Influence of doctor-patient relationships and health-related factors on the medical satisfaction of patients with Sjögren's disease.

OBJECTIVES: Patients with chronic, incurable conditions rely on their providers to help relieve their symptoms. Dissatisfaction with their care can erode the doctor-patient relationship and reduce the effectiveness of treatment. We investigated the relationships between satisfaction and symptoms, the doctor-patient relationship, and health-related factors in patients with Sjögren's disease (SjD) in Japan. METHODS: Using a questionnaire survey, we evaluated via multinomial logistic regression associations between satisfaction [satisfied, neither (neither satisfied nor dissatisfied), dissatisfied] and symptoms, prescribed medications, anxiety, distress, expectations from treatments, and doctor-patient relationships. RESULTS: Of 259 patients, 101 (39%) were satisfied, 111 (42.9%) were neither, and 47 (18.2%) were dissatisfied. Patients who were neither or dissatisfied with their current treatment wanted their systemic pain to disappear (adjusted relative risk ratio [aRRR] 3.38, 95% CI 1.66-6.91; aRRR 3.04, 95% CI 1.30-7.15, respectively). Patients who used artificial saliva only were significantly more dissatisfied (aRRR 3.52, 95% CI 1.03-2.04). Both the neither and dissatisfied patients dissatisfied with their doctor's limited understanding of SiD (aRRR 12.69, 95% CI 4.21-38.24; aRRR 32.76, 95% CI 10.09-106.34, respectively) and with the limited opportunities to ask their doctor about their disease (aRRR 0.19, 95% CI 0.06-0.59; aRRR 0.08, 95% CI 0.02-0.24, respectively). CONCLUSIONS: Pain and the use of artificial saliva alone markedly affected medical satisfaction and we expected the future advance in these two areas, pain and dryness, will improve satisfaction. It is most important for doctors to better understand SjD.

Questionnaire survey on the prevention and development of cervical cancer in patients with systemic lupus erythematosus in Japan.

OBJECTIVES: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey. METHODS: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed. RESULTS: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant. CONCLUSIONS: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients.

The long-term safety and tolerability of anifrolumab for patients with systemic lupus erythematosus in Japan: TULIP-LTE subgroup analysis.

OBJECTIVES: Evaluate the long-term safety and tolerability of anifrolumab 300 mg, alongside standard therapy, in patients from Japan with systemic lupus erythematosus (SLE) in the TULIP-LTE trial (NCT02794285). METHODS: TULIP-LTE was a 3-year, randomized, double-blind, placebo-controlled long-term extension (LTE) of the TULIP trials. The primary safety outcome included serious adverse events (SAEs) and AEs of special interest (AESIs) during the LTE period. Exploratory efficacy outcomes included SLE Disease Activity Index 2000 (SLEDAI-2K) scores and glucocorticoid use. We performed a post hoc subgroup analysis of patients who enrolled in Japan. RESULTS: Exposure-adjusted incidence rates of SAEs during the LTE and follow-up for patients receiving anifrolumab 300 mg (n=21) were 8.7 per 100 patient-years; AESIs included influenza (6.9) and herpes zoster (3.5). One of three patients receiving placebo had an SAE (13.9). One patient per group discontinued due to an AE. There were no deaths. During the TULIP+LTE period, patients receiving anifrolumab 300 mg (n=24) had sustained reduction from baseline in mean SLEDAI-2K scores and cumulative glucocorticoid dosage. CONCLUSIONS: Anifrolumab 300 mg showed a favourable benefit-risk profile for the long-term treatment of adult patients with moderate to severe SLE from Japan, with safety, tolerability, and efficacy profiles consistent with the overall population.

The efficacy and safety of anifrolumab in Japanese patients with systemic lupus erythematosus: TULIP-2 subanalysis.

