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ABSTRACT: OBJECTIVE: To analyze the efficacy of tocilizumab (TCZ) and the factors that influence achievement of Boolean-based remission in patients with rheumatoid arthritis (RA) treated with TCZ in daily clinical practice. METHODS: The efficacy of TCZ at 24 weeks after initiation of TCZ in 80 patients with RA was analyzed by comparing achievement of "DAS28 remission" with that of "Boolean-based remission". The predictive factors that influence achievement of Boolean-based remission were determined using multiple logistic regression analysis using a step-wise method. RESULTS: DAS28 remission and Boolean-based remission were achieved in 50.0 and 12.5 % of patients, respectively. Significant differences in achieving Boolean-based remission were observed when patients were stratified by disease duration in tertiles (p < 0.05) and by physical function in tertiles (p < 0.05); no such differences were observed for achieving DAS28 remission. The least achievable component among the Boolean-based remission criteria was patient's global assessment. The predictive factor for not achieving Boolean-based remission at 24 weeks was having a worse baseline physical function (odds ratio, 3.66; 95 % confidence interval, 1.17-14.48). CONCLUSIONS: This study suggests that baseline disability predicts a lack of achievement of Boolean-based remission. Thus, better responses to TCZ may be obtained when TCZ is initiated in RA patients before disability develops.
Modern Rheumatology 03/2013; · 1.58 Impact Factor
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Yohei Seto,
Eisuke Inoue,
Kumi Shidara, Daisuke Hoshi,
Naoki Sugimoto,
Eri Sato,
Eiichi Tanaka,
Ayako Nakajima,
Atsuo Taniguchi,
Shigeki Momohara,
Hisashi Yamanaka
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ABSTRACT: OBJECTIVE: To analyze the relationship between the progression of disability and disease activity in patients with rheumatoid arthritis (RA) in daily practice. METHODS: Patients from an observational cohort, IORRA, who completed surveys during 2009-2011 were eligible. Linear regression of disease activity score 28 (DAS28), Japanese version of Health Assessment Questionnaire (J-HAQ), and EQ-5D from baseline were calculated, and the angles of the regression lines were designated DAS28 slope, J-HAQ slope, and EQ-5D slope, respectively, in each patient; averages were compared between treatment groups. RESULTS: A total of 5,038 patients [84.0 % female, mean age 59.4 (SD 13.1) years, disease duration 13.2 (9.6) years, DAS28 3.29 (1.14), and J-HAQ 0.715 (0.760)] were analyzed. The average DAS28 slope indicated improvement in all groups, whereas J-HAQ slopes were negative in patients on methotrexate (MTX), biologics, combination biologics/disease-modifying antirheumatic drugs (DMARDs), and combination biologics/MTX at baseline, but positive in patients on prednisolone >5 mg/day [0.010 (0.153)] and not on MTX at baseline [0.007 (0.122)], representing a worsening of disability. CONCLUSION: There is some disparity between improvement of disease activity and progression of disability, suggesting that quality of remission must be considered.
Modern Rheumatology 01/2013; · 1.58 Impact Factor
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Eiichi Tanaka, Daisuke Hoshi,
Ataru Igarashi,
Eisuke Inoue,
Kumi Shidara,
Naoki Sugimoto,
Eri Sato,
Yohei Seto,
Ayako Nakajima,
Shigeki Momohara,
Atsuo Taniguchi,
Kiichiro Tsutani,
Hisashi Yamanaka
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ABSTRACT: OBJECTIVES: Our goal was to determine the annual direct medical and nonmedical costs for the care of patients with rheumatoid arthritis (RA) using data from a large cohort database in Japan. METHODS: Direct medical costs [out of pocket to hospitals and pharmacies and for complementary and alternative medicine (CAM)] and nonmedical costs (caregiving, transportation, self-help devices, house modifications) were determined for RA patients who were participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) studies conducted in October 2007 and April 2008. Correlations between these costs and RA disease activity, disability level, and quality of life (QOL) were assessed. RESULTS: Data were analyzed from 5,204 and 5,265 RA patients in October 2007 and April 2008, respectively. The annual direct medical costs were JPY132,000 [out of pocket to hospital (US$1 = JPY90 in 2007)], JPY84,000 (out of pocket to pharmacy), and JPY146,000 (CAM). Annual direct nonmedical costs were JPY105,000 (caregiving), JPY22,000 (transportation), JPY30,000 (self-help devices), and JPY188,000 (house modifications). Based on the utilization rate for each cost component, the annual medical and nonmedical costs for each RA patient were JPY262,136 and JPY61,441, respectively. Costs increased with increasing RA disease activity and disability level or worsening quality of life (QOL). CONCLUSIONS: Based on the IORRA database, patients with RA bear heavy economic burdens that increase as the disease is exacerbated. The results also suggest that the increase in medical and nonmedical costs may be ameliorated by the proactive control of disease activity.
