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1.
Immunol Med ; 42(1): 29-38, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31067155

ABSTRACT

The aim of this study was to assess abatacept in rheumatoid arthritis (RA) patient. Patients (20 men, 89 women, aged 61.9 ± 10.4 y) who responded inadequately to conventional synthetic disease-modifying anti-rheumatic drug were treated with abatacept for 24-months. Disease activity score in 28 joints (DAS28-CRP) was evaluated. Of 109 patients, 82 (75.2%) were on methotrexate (MTX; mean dosage 9.0 ± 2.7 mg/week); 48 (44.0%) were naive to biologics and 61 (56.0%) had failed biologics. The 1- and 2-year retention rates were 77% and 53%, respectively. At 24-months, the DAS28-CRP remission rates were 54.5% in the biologic-naïve patients, and 28.2% in the biologic-failure patients (p < .01), while the structural remission rates were 83.9% and 73.1%, respectively (p = .461). Abatacept was equally effective in RA patients who were and were not on concomitant MTX. Biologic-naïve was associated with better clinical outcome. Abatacept was effective in patients who showed decreasing anti-CCP antibody titers or serum MMP-3 levels during treatment. Infection was the most frequent adverse effect of abatacept therapy. In conclusion, abatacept is more effective in biologic-naïve than in biologic-failure RA patients with or without concomitant use of MTX. Abatacept is more effective in RA patients with than without decreasing serum MMP-3 or anti-CCP antibody titers during treatment.


Subject(s)
Abatacept/administration & dosage , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Immunosuppressive Agents/administration & dosage , Adult , Aged , Aged, 80 and over , Anti-Citrullinated Protein Antibodies/blood , Arthritis, Rheumatoid/diagnosis , Asian People , Biomarkers/blood , Dose-Response Relationship, Drug , Female , Humans , Male , Matrix Metalloproteinase 3 , Methotrexate/administration & dosage , Middle Aged , Remission Induction , Treatment Outcome
2.
Article in Japanese | MEDLINE | ID: mdl-21720103

ABSTRACT

Background. MZB is a purine analog, and is used as a disease modifying anti-rheumatic drug (DMARD). We conducted an open label uncontrolled clinical trial to evaluate the efficacy and safety of combination therapy with methotrexate (MTX) and mizoribine (MZB). Methods. Thirty one RA patients (9 males, 22 females, 68±12 year-old) who fulfilled ACR criteria of RA and did not show sufficient clinical response to MTX were included. MZB (150 mg/day, once a day) were added to MTX. DAS28-CRP was measured at day 0 and 1, 3, 6, and 12 months after the treatment. Adverse events were recorded. Results. Overall DAS28-CRP was significantly decreased from 4.4±1.0 to 3.1±1.3 at 3 months (p<0.01), 2.7±0.68 at 6 months (p<0.01), 2.4±1.4 at 12 months (p<0.01). Seventeen patients (55%) achieved significant improvement of DAS28-CRP. Number of swollen joints of responders before the treatment was significantly fewer than that of non-responders. Improvement of DAS28-CRP was significantly different between the responders (0.91±0.74) and non-responders (0.18±0.66) at 1 month (p<0.01). Nine patients (29%) could achieve remission Four patients experienced adverse events. Conclusions. MTX and MZB combination therapy was effective and relatively safety.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Methotrexate/administration & dosage , Ribonucleosides/administration & dosage , Aged , Aged, 80 and over , Antirheumatic Agents/adverse effects , Drug Resistance , Drug Therapy, Combination , Female , Humans , Male , Methotrexate/adverse effects , Middle Aged , Ribonucleosides/adverse effects , Treatment Outcome
3.
J Rheumatol ; 38(2): 310-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21078725

ABSTRACT

OBJECTIVE: DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were performed to identify key target genes in peripheral blood from patients with Sjögren's syndrome (SS). METHODS: DNA microarray analysis was performed in 19 patients with SS (all women) and 10 healthy controls (5 men and 5 women) using a low-density DNA microarray system with 778 genes. For confirmation, the expression of upregulated genes was analyzed by quantitative real-time PCR in another 37 SS patients (35 women and 2 men) and 9 healthy controls (8 women and 1 man). Relationships between gene signatures and various clinical measures, such as disease duration, symptoms and signs, complications, immunological findings, and salivary and lacrimal functions, were analyzed. RESULTS: Interferon-α (IFN-α)-inducible protein 27 (IFI27) showed the most significant difference between SS patients and controls in the microarray screening. We performed quantitative RT-PCR for IFI27. IFI27 gene expression level was increased in patients with SS compared with controls (p < 0.01) by real-time PCR, supporting our observations from the microarray data. The level of IFI27 was significantly correlated with serum IgG levels (r = 0.462, p < 0.01) and ß(2)-microglobulin (r = 0.385, p < 0.05), soluble interleukin 2 receptor (r = 0.473, p < 0.01), erythrocyte sedimentation rate (r = 0.333, p < 0.05), and antinuclear antibody titer (speckled pattern; r = 0.445, p < 0.01). CONCLUSION: Our results suggest that upregulation of IFN-inducible genes in SS patients is a systemic phenomenon, and IFN may play an important role in the pathogenesis of SS. The expression level of IFI27 could be an effective and specific biomarker associated with SS.


