論文 - 竹内　勤

Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs

竹内 勤

BMC Gastroenterology （BMC Gastroenterology）  13 （ 1 ） 189 - 190 2013年03月

研究論文（学術雑誌）, 査読有り,  ISSN  1471-230X

　概要を見る

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan.Methods: This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive.Results: A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year.Conclusion: Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer.Trial registration: ClinicalTrials.gov identifier NCT00595517. © 2013 Sugano et al.; licensee BioMed Central Ltd.

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Validation of different sets of criteria for the diagnosis of Sjögren's syndrome in Japanese patients

Tsuboi H., Hagiwara S., Asashima H., Umehara H., Kawakami A., Nakamura H., Sano H., Tsubota K., Ogawa Y., Takamura E., Saito I., Inoue H., Nakamura S., Moriyama M., Takeuchi T., Tanaka Y., Hirata S., Mimori T., Matsumoto I., Sumida T.

Modern Rheumatology （Modern Rheumatology）  23 （ 2 ） 219 - 225 2013年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1439-7595

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Objective: To validate the revised Japanese Ministry of Health criteria for the diagnosis of Sjögren's syndrome (SS) (JPN) (1999), The American-European Consensus Group classification criteria for SS (AECG) (2002), and American College of Rheumatology classification criteria for SS (ACR) (2012). Methods: The study subjects were 694 patients with SS or suspected SS who were followed-up in June 2012 at ten hospitals that form part of the Research Team for Autoimmune Diseases, The Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW). All patients had been checked for all four criteria of the JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). We studied the clinical diagnosis made by the physician in charge and the satisfaction of the above criteria. Results: Of the 694 patients, 499 patients did not have other connective tissue diseases (CTDs). SS was diagnosed in 476 patients (primary SS in 302, secondary SS in 174), whereas non-SS was diagnosed in 218 patients (without other CTDs in 197, with other CTDs in 21) by the physician in charge. The sensitivities of JPN, AECG, and ACR in the diagnosis of all forms of SS (both primary and secondary SS) were 79.6, 78.6, and 77.5 %, respectively, with respective specificities of 90.4, 90.4, and 83.5 %. The sensitivities of the same systems in the diagnosis of primary SS were 82.1, 83.1, and 79.1 %, respectively, with specificities of 90.9, 90.9, and 84.8 %, respectively. The sensitivities of the same systems in the diagnosis of secondary SS were 75.3, 70.7, and 74.7 %, respectively, with specificities of 85.7, 85.7, and 71.4 %, respectively. Conclusion: The sensitivity of JPN to all forms of SS and secondary SS, the sensitivity of AECG to primary SS, and the specificities of JPN and AECG for all forms of SS, primary SS, and secondary SS were highest in the diagnosis of SS in Japanese patients. These results indicate that the JPN criteria for the diagnosis of SS in Japanese patients are superior to ACR and AECG. © Japan College of Rheumatology 2012.

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A merged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study

Kameda Hideto, Kanbe Katsuaki, Sato Eri, Ueki Yukitaka, Saito Kazuyoshi, Nagaoka Shouhei, Hidaka Toshihiko, Atsumi Tatsuya, Tsukano Michishi, Kasama Tsuyoshi, Shiozawa Shunichi, Tanaka Yoshiya, Yamanaka Hisashi, Takeuchi Tsutomu

Annals of the Rheumatic Diseases 72 （ 2 ） 310 - 312 2013年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0003-4967

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Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis

Nishi E., Kameda H., Ogawa H., Nagasawa H., Takei H., Okuyama A., Kurasawa T., Kondo T., Nishimura K., Shirai Y., Sakai R., Ito T., Takeuchi T., Amano K.