Modern Rheumatology 08/2012; · 1.58 Impact Factor
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ABSTRACT: To clarify the influence of individual joint impairment on functional capacity through a retrospective study with a 3-year interval, using a large cohort of Japanese patients with rheumatoid arthritis (RA).
Subjects included 3457 patients with RA who participated in a large observational cohort study in both April 2004 and April 2007; 43 joints were assessed and classified into 10 joint areas. Impairment of each joint area was scored based on the presence of swelling or tenderness: score 0 (no swelling or tenderness in either joint), score 1 (swelling or tenderness in a unilateral joint), and score 2 (swelling or tenderness in bilateral joints). Score change was defined as the difference between scores from 2004 and 2007. The Japanese validated version of the Health Assessment Questionnaire is the J-HAQ; ΔJ-HAQ score was determined by subtracting J-HAQ score in 2007 from that in 2004. The relationship between score change and ΔJ-HAQ score, and the effect of joint impairment on ΔJ-HAQ score were assessed.
Major joint areas that contributed to ΔJ-HAQ score included the wrist (31%), shoulder (21%), knee (13%), and ankle (10%). The shoulder, wrist, knee, and ankle in the worsening group were associated with a J-HAQ score increase of 0.13 to 0.18 compared to the improvement group.
Our study demonstrated that impairment of the shoulder, wrist, knee, and ankle significantly affects functional capacity in patients with RA. Care of these joints is suggested to be especially important for better functional outcomes.
The Journal of Rheumatology 03/2012; 39(3):476-80. · 3.69 Impact Factor
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Tsutomu Takeuchi,
Yoshiya Tanaka,
Koichi Amano, Daisuke Hoshi,
Masao Nawata,
Hayato Nagasawa,
Eri Sato,
Kazuyoshi Saito,
Yuko Kaneko,
Shunsuke Fukuyo,
Takahiko Kurasawa,
Kentaro Hanami,
Hideto Kameda,
Hisashi Yamanaka
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ABSTRACT: To evaluate the effectiveness and safety of tocilizumab in RA patients in clinical practice.
We observed 232 consecutive RA patients who began tocilizumab in three rheumatology centres in Japan for 52 weeks. Clinical, radiographic and functional status and safety were evaluated.
Mean age of the 232 patients was 59.1 years, mean duration of disease was 12.4 years and average DAS using the 28-joint count (DAS-28) was 5.6. Although 62.8% of the patients had been treated previously with anti-TNF biologics, clinical remission at Week 52 was achieved in 43.7%, radiographic non-progression in 62.8% and functional remission in 26.4%. Retention rate at Week 52 was 71.1%, and the same for those with or without previous anti-TNF treatment. Adverse drug reactions leading to tocilizumab discontinuation were observed in 15.5% of patients, the most frequent adverse drug reaction being pneumonia in eight cases. On multivariate logistic regression analysis, DAS-28, HAQ-disability index (HAQ-DI), concomitant MTX and concomitant glucocorticoids (GCs) were predictive variables for clinical remission at Week 52 of tocilizumab treatment. In particular, HAQ-DI was found to be a predictive variable for remission of all three types-clinical, radiographic and functional-at Week 52 of tocilizumab treatment.
In daily clinical practice, tocilizumab exhibited excellent effectiveness in established RA patients, some of whom had failed to respond to previous anti-TNF treatment. Although further detailed safety findings are required, this study provides valuable real-world findings on the management of RA with tocilizumab.
Rheumatology (Oxford, England) 07/2011; 50(10):1908-15. · 4.24 Impact Factor
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Daisuke Hoshi,
Ayako Nakajima,
Eisuke Inoue,
Kumi Shidara,
Eri Sato,
Mariko Kitahama,
Yohei Seto,
Eiichi Tanaka,
Wako Urano,
Naomi Ichikawa,
Yumi Koseki,
Shigeki Momohara,
Astuo Taniguchi,
Norihiro Nishimoto,
Hisashi Yamanaka
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ABSTRACT: We aimed to demonstrate the incidence of serious respiratory infections in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) monotherapy. We analyzed the incidence of serious respiratory infections in 601 RA patients enrolled in TCZ clinical trials and their extension studies (TCZ cohort) and in 601 age- and sex-standardized RA patients treated in daily clinical practice at Tokyo Women's Medical University (IORRA subsample cohort). The rates of serious respiratory infections were 1.77 per 100 patient-years from 1999 to 2008 in the TCZ cohort and 0.53 per 100 patient-years from 2000 to 2009 in the IORRA subsample cohort. With the IORRA subsample cohort regarded as a standard population, the standardized incidence ratio (SIR) of serious respiratory infection in the TCZ cohort was 3.64 [95% confidence interval (CI) 2.56-5.01], standardized for age and sex; 2.35 (95% CI 1.66-3.24), standardized for age sex, and corticosteroid use; 1.85 (95% CI 1.30-2.55), standardized for age sex, and pre-existing pulmonary involvement; and 2.41 (95% CI 1.68-3.34) standardized for age sex, and disease activity. The risk of serious respiratory infection in the TCZ cohort was approximately double that in the IORRA subsample cohort after standardizing for corticosteroid use, pre-existing pulmonary involvement, or disease activity. This is comparable to the risk reported when tumor necrosis factor (TNF) inhibitors are used.