OBJECTIVES: Evaluate the efficacy and safety of anifrolumab in the subpopulation of Japanese patients with systemic lupus erythematosus (SLE) in phase 3 TULIP-2 trial. METHODS: TULIP-2 was a 52-week randomized placebo-controlled trial (N = 362) that evaluated efficacy and safety of anifrolumab 300 mg IV every 4 weeks vs. placebo in patients with moderate to severe SLE who were receiving standard therapy. We performed a post hoc analysis of the primary and key secondary endpoints, and safety, of TULIP-2 in the Japanese subpopulation. RESULTS: In the Japanese subpopulation (anifrolumab, n = 24; placebo, n = 19), the proportion of patients who achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment response at Week 52 (primary endpoint) was greater in the anifrolumab group vs. placebo [50.0% (12/24) vs. 15.8% (3/19); treatment difference: 34.2%, 95% confidence interval 6.9, 61.5; nominal p = .014]. Improvement in skin activity and flare rates (key secondary endpoints) were favourable for anifrolumab vs. placebo. Consistent with the overall population, anifrolumab had an acceptable safety and tolerability profile. CONCLUSIONS: The efficacy and safety of anifrolumab 300 mg in Japanese patients with SLE was consistent with the demonstrated clinical profile of anifrolumab for the overall TULIP-2 population.

Abatacept ameliorates both glandular and extraglandular involvements in patients with Sjögren's syndrome associated with rheumatoid arthritis: Findings from an open-label, multicentre, 1-year, prospective study: The ROSE (Rheumatoid Arthritis with Orencia Trial Toward Sjögren's Syndrome Endocrinopathy) and ROSE II trials.

OBJECTIVE: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). MATERIALS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.

Social independence evaluation index for Japanese patients with childhood-onset chronic diseases.

Introduction: This study established an independent evaluation index for patients with childhood-onset chronic diseases in Japan. Methods: From November to December 2020, three Delphi rounds were conducted. Thirty-nine participants completed at least one survey. We asked them about targets of social independence for 10 types of activities (education/labor/finance/acquisition of necessities/housing/transportation/leisure/social relationship/intimate relationships/sexuality). The Delphi technique was to be repeated until a consensus of over 80% of participants was reached. Results: The targets chosen for measuring independence in patients with childhood-onset chronic diseases were as follows: "Graduation from high school," "Labor for livelihood (including temporary turnover)," "Financially independent (including temporary turnover, excluding students)," "Buy or rent a house and buy the daily necessities and get the public services you need to live," "Do housework alone," "Plan alone and use transportation to get around," "Participate in play/recreation/leisure activities on own initiative," "Engage in relationships with other people outside of a limited environment (home, school, office, hospital, etc.)," "Create and maintain intimate or romantic relationships between individuals (couples, lovers, sexual partners)," and "Use or know how to use contraceptives and how to prevent sexually transmitted diseases." Conclusions: We established an independent evaluation index for patients with childhood-onset chronic diseases in Japan through a three-round Delphi process. The assessment of social independence using our independent evaluation index may help plan for and provide appropriate support and assistance to these patients.

Clinical variables, including novel joint index, associated with future patient-physician discordance in global assessment of rheumatoid arthritis (RA) disease activity based on a large RA database in Japan.

BACKGROUND: Discordance between patient global assessment (PGA) and physician global assessment (PhGA) of rheumatoid arthritis (RA) disease activity is mainly determined by pain and functional disabilities. This study aimed to investigate the shift in PGA-PhGA discordance and the variables associated with future positive discordance (PGA > PhGA) based on the NinJa database in Japan. METHODS: We examined 7557 adults with RA registered in both NinJa 2014 and 2018, with a discordance cutoff of 3 on a 10-cm scale. The affected joint distribution was investigated using the joint indices x, y, and z, which were calculated as indices for the upper joint, lower joint, and large joint involvement, respectively. The variables in NinJa 2014 that were associated with positive discordance in NinJa 2018 were examined using binary stepwise logistic regression analysis. RESULTS: Due to the small number of patients with RA categorized as having negative discordance (PGA < PhGA), we focused on patients with RA categorized as having either concordance or positive discordance. Logistic regression analysis revealed that positive discordance in NinJa 2018 was associated with age, pain, modified Health Assessment Questionnaire (mHAQ) score, corticosteroid use, and existent positive discordance and was inversely associated with C-reactive protein (CRP) and x at baseline (NinJa 2014). The same findings were observed when patients with RA were divided based on the discordance status at baseline. Persistence (positive discordance to positive discordance) was associated with pain and mHAQ scores but inversely associated with CRP. CONCLUSIONS: Positive discordance may persist. Circumventing this requires adequate management of pain and functional impairment.

Distal Interphalangeal Joint Involvement May Be Associated with Disease Activity and Affected Joint Distribution in Rheumatoid Arthritis.

