Incidence of falls and fear of falling in Japanese patients with rheumatoid arthritis

The objective of this study is to determine the incidence of falls and fear of falling by gender and age in Japanese patients with rheumatoid arthritis (RA). Among the Japanese patients who participated in a single-institute-based prospective observational cohort study of patients with RA, namely the Institute of Rheumatology Rheumatoid Arthritis, 765 men (median age 63 years) and 4,231 women (median age 60 years) with RA responded to questions related to falls. Eight percent of men and 11% of women reported one or more falls during the previous 6 months. At least one fall and multiple falls were significantly more frequent in men (p < 0.05) and in women (p < 0.001) with RA over age 65 and age 75 years, respectively, although there was no significant linear increase in risk with age. Sixteen percent of men and 22% of women reported fear of falling. More men over age 65 tended to report fear of falling than those under age 65 (p < 0.001), although the incidence of women with fear of falling increased with advancing age. Japanese patients with RA over age 65 and age 75 appeared to have a high risk of at least one fall and multiple falls, respectively.     

Incidence of herpes zoster in Japanese patients with rheumatoid arthritis from 2005 to 2010

Abstract

Objective. To clarify the incidence and the risks of herpes zoster infection in Japanese patients with rheumatoid arthritis (RA).

Methods. By using a self-report of occurrence of herpes zoster in patients with RA in a large observational cohort study from 2005 to 2010, the standardized incidence rate was calculated. A Cox model was used to analyze risk factors for occurrence of herpes zoster.

Results. A total of 7,986 patients (female 83.1%) accumulated 30,140 patient-years of observation, and 366 events were confirmed. The standardized incidence rate per 1,000 patient-years was 9.1 (95% confidence interval (CI) 6.2–12.9) in total, 7.8 (3.6–14.8) in men, and 10.3 (6.8–15.0) in women. The risk factors for herpes zoster were age [/10 years: Hazard ratio (HR) 1.268, 95% CI 1.153–1.393, p < 0.0001), high disease activity compared with remission (HR 1.642, 95% CI 1.067–2.528, p < 0.05), prednisolone (< 5 mg/day compared with 0 mg/day: HR 1.531, 95% CI 1.211–1.936, p < 0.001; ≥ 5 mg/day compared with 0 mg/day: HR 1.471, 95% CI 1.034–2.093, p < 0.05), and methotrexate (HR 1.382, 95% CI 1.076–1.774, p < 0.05).

Conclusion. This study quantified the historical incidence and risk for herpes zoster in Japanese RA patients, and is a benchmark for future studies.     

Incidence of anti-human Ig with restricted specificity in Japanese, Kuwaiti, and Swedish patients with rheumatoid arthritis

Assuming that anti-allotypic anti-Ig in rheumatoid arthritis is stimulated by the individual's allotype, it would be reasonable to expect a higher incidence of anti-G1m(a) in individuals carrying G1m(a). There is marked divergence among various populations in allotype frequencies. G1m(a) allotype and the prevalence of anti-Ig reactive with G1m(a) Ig were determined in 18 Kuwaiti, 23 Japanese, and 41 Swedish rheumatoid arthritis patients. An inverse relationship was observed between the frequency distribution of allotype G1m(a) and anti-allotype; thus, the stimulus for the anti-allotype is not the patient's own allotype.     

Antibodies to rheumatoid arthritis nuclear antigen (RANA) in Japanese patients with rheumatoid arthritis

Summary We studied antibodies to rheumatoid arthritis nuclear antigen (RANA) by the Ouchterlony method in 0.5% agarose plates, using soluble antigen extracted with 0.25 M sucrose solution from cultured Raji cells. Anti-RANA antibody was found in sera from 24 to 40 (60%) patients with rheumatoid arthritis (RA), from 4 of 20 (20%) patients with systemic lupus erythematosus (SLE), and from 2 of 30 (7%) healthy controls. When sucrose extracts from BJAB, Ramos, and JM cells were used as the cellular antigens, no anti-RANA precipitin lines were detected. Indirect immunofluorescence study, using Raji cells or human B lymphocytes transformed by EB virus as substrate tissues, demonstrated anti-RANA antibody as fine speckled nuclear staining. Although RA patients with positive anti-RANA antibody usually had high titers of anti-Epstein-Barr nuclear antigen (EBNA) and anti-viral capsid antigen (VCA) IgG antibodies, the Wilcoxon ranks sum test showed no close statistical correlation between the presence of anti-RANA antibodies and the titers of anti-EBNA or anti-VCA (IgG) antibodies. These data showed that the incidence of positivity of anti-RANA antibodies in Japanese RA patients is almost the same as that in American and European RA patients.     