Modern Rheumatology 07/2011; 22(1):122-7. · 1.58 Impact Factor
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ABSTRACT: The anti-cyclic citrullinated peptide (CCP) antibody has become increasingly important in the diagnosis of rheumatoid arthritis (RA), especially for early diagnosis. The purpose of this study is to compare the diagnostic usefulness of the second and third generation anti-CCP antibody kits among Japanese patients with RA. Anti-CCP antibody titers were measured with the second generation (MESACUP CCP test, Medical and biological laboratories) and third generation (QUANTA Lite CCP3 IgG ELISA, Inova Diagnostics) kits using serum samples from 106 rheumatoid arthritis (RA) patients and 57 non-RA patients. Sensitivities and specificities were compared. The sensitivity and specificity of the second generation anti-CCP (anti-CCP2) kit were 88.7 and 89.5%, and those of the third generation anti-CCP (anti-CCP3) kit were 91.5 and 87.7%. Area under the receiver operating curve showed that anti-CCP2 and anti-CCP3 had similar diagnostic performances. Diagnostic performance of the anti-CCP3 assay was comparable with the anti-CCP2 assay in Japanese patients with RA.
Rheumatology International 05/2011; 31(5):617-22. · 1.88 Impact Factor
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ABSTRACT: We aimed to clarify the degree of improvement in disease control following early treatment of rheumatoid arthritis (RA) in daily clinical practice in 2006 compared to that in 2001. Using a large observational Japanese RA cohort (IORRA), we analyzed changes in clinical parameters, including disease activity assessed by the disease activity score 28 (DAS28) and physical disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), which occurred within 2 years of cohort inception. All patients had enrolled in the IORRA cohort within 1 year of RA onset, in either 2001 (2001-cohort) or 2006 (2006-cohort). For both cohorts, changes in clinical features over 2 years were compared by Fisher's exact test or the Wilcoxon test. The 2001-cohort included 71 patients and the 2006-cohort included 56 patients. Over the 2-year period for each cohort, DAS28 significantly decreased from 3.9 to 3.5 in the 2001-cohort (p < 0.001) and from 4.1 to 3.1 in the 2006-cohort (p < 0.0001), and J-HAQ significantly decreased from 0.62 to 0.49 (p < 0.02) in the 2001-cohort and from 0.71 to 0.41 (p < 0.001) in the 2006-cohort. Greater improvement in disease activity over 2 years occurred in the 2006-cohort than in the 2001-cohort (p < 0.05). Better disease control was obtained following changes in RA treatment strategy that occurred in Japan between 2001 and 2006.
Modern Rheumatology 04/2011; 21(6):594-7. · 1.58 Impact Factor
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ABSTRACT: To clarify the clinical significance of anti-cyclic citrullinated peptide antibody (anti-CCP) in the long-term outcome of RA, we established a large observational cohort of RA patients (IORRA) in our institute beginning in 2000. Essentially all RA patients who consulted our institute were registered, and clinical parameters, including disease activity and drug use, were assessed biannually based on patient reports, physician examinations, and laboratory data. In the third phase (October 2001) of the IORRA survey, anti-CCP levels were measured in 1,226 RA patients. In a cross-sectional analysis, clinical variables were compared in anti-CCP-positive versus -negative patients and in RF-positive versus -negative patients. In a longitudinal analysis, subsequent progression of disability was analyzed in anti-CCP-positive versus -negative and in RF-positive versus -negative patients. A verified Japanese version of the Health Assessment Questionnaire (J-HAQ) was used to measure functional disability. In the cross-sectional analysis, anti-CCP-positive patients (84.2%) had a significantly longer disease duration and higher disease activity score and more frequently used corticosteroids and methotrexate compared to anti-CCP-negative patients statistically. Similar phenomena were noted between RF-positive and -negative patients. In contrast, the longitudinal analysis revealed that J-HAQ slopes-a measure of progression of functional disability-were strongly associated with anti-CCP positivity but not with RF positivity. In a linear regression model, J-HAQ scores significantly worsened in anti-CCP-positive patients compared to anti-CCP-negative patients at the third year (annual progression 0.0317, P = 0.001) and the fifth year (annual progression 0.0199, P = 0.0012); however, J-HAQ progression was not influenced by RF status. Anti-CCP is a better predictive and discriminative marker for progression of disability in the long-term outcome of RA patients compared to RF.
