We tested the efficacy of infliximab treatment in 20 patients with rheumatoid arthritis (RA) using the following outcome measures; ACR (The American College of Rheumatology) core set, ACR-N, DAS (Disease Activity Score)28, and SDAI (Simplified Disease Activity Index). We also assessed the value of these indices and the adverse effects. The dosage of infliximab was adjusted for 3 mg/kg of body weight during the observation period (24 months). Of the 20 patients (average age 47 years old), 55% of patients achieved an ACR20 response at week 6.40% achieved ACR50 and 17% achieved ACR70 responses. In accordance with DAS28CRP, 60% of patients achieved good response. 20% achieved moderate response and 20% achieved no response. ACR-N and SDAI reflect disease activity in the same way as DAS28CRP, and these indices statistically showed a significant correlation. These results suggested that ACR-N, DAS and SDAI which numerically evaluate disease activity showed a good criterion-related validity. It was difficult to predict the prognosis using these indices at week 6 because there were some cases with amelioration after 6 weeks. It raised the possibility that CRP, ESR, rheumatoid factor, tender joint count and pain VAS might be prognostic factors, but there were individually no statistically significant differences. Frequent adverse effects of infliximab are pyrexia, headache, eruption, bacterial pneumonia, etc, and the trend was similar to previous reports. Further, we experienced a rare case of thrombocytopenia associated with the appearance of IgM anticardiolipin antibody, and we naturally need to take care of adverse effects such as infectious diseases.

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Background and Aims: To study the efficacy and safety of etanercept in patients with rheumatoid arthritis (RA) according to the American College of Rheumatology (ACR) case definitions and their clinical associations.
Methods: Patients with RA who were treated with etanercept have been followed from May 2005. Twenty-five mg twice a week of etanercept was injected into each patient. We assessed the ACR revised criteria for 20％ improvement (ACR20), ACR50, and ACR70 response rates, the Stanford Health Assessment Questionnaire (HAQ) scores, disease activity score (DAS) 28, serum markers such as CRP, and ESR were assessed. Safety measures included monitoring of adverse events and laboratory values.
Results: A total of 35 patients with RA were studied. The female to male ratio was 5 to 1, and the mean age was 58.9 years (range 37-77). The mean duration of disease was 12.8 years (range 0.5-49). 33 patients were improved in CRP levels after 2 weeks. DAS 28 of 65 patients has improved from 5.08 to 3.8 (2W), 3.5 (4W), and 3.0 (8W); respectively. Etanercept was withdrawn in only one patient due to exacerbation of chronic bronchitis.
Conclusions: The improvements in both functional ability and physician-based efficacy measures seen with etanercept demonstrated the early efficacy of etanercept in patients with RA. One patient withdrew from etanercept treatment because of adverse drug reactions.

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    We examined the efficacy and safety of tacrolimus used in combination with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with insufficient response to treatment by one or more DMARDs. Thirty eight patients(male: 8, female: 30) who had active RA at baseline despite treatment with DMARDs were administered 1-3 (mean 1.4) mg tacrolimus daily for 12 weeks while continuing to receive DMARDs at the existing stable dosage. The patients’ age was 60±15 years. The number of patients who continued to receive methotrexate, salazosulfapyridine or bucillamine was 27, 28 and 20, respectively. Disease activity was evaluated by disease activity score 28 (DAS28). Good response and moderate response in DAS28 improvement were achieved in 12 patients (32%) and 13 patients (34%), respectively. The mean DAS28 decreased from 4.3±0.8 to 3.1±1.1 (P＜0.01) after 12 weeks of treatment. In high disease activity patients (n＝7), DAS28 was markedly improved from 5.4±0.4 to 3.4±1.4 (P＜0.01). Tender joint count was rapidly decreased, although C-reactive protein and swollen joint count were slowly reduced. Two patients discontinued tacrolimus treatment by reason of adverse Events (nausea, loss of appetite). The mean plasma creatinine was slightly increased (0.63±0.23 to 0.65±0.23 mg/dl), but the increase was not significant. These data show that tacrolimus combination therapy with DMARDs is efficacious and safe in refractory RA patients.

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    Filtration Leukocytapheresis (LCAP) is a treatment of removing responsible leukocytes from the peripheral blood.
    Although several clinical trials have demonstrated the efficacy and safety of LCAP in refractory cases of rheumatoid arthritis (RA), it remains unclear how patient characteristics are applicable for LCAP in RA therapeutic strategy. Here, we retrospectively reviewed a total of thirteen RA patients with refractory to conventional disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibitors, who were treated with LCAP while staying at our hospital, and studied the relationship between the patient background and the efficacy of LCAP.
    8 patients were eligible for twelve-week follow-up assessment after LCAP treatment. The efficacy of LCAP was assessed by 3 evaluation items of CRP, swollen joint count, and tender joint count. As a result, at least 36.4％ of patients achieved 20％ improvement of all items and 27.3％ achieved 50％ improvement, which showed satisfactory results.
    The background of patients treated with LCAP were 1) having relatively advanced joint destruction, 2) refractory to conventional DMARDs therapy, 3) resistant to or failed with methotrexate due to ineffectiveness or its side effect, suggesting that patients filling these characteristics were applicable for LCAP.

