[in Japanese]

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【Objective】To investigate the efficacy and the safety of Methotrexate(MTX)at dosages over 8 mg/week in patients with rheumatoid arthritis(RA).
【Methods】80 RA patients(19 male,61 female),treated with MTX at dosages over 8 mg/week, were included in this study. We assessed the efficacy of MTX using DAS28-CRP, MMP3, and CRP at initiation of dose escalation and during 6 months after dose escalation. Adverse events were also assessed.
【Results】Mean age is 57±13 years old. Biological agents were concomitantly administered in 30 patients (38%). Folic acid was administered in all patients. MTX at dosages over 8 mg/week was continued for 6 months in 67 patients (84%). In the 6 month continuation group, mean DAS28-CRP, MMP-3 and CRP were significantly decreased during 6 months. With regard to adverse events, nausea occurred in 5 patients, abnormal decrease of white blood cell counts occurred in 3 patients, abnormal increase of hepatic enzyme occurred in 7 patients, malaise occurred in 1 patient, pneumonia occurred in 1 patient. All adverse events were improved by discontinuation or decreasing the dose of MTX.
【Conclusion】MTX at dosages over 8 mg/week in patients with RA was effective. There were no cases leading to severe adverse events. In this study, the value of hepatic enzyme at initiation of dose escalation over 8 mg/week was significantly higher in the discontinuation/decreasing dose group than that in the 6 month continuation group.

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    The pooled results from 16 institutions participating in the Fukuoka RA Biologics Registry are reported in order to evaluate the efficacy and safety of abatacept in clinical practice. Enrollment began in September 2010. One hundred eleven patients who received treatment with abatacept for 24 weeks were included in the study. The dose regimen used is approved in Japan. The clinical effects were measured by DAS28 and SDAI. Fifty seven patients were switched from biologics (S group) and 54 patients were biologics-naïve (N group). Of the S group, 24 patients had Received 2 or more biologics. In addition, 62 patients received a combination of abatacept and MTX and 49 patients received abatacept alone. The mean DAS28ESR was 4.96 at baseline and improved to 4.30, 3.89, and 3.73 at Weeks 4, 12, and 24, respectively. The mean SDAI was 23.51 at baseline and improved to 17.00, 14.02, and 13.43 at Weeks 4, 12, and 24, respectively. In the N group, the mean DAS28 was 4.90 at baseline and 3.12 at Weeks 24. The SDAI remission rate at Week 24 was significantly higher in the N group than in the S group, 31.5% and 3.5%, respectively (p＝0.001). No significant difference was found in the DAS28 remission rate at Week 24 with or without MTX; 30.0% in the abatacept plus MTX group and 16.3% in the abatacept alone group (p＝0.32). A total of 15 patients discontinued treatment due to lack of response, 8 patients due to adverse reactions, and1patient due to personal reasons. The treatment retention rate at Week 24 showed good results; and was 86.5% in all the patients who received abatacept.

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［Objectives］To evaluate the radiological efficacy of abatacept in rheumatoid arthritis (RA) patients. ［Methods］ 41 patients received abatacept for at least 52 weeks; 21 patients had just started ABT, mean age was 65.2 years and the mean disease duration was 9.7 years. ［Results］ The mean values of each factor at baseline/Week 52 were as follows: CRP 2.04/0.45, ESR 43.8/24.3, MMP-3 194.4/74.7, DAS28-CRP 4.05/2.44, DAS28-ESR 4.69/3.08, SDAI 22.8/7.5, and ΔmTSS 8.59/0.63. The remission rates of DAS28-CRP, DAS-28ESR, and SDAI were 43.9％, 39.0％, and 26.8％. Total CRP and total MMP-3 until Week 52 were significantly lower in patients with structural remission compared to patients without structural remission. Factors related to the progression of joint destruction were RF negative, no use of MTX, and switching treatments. ［Conclusion］ In RA treatment by abatacept, it is useful to monitor total CRP and total MMP-3 for the evaluation of structural remission. Patients with risk factors for joint destruction should be closely monitored including more frequent TSS assessments.