Modern Rheumatology （Modern Rheumatology）  23 （ 1 ） 97 - 103 2013年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1439-7595

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Objective: We investigated the efficacy of a high-dose intermittent dosing treatment method (weekly mizoribine pulse therapy) conceived in the hope of achieving better efficacy by increasing the peak blood levels of mizoribine in patients with refractory lupus nephritis. Methods: Seventeen patients with lupus nephritis who had been resistant to corticosteroid and immunosuppressant therapy received weekly mizoribine pulse therapy. Mizoribine (350 mg) was administered three times at 12 h intervals over 2 consecutive days (700 mg for day 1 and 350 mg for day 2), followed by a washout period from day 3 to day 7. Results: This therapeutic strategy enabled the peak blood levels of mizoribine to be increased to more than 3 μg/mL in most of the patients. Although SLEDAI, anti-ds-DNA antibody titer, CH-50, and serum albumin level did not significantly improve, urinary protein levels decreased, and it was possible to taper the dose of concomitant steroids. Using our definition of clinical response, 10 of the 17 patients were responders and 4 of them were nonresponders. The average peak serum mizoribine concentration of the responders was as high as 3.5 μg/mL. Elevation of serum liver enzymes was seen in 1 patient, and hyperuricemia occurred in 4 cases, but none of these adverse events were serious. Conclusion: Intermittent administration of mizoribine can increase blood levels and may be effective for refractory lupus nephritis. © 2012 Japan College of Rheumatology.

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Interferon α-targeted therapy

Hanaoka H., Takeuchi T.

Japanese Journal of Clinical Immunology （Japanese Journal of Clinical Immunology）  36 （ 4 ） 181 - 188 2013年

研究論文（学術雑誌）, 査読有り,  ISSN  09114300

　概要を見る

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies to various cellular components. Although many of therapies have shown great efficacy, they often associate with adverse effects. The development of safer therapies for SLE has led to recent emphasis on targeting selected pathways that can be important in the inflammatory process in SLE. The cytokine family of type I interferons (IFNs), and especially the IFNα subtypes, are implicated in pathogenesis of SLE. Genetic polymorphisms of several components of the IFN signaling pathway have been associated with an increased risk of SLE. Therefore, IFNα subtypes have been identified as a potential target for drug development in SLE. There have been developed three agents, IFNα-targeted therapy, Sifalimumab, Rontalizumab and NNC 0152-0000-0001. They are anti-IFNα monoclonal antibodies that bind to and specifically neutralizes most IFNα subtypes, preventing signaling through the type I IFN receptor. The safety and dose-proportional pharmacokinetics of those agents were demonstrated. A larger study is currently ongoing, further safety profile will be evaluated. This review provides an update on the ongoing clinical trials of anti-IFNα therapy and the promise and obstacles in the use of biologics in SLE. © 2013 The Japan Society for Clinical Immunology.

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Discontinuation of adalimumab treatment in rheumatoid arthritis patients after achieving low disease activity

Harigai M., Takeuchi T., Tanaka Y., Matsubara T., Yamanaka H., Miyasaka N.

Modern Rheumatology （Modern Rheumatology）  22 （ 6 ） 814 - 822 2012年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1439-7595

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Objective We implemented a retrospective study to explore discontinuation of therapy with adalimumab (ADA) without exacerbation in rheumatoid arthritis (RA) patients who had achieved low disease activity (LDA) with the biological agent. Methods We enrolled 46 RA patients who had completed open extension of a double-blind, placebo-controlled trial of ADA monotherapy in Japan and who had LDA (DAS28- CRP <2.7) at the last administration of ADA in the extension trials; this date was defined as week 0 in the present study. Treatment of RA was at the discretion of the attending physician after week 0. The primary endpoint of this study was the percentage of patients who maintained discontinuation of biological agents and LDA for 52 weeks. Results Twenty-four of the enrolled patients continued ADA while the rest discontinued ADA after the administration of the drug at week 0. Fourteen of the 22 patients did not restart biological agents, and 4 (18.2%) of these maintained LDA through week 52. All 4 of these patients had received ADA monotherapy before week 0. Conclusion Some RA patients who have achieved LDA with ADA monotherapy can discontinue the biologic without incurring increased disease activity. A prospective randomized study is required to confirm the results of our study. © Japan College of Rheumatology 2012.

