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Rituximab (RTX) has been reported to effectively maintain remission in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). In this multicenter study involving 57 patients who achieved remission after 24 weeks, we evaluated the effectiveness of RTX in maintaining remission in patients with AAV. Patients were divided into three groups based on RTX administration: continuous, induction phase-only, and maintenance phase-only groups. The continuous group had a remission maintenance rate after 48 weeks of treatment compared with the induction phase-only group (100% vs. 88.2%, p  = 0.29). More patients in the continuous group received three or more RTX doses during the induction period (82.4% vs. 52.9%, p  = 0.06), and this group had a lower incidence of infection (5.9% vs. 29.4%, p  = 0.08). Compared with the maintenance-only group, the continuous group had a numerically higher proportion of patients in remission after 48 weeks of treatment (100% vs. 83.3%, p  = 0.26) and a lower incidence of infection (5.9% vs. 50%, p  = 0.04); however, the N in the maintenance phase was small and suspected to have low power. Regardless of the method of RTX administration (induction phase-only or continuous), administering RTX during the induction phase may be crucial for achieving remission.

Objectives: To clarify the differences in clinical phenotypes, therapeutic patterns, and outcomes of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) across geographic regions using a multinational cohort., Methods: Data were collected from patients with newly diagnosed or relapsing GPA or MPA in Europe, Japan, and the United States (US) from January to July 2020. The composite outcome of kidney failure and/or death within 52 weeks after treatment was evaluated, and the hazard ratios across the regions were estimated using the Cox proportional hazard model. Heterogeneities of the effects were investigated via thorough subgroup analyses., Results: Among the 254 eligible patients (Europe, 137; Japan, 73; the US, 44), those in Japan were older and had higher proportions of MPO-ANCA positivity and lung involvement compared with Europe and the US. The estimated glomerular filtration rate at diagnosis varied across regions, with the highest dialysis requirement in the US. Cyclophosphamide and rituximab use were 57% and 63% in Europe, 29% and 40% in Japan, and 34% and 86% in the US. Within 52 weeks, 8%, 10%, and 18% developed kidney failure, while 9%, 7%, and 7% died in Europe, Japan, and the US, respectively; and the composite outcome occurred in 15%, 14%, and 23% of patients. The hazard ratios for kidney failure and/or death were comparable across regions; however, they varied among certain subgroups., Conclusions: Although the kidney failure-free survival was comparable across continents, regional differences existed in clinical phenotypes and therapeutic patterns., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Altered gut microbiota is linked to systemic lupus erythematosus (SLE), but its association with disease development, disease activity, and post-intervention changes remains unclear. We compared new-onset SLE (NOSLE, n = 25), SLE in remission (RemSLE, n = 30), and healthy controls (HC, n = 30) cross-sectionally and conducted the first longitudinal analysis of NOSLE patients (n = 22) from pre-intervention to remission over 12 months. Significant β-diversity differences were observed in both NOSLE and RemSLE compared to HC, but not between NOSLE and RemSLE. Only four operational taxonomic units (OTUs) were enriched in NOSLE versus HC. However, 26 OTUs, including butyrate-producing bacteria (BPB), were depleted, and seven (including five BPBs) remained depleted in RemSLE compared to HC. OTUs positively and negatively correlated with disease activity were also identified. Longitudinal analysis revealed a reversal of several OTUs altered at onset and an increase in Streptococci, unrelated to the disease. Significant β-diversity differences were observed in patients with anti-SSA or anti-RNP antibodies and those with complement reduction compared to their counterparts. Our study identified gut microbiota alterations, including BPB depletion, in SLE regardless of onset or remission status, bacteria linked to disease activity, and a reversal of disease-associated bacteria along with the enrichment of Streptococci through intervention., Competing Interests: Declarations. Competing interests: EW received a grant from GSK plc. All other authors declare no competing interests., (© 2024. The Author(s).)