Glutathione S-transferase gene polymorphisms in Japanese patients with rheumatoid arthritis

OBJECTIVE: To investigate the role of polymorphisms of the glutathione S-transferase M1 (GSTM1), GSTT1, and GSTP1 genes in determining susceptibility to rheumatoid arthritis (RA) and association with the clinical features. METHODS: Polymorphisms of the GSTM1, GSTT1, and GSTP1 genes in 108 Japanese patients with RA and in 143 healthy controls were analyzed by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism. RESULTS: The frequency of the GSTM1 null genotype was significantly higher among RA patients than among control subjects (60.2% and 44.1%, respectively. P = 0.011). Moreover, the female patients with GSTM1 homozygous null genotype showed significantly higher serum MMP-3 level than the female patients with non-null genotype (P = 0.030). Frequencies of the GSTT1 and GSTP1 gene polymorphism were not different between RA patients and controls. CONCLUSION: The GSTM1 homozygous null genotype could be a genetic factor that determines susceptibility to RA and may have influence on the disease process.     

CTLA-4 gene polymorphism in Japanese patients with rheumatoid arthritis

OBJECTIVE: To examine whether CTLA-4 gene confers susceptibility to rheumatoid arthritis (RA) in Japanese. METHODS: We investigated the distribution of a CTLA-4 gene polymorphism in 85 Japanese patients with RA and 200 controls. An A/G transition at position 49 of exon 1 was analyzed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The patients were also analyzed with respect to HLA-DR status. HLA-DR typing was performed by PCR sequence-specific oligonucleotide typing. RESULTS: The distribution of genotype frequencies differed between RA and controls (chi-squared 8.63, 2 df, p = 0.013). The CTLA-4 AG genotype occurred more frequently in patients with RA (59 vs 44%), and the presence of at least one G allele (GG or AG) conferred an odds ratio of 2.53 (95% CI 1.74-3.32). When the patients were analyzed with respect to HLA-DR status, this association was restricted to patients carrying the susceptible HLA allele (HLA-DRB1*0405). CONCLUSION: The CTLA-4 gene is associated with Japanese patients with RA carrying the susceptible HLA allele.     

Incidence of serious respiratory infections in patients with rheumatoid arthritis treated with tocilizumab

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.     

Incidence of serious respiratory infections in patients with rheumatoid arthritis treated with tocilizumab

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.     

Preferences of Japanese rheumatoid arthritis patients in treatment decision-making

Objectives

We investigated the decision-making preferences of rheumatoid arthritis (RA) patients using two different scales: the Decision Making Preference Scale (DMPS) and the modified Control Preference Scale (CPS). In addition, we evaluated the factors associated with patients’ preferences for decision-making.

Methods

A cross-sectional study was performed using a self-administered anonymous questionnaire between October and December 2010 on 406 RA outpatients who consecutively visited 3 hospitals in Japan. The following variables were investigated: (1) DMPS, which is a subscale of the Autonomy Preference Index, composed of six items; patients responded on a 5-point Likert scale. (2) The modified CPS, in which patients were asked to choose one actual and one desired role in decision-making from among three options (passive role, collaborative role, and active role). (3) Sociodemographic data and RA-specific characteristics. Multivariate analyses were used to assess the relationship between patients’ preferences and selected variables.

Results

The response rate was 58.6 %. There were few patients who wished to make their own decisions when they were hospitalized or illness became worse. However, the majority of patients desired to collaborate with the doctor in making treatment decisions according to the results of modified CPS. The results of modified CPS were significantly associated with the total scores of DMPS. Multivariate analysis demonstrated they younger age and not-housewife were associated with high scores of DMPS.

Conclusions

Patient preferences in decision-making vary at RA outpatient clinic. Physicians need to assess decision-making preferences on an individual basis.     

Radiographic repair in three Japanese patients with rheumatoid arthritis treated with bucillamine

Abstract

Bucillamine (Bc) is a cysteine derivative with two SH groups, and a homolog of d-penicillamine, a disease-modifying antirheumatic drug (DMARD) widely used in Japan. However, it remains unclear whether Bc repairs bone erosion in patients with RA. Here, we treated three RA patients with Bc who subsequently showed radiographic repair of erosions and cysts.     