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Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: A retrospective review of 15 cases and analysis of risk factors

Tanaka M., Sakai R., Koike R., Komano Y., Nanki T., Sakai F., Sugiyama H., Matsushima H., Kojima T., Ohta S., Ishibe Y., Sawabe T., Ota Y., Ohishi K., Miyazato H., Nonomura Y., Saito K., Tanaka Y., Nagasawa H., Takeuchi T., Nakajima A., Ohtsubo H., Onishi M., Goto Y., Dobashi H., Miyasaka N., Harigai M.

Modern Rheumatology （Modern Rheumatology）  22 （ 6 ） 849 - 858 2012年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1439-7595

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Objectives The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. Methods We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. Results PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p<0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor). Conclusion Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present. © Japan College of Rheumatology 2012.

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[Rheumatoid arthritis].

Tsukamoto M., Takeuchi T.

Nihon rinsho. Japanese journal of clinical medicine （Nihon rinsho. Japanese journal of clinical medicine）  70 Suppl 8   534 - 538 2012年11月

研究論文（学術雑誌）, 査読有り,  ISSN  00471852

[Discussion meeting on rheumatoid arthritis: progress in diagnosis and treatment].

Takeuchi T., Atsumi T., Nagaoka S., Oribe M., Kikuchi J.

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine （Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine）  101 （ 10 ） 2926 - 2942 2012年10月

研究論文（学術雑誌）, 査読有り,  ISSN  00215384

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Clinical characteristics and survival of japanese patients with connective tissue disease and pulmonary arterial hypertension: A single-centre cohort

Shirai Y., Yasuoka H., Okano Y., Takeuchi T., Satoh T., Kuwana M.

Rheumatology (United Kingdom) （Rheumatology (United Kingdom)）  51 （ 10 ） 1846 - 1854 2012年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1462-0324

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Objective. To clarify the characteristics, survival and predictors of mortality in Japanese patients with pulmonary arterial hypertension (PAH) associated with CTD.Methods. This single-centre cohort study enrolled 70 consecutive patients with PAH-CTD who visited a tertiary referral centre in Japan between 1970 and 1990 (n = 30, historical group) and between 2000 and 2009 (n = 40, recent group). Baseline clinical features, haemodynamic parameters and ANA profiles were recorded. The Cox proportional hazards regression model was used to determine independent factors associated with an increased risk of mortality.Results. MCTD and SLE were the major underlying CTDs, comprising 43% and 29% of PAH patients respectively, whereas SSc was less common (19%). Anti-U1RNP antibody was the most prevalent ANA (61%). The cumulative survival rate was significantly better in the recent group in comparison with the historical group (76% vs 26% at 3 years; P < 0.001). When both groups were combined, World Health Organization functional class III or IV at diagnosis was identified as an independent predictor of mortality, whereas modern PAH drug use was associated with a favourable outcome.Conclusion. The major PAH-CTD population in Japan suffers from MCTD or SLE with anti-U1RNP antibody, in contrast to PAH-CTD patients in the USA and Europe. Modern PAH treatment has improved survival rates, but long-term outcomes are still unsatisfactory. Independent predictors of mortality indicate that early diagnosis and the prompt use of PAH drugs should improve survival. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

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Inhibition of plasma IL-6 in addition to maintenance of an efficacious trough level of infliximab associated with clinical remission in patients with rheumatoid arthritis

Takeuchi Tsutomu, Miyasaka Nobuyuki, Tatsuki Yoshihiko, Yano Toshiro, Yoshinari Toru, Abe Tohru, Koike Takao

Annals of the Rheumatic Diseases 71 （ 9 ） 1583 - 1585 2012年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0003-4967

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JAK3 is involved in BAFF-mediated abnormal production of IL-6 by peripheral monocytes of patients with primary Sjogren's syndrome

竹内 勤

Cytokine 59 （ 3 ） 545 - 545 2012年09月

研究論文（学術雑誌）,  ISSN  1043-4666

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Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi

Miyata Y., Fujii H., Uenohara Y., Kobayashi S., Takeuchi T., Nagase H.