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    Concomitant treatment of methotrexate (MTX) up to 8 mg/week and adalimumab was initiated. However, MTX dose increment was performed for 17 (1 male, 16 females, mean age 59.7 years, and mean duration of illness 16.2 years)no response cases or loss of response cases to examine and investigate the efficacy and safety. Mean MTX dose for no response cases or loss of response cases, and at base line and final evaluation were 6.1 mg/week and 9.4 mg/week, respectively, showing a mean increment of 3.3 mg/week. The maximal dose of MTX at the final evaluation was 12 mg/week. Efficacy evaluation based on DAS28CRP revealed that 15 (88.2%) of the 17 patients achieved remission. On the other hand, there were no adverse effects due to dose increment of MTX up to 12 mg/week. These findings suggested that MTX dose increment in concomitant therapy of MTX and ADA is a useful measure for no response cases and loss of response cases.

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    A 72-year-old woman was admitted to our hospital with complaints of general malaise, mild fever, and polyarthlargia in February 2010. She had been diagnosed as having rheumatoid arthritis in 1999, and in spite of the treatment with conventional DMARDs therapy followed by TNFαinhibitors of etenercept and adalimumab, her disease activity was not well controlled. Her Steinblocker Classification was Stage IV, and her Functional Class was Class 4.Investigations showed that her symptoms were derived from disease activity of her rheumatoid arthritis. We started 40 mg/day prednisolone, however opportunistic infection occurred, and anemia and hypoalbuminemia progressed. Her activities of daily living (ADL) worsened and a pressure ulcer appeared. Although she had some risk factors such as her age being over 65 years and being Functional Class 4, we administered Tocilizumab (TCZ) 8 mg/kg with cyclophosphamide 50 mg/day in order to control the disease activity. After the administration of TCZ, her disease activity was well controlled and anemia and hypoalubuminemia dramatically improved without any infections and adverse events. The pressure ulcer was cured and TCZ was stopped after the fourth administration.
    This case suggests that TCZ can strongly suppress inflammation and improve anemia, hypoalbuminemia induced by the disease activity itself. The pressure ulcer was then cured, accompanied by improvement of ADL. Although TCZ carries an increased risk of infections, TCZ can be used carefully for the treatment of severe rheumatoid arthritis with some risk factors.

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    Biologics for rheumatoid arthritis (RA) are new class of drugs that have been used since about 10 years ago. Abatacept is one of the biologics for RA with relatively low risk of infection; however, the long-standing safety of abatacept is not well known. In this paper, we will report an elderly Japanese RA patient with long-standing abatacept and methotrexate therapy became severe empyema by Streptococcus intermedius.
    A 72-year-old woman with RA was suffering from severe dyspnea and right chest pain. The disease activity of RA was kept in check by abatacept and methotrexate for about six years. The radiological examination of the chest showed the capsuled pleural effusion on the right chest. A pleural cavity tube was inserted and pus with Streptococcus intermedius was drained. At first, the conservative therapy with antibiotics was performed, but it was ineffective and video-assisted thracolysis was carried out. During the thracolysis, there was a fistula on the right lower lobe and partial thorarectomy was performed. After the procedure, she became well.
    As we know, there are no reports about primary empyema during abatacept therapy. Longstanding biologic therapy increases the risk of serious infections and the similar phenomena could be developed in the administration of abatacept. In our case, the empyema was caused by normal bacterial flora and abatacept was thought to relate to the pathogenesis of the empyema. We have to take note that the long-standing abatacept therapy would increase the risk of serious infections and would develop cases like ours.

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    A 66-year-old man with bronchial asthma had been treated with inhaled fluticasone/salmeterol (500/100 g/day), planrukast (450 mg/day) and theophylline (200 mg/day) since October 200X. Because the bronchial asthma was refractory to these agents, treatment with oral prednisolone (5 mg/day) was added, but this resulted in repeated attacks of exacerbated asthma. In June 200X＋2, fluticasone/salmeterol was switched to budesonide/formeterol (640/18 g/day). In February, 200X＋3, the serum level of myeloperoxidase anti-neutrophil cytoplasmic antibody became elevated (145 IU/ml), suggesting occult Churg-Strauss syndrome, and the dose of prednisolone was increased from 5 to 50 mg/day for stepping up to his refractory asthma control levels and suspected latent Churg-Strauss syndrome. In early April, 200X＋4, because symptoms of suspected multiple mononeuritis and myositis appeared during treatment with prednisolone at 5 mg/day, the patient met the criteria for Churg-Strauss syndrome. His condition was improved after the dose of corticosteroid had been increased and intravenous immunoglobulin started. The present case of Churg-Strauss syndrome associated with tapering of corticosteroid treatment and elevation of the serum myeloperoxidase anti-neutrophil cytoplasmic antibody level before diagnosis is considered to be rare.

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