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    Amyloidosis is a serious complication of rheumatoid arthritis (RA). Amyloidosis, related to RA, mainly results from the deposition of amyloid A protein into the kidney, intestine and heart. Amyloid A protein is derived from serum amyloid A protein, which behaves as an acute-phase reactant.
    A 68-year-old woman was diagnosed with RA in June 1994. Because she noticed pitting-edema in her legs in January 1997, and it did not improve in spite of diuretics-administration, she was admitted to our university hospital in April 1998. She was found to have nephrotic syndrome with daily urinary protein of 4.6 g and serum albumin concentration of 1.7 g/dl. Renal biopsy revealed amyloid deposits in her glomeruli and interstitial matrix. Actarit, sulfasalazine, and prednisolone were prescribed to her without any beneficial effects. These DMARDs were then changed to methotrexate, which gave excellent effects not only on joint inflammation but also on nephrotic syndrome in December 1998; daily urinary protein decreased to 1 g, and serum albumin concentration increased to 2.9 g/dl in March 2005, while creatinine clearance did not change remarkably (from 38.4 ml/min to 30.0 ml/min). Meticulous use of methotrexate in renal amyloidosis associated with rheumatoid arthritis could be very effective and powerful in amelioration of arthritis and nephrotic syndrome due to secondary amyloidosis even in the state of decreased creatinine clearance.

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    A 61-year-old female developed a fever and productive cough in April 2005. Chest radiography showed a reticular shadow, and she was admitted to a local hospital. Chest CT scanning revealed streaky shadows and patchy consolidations surrounded by ground-glass opacities predominantly on the dorsal side of bilateral lungs. Although steroid pulse therapy and several antibiotics were administered, she was transferred to our hospital due to rapid progression of respiratory failure. Laboratory findings showed the following; LDH 726 U/I; CK 490 U/I; and KL-6 824 U/ml. Autoantibodies such as anti-Jo-1 antibody were all negative. Eruptions consistent with heliotrope rash and Gottron’s sign were observed, but muscle symptoms were mild, and CK levels were slightly increased. She was diagnosed as having rapidly progressive interstitial pneumonia accompanied by dermatomyositis without muscle symptoms. Under mechanical ventilation, she received steroid pulse therapy, cyclosporine-A, and cyclophosphamide pulse therapy. On the 10^th hospital day, she was liberated from artificial ventilation. Follow up chest CT scanning showed a marked improvement of interstitial pneumonia. Cases of progressive interstitial pneumonia complicated with dermatomyositis that are negative for anti-Jo-1 antibody and show a low ratio of CK/LDH are resistant to various treatments. The 3-drug combination therapy consisted of corticosteroids, cyclosporine-A and cyclophosphamide may be effective for rapidly progressive interstitial pneumonia complicated with dermatomyositis.

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    We report a case of Takayasu Arteritis (TA) with positive anti-U1-RNP antibodies. In June 2004, a 68-year-old man was referred to the Iwate Prefectural Miyako Hospital because of leukocytosis, increased C-reactive protein (CRP) and blood pressure discrepancy. Magnetic resonance angiography (MRA) and angiography examination demonstrated marked constrictions of his left subclavian artery, left vertebral artery, anterior descending branch of left coronary artery and bilateral common iliac arteries near their origins. Contrasted magnetic resonance imaging (MRI) showed gadolinium enhancement on the abdominal aortal wall. Lung perfusion scintigraphy showed defects in the anterior segment of the left superior lobe and the lateral basal segment of the left inferior lobe. Laboratory studies revealed positive result for rheumatoid factor (RF), anti-U1-RNP antibody, anti-cardiolipin antibody, 40KDa-band of anti-endothelium antibody and HLA B51.However no other abnormal findings compatible with the diagnosis of mixed connected tissue disease (MCTD), Sjögren syndrome (SjS), Behçet disease or other collagen disease were seen. In October 2004, percutaneus transluminal angioplasty was performed by vasculostents due to the very small orifices of the common iliac arteries, and treatment with ticlopidine was started. Thereafter no symptoms of TA occurred. Since March 2005, The CRP level fell below the normal threshold. TA usually coexists with 74Kda-band of anti-endothelium antibodies, but rarely coexists with systemic lupus erythematosus (SLE) or other autoimmune disease, and with positive specific antinucleolar antibodies. Therefore, this study seemed to report a rare case.

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    We tried to characterize the serologic variables and MRI detection of early changes in the wrists and finger joints, allowing the differentiation of RA from rheumatic diseases other than RA (non-RA) at the earliest stage.113 consecutive, newly referred patients with polyarthritis, suspected of having early-stage RA, were enrolled in this study, and the diagnosis of having either RA or non-RA was established during the follow-up period. Logistic regression analysis was used to determine the variables at the entry that discriminated early-stage RA from non-RA, and statistical weight was calculated for each variable. 113 subjects included 80 early-stage RA (mean disease duration of 80 patients were 4.8 months) and 33 non-RA. Logistic regression analysis identified the presence of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and/or IgM rheumatoid factor (IgM-RF), symmetrical synovitis and bone marrow oedema and/or bone erosion on MRI as significant characteristic variables for early-stage RA. The sensitivity and specificity in total score of 2 or more of the three objective parameters (anti-CCP antibody and/or IgM-RF: 1, symmetrical synovitis on MRI: 1, bone marrow oedema and/or bone erosion on MRI: 1) in the classcification of RA were 82.5% and 84.8%. Our present data may indicate that the prediction of autoantibodies as well as MRI detection of early joint changes contribute to the accurate diagnosis of early-stage RA. In addition, the numbers of MRI-evidence of synovitis, bone erosion, mean E-rate, serum CRP, MMP-3 and IL-6 levels and percentage of patients with HLA-DRB1 *0405 allele carriership in early-stage RA patients were significantly higher in bone marrow oedema-positive than-negative group, suggesting bone marrow oedema reflects severe disease status in patients with early-stage RA, and could be clinically useful for monitoring disease outcome.

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