Objectives: This cross-sectional study aimed to determine the relationship between falls and the use of psychotropic medications in patients with rheumatoid arthritis (RA)., Methods: The psychotropic medication group included patients with RA prescribed psychotropic medications [hypnotics/sedatives, antidepressants, antipsychotics, and anxiolytic (benzodiazepines) drugs]. Poisson regression with robust variance was performed to investigate the relationship between falls and the use of psychotropic medications, with adjustment for age, sex, RA disease activity, stroke, dementia, diabetes mellitus, and osteoarthritis., Results: Of the 307 patients enrolled, 49 (16.0%) used psychotropic medications and 70 (22.8%) experienced at least one fall per year. Nineteen of the 49 patients (38.8%) taking psychotropic medications and 51 of 258 (19.8%) not taking psychotropic medications experienced at least one fall per year. Falls were significantly more frequent in the group with psychotropic medications than in the group without psychotropic medications (adjusted incidence rate ratio, 1.63; 95% confidence interval, 1.08-2.48; P = .02). No relationship was found between the number of falls and the use of psychotropic medications (adjusted incidence rate ratio, 1.16; 95% confidence interval, 0.39-3.44; P = .78)., Conclusions: There may be a relationship between psychotropic medication use and falls in patients with RA., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: This study aimed at identifying challenges nurses face in caring for patients with juvenile idiopathic arthritis (JIA) in Japan., Methods: Nurses certified by the Japan Rheumatism Foundation were asked to describe their challenges in caring for JIA patients. Data were analysed using qualitative content analysis., Results: Responses were collected from 89 participants. Fifty-eight issues were identified from 40 participants with experience in caring for JIA patients. Sixteen categories emerged, which were grouped into five challenges: communication, understanding, expertise, system, and collaboration. Care for JIA patients included different challenges from adult patients with rheumatoid arthritis, such as complicated patient-parent relationships, inadequate patient independence, and insufficient patient information. Moreover, 76 issues from 49 participants with no experience were identified. Seven categories emerged, which were grouped into two challenges: expertise and opportunity. Issues included in expertise between both groups were similar. Even with no experience in caring for JIA patients, nurses recognized the importance of acquiring knowledge., Conclusions: This is the first study in Japan regarding the difficulties nurses face in caring for JIA patients. Multidisciplinary team care and a comprehensive understanding of the patient journey, including relationships with guardians, acquaintances, and healthcare providers, are crucial to improve treatment outcome and overall patient quality of life., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objective: To assess the prevalence and outcomes among regimens of glucocorticoid tapering for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in real-world practice., Methods: We retrospectively examined the Japan Collaborative Registry of ANCA-associated Vasculitis (J-CANVAS) registry, and evaluated the prevalence of glucocorticoid tapering regimens in the PEXIVAS trial. In patients with newly diagnosed MPA and GPA, we compared outcomes among standard and reduced pace regimens. Relapse-free survival rates were compared after propensity score matching., Results: Of 364 eligible patients, 113 (31.0%) received standard tapering and 251 slower tapering. After matching, 87 pairs no significant difference was observed in relapse-free survival (p=0.506). Regarding the reduced regimen, there were so few patients (14/364, 3.8%) that statistical analysis was not performed., Conclusions: The glucocorticoid tapering for MPA and GPA in Japanese real-world practice was found to be generally slower than the standard regimen revealing a huge evidence-practice gap. Additionally, slower tapering did not improve relapse-free survival and might cause unnecessary glucocorticoid exposure., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

The association between environmental greenness and childhood asthma remains unclear. Pollen has been proposed as a potential mechanism of detrimental associations. This study aimed to elucidate the mechanisms underlying the association between environmental greenness during the pre-, peri-, and postnatal periods and childhood persistent asthma. A nationwide retrospective birth cohort study was conducted using data from the Japan Medical Data Center (JMDC). Child-mother dyads between January 2010 and January 2017 were identified, and four subcohorts were developed based on the timing of exposure to the highest greenness season. The exposure of interest was environmental greenness levels between June and September, quantified using the normalized difference vegetation index (NDVI). The primary outcome was persistent asthma in children aged 4-5 years. Causal mediation analysis was conducted to evaluate pollen as a mediator between NDVI and asthma. In these analyses, linear and modified Poisson regression models were used to evaluate the association of NDVI with pollen levels and childhood persistent asthma. The analyses were stratified by metropolitan and non-metropolitan areas. Clinically meaningful confounders and predictors of asthma were adjusted in the statistical models. A total of 100,273 child-mother dyads were included in the entire cohort, with 24.1% of the children having persistent asthma at the ages of 4-5 years. Higher environmental greenness was associated with higher pollen levels. The modified Poisson regression models showed higher environmental greenness was associated with a slightly higher risk of persistent childhood asthma. In metropolitan areas, significant detrimental natural direct effects of NDVI were observed; however, the natural indirect effects were uncertain. A large part of the association between environmental greenness and childhood persistent asthma in metropolitan areas was attributed to mechanisms other than those involving pollen. The associations in non-metropolitan areas remain uncertain. Further studies are required to elucidate the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AS received funding from the Japanese Respiratory Society Research Grants Program and the Japanese Respiratory Foundation Grant. The funders played no role in the study design, execution, analysis, interpretation, or decision to submit the results. Other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Few studies have explored whether the involvement of patients in shared decision-making (SDM) is beneficial to the management of systemic lupus erythematosus (SLE). Therefore, this study investigated the relationship between patient participation in SDM and their trust in physicians using data from the Trust Measurement in Physicians and Patients With SLE (TRUMP2-SLE) study., Methods: Data regarding the nine-item Japanese version of the Shared Decision-Making Questionnaire (SDM-Q-9) scores, Trust in Physician Scale (TIPS) scores, and Abbreviated Wake Forest Physician Trust Scale (A-WFPTS) scores for interpersonal trust in a physician and trust in the medical profession were collected from patients with SLE who visited the outpatient clinics of five facilities in Japan through a self-administered questionnaire. The relationships among these scores were analyzed by general linear models with cluster-robust variance., Results: This study included 433 patients with SLE. The median baseline TIPS and A-WFPTS (attending physician version) scores were 82 (73-93) and 80 (70-95), respectively. A higher baseline SDM-Q-9 score was correlated with an increase in the TIPS score at one year (coefficient per 10-point [pt] increase, 0.94 pts, 95% confidence interval [CI] 0.16-1.72). A higher baseline SDM-Q-9 score was correlated with a higher A-WFPTS score for interpersonal trust (coefficient per 10-pt increase, 2.20 pts, 95% CI 1.44-2.96). The baseline SDM-Q-9 score was also correlated with an increase in the general physician version of the A-WFPTS score at one year (coefficient per 10-pt increase, 1.29 pts, 95% CI 0.41-2.18)., Conclusion: Engagement of patients with SLE in SDM elevates their trust in the attending physicians and health care providers, potentially enhancing doctor-patient relationships and overall health care trust., (© 2024 American College of Rheumatology.)

Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis., Methods: This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage., Results: Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5 mg, 5.2 for 7.5 ≤ PSL < 10 mg, 9.0 for 10 ≤ PSL < 20 mg, and 43.1 for PSL ≥ 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis., Conclusion: This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use., Competing Interests: Declarations Ethics approval and informed consent This study was conducted in accordance with the Declaration of Helsinki and Ethical Guidelines for Epidemiologic Research in Japan. The study protocol was approved by the Ethics Committee of Kakogawa Central City Hospital (authorization number: 2021–04). The patients provided written informed consent to participate in the and permission to publish their data. Consent for publication Not applicable. Competing interests KS received speaker fees from Glaxo Smith Kline and a research grant from Pfizer Inc. TY received speaker fees from Glaxo Smith Kline., (© 2024. The Author(s).)

Background: Patient trust plays a central role in the patient-physician relationship. This study aimed to determine whether the number of outpatient visits with a covering rheumatologist is associated with patient trust in their usual rheumatologist., Methods: Japanese adults with systemic lupus erythematosus (SLE) who met the 1997 revised classification criteria of the American College of Rheumatology and had outpatient visits with a covering rheumatologist in the past year were included. We used the 11-item Japanese version of the modified Trust in Physician Scale (range 0-100) to assess patient trust. A general linear model with cluster-robust variance estimation was used to evaluate the association between the number of outpatient visits with covering rheumatologists and the patient's trust in their usual rheumatologist., Results: Of the 515 enrolled participants, 421 patients with SLE were included in our analyses. Patients were divided into groups according to the number of outpatient visits with a covering rheumatologist in the past year as follows: no visits (59.9%; reference group), one to three visits (24.2%; low-frequency group), and four or more visits (15.9%; high-frequency group). The median Trust in Physician Scale score was 81.8 (interquartile range: 72.7-93.2). Both the low-frequency group (mean difference: -3.03; 95% confidence interval [CI] -5.93 to -0.80) and high-frequency group (mean difference: -4.17; 95% CI -7.77 to -0.58) exhibited lower trust in their usual rheumatologist., Conclusion: This study revealed that the number of outpatient visits with a covering rheumatologist was associated with lower trust in a patient's usual rheumatologist., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the Graduate School of Medical and Dental Sciences of Okayama University and the Okayama University Hospital Ethics Committee (approval number: 2204–020). Consent for publication All patients provided informed consent before enrolment. Competing interests Dr. Kurita reported receiving grants from the Japan Society for the Promotion of Science, consulting fees from GlaxoSmithKline K.K., and payments for speaking at and participating in educational events from Chugai Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, and the Japan College of Rheumatology. Dr. Sada reported receiving a research grant from Pfizer, Inc. and a payment for speaking at and participating in educational events from GlaxoSmithKline K.K. Dr. Wada reported receiving speaker honoraria from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kyowa Kirin, Novo Nordisk, and Mitsubishi Tanabe, and received grant support from Bayer, Chugai, Kyowa Kirin, Otsuka, Shionogi, Sumitomo, and Mitsubishi Tanabe. Dr. Matsumoto reported receiving grants from Asahi Kasei Pharma, Taisho, and AbbVie; received speaker honoraria from Astra Zeneca, Asahi Kasei Pharma, GlaxoSmithKline, and Pfizer, Inc.; and received a payment for participating in educational events from GlaxoSmithKline., (© 2024. The Author(s).)