Bioorganic and Medicinal Chemistry Letters （Bioorganic and Medicinal Chemistry Letters）  22 （ 16 ） 5174 - 5176 2012年08月

研究論文（学術雑誌）, 査読有り,  ISSN  0960894X

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Derivatives of 7-benzylidenenaltrexone (BNTX), which was recently reported to be an effective chloroquine (CQ)-resistance reverser, were synthesized and evaluated for their CQ-resistance reversing activities. The synthesized derivatives showed CQ-resistance reversing effects. They also reacted with glutathione (GSH) both enzymatically and chemically, and inhibited glutathione reductase activity. 7-Benzyl derivative, which was obtained by reduction of the olefin group in α,β-unsaturated ketone structure of BNTX, also exhibited CQ-resistance reversing effect, but its potency was significantly lower than that of BNTX. These outcomes suggested that the decrease in GSH level could be one of the mechanisms of CQ-resistance reversing effects induced by BNTX derivatives. © 2012 Elsevier B.V. All rights reserved.

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Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: Postmarketing surveillance report of the first 3,000 patients

Koike T., Harigai M., Ishiguro N., Inokuma S., Takei S., Takeuchi T., Yamanaka H., Tanaka Y.

Modern Rheumatology （Modern Rheumatology）  22 （ 4 ） 498 - 508 2012年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1439-7595

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This interim analysis of postmarketing surveillance data for adalimumab-treated rheumatoid arthritis (RA) patients summarizes safety and effectiveness during the first 24 weeks of therapy for the first 3,000 patients treated in Japan (June 2008-December 2009). Patient eligibility for antitumor necrosis factor therapy was based on the Japanese College of Rheumatology treatment guidelines and Japanese labeling. All patients were screened for tuberculosis. Approximately 50% of the population was biologic näve, 66% received concomitant methotrexate (MTX), and 72% received concomitant glucocorticoids. The overall incidence rate of adverse events was 31% (5.5% serious) and that of adverse drug reactions (ADRs) was 27% (4.1% serious). Incidence rates of ADRs and serious ADRs were similar regardless of prior biologic therapy or concomitant MTX use but were significantly higher in patients receiving glucocorticoids compared with those not receiving glucocorticoids. Bacterial/bronchial pneumonia occurred in 1.2% of patients; Interstitial pneumonia, 0.6%; Pneumocystis jirovecii pneumonia, 0.3%; tuberculosis, 0.13%; and administration-site reactions, 6.1%. Mean 28-joint Disease Activity Scores decreased significantly after 24 weeks from 5.29 to 3.91. All subgroups showed significant improvement, particularly the biologic-naïve patients receiving concomitant MTX. No new safety concerns were identified. ADR Incidence rates were similar to those of other biologic agents approved for RA. © Japan College of Rheumatology 2011.

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Randomised clinical trial: Esomeprazole for the prevention of nonsteroidal anti-inflammatory drug-related peptic ulcers in Japanese patients

竹内 勤

Alimentary Pharmacology and Therapeutics （Alimentary Pharmacology and Therapeutics）  36 （ 2 ） 115 - 125 2012年07月

