kaneko Y., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   853 - 853 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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ARYL HYDROCARBON RECEPTOR EXPRESSION IS ASSOCIATED WITH LUNG INVOLVEMENT IN SYSTEMIC SCLEROSIS

Takei H., Yasuoka H., Yoshimoto K., Yamaoka K., Takeuchi T.

ANNALS OF THE RHEUMATIC DISEASES 77   738 - 738 2018年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0003-4967

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