Subject(s)
Interferons/genetics , Membrane Proteins/genetics , Sjogren's Syndrome/genetics , Aged , Female , Gene Expression , Humans , Interferons/immunology , Male , Membrane Proteins/immunology , Middle Aged , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction , Sjogren's Syndrome/immunology , Statistics, Nonparametric
4.
Nihon Rinsho Meneki Gakkai Kaishi ; 32(4): 263-8, 2009 Aug.
Article in Japanese | MEDLINE | ID: mdl-19721347

ABSTRACT

Systemic lupus erythematosus (SLE) is usually treated with corticosteroids and immunosuppressive agents. However, some patients are refractory to these agents, others show adverse effects. Usefulness of mycophenolate mofetil (MMF) in SLE has been reported in several studies. In this study, we evaluated the clinical efficacy and adverse effects of MMF in SLE. Sixteen cases which were difficult to reduce the dose of corticosteroid, resistant to immunosuppressive agents or could not use them for adverse effects were treated with MMF. Thirteen cases were females and three were males. Mean age was 44.4+/-9.2 year-old. Mean duration of SLE was 12.5+/-6.9 years. Mean observational duration was 12.0+/-5.5 months. Mean maintenance dose of MMF was 1.95+/-0.61 g/day. Good clinical response was obtained in 69% of total cases. In laboratory data, serum IgG (p<0.05) decreased and the levels of serum albumin (p<0.01) and complement (p<0.05) increased significantly. Adverse effects, mainly infections, were observed, but severe infection was not experienced. This study suggests that MMF is effective and relatively safe for SLE.


Subject(s)
Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Mycophenolic Acid/analogs & derivatives , Adult , Female , Humans , Immunosuppressive Agents/adverse effects , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Prednisolone/administration & dosage
5.
Nihon Rinsho Meneki Gakkai Kaishi ; 32(1): 53-60, 2009 Feb.
Article in Japanese | MEDLINE | ID: mdl-19252379

ABSTRACT

Minor salivary gland biopsy is useful for diagnosis of Sjögren's Syndrome, because it has 87.4% of sensitivity, 87.3% of specificity and 87.4% of accuracy. However, SS cannot be diagnosed solely on focus score (FS). Moreover, FS is at most semi-quantitative. We questioned 30 registered facilities of Society of Japan Sjögren's Syndrome about the method and evaluation of minor salivary gland biopsy. As a result, it turned out that there were no standard methods in the procedure of salivary gland biopsy. The small salivary gland can be reached easily with little invasive method, however there are several problems, which include 1. necessity of a standard technique, 2. minimization of the pain and 3. establishment of proper evaluation system. It is thought that the establishment of a standard technique and evaluation method is necessary to minimize the pain and collect the sufficient amount of tissue. Here we report the analysis of the procedure of minor salivary gland biopsy performed in other institutions as well as in our hospital in order to propose a standardized procedure and evaluation system.


Subject(s)
Biopsy/methods , Salivary Glands, Minor/pathology , Sjogren's Syndrome/pathology , Biopsy/standards , Humans , Surveys and Questionnaires
6.
Nihon Rinsho Meneki Gakkai Kaishi ; 32(6): 499-505, 2009 Dec.
Article in Japanese | MEDLINE | ID: mdl-20046018

ABSTRACT

PURPOSE: To examine therapeutic effect of leukocytapheresis (LCAP) for rheumatoid arthritis (RA) resistant to various treatments. METHOD: Thirteen patients with RA (mean age : 60.8+/-11.4, male : female=5 : 8), 1 who were resistant to disease-modifying anti-rheumatic drugs (DMARDs) and biologics, or 2 who failed with those medicines because of side effects or complications. We performed LCAP, which was carried out once a week for a total of five sessions, with a throughput of about 0.1 L/kg. Before and after LCAP, we evaluated the effect of LCAP therapy. RESULT: DAS28 (CRP) score was 5.70+/-1.12 before LCAP, 4.57+/-1.19 (P<0.05) just after the final LCAP and 4.83+/-1.35 (P<0.05) about 4 weeks after LCAP. DAS28 score decreased in all patients after LCAP. No serious adverse events were observed except temporary anemia. CONCLUSION: LCAP therapy may be useful and safe for patients with RA resistant to conventional medication. Patients who show good clinical response by LCAP needs to be clarified.


Subject(s)
Arthritis, Rheumatoid/therapy , Leukapheresis , Adult , Aged , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , C-Reactive Protein/analysis , Drug Resistance , Female , Humans , Male , Middle Aged , Time Factors , Treatment Failure , Treatment Outcome
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