玉井 博也 (タマイ ヒロヤ)

Tamai, Hiroya

写真a

所属(所属キャンパス)

医学部 臨床研究推進センター (信濃町)

職名

特任助教(有期)

 

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  • Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): a randomised, open-label, non-inferiority trial

    Tamai H., Ikeda K., Miyamoto T., Taguchi H., Kuo C.F., Shin K., Hirata S., Okano Y., Sato S., Yasuoka H., Kuwana M., Ishii T., Kameda H., Kojima T., Taninaga T., Mori M., Miyagishi H., Sato Y., Tsai W.C., Takeuchi T., Kaneko Y., Izumi K., Kondo Y., Yoshimoto K., Gono T., Park S.H., Baek H.J., Lee Y.J., Choi I.A., Kim J., Hsu P.N., Huan C.M., Weng M.Y., Sung W.Y., Cheng T.T.

    The Lancet Rheumatology (The Lancet Rheumatology)  5 ( 4 ) e215 - e224 2023年04月

     概要を見る

    Background: Efficacy of combination therapy with methotrexate and biological disease-modifying antirheumatic drugs is well established in the management of patients with rheumatoid arthritis; however, the optimal dose of methotrexate to administer with a tumour necrosis factor inhibitor remains unclear. We aimed to clarify the efficacy and safety of adalimumab combined with reduced methotrexate dose compared with the maximum tolerated methotrexate dose in patients with rheumatoid arthritis and an inadequate response to methotrexate monotherapy. Methods: In this open-label, randomised controlled trial, we recruited methotrexate-naive patients with rheumatoid arthritis and a disease duration of less than 2 years across 24 secondary or tertiary care hospitals across Japan, South Korea, and Taiwan. At initiation, methotrexate was given orally and increased to the maximum tolerated dose by week 12. Patients who did not achieve remission on the basis of the Simplified Disease Activity Index (SDAI) at week 24 were randomly assigned (1:1) to receive adalimumab (40 mg biweekly) combined with a continued maximum tolerated dose of methotrexate or adalimumab combined with a reduced dose of methotrexate. The primary endpoint was non-inferiority of adalimumab plus reduced-dose methotrexate to adalimumab plus maximal-dose methotrexate based on SDAI remission at week 48, assessed in the modified full-analysis set with a pre-specified non-inferiority margin of −15%, based on a two-sided 90% CI. Adverse events were assessed in the safety analysis set. This trial is registered with ClinicalTrials.gov, NCT03505008 and has been completed. Findings: From April 18, 2018, to June 2, 2020, from 323 patients screened, 300 were enrolled, and 291 patients were included in the full analysis set. The mean age was 57·7 years (SD 15·2), 217 (75%) were female, 74 (25%) were male, and all patients were of Asian ethnicity. The mean SDAI at study enrolment was 26·5 (SD 12·4). 52 patients discontinued the study before week 24 or at week 24 before randomisation. At week 24, 105 (36%) of 291 patients achieved remission and continued methotrexate monotherapy through week 48. 134 (46%) did not achieve remission at week 24 and were randomly assigned to receive adalimumab plus the maximum tolerated dose of methotrexate (n=68) or adalimumab plus reduced-dose methotrexate (n=66). Remission at week 48 was achieved in 25 (38%) of 66 and 27 (44%) of 61 patients, respectively, with an adjusted risk difference of 6·4% (90% CI −7·0 to 19·8), which met the non-inferiority margin of −15%. Adverse events after week 24 tended to be more frequent in the maximum tolerated dose group than in the reduced-dose group (24 [35%] vs 13 [20%], p=0·054). Between week 24 and 48, there were 14 serious adverse events (6 in the methotrexate monotherapy group, 5 in the adalimumab plus maximal-dose methotrexate, and 3 in the adalimumab plus reduced-dose methotrexate group), and no deaths. Interpretation: The MIRACLE study showed that the efficacy of adalimumab combined with reduced methotrexate dose was not inferior to that with the maximum tolerated methotrexate dose, with a tendency to a better safety profile. Funding: Eisai.

  • Serum cytokines and bone metabolic markers in patients with rheumatoid arthritis treated with biological disease modifying anti-rheumatic drugs

    Tamai H., Nishina N., Kikuchi J., Izumi K., Otomo K., Yoshimoto K., Yamaoka K., Takeuchi T., Kaneko Y.

    Clinical Rheumatology (Clinical Rheumatology)  42 ( 3 ) 721 - 730 2023年03月

    ISSN  07703198

     概要を見る

    Introduction: /objectives Several biological disease-modifying anti-rheumatic drugs (bDMARDs) have been widely used for the management of rheumatoid arthritis (RA). These drugs target different molecules important for the pathophysiology of RA; however, only a few studies have compared the effects of these biological drugs on cytokines and bone metabolic markers. The main aim of this study is to clarify the effects of bDMARDs with different modes of action on the cytokine and bone metabolic marker levels in patients with RA. Methods: Patients with RA who were initiated on infliximab, tocilizumab, or abatacept as the first bDMARD were prospectively enrolled in this study. Serum cytokine and bone metabolic marker levels were measured longitudinally, and changes in their levels were compared. Results: A total of 174 patients were enrolled in this study, with 55, 70, and 49 patients in the infliximab, tocilizumab, and abatacept groups, respectively. At six months, despite the similar clinical effectiveness of the three drugs, changes in the cytokine and bone metabolic marker levels were distinct; interferon-γ and tumor necrosis factor-α levels were significantly increased with infliximab, interleukin-6 levels were increased with tocilizumab, and interleukin-1β and interleukin-8 levels were increased with abatacept treatment. Bone-specific alkaline phosphatase and osteocalcin levels increased more significantly with tocilizumab than with infliximab, while osteopontin and osteonectin levels decreased with infliximab treatment. Conclusions: bDMARDs with different modes of action exert different effects on the cytokine and bone metabolic marker levels in patients with RA.

  • Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study

    Waki D., Tamai H., Yokochi R., Kido T., Yagyu Y., Yanai R., Sada K.E.

    PLoS ONE (PLoS ONE)  17 ( 7 July )  2022年07月

     概要を見る

    Comparison of clinical response to methotrexate between anti-SSA antibody-positive and -negative patients with methotrexate-naïve rheumatoid arthritis and investigate the reasons for the differences in the response. For this multicenter retrospective cohort study, a total of 210 consecutive patients with rheumatoid arthritis who newly initiated methotrexate were recruited. The effects of anti-SSA antibody positivity on achieving a low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein after 6 months of methotrexate administration were investigated using a logistic regression analysis. This study involved 32 and 178 anti-SSA antibody-positive and -negative patients, respectively. The rate of achieving low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein at 6 months was significantly lower in the anti-SSA antibody-positive group than in the anti-SSA antibody-negative group (56.2% vs. 75.8%, P = 0.030). After 6 months, anti-SSA antibody-positive patients had significantly higher scores on the visual analogue scale (median [interquartile range]: 22 [15–41] vs. 19 [5–30], P = 0.038) and were frequently prescribed nonsteroidal anti-inflammatory drugs (37.5% vs. 18.0%, P = 0.018). In conclusion, the presence of anti-SSA antibodies might be a predictive factor for insufficient responses to treat-to-target strategy in rheumatoid arthritis. Residual pain might contribute to the reduced clinical response to methotrexate in anti-SSA antibody-positive patients with rheumatoid arthritis.

  • Systematic review and meta-analysis of biosimilar for the treatment of rheumatoid arthritis informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis

    Tanaka E., Kawahito Y., Kohno M., Hirata S., Kishimoto M., Kaneko Y., Tamai H., Seto Y., Morinobu A., Sugihara T., Murashima A., Kojima M., Mori M., Ito H., Kojima T., Sobue Y., Nishida K., Matsushita I., Nakayama T., Yamanaka H., Harigai M.

    Modern Rheumatology (Modern Rheumatology)  32 ( 1 ) 74 - 86 2022年01月

    ISSN  14397595

     概要を見る

    Objectives: To evaluate the efficacy and safety of biosimilars compared with reference biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) as a part of the process of developing the 2020 update of the Japan College of Rheumatology guidelines for the management of RA. Methods: PubMed, Cochrane Library, and Japan Centra Revuo Medicina were searched for articles to conduct a systematic review (SR). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results: Twenty randomized controlled trials were included (biosimilars of infliximab, etanercept, and adalimumab). A meta-analysis revealed that the risk ratios (RRs) and 95% confidence intervals (CIs) of achieving the American College of Rheumatology 50% response (ACR50) at week 24 and serious adverse events (SAEs) for biosimilars compared with the reference bDMARDs were 1.04 (0.98-1.10) and 0.84 (0.61-1.18), respectively. The RRs of achieving ACR50 and SAEs at week 24 were respectively 0.93 (0.69-1.26) and 2.15 (0.55-8.35) in the patients who switched to biosimilars from the reference bDMARDs and 0.92 (0.76-1.12) and 1.41 (0.32-6.15) in those who continued the reference bDMARDs. Conclusion: Biosimilars and reference bDMARDs were equally useful for the management of RA.

  • COVID-19 shares clinical features with anti-melanoma differentiation-associated protein 5 positive dermatomyositis and adult Still’s disease

    Kondo Y., Kaneko Y., Takei H., Tamai H., Kabata H., Suhara T., Yamamoto R., Nagata H., Ishii M., Sasaki J., Hasegawa N., Fukunaga K., Takeuchi T.

    Clinical and Experimental Rheumatology (Clinical and Experimental Rheumatology)  39 ( 3 ) 631 - 638 2021年05月

    ISSN  0392856X

     概要を見る

    Objective To investigate the similarities and differences between Coronavirus disease 2019 (COVID-19) and autoimmune and autoinflammatory rheumatic diseases characterised by hyperferritinaemia, such as antimelanoma differentiation-associated protein 5 (MDA5) autoantibody-positive dermatomyositis and adult Still’s disease. Methods We reviewed consecutive, newly diagnosed, untreated patients with COVID-19, anti-MDA5 dermatomyositis, or adult Still’s disease. We compared their clinical, laboratory, and radiological characteristics, including the prevalence of macrophage activation syndrome and lung involvement in each disease. Results The numbers of patients with COVID-19, anti-MDA5 dermatomyositis, and adult-onset Still’s disease with hyperferritinaemia (serum ferritin ≥500ng/dL) who were included for main analysis were 22, 14, and 59, respectively. COVID-19 and adult Still’s disease both featured hyperinflammatory status, such as high fever and elevated serum C-reactive protein, whereas COVID-19 and anti-MDA5 dermatomyositis both presented with severe interstitial lung disease and hypoxaemia. While two-thirds of the patients in each group met the criteria for macrophage-activated syndrome that is used in systemic juvenile idiopathic arthritis, the HScore, an indicator of haemophagocytic lymphohistiocytosis, was low in anti-MDA5 dermatomyositis and COVID-19 even in severe or critical cases. The findings of chest computed tomography were similar between COVID-19 and anti-MDA5 dermatomyositis. Conclusion COVID-19 shared clinical features with rheumatic diseases characterised by hyperferritinaemia, including anti-MDA5 dermatomyositis and adult Still’s disease. These findings should be investigated further in order to shed light on the pathogenesis of not only COVID-19 but also the aforementioned rheumatic diseases.