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B cell extranodal lymphoma characterized by clonal marginal zone lymphocyte proliferation. We report a case of MALT lymphoma with a relapsing polychondritis (RP)-like phenotype, manifesting as rapidly progressive tracheal stenosis requiring tracheotomy.

Objectives: The aim of this article is to update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA)., Methods: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, two independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses., Results: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to conventional synthetic DMARD (csDMARD). Rituximab with and without concomitant csDMARDs showed similar efficacy to other biological DMARDs (bDMARDs) in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients., Conclusions: This systematic review provides latest evidence for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for RA management., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: A quality indicator (QI) for the treatment of systemic lupus erythematosus (SLE) during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a QI for SLE associated with pregnancy and childbirth., Methods: To identify candidate QIs, we conducted a systematic literature review on the development of QIs for SLE related to pregnancy and childbirth and on clinical practice guidelines. Candidate QI items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as QIs. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related SLE QIs., Results: Four articles on SLE QI development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate QIs were extracted that were limited to items related to pregnancy and childbirth and 41 items were selected on which all panel members agreed., Conclusion: We developed pregnancy-related SLE QIs using the RAND/UCLA method and selected 41 items, which could be used clinically., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objective: Late-onset systemic lupus erythematosus (LoSLE) is known to possess characteristics different from those of early-onset SLE (EoSLE), thereby making their diagnosis difficult. This study aimed to assess the characteristic features of LoSLE in Japan, a model country with a super-aged society., Methods: Data were obtained from the Lupus Registry of Nationwide Institutions, which includes a multicenter cohort of patients with SLE in Japan who satisfied the 1997 American College of Rheumatology revised classification criteria for SLE. Data were compared between patients with LoSLE (≥50 years old at onset) and EoSLE (<50 years old at onset). To identify factors associated with LoSLE, binary logistic regression was used for the multivariate analysis, and missing values were complemented by multiple imputations. We also conducted a sub-analysis for patients diagnosed within 5 years of onset., Results: Out of 929 enrolled patients, 34 were excluded owing to a lack of data regarding onset age. Among the 895 remaining patients, 100 had LoSLE, whereas 795 had EoSLE. The male-to-female ratio was significantly higher in the LoSLE group than in the EoSLE group (0.32 vs 0.11, p < 0.001). With respect to SLEDAI components at onset, patients with LoSLE exhibited a higher frequency of myositis (11.9% vs 3.75%, p = 0.031), lower frequency of skin rash (33.3% vs 67.7%, p < 0.001), and lower frequency of alopecia (7.32% vs 24.7%, p = 0.012). No significant differences in overall disease activity at onset were observed between the two groups. Regarding medical history, immunosuppressants were more commonly used in EoSLE. A multivariate analysis revealed that a higher male proportion and a lower proportion of new rash at onset were independent characteristic features of LoSLE. We also identified late onset as an independent risk factor for a high SDI score at enrollment and replicated the result in a sub-analysis for the population with a shorter time since onset., Conclusions: We clarified that LoSLE was characterized by a higher male proportion, a lower frequency of skin rash and a tendency to organ damage. Now that the world is faced with aging, our results may be helpful at diagnosis of LoSLE., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ken-ei Sada received a speaker’s fee from GlaxoSmithKline PLC and research grants from Pfizer Inc. Yohei Kirino received a speaker’s fee from Amgen and Novartis and research funding from Nippon Shinyaku. Ryusuke Yoshimi received a speaker’s fee from GlaxoSmithKline PLC, AstraZeneca PLC, and Sanofi S.A.

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47-3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97-9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV., (© 2024. The Author(s).)