Rheumatology International 11/2010; 32(2):361-6. · 1.88 Impact Factor
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Hisashi Yamanaka,
Yoshiya Tanaka,
Eisuke Inoue, Daisuke Hoshi,
Shigeki Momohara,
Kentaro Hanami,
Naoki Yunoue,
Kazuyoshi Saito,
Kouichi Amano,
Hideto Kameda,
Tsutomu Takeuchi
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ABSTRACT: Tocilizumab, a humanized monoclonal antibody to the interleukin 6 (IL-6) receptor, was approved for use as rheumatoid arthritis (RA) therapy in Japan in 2008, but its efficacy and tolerability in daily practice has not yet been reported. We report the results of a multicenter retrospective study on the efficacy and safety of tocilizumab involving all patients (n = 229) who were started on tocilizumab therapy at three rheumatology institutes in Japan from April 2008 through to March 2009. Tocilizumab was infused every 4 weeks at a dose of 8 mg/kg according to the drug labeling. Among the 229 patients, 55% concomitantly received methotrexate (MTX) and 63% had previously received anti-tumor necrosis factor (TNF) therapy. Average disease activity score (DAS) 28 of all 229 patients significantly decreased from 5.70 to 3.25 after 24 weeks of therapy. A European League Against Rheumatism (EULAR) good response and DAS28 remission was achieved in 57.4 and 40.7% of the patients, respectively, at 24 weeks. White blood cell counts significantly decreased and liver enzymes and total cholesterol slightly but significantly increased; however, liver enzyme levels did not increase in patients without MTX. Tocilizumab was discontinued in 47 cases (20.5%) due to lack of efficacy (5.2%), adverse events (11.4%), and other reasons (3.9%). The overall retention rate at 24 weeks was 79.5%. Based on these results, we conclude that tocilizumab therapy in daily rheumatology practice appears to be highly efficacious and well tolerated among active RA patients, including the anti-TNF therapy-refractory population. Tocilizumab infusion is therefore applicable not only as an alternative approach for anti-TNF therapy-resistant patients, but also as primary biologic therapy for active RA patients.
Modern Rheumatology 10/2010; 21(2):122-33. · 1.58 Impact Factor
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ABSTRACT: Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case-control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.
Modern Rheumatology 03/2010; 20(3):280-6. · 1.58 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is a multifactorial disease characterized by chronic inflammation of the joints. Both genetic and environmental factors are involved in the pathogenesis of joint destruction and disability. In the inflamed RA joint, the synovium is highly infiltrated by CD4+ T cells, B cells, and macrophages. Furthermore, the intimal lining becomes hyperplastic due to the increased numbers of macrophage-like and fibroblast-like synoviocytes. This hyperplastic intimal synovial lining forms an aggressive front, called pannus, which invades cartilage and bone structures, leading to compromised function and/or destruction of affected joints. RA pathology is mediated by a number of cytokines (TNF-alpha, IL-1, IL-6, IL-17, IFN gamma, etc.), chemokines (MCP-1, MCP-4, CCL18, etc.), cell adhesion molecules (ICAM-1, VCAM-1, etc.) and matrix metalloproteinases. Currently, treatment strategies targeted against TNF-alpha, IL-1 and IL-6 are available. In this review, we will summarize the use of biologics, the pros and cons of the use of biologics, and discuss on the potential molecular targets of RA.
Inflammation & Allergy - Drug Targets (Formerly ?Current Drug Targets - Inflammation & Allergy) 04/2008; 7(1):53-66.
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ABSTRACT: Vitamin K(2) (menaquinone-4, MK-4) has been reported to induce apoptosis in hepatocellular carcinoma, leukemia and myelodysplastic syndrome cell lines. The effects of MK-4 on the development of arthritis have never been addressed thus far. In the present study, we investigated the effect of MK-4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen-induced arthritis. We analyzed the effect of MK-4 on the proliferation of fibroblast-like synoviocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The pro-apoptotic effect of MK-4 upon fibroblast-like synoviocytes was investigated with annexin V staining and DNA fragmentation and caspase 3/7 assays. Moreover, we analyzed the effect of MK-4 on the development of collagen-induced arthritis in female dark agouti rats. Our results indicated that MK-4 inhibited the proliferation of fibroblast-like synoviocytes and the development of collagen-induced arthritis in a dose-dependent manner. We conclude that MK-4 may represent a new agent for the treatment of rheumatoid arthritis in the setting of combination therapy with other disease-modifying antirheumatic drugs.
FEBS Journal 10/2007; 274(17):4588-94. · 3.79 Impact Factor