We investigated the relationship between distal interphalangeal (DIP) joint involvement and disease activity in 10,038 patients with adult-onset rheumatoid arthritis (RA). The affected joint distribution was investigated using the joint indices (JI) x, y, and z, corresponding to the upper and lower joints, and the predominance of large-joint involvement, respectively. DIP joint involvement (defined by the presence of tenderness and/or swelling in DIP joints) was present in 206 (2.1%) of 10,038 patients with RA. Patients with RA exhibiting DIP joint involvement were significantly younger, and more frequently women. DIP joint involvement was positively associated with Disease Activity Score-28 using C-reactive protein, and clinical variables related to high RA disease activity, including JIs x and y, and was negatively associated with JI z. JI x was significantly higher than JI y in RA patients with DIP joint involvement. An odds ratio analysis revealed that small-to-medium sized and upper-extremity joints ranked first, second, and fourth among the eight variables significantly associated with DIP joint involvement. The correlation coefficients revealed that small-sized and upper-extremity joints ranked first and second among the five significant variables. DIP joint involvement, albeit rare, is significantly associated with high RA disease activity with predominance of small-sized and upper-extremity joints.

Transitioning from paediatric to adult rheumatological healthcare: English summary of the Japanese Transition Support Guide.

Issues related to transitioning from paediatric to adult healthcare are currently receiving international attention. In Japan, 1000 patients with childhood-onset chronic rheumatological diseases reach adulthood every year and require transition from care by paediatric to care by adult rheumatologists. Here, we propose a guide for the latter, wherein the adult caregiver poses the clinical questions about transitional support that they need to have answered, and the paediatric caregiver mainly compiles the plans for the transition. To formulate the guide, we sought comments from both the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan and obtained their approval. Here, we present the outcome of this consultation in the form of a Guide for Supporting Transitional Care, aiming to provide essential knowledge to physicians in the fields of adult internal medicine and orthopaedics who may be involved in treating patients with rheumatic disease during the transition from paediatric to adult care. The features of transitional support that are common for patients with various different rheumatic diseases are presented in this guide, with the aim of informing policy and strategies to deliver optimal outcomes in transitional care by non-paediatric rheumatologists.

Factors associated with delayed diagnosis of Sjögren's syndrome among members of the Japanese Sjögren's Association for Patients.

OBJECTIVES: The heterogeneous nature of the signs and symptoms of Sjögren's syndrome (SS) often causes delays in diagnosis. The reasons for these delays have not been investigated in Japan and need to be determined. METHODS: We conducted a questionnaire survey of members of the Japanese Sjögren's Association for Patients (JSAP). Questionnaire items were demographic (sex, age at diagnosis and current age) and factors associated with delayed diagnosis (age at first visit to hospital or clinic, medical department first attended, and initial symptoms). Patients were classified into those diagnosed in <1 year and those diagnosed in ≥1 year. RESULTS: Of the 510 patients questioned, 276 returned the questionnaire, and 255 questionnaires were assessed. The average time to diagnosis was 3.47 years. After adjustment, risk factors for delayed diagnosis were initial visit to an internal medicine department [adjusted odds ratio (aOR) 3.13, 95% confidence interval (CI) 1.42-6.92] or ophthalmology department (aOR, 2.63, 95% CI 1.07-6.50), younger age at initial visit to hospital or clinic (aOR, 0.96, 95% CI 0.94-0.99), and having symptoms of only dry eye (aOR, 2.69, 95% CI 1.09-6.64). Diagnosis was faster when patients had a dry mouth (aOR, 0.55, 95% CI 0.30-1.00) or cutaneous symptoms (aOR, 0.29, 95% CI 0.11-0.82). CONCLUSIONS: Risk factors for delayed SS diagnosis were younger age, initial visit to internal medicine or ophthalmology department, and having only dry eye. We need to raise awareness of SS among doctors and the general public to improve early diagnosis and therapeutic potential.

The impact of shrunken pore syndrome in patient with rheumatic diseases on bone mineral metabolism.