研究論文（学術雑誌）, 査読有り,  ISSN  0269-2813

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Summary Background The use of proton pump inhibitors for prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal adverse events is well documented. However, data regarding the efficacy and safety of this approach in Japan are scarce. Aim To evaluate the efficacy and tolerability of esomeprazole in preventing NSAID-induced peptic ulcers in Japanese at-risk patients. Methods Male and female Japanese adult patients (aged ≥20 years) with endoscopically confirmed history of peptic ulcers who required long-term oral NSAID therapy for a chronic inflammatory condition were randomised to 24 weeks' treatment with esomeprazole 20 mg once daily or matching placebo. The primary end point was the Kaplan-Meier estimated proportion of ulcer-free patients. Results Overall, 343 patients were randomised to treatment (esomeprazole, n = 175; placebo, n = 168). The Kaplan-Meier estimated ulcer-free rate over the 24-week treatment period was significantly higher (log-rank P < 0.001) in esomeprazole-treated patients (96.0%; 95% CI 92.8, 99.1) than in placebo recipients (64.4%; 95% CI 56.8, 71.9). Esomeprazole was effective at preventing peptic ulcers in both Helicobacter pylori-positive and -negative patients (96.3% vs. 95.5% of patients ulcer-free, respectively); however, in the placebo group, the proportion of ulcer-free patients at 24 weeks was markedly lower among H. pylori-positive than -negative patients (59.7% vs. 69.9%). The NSAID type did not seem to affect the estimated ulcer-free rate with esomeprazole. Treatment with esomeprazole was well tolerated. Conclusion Esomeprazole 20 mg once daily is effective and safe in preventing ulcer recurrence in Japanese patients with a definite history of peptic ulcers who were taking an NSAID (identifier: NCT00542789). © 2012 Blackwell Publishing Ltd.

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Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: A sub-analysis of a post-marketing surveillance study focusing on the duration of rheumatoid arthritis

Koike T., Harigai M., Inokuma S., Ishiguro N., Ryu J., Takeuchi T., Tanaka Y., Yamanaka H., Fujii K., Yoshinaga T., Freundlich B., Suzukawa M.

Rheumatology International （Rheumatology International）  32 （ 6 ） 1511 - 1519 2012年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0172-8172

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The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2-5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pretreatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for <2 years. Less AEs and SAEs were observed among patients with shorter duration of RA. These results suggest that RA treatment in Japan in the era pre-biologics may not have been adequate to control disease activity and prevent joint destruction. Patients with shorter duration of RA may have better physical status which allows the opportunity to treat more intensively putting a higher percentage of patients in remission and possibly decreasing exposure to SAEs. © Springer-Verlag 2011.

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A MULTI-CENTER, DOUBLE-DUMMY, DOUBLE-BLIND STUDY OF SUBCUTANEOUS (SC) ABATACEPT (ABA) COMPARED WITH INTRAVENEOUS (IV) ABA IN JAPANESE RHEUMATOID ARTHRITIS PATIENTS WITH INADEQUATE RESPONSE TO METHOTREXATE

竹内 勤

Annals of the Rheumatic Diseases 71   197 - 197 2012年06月

研究論文（学術雑誌）,  ISSN  0003-4967

Safety and effectiveness of switching from infliximab to etanercept in patients with rheumatoid arthritis: Results from a large Japanese postmarketing surveillance study

竹内 勤

Rheumatology International （Rheumatology International）  32 （ 6 ） 1617 - 1624 2012年06月

研究論文（学術雑誌）, 査読有り,  ISSN  0172-8172

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Finding an effective treatment strategy for rheumatoid arthritis (RA) patients who have not benefited from previous tumor necrosis factor-α antagonist treatment is important for minimizing RA disease activity and improving patient outcomes. The aim of this study was to compare the safety and effectiveness of etanercept in patients with and without infliximab (IFX) treatment experience. Patients (n = 7,099) from a large postmarketing observational study of etanercept use in Japan were divided into 2 cohorts based on previous IFX use (pre-IFX and non-IFX). Baseline characteristics were assessed in each cohort. Adverse events (AEs) and European League Against Rheumatism (EULAR) responses were monitored every 4 weeks for 24 weeks. At baseline, pre-IFX patients were younger and had fewer comorbidities and a shorter RA duration than non-IFX patients. During the study, pre-IFX patients received concomitant methotrexate more often than non-IFX patients. The incidence of AEs and serious AEs were significantly lower in pre-IFX patients, as was the percentage of patients who discontinued treatment. Both cohorts had significant improvement (P<0.001) in EULAR responses at the end of the treatment period. This study demonstrated that etanercept was effective and well tolerated in active RA patients with and without prior IFX treatment. © Springer-Verlag 2011.