Clinical efficacy of abatacept in Japanese rheumatoid arthritis patients

Objectives

The purpose of this study was to examine the treatment retention and efficacy of abatacept, the first member of a new class of biologic agents, in Japanese rheumatoid arthritis (RA) patients during clinical practice.

Methods

A retrospective multicenter study was conducted with patients who underwent abatacept therapy for 24 weeks (n = 143).

Results

Patients at baseline had a mean age of 63.5 years, a mean disease duration of 11.3 years, and a mean disease activity score in 28 joints (DAS28) of 4.5. Overall retention of abatacept treatment was 83.2 % at 24 weeks, when 46.2 % of patients achieved DAS28-defined low disease activity (LDA; DAS28 <3.2) and 26.6 % achieved DAS28-defined remission (DAS28 <2.6). LDA was achieved in a significantly higher proportion of patients without prior biologics therapy compared to those with prior biologics (60.9 vs. 34.2 %, p = 0.001). There was no significant difference between patients with or without concomitant methotrexate (MTX) therapy (45.2 vs. 47.5 %).

Conclusions

Abatacept therapy appears to be highly effective and well tolerated during clinical treatment of RA. Abatacept was particularly effective in patients with no history of biologics use, and did not appear to be dependent on concomitant MTX therapy.     

Radiographic repair in three Japanese patients with rheumatoid arthritis treated with bucillamine

Bucillamine (Bc) is a cysteine derivative with two SH groups, and a homolog of d-penicillamine, a disease-modifying antirheumatic drug (DMARD) widely used in Japan. However, it remains unclear whether Bc repairs bone erosion in patients with RA. Here, we treated three RA patients with Bc who subsequently showed radiographic repair of erosions and cysts.     

Associations between rheumatoid arthritis and malignancy

There are many complex associations between rheumatoid arthritis(RA) and malignancy. Patients with rheumatic diseases on the whole appear to be at increased risk for the development of certain malignancies. The data from several studies are persuasive that the presence of RA conveys an increased risk for the development of lymphoproliferative disorders and may convey a decreased risk for the development of malignancies of the digestive tract. Understanding the complex interrelationships between RA and malignancy will lead to more accurate diagnosis of underlying pathology, more effective treatment of symptoms and underlying disease, and appropriate surveillance for the development of later complications.     

Incidence of clinically manifest ulcers and their complications in patients with rheumatoid arthritis

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed in patients with rheumatoid arthritis (RA). Because of its frequency and severity, NSAID gastropathy is the most important side effect. The clinical spectrum of NSAID gastropathy includes gastrointestinal complaints, ulcers and their complications. To reduce NSAID gastropathy, rheumatologists in greater Amsterdam decided in January 1997 that prophylactic agents should be prescribed for patients with RA at high risk for NSAID gastropathy, defined as age 60 or older or a history of gastrointestinal (GI) ulcers, or both. OBJECTIVE: To determine the incidence of clinically manifest ulcers and their complications in patients with RA at high risk for NSAID gastropathy during a period in which prophylaxis was recommended. Published reports show that the incidence of clinically manifest ulcers and their complications varies from 1.3% to 5%. PATIENTS AND METHODS: Within one year, three questionnaires were sent to all outpatients with RA of our clinic (n=2680). The patients were asked if they had had a gastroscopy and/or complication of an ulcer in the preceding months. When a GI event (ulcer or complication) had occurred an analysis was carried out to determine whether the event was possibly related to a compliance failure or a policy failure-for example, no prophylaxis prescribed when it was recommended. RESULTS: The response rate for the three questionnaires was 88%, 76%, and 77%, respectively. All three questionnaires were returned by 1856 patients; NSAIDs were used in 1246 (67%) of them. Of the NSAID users 731 (59%) were in the high risk group. Clinically manifest ulcers occurred in seven high risk NSAID users (four gastric ulcers, two duodenal ulcers, and in one patient both types of ulcer). Complications of ulcers were diagnosed in eight (other) patients: seven (upper) GI bleedings and one perforation. Thus the incidence during one year of clinically manifest ulcers in the high risk group was 1.0% and of complications of ulcers 1.1%, together 2.1%. In the group of 15 patients with GI events, only one patient had not taken the adequately prescribed gastroprotective drugs (compliance failure). Misguidedly, gastroprotective drugs were not prescribed in seven patients (policy failure), but in the remaining seven patients gastroprotective drugs were adequately prescribed and used. CONCLUSION: The incidence of clinically manifest ulcers and of complications of ulcers in patients with RA at high risk for NSAID gastropathy is relatively low, and might be related to our strategy to prescribe prophylactic agents in these patients.