[in Japanese]

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[in Japanese]

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[in Japanese]

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    It is thought that serum levels of MMP-3 reflects synovial inflammation. However, it is our experience that discrepancy occurs in the case of evaluation of inflammatory activity in RA. The objective of this study is to investigate clinical features of serum levels of MMP-3. We investigated the 46 patients with RA who fulfilled the 1987 criteria of the American Rheumatism Association, and who were treated at the Department of Orthopedic Surgery, Fujigaoka Hospital, Showa University School of Medicine. There were 9 males and 37 females, aged from 41 to 76 years (average 59.5 years). Steinbrocker RA stage was I in 14 patients, II in 16, III in 11, IV in 5. Useof MTX was 5.6 mg/dl on average, and administered to 41 patients (89.1%). Use of corticosteroids was 3.1 mg/dl on average, and administered to 35 patients (76.1%).
    We measured, DAS28-CRP, CRP, tender joints count, swollen joints count, and VAS, and investigated their relation with serum levels of MMP-3. Serum levels of MMP-3 and the values of CRP, tender joints count, swollen joints count, DAS28-CRP showed correlation. A correlation coefficient more than 0.4 was only found for the swollen joints count. The correlation between serum levels of MMP-3 and DAS 28-CRP was not strong.

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Background: The validity and safety in high-dose infliximab (IFX) medication for patients with rheumatoid arthritis (RA) were shown by the RISING study. However, there are few reports using the dose-escalation IFX method according to disease activity.
Methods: We established a dose-escalation IFX protocol for RA, and have treated patients with RA according to this protocol since2009. The efficacy and safety were retrospectively compared with a historical control protocol with dose-fixed IFX.
Results: Nineteen patients were treated with the dose-escalation IFX protocol (dose-escalation group) and their outcomes were compared with those of 22historical controls treated with the dose-fixed IFX protocol (control group). No significant differences were found in the backgrounds between the groups. Since there were no early discontinuations due to poor response to IFX among the dose-escalation group, the rate of IFX continuation was increased in doseescalation group. The remission rates of the dose-escalation group, using the measures of DAS28＜2.6, SDAI≦3.3 and CDAI≦2.8, were significantly improved compared to those of control group (p＜0.05, chi-square test). The incidence rates of adverse events between these groups were not significantly different during the follow-up periods.
Conclusion: The dose-escalation IFX therapy was well tolerated for RA and contributed to better remission induction.

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    We have held a public program for rheumatoid arthritis (RA) targeting citizen in Nagasaki prefecture 9times since 2007. Here we showed tendencies and problems of the public program. The program was composed of 3 parts including lecture of physicians and an orthopedist, an exercise of RA performed by a physical therapist,and a panel discussion that took questions from the floor. A questionnaire regarding annual shift of participants and therapeutic medicines. Results from Sasebo city and Goto city that is located on an isolated island were also analyzed. During the 9times the program was carried out, participants were frequently aged over 50years old and the proportion of health personnel was 14%. The percentage of RA disease duration within 3years was around 30%. Usage rate of disease modifying anti-rheumatic drugs was 67% and 59% without statistical significance. However, usage rate of biologics in Sasebo city (30%) was significantly greater than that in Goto city (p＝6.64×10⁻⁸). In the same places, the desire to participate in this program in the future statistically showed a declining trend (p＝4.86×10⁻⁵). Although participants’ motivation for collecting information for RA was high, there was large difference between an isolated island and other places with respect to the frequency of use of biologics. According to these data, we suggest continuous familiarizing efforts must be performed to devise how to proceed with the program.

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    A-72-year-old woman with rheumatoid arthritis (RA) was transferred to our hospital because of rapid progressive hypoxemia. She had RA for 21years and had been treated with tocilizumab (TCZ) for 3months before this hospitalization. She had few symptoms except loss of appetite for a few days, then oxygen desaturation was detected by pulse oximeter when she visited family doctor to receive annual influenza vaccination. Instead of giving her a vaccination, she was instructed to go to another hospital on the same day to be examined in relation to oxygen desaturation. Marked hypoxemia and diffuse pulmonary lesions by chest X-ray were revealed there, and she was transported to our intensive-care unit. She was intubated immediately, and then severe hypotension occurred. Fluid administration and large doses of catecholamines were needed to maintain her blood pressure. Steroid pulse therapy, antimicrobial agents and sivelestat were used simultaneously. She was intubated for 13days, and was discharged from hospital on foot after 58days of hospitalization. We considered her illness as severe pneumonia with shock based on clinical, laboratory and radiological findings and therapeutic response. However, we were not able to examine the causative microorganisms sufficiently owing to her severe circulatory and respiratory condition. Severe infections with circulatory collapse appear to be a rare but serious complication during treatment with TCZ.

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    A girl, 8 years of age, was reported to be diagnosed as systemic juvenile idiopathic arthritis. Refractory to corticosteroid therapy, she was introduced tocillizumab. After 4^th administration, she was suffering from liver dysfunction. Since viral hepatitis, bacterial infection and metabolic disorders were failed to be demonstrated, and additionally an obstructive biliary tract abnormalities were observed, liver biopsy was performed. Histological examinations revealed denaturation of a bile duct and fibrosis of a portal vein region suggesting drug-induced hepatitis. To confirm the diagnosis, drug lymphocyte stimulation test (DLST) was performed to find 3 suspected drugs, famotidine, sodium alendronate and acyclovir, all of which were terminated to prescribe.
    After terminated these drugs and add Ursodeoxycholic acid (UDCA), she was relieved jaundice, and liver function was normalized. After discharge, tocilizumab which DLST was negative, was administered again for s-JIA, and liver dysfunction did not occur. During the course of s-JIA treatment, there are many kinds of liver dysfunction, we should think drug-induced liver failure as one of the differential diagnosis. Tocilizumab was safely administered again to control inflammation of systemic JIA.

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    In recent years, the biologic response modifiers show early and sustained efficacy and tolerability for treating children with polyarticular juvenile idiopathic arthritis intractable to conventional therapy including methotrexate. However, there are cases with more severe disease activity and secondary failure of the treatment due to side effects or antibody formation against the biologic drugs. Thus, a second line of treatment is required. Two cases of polyarticular juvenile idiopathic arthritis were reported refractory to TNF-alpha blockers, one is etanercept and the other infliximab. TNF blockers used in both cases were successfully switched to tocilizumab, an anti-IL-6-receptor monoclonal antibody. There are no guidelines in the pediatric field for the selection of biologic response modifiers as the primary treatment regimen and the second line for switching. We suggest that the switching of biologic response modifiers TNFalpha blockers to IL-6 receptor blocker or vice versa will be beneficial in some cases of polyarticular juvenile idiopathic arthritis. More experiences should be accumulated for better selection of these types of drugs.

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