Objectives: This study aims to identify challenges nurses face in providing care to older patients with rheumatoid arthritis (RA) in Japan. Methods: Nurses certified by the Japan Rheumatism Foundation were requested via mail to describe challenges in providing care to older RA patients. Qualitative content analysis was used., Results: 182 issues were identified from 152 responses. Twenty categories were grouped into seven components, five of which focused on patients: (1) lack of patient understanding, (2) lack of understanding and support from surrounding people, (3) numerous comorbidities and complications, (4) challenges related to physical strength, and (5) financial issues. Two focused on nurses: (6) lack of knowledge of nurses, and (7) inadequate systems and environment in the workplace. Various difficulties, such as polypharmacy due to multimorbidity, lifestyle issues due to aged couples or those living alone, as well as inadequate decision-making and informed consent due to cognitive decline were also identified., Conclusion: Nurses experienced numerous medical and non-medical difficulties in providing care to older RA patients. Assessing patients' comprehension and self-management, and grasping their situations at home are necessary. Along with the improvement of nurses' knowledge and skills, support from their workplace and multidisciplinary team care including families is crucial., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA)., Methods: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used., Results: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively., Conclusion: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives Pneumocystis pneumonia (PCP) has a poor prognosis in patients with autoimmune diseases. Additionally, the mortality of PCP in autoimmune diseases is higher than that of human immunodeficiency virus-PCP. Therefore, this study aimed to assess the risk factors associated with mortality in patients with autoimmune diseases complicated with PCP. Methods We conducted a retrospective observational study involving 38 patients treated for PCP at Showa University School of Medicine from January 2010 to August 2014. Diagnoses were established based on clinical symptoms, imaging, and laboratory tests, including hypoxemia (partial pressure of oxygen (PaO2) < 70 mmHg), chest computed tomography findings, elevated (1,3)-β-D-glucan, and positive Pneumocystis jirovecii polymerase chain reaction tests from sputum samples. Data regarding patient demographics, underlying diseases, therapeutic interventions, and laboratory findings were collected. Statistical comparisons between survivors and non-survivors were performed using Fisher's exact probability test and Mann-Whitney U test for independence test with Stata/SE version 17.0 (StataCorp LLC, College Station, TX). Results The median age of the study group was 72.4 years old, with the majority having rheumatoid arthritis. Mortality occurred in 18% (seven out of 38) of cases. Factors associated with increased mortality include males, higher serum creatinine and C-reactive protein levels, lower albumin and immunoglobulin A levels, and lower PaO2/fraction of inspired oxygen (FiO2) ratio. No significant difference was observed in the rate of intratracheal intubation, ICU management, and hospitalization period. Prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX) was not performed in any of the cases. Conclusions This study examined the risk of mortality for PCP in patients with autoimmune diseases. The male gender, low IgA and albumin levels, low PaO2/FiO2 ratio, as well as high creatinine and CRP levels, were identified as significant factors for poor prognosis. These factors can help identify patients at high risk for PCP and guide the consideration of prophylactic TMP-SMX administration. They may also provide insights into when to discontinue prophylactic treatment. Future studies should investigate the administration of prophylactic TMP-SMX. Additionally, the risk of mortality for PCP under the administration of new biological agents, such as anifrolumab, belimumab, and rituximab, or immunosuppressants, such as mycophenolate mofetil and voclosporin, should be evaluated. These findings can contribute to improving PCP prevention and treatment strategies in patients with autoimmune diseases, ultimately leading to better patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Bio-Ethical Committee of Showa University School of Medicine issued approval 1644. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Yusuke Miwa declare(s) a grant from Mitsubishi Tanabe Pharma Corporation. Yusuke Miwa received research grants from Mitsubishi Tanabe Pharma Corporation. Yusuke Miwa declare(s) a grant from AbbVie CK. Yusuke Miwa received research grants from AbbVie CK. Yusuke Miwa declare(s) a grant from Chugai Pharmaceutical Co., Ltd. Yusuke Miwa received research grants from Chugai Pharmaceutical Co., Ltd. Yusuke Miwa declare(s) a grant from Eizai Co., Ltd. Yusuke Miwa received research grants from Eizai Co., Ltd. Yusuke Miwa declare(s) a grant from Astellas Pharma Inc. Yusuke Miwa received research grants from Astellas Pharma Inc. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shimizu et al.)

Objectives: To update an evidence base informing the 2024 Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA) in older adults., Methods: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs, CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system., Results: Observational studies confirmed a pivotal role of methotrexate in the treatment of older RA patients. The meta-analysis showed that tumour necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that biological disease-modifying antirheumatic drugs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs., Conclusions: This systematic review provides the necessary evidence for developing 2024 Japan College of Rheumatology clinical practice guidelines for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