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Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: Retrospective analyses of data collectedduring the first year of adalimumab treatment in routine clinical practice (HARMONY study)

Takeuchi T., Tanaka Y., Kaneko Y., Tanaka E., Hirata S., Kurasawa T., Kubo S., Saito K., Shidara K., Kimura N., Nagasawa H., Kameda H., Amano K., Yamanaka H.

Modern Rheumatology （Modern Rheumatology）  22 （ 3 ） 327 - 338 2012年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1439-7595

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We retrospectively investigated the ability of adalimumab (ADA) to reduce disease activity, improve physical function, and retard the progression of structural damage in 167 patients with rheumatoid arthritis. Clinicaland functional outcomes were compared between patients with or without prior biologic treatment and those with or without concomitant methotrexate (MTX) treatment. At week 52, 38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission in those without and with previous biologics, respectively, while 42.7 and 12.5% of patients achieved remission in those with and without concomitant MTX, respectively. ADA treatment significantly reduced the rate of radiographic progression from 27.1 ± 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9) at baseline to 0.8 ± 5.0 (median 0.0; 25th-75th percentiles -0.9 to 2.0) at week 52 (P\0.0001). Radiographic progression was absent in 59.8% of patients. Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were serious (9.12/100 patient-years). ADA therapy is highly effective for reducing disease activity, improving physical function, and limiting radiographic progression. It is generally safe and well tolerated by Japanese RA patients in routine clinical practice. © Japan College of Rheumatology 2011.

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Golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis: Results of the GO-FORTH study

Tanaka Y., Harigai M., Takeuchi T., Yamanaka H., Ishiguro N., Yamamoto K., Miyasaka N., Koike T., Kanazawa M., Oba T., Yoshinari T., Baker D.

Annals of the Rheumatic Diseases （Annals of the Rheumatic Diseases）  71 （ 6 ） 817 - 824 2012年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0003-4967

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Objective: To assess the efficacy and safety of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA). Methods: 269 Japanese patients with active RA despite treatment with MTX were randomised (1:1:1) to placebo + MTX (Group 1), golimumab 50 mg + MTX (Group 2) or golimumab 100 mg + MTX (Group 3). Subcutaneous golimumab/placebo was injected every 4 weeks; stable doses of oral MTX (6-8 mg/week) were continued. Patients were allowed to enter early escape (Group 1 added golimumab 50 mg, Group 2 increased golimumab to 100 mg, Group 3 continued golimumab 100 mg) based on swollen/tender joint counts at week 14. The primary study endpoint was achievement of at least 20% improvement in the American College of Rheumatology (ACR20) response criteria at week 14. To control for multiplicity of testing, treatment group comparisons were first made between combined Groups 2 and 3 versus Group 1, followed by comparisons of Group 2 and Group 3 versus Group 1. Results: The proportion of patients with an ACR20 response at week 14 was significantly higher in combined Groups 2 and 3 (73.4%, 127/173) and in each of Group 2 (72.1%, 62/86) and Group 3 (74.7%, 65/87) compared with Group 1 (27.3%, 24/88; p<0.0001 for all comparisons). Golimumab + MTX also elicited a significantly better response than placebo + MTX in other efficacy parameters, including disease activity score (DAS28) response/remission and radiographic assessments. During the 16-week fixed treatment regimen study period, 72.7%, 75.6% and 78.2% of patients had adverse events and 1.1%, 1.2% and 2.3% had serious adverse events in Groups 1, 2 and 3, respectively. Conclusion: In Japanese patients with active RA despite MTX therapy, golimumab + MTX was significantly more effective than MTX monotherapy in reducing RA signs/symptoms and limiting radiographic progression with no unexpected safety concerns.

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