The study aimed to investigate the influence of shrunken pore syndrome (SPS), defined as a cystatin C (CysC)-based estimated glomerular filtration rate (eGFRCysC) <60% of the creatinine (Cr)-based eGFR (eGFRCr), on bone mineral density (BMD) in patients with rheumatic diseases. A total of 831 patients with rheumatic diseases were enrolled in the study. Patients were classified into the SPS group (G-SPS) and non-SPS group (G-nSPS). The correlation between the presence of SPS and BMD of the lumbar spine (BMD_LS), BMD of the femoral neck (BMD_FN), serum parathyroid hormone (PTH) level, chronic kidney dysfunction (CKD), and parameters were evaluated statistically. The prevalence of SPS was 4.0%. Serum PTH level, tartrate-resistant acid phosphatase-5b (TRACP-5b), and eGFRCr in the G-SPS were significantly higher than in the G-nSPS, whereas BMD_LS and BMD_FN in the G-SPS were significantly lower than in the G-nSPS. Serum PTH level was significantly correlated with CysC. BMD_LS had no significant correlation with BMD_FN. The presence of SPS was the only factor that demonstrated significant negative correlation with both BMD_LS and BMD_FN. Relationship between BMD_LS and the presence of SPS was present regardless of CKD stage; however, the negative relationship between BMD_LS and serum PTH was observed only in CKD stage 1 and 2 patients. BMD_FN demonstrated significant negative correlation with serum PTH in the group with progression of CKD. These results suggest that there is a serious potential risk of osteoporosis in patients with SPS and increased PTH, and BMD_LS poses a higher risk in CKD stage 1 and 2.

Influence of seasonal changes on disease activity and distribution of affected joints in rheumatoid arthritis.

BACKGROUND: Previous studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan. METHODS: We investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance. RESULTS: Mean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index. CONCLUSIONS: RA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.

Influence of large joint involvement on patient-physician discordance in global assessment of rheumatoid arthritis disease activity analyzed by a novel joint index.

OBJECTIVES: The discordance between patient global assessment (PGA) and physician global assessment (PhGA) of rheumatoid arthritis (RA) disease activity may be problematic in clinical practice. The aim of this study was to identify determinants of this discordance using a nationwide RA database in Japan (NinJa) with special attention to large joint involvement. METHODS: We investigated 12 043 adults with RA and used a discordance cutoff of 3 cm. Large joint involvement was investigated using novel joint indices (x, y, z), where x and y were the indices for upper and lower joints, respectively, and z was for large joint predominance. Predictors of PGA-PhGA discordance and determinants of PGA and PhGA were analyzed by multivariate logistic and linear regression models, respectively. RESULTS: Multivariate logistic regression identified age, pain and high modified Health Assessment Questionnaire score as predictors of positive discordance (PGA ≥ PhGA), whereas parameters of disease activity in RA (C-reactive protein, x and y), class 3-4 functional status, and z were found to predict against positive discordance. Linear regression analysis revealed that PGA was mainly determined by pain, whereas PhGA was determined by various other factors. CONCLUSIONS: RA care providers should focus on pain and functional disability to decrease PGA-PhGA discordance. High disease activity and large joint involvement decreased PGA-PhGA discordance, indicating that the number and distribution of affected joints influenced the perception of disease activity by patients with RA and their physicians.

Clinical practice guideline for Sjögren's syndrome 2017.

OBJECTIVES: The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences. METHODS: The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS. RESULTS: The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG. CONCLUSION: The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.

Anticentromere antibody-positive primary Sjögren's syndrome: Epitope analysis of a subset of anticentromere antibody-positive patients.

OBJECTIVES: Anticentromere antibody (ACA) is generally considered to be a serological marker for systemic sclerosis (SSc). ACA-positive patients with primary Sjögren's syndrome (pSS) have also been reported. ACA often recognizes centromere proteins (CENPs): CENP-A, CENP-B, and CENP-C, and sometimes reacts to heterochromatin protein 1 (HP1)α. We compared the reactivity against six different epitopes for three ACA-positive clinical subgroups: 29 patients with pSS, 36 SSc patients with sicca symptoms, and 28 SSc patients without sicca symptoms. METHODS: We utilized enzyme-linked immunosorbent assays (ELISAs) with recombinant proteins covering six different epitope regions of ACA (the amino terminus (Nt) of CENP-A, CENP-B, and CENP-C, the carboxyl terminus (Ct) of CENP-B and CENP-C, and HP1α). RESULTS: The patients with pSS were found to have IgG-class autoantibodies against CENP-C-Nt and HP1α, and IgA-class autoantibodies against CENP-C-Ct with significantly higher frequencies than the SSc patients with or without sicca symptoms. The positive predictive value and the negative predictive value of the combination of these three autoantibodies for pSS were 73% and 82%, respectively, for pSS. CONCLUSIONS: Based on the result that reactivities against CENP-C and HP1α in patients with pSS differ from those in patients with SSc, we propose ACA-positive pSS as a clinical subset of SS that is independent of SSc.