The joint effect of air pollutants at relatively low levels requires further investigation. Here, a database study was performed to evaluate the effects of exposure to mixtures of air pollutants during pregnancy, infancy, and childhood on childhood persistent asthma. We used the Japan Medical Data Center database, which provides access to family linkages and healthcare provider addresses, and included child-mother dyads in which the child was born between January 2010 and January 2017. The exposure of interest was ground-level air pollutants, and the primary outcome was childhood persistent asthma at 45 years of age, as defined based on outpatient and inpatient asthma disease codes and/or asthma medication dispensing claims. The weighted quantile sum (WQS) regression was used to evaluate the effects of air pollutant mixtures on 52,526 child-mother dyads from 1149 of 1907 municipalities (60.3 %) in Japan. The WQS regression models showed that with every 10th percentile increase in the WQS index, ground-level air pollutants during pregnancy, infancy, and childhood increased the risk of childhood persistent asthma by an odds ratio of 1.04 (95 % CI: 1.02-1.05; p<0.001), 1.02 (95 % CI: 1.01-1.03; p<0.001), and 1.03 (95 % CI: 1.01-1.04; p<0.001), respectively. Moreover, particulate matter with an aerodynamic diameter ≤ 2.5 µm was assigned the highest weight across all three exposure periods. Relatively high weights were assigned to suspended particulate matter and photochemical oxidants during pregnancy, carbon monoxide during infancy, and photochemical oxidants during childhood. Our study showed that a mixture of low-level air pollutants has a detrimental association with childhood persistent asthma., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akihiro Shiroshita reports financial support was provided by the Japanese Respiratory Society Research Grants Program and Japanese Respiratory Foundation Grant. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigated the clinically relevant factors for headaches in patients with systemic lupus erythematosus (SLE) using a registry from a Japanese multicenter cohort., Methods: This cross-sectional study analysed the clinical information of patients with SLE who experienced headache episodes using the Migraine Disability Assessment (MIDAS) questionnaire. Significant findings in the comparisons between patients with headache (HA patients) and those without headache (non-HA patients) and in the comparisons depending on the grades of headache-induced disability in daily life based on the MIDAS scores were evaluated. Multivariate logistic regression analyses were performed to identify the relevant factors for headache., Results: We analyzed 369 patients (median age, 45 years; female, 90.8%), including 113 HA patients who were significantly younger than non-HA patients ( p < .005). HA patients had significantly higher frequencies of photosensitivity, rashes, and mucosal ulcers than non-HA patients ( p < .05). Age and photosensitivity were significantly associated with headache (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.95-0.99; OR 2.11, 95% CI 1.29-3.49, respectively). In the HA patients, hypocomplementemia was significantly associated with a disability of more than mild grade (OR 2.89, 95% CI 1.14-7.74), while rash was significantly observed in those presenting with moderate and severe disability., Conclusion: This study suggests that photosensitivity is a relevant manifestation of headache in patients with SLE. Persistent hypocomplementemia can contribute to headache-induced disability in daily life, whereas a rash may be a dominant manifestation in patients presenting with moderate/severe headache-induced disability., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Thoracoscopic esophagectomy (TE) with carbon dioxide (CO 2 )   insufflation is increasingly performed for esophageal cancer; however, there is limited evidence of the long-term outcomes of CO 2 insufflation on postoperative survival., Objectives: We investigated the long-term outcomes of TE with or without CO 2 insufflation., Methods: We enrolled 182 patients who underwent TE for esophageal cancer between January 2003 and October 2013 and categorized them into two groups: with and without CO 2 insufflation. The primary endpoint was five-year overall survival (5y-OS). Secondary endpoints included long-term outcomes, such as five-year relapse-free survival (5y-RFS) and five-year cancer-specific survival (5y-CSS), and short-term outcomes, such as surgical and non-surgical complications and reoperation within 30 days., Results: Follow-up until death or the five-year postoperative period was 98.9% (median follow-up duration was six years in survivors). After adjusting for age, sex, and yield pathologic tumor, node, and metastasis (TNM) stage, we found no significant differences in 5y-OS (HR 1.12, 95% CI 0.66-1.91), 5y-RFS (HR 1.12, 95% CI 0.67-1.83), or 5y-CSS rates (HR 1.00, 95% CI 0.57-1.75). For short-term outcomes, significant intergroup differences in operation time (p=0.02), blood loss (p<0.001), postoperative length of stay (p<0.001), and incidence of atelectasis (p=0.004) were observed. The results of the sensitivity analysis were similar to the main results., Conclusions: In thoracoscopic procedures, CO 2 insufflation significantly improved short-term outcomes, and it appears that the recurrence risk of esophageal cancer may not impact the long-term prognosis. While the influence of CO 2 insufflation in thoracoscopic esophageal surgery remains unclear, our study suggests that the long-term prognosis is not compromised in other thoracic surgeries., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Showa University School of Medicine issued approval 2256. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Otsuka et al.)

Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis is associated with rapidly progressive interstitial lung disease (RP-ILD). We encountered a man in his 40s who presented with a history of a fever and dry cough. Based on laboratory tests and computed tomography scans of his chest, he was diagnosed with anti-MDA5 antibody-positive dermatomyositis with RP-ILD refractory to antimicrobial agents. Although the patient was treated with glucocorticoids, calcineurin inhibitors, intravenous cyclophosphamide, and plasma exchange, ventilatory management was still required. The patient survived additional therapy with tofacitinib; however, he developed a catheter-related pulmonary embolism as a complication.

Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis., Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated., Results: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly., Conclusion: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg)., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: This study aimed to identify the challenges faced by nurses engaged in rheumatology care in Japan., Methods: We conducted a questionnaire survey of nurses in Japan in 2020 on challenges experienced in rheumatology care. The participants were nurses certified by the Japan Rheumatism Foundation. Participants' answers were coded and categorized based on relevant phrases and words. Content analysis was performed on the findings., Results: Responses were collected from 162 participants, and a total of 228 issues were identified. Eighteen categories with 56 subcategories emerged from the data analysis, which were grouped into five types of challenges: (1) communication, (2) understanding, (3) expertise, (4) system, and (5) collaboration. In particular, the results highlighted deficiencies in needs-based multidisciplinary team care., Conclusion: This study elucidated issues experienced by rheumatology nurses in clinical settings in Japan. Furthermore, this investigation revealed the necessity of patient-centred multidisciplinary team care, including health professionals, patients, and other relevant individuals. This study provided practical directions to facilitate the implementation of effective care focused on improving patients' quality of life., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The European League Against Rheumatism recommends that the disease activity of systemic lupus erythematosus should be stable before pregnancy because complications and disease flares increase if pregnancy occurs while disease activity is high. However, some patients have ongoing serological activity even after treatment. Herein, we investigated how physicians decide on the acceptability of pregnancy in patients showing only serological activity., Methods: A questionnaire was administered from December 2020 to January 2021. It included the characteristics of physicians, facilities, and the allowance for pregnancies of patients using vignette scenarios., Results: The questionnaire was distributed to 4946 physicians, and 9.4% responded. The median age of respondents was 46 years, and 85% were rheumatologists. Pregnancy allowance was significantly affected by the duration of the stable period and status of serological activity [duration: proportion difference 11.8 percentage points (p.p.), P < .001; mild activity: proportion difference -25.8 p.p., P < .001; high activity: proportion difference -65.6 p.p., P < .001]. For patients with high-level serological activity, 20.5% of physicians allowed pregnancy if there were no clinical symptoms for 6 months., Conclusions: Serological activity had a significant effect on the acceptability of pregnancy. However, some physicians allowed patients with serological activity alone to become pregnant. Further observational studies are required to clarify such prognoses., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk., Methods: The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history., Results: The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66)., Conclusions: The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development., (© 2024. The Author(s).)

Objective: Differences in communication styles based on physicians' personality traits have been identified, particularly in primary care, and these physician-related factors can be important in building patient-physician trust. This study examined the effects of rheumatologists' personality traits on patients' trust in their attending rheumatologists., Methods: This cross-sectional study included adult Japanese patients with systemic lupus erythematosus (SLE) at 5 academic medical centers between June 2020 and August 2021. The exposures were the Big 5 personality traits (ie, extraversion, agreeableness, openness, conscientiousness, and emotional stability) of attending rheumatologists using the Japanese version of the 10-Item Personality Inventory scale (1-7 points each). The outcome was the patients' trust in their attending rheumatologist using the Japanese version of the 5-item Wake Forest Physician Trust Scale (0-100 points). A general linear model was fitted., Results: The study included 505 patients with a mean age of 46.8 years; 88.1% were women. Forty-three attending rheumatologists (mean age: 39.6 years; 23.3% female) were identified. After multivariable adjustment, higher extraversion and agreeableness were associated with higher trust (per 1-point increase, 3.76 points [95% CI 1.07-6.45] and 4.49 points [95% CI 1.74-7.24], respectively), and higher conscientiousness was associated with lower trust (per 1-point increase, -2.17 points [95% CI -3.31 to -1.03])., Conclusion: Whereas higher extraversion and agreeableness of attending rheumatologists led to higher patient trust in their rheumatologist, overly high conscientiousness may lead to lower trust resulting from the physicians' demand of responsibility and adherence to instructions from patients with SLE., (Copyright © 2024 by the Journal of Rheumatology.)

Objectives: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections., Methods: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups., Results: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens., Conclusion: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Providing appropriate health information to patients with systemic lupus erythematosus (SLE) is advantageous in the treatment decision-making process. We aimed to investigate how online health information-seeking behaviors affect shared decision-making (SDM) in patients with SLE., Methods: This cross-sectional study included 464 patients with SLE from five institutions. The main exposure was time spent on the internet per day, divided into four categories (none, <1 h, 1- < 2 h, ≥2 h). Participants categorized their preferred first source of health information as physicians, the internet, or other media. The outcome was the degree of SDM measured via the 9-item Shared Decision-Making Questionnaire (SDM-Q-9). A general linear model was applied., Results: Compared to no internet use, longer internet use was associated with a higher SDM-Q-9 score: <1 h, 6.9 points (95% confidence interval [CI] 0.32 to 13.6) and ≥2 h, 8.75 points, (95% CI 0.61 to 16.9). The SDM-Q-9 did not differ between the individuals who chose physicians and those who chose the Internet as their preferred first source of health information (-2.1 points, 95% CI -6.7 to 2.6). Individuals who chose other media had significantly lower SDM-Q-9 scores than those who chose physicians (-7.6 points, 95% CI -13.2 to -1.9)., Conclusions: The present study suggests that SDM between physicians and patients is positively associated with online information-seeking behavior, with no negative influence associated with accessing the Internet before clinical consultations. Rheumatologists may need to introduce their patients to websites offering high-quality health information to establish a good physician-patient relationship for SDM., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NK is a member of the Committee on Clinical Research, Japan College of Rheumatology, and has received grants from the Japan Society for the Promotion of Science, consulting fees from GlaxoSmithKline K.K., and payments for speaking and educational events from Chugai Pharmaceutical Co. Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, and Japan College of Rheumatology. K. Sada has received a research grant from Pfizer Inc. and payments for speaking and educational events from GlaxoSmithKline K.K. Other authors declare no competing interests.