Validation of EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI).

OBJECTIVES: To validate the two recently developed disease activity indexes for assessment of primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). METHODS: A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjögren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores. RESULTS: Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r=0.59; ESSRPI with PGA: r=0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores. CONCLUSIONS: ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.

The effect of methotrexate on improving serological abnormalities of patients with systemic lupus erythematosus.

OBJECTIVE: This was an open-labeled, prospective, control study to determine the efficacy of methotrexate (MTX) for improving serological abnormalities in patients with systemic lupus erythematosus (SLE). METHODS: Thirty patients with a low serum complement and/or high anti-double-stranded DNA (dsDNA) antibody levels during a prednisolone taper received MTX orally at a dose of 7.5 mg/week over 12-18 months (MTX group). Eighteen SLE patients were selected as controls (control group). At the time of entrance into the study, all patients were receiving <15 mg/day of prednisolone. The C3, C4, and immunoglobulin (Ig)G, IgA, and IgM levels were measured using a turbidimetric immunoassay. The anti-dsDNA antibody level was measured using the Farr assay. RESULTS: Significant increases in C3 and C4 levels and significant decreases in anti-dsDNA antibody, IgG, IgA, and IgM levels from baseline were observed for 3-18 months after the trial in the MTX group but not in the control group. At the end of the study, C3 and/or C4 levels in 96.7% of the MTX patients and 33.3% of the control patients were normalized or elevated (p = 0.0001), and anti-dsDNA antibody levels were normalized or lowered in 24 of the 26 MTX patients (92.3%) and in 50.0% of the control patients (p = 0.0022). In addition, a significant reduction in SLE Disease Activity Index (SLEDAI) score and a prednisolone-sparing effect were observed for the MTX group but not the control group. A significant increase in mean corpuscular volume of red blood cells, which is indicative of an anti-folic-acid metabolic disorder induced by MTX, was observed only for patients in the MTX group. Five patients (16.7%) discontinued MTX treatment because of disease flare, and another three (10.0%) discontinued due to treatment side effects. CONCLUSION: MTX appears to be effective for improving serological abnormalities frequently observed before disease flares in SLE patients on a prednisolone taper.

Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease.

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135 mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed.

Proposing a method of regional assessment and a novel outcome measure in rheumatoid arthritis.

We proposed a method of regional assessment in patients with rheumatoid arthritis. The utility of this method was demonstrated by assessing drug efficacy in patients who received infliximab (n = 31) or tocilizumab (n = 6). Joints were divided into four regions: upper/large, upper/small, lower/large, and lower/small. The total joint index was calculated as follows: the sum of tender and swollen joint counts divided by the number of evaluable joints in each region. At the baseline, the total joint index of the upper/small region was the lowest and that of the lower/large region was the highest compared with other regions. The change in the total joint index from the baseline to the 30-week point (Δ) did not differ among the four regions. There were significant close relations of Δ between the upper/small and the upper/large region and between the lower/small and the lower/large region. This method allows us to focus on a specific region and to compare and contrast among them.

Efficacy and safety of rebamipide for the treatment of dry mouth symptoms in patients with Sjögren's syndrome: a double-blind placebo-controlled multicenter trial.

The effects of rebamipide on dry mouth and salivary secretion in Sjögren's syndrome patients were investigated in a double-blind placebo-controlled study. Rebamipide (100 mg TID) or placebo was administered for eight weeks and patient-assessed improvement of dry mouth and increase in salivary secretion measured by the Saxon test were evaluated. At two, four, and eight weeks, dry mouth improvement rates were, respectively, 26.0, 44.0, and 46.9% for rebamipide and 20.0, 27.1, and 39.1% for placebo, and mean increases in salivary secretion were, respectively, 0.14, 0.24, and 0.35 g for rebamipide and 0.03, 0.09, and 0.17 g for placebo, indicating higher values in the rebamipide group for both parameters at all timepoints but no significant differences between the two groups. Analysis by baseline characteristics suggested a statistically significant salivary secretion increasing effect of rebamipide in cases of primary Sjögren's syndrome. No difference in the incidence of adverse events was seen between the two groups, confirming the safety of rebamipide. As a salivary secretion increasing effect was strongly suggested in cases of primary Sjögren's syndrome, further study on the administration of rebamipide for the treatment of dry mouth in patients with Sjögren's syndrome is required.