Objectives: There is a high prevalence of burnout among rheumatologists. Grit, which is defined as possessing perseverance and a passion to achieve long-term goals, is predictive of success in many professions; however, whether grit is associated with burnout remains unclear, especially among academic rheumatologists, who have multiple simultaneous responsibilities. Thus, the purpose of this study was to examine the associations between grit and self-reported burnout components-professional efficacy, exhaustion, and cynicism-in academic rheumatologists., Methods: This cross-sectional study involved 51 rheumatologists from 5 university hospitals. The exposure was grit, measured using mean scores for the 8-item Short Grit Scale (range, 1-5 [5 = extremely high grit]). The outcome measures were mean scores for 3 burnout domains (exhaustion, professional efficacy, and cynicism; range, 1-6; measured using the 16-item Maslach Burnout Inventory-General Survey). General linear models were fitted with covariates (age, sex, job title [assistant professor or higher vs lower], marital status, and having children)., Results: Overall, 51 physicians (median age, 45 years; interquartile range, 36-57; 76% men) were included. Burnout positivity was found in 68.6% of participants (n = 35/51; 95% confidence interval [CI], 54.1, 80.9). Higher grit was associated with higher professional efficacy (per 1-point increase; 0.51 point; 95% CI, 0.18, 0.84) but not with exhaustion or cynicism. Being male and having children were associated with lower exhaustion (-0.69; 95% CI, -1.28, -0.10; p = 0.02; and -0.85; 95% CI, -1.46, -0.24; p = 0.006). Lower job title (fellow or part-time lecturer) was associated with higher cynicism (0.90; 95% CI, 0.04, 1.75; p = 0.04)., Conclusions: Grit is associated with higher professional efficacy among academic rheumatologists. To prevent burnout among staff, supervisors who manage academic rheumatologists should assess their staff's individual grit., Competing Interests: N.K. is a member of the Committee on Clinical Research, Japan College of Rheumatology, and has received grants from the Japan Society for the Promotion of Science, consulting fees from GlaxoSmithKline K.K., and payments for speaking at and participating in educational events from Chugai Pharmaceutical Co, Ltd, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, and the Japan College of Rheumatology. K.S. received a research grant from Pfizer Inc and a payment for speaking at and participating in educational events from GlaxoSmithKline K.K. The other authors declare that they have no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Infection is a leading cause of death in patients with systemic lupus erythematosus (SLE). Alt hough hydroxychloroquine (HCQ) has been reported to inhibit infection, evidence from Asian populations remains insufficient. We investigated this effect in Japanese SLE patients., Methods: Data from the Lupus Registry of Nationwide Institutions were used in this study. The patients were ≥20 years old and met the American College of Rheumatology (ACR) classification criteria revised in 1997. We defined "severe infections" as those requiring hospitalization. We analyzed the HCQ's effect on infection suppression using a generalized estimating equation (GEE) logistic regression model as the primary endpoint and performed a survival analysis for the duration until the first severe infection., Results: Data from 925 patients were used (median age, 45 [interquartile range 35-57] years; female, 88.1%). GEE analysis revealed that severe infections were significantly associated with glucocorticoid dose (odds ratio [OR] 1.968 [95% confidence interval, 1.379-2.810], p <0.001), immunosuppressants (OR 1.561 [1.025-2.380], p =0.038), and baseline age (OR 1.043 [1.027-1.060], p <0.001). HCQ tended to suppress severe infections, although not significantly (OR 0.590 [0.329-1.058], p =0.077). Survival time analysis revealed a lower incidence of severe infections in the HCQ group than in the non-HCQ group ( p <0.001). In a Cox proportional hazards model, baseline age (hazard ratio [HR] 1.029 [1.009-1.050], p =0.005) and HCQ (HR 0.322 [0.142-0.728], p =0.006) were significantly related to incidence., Conclusion: HCQ may help extend the time until the occurrence of infection complications and tends to decrease infection rates., Competing Interests: KS received a speaker’s fee from GlaxoSmithKline PLC and research grants from Pfizer Inc. YKi received a speaker’s fee from Amgen and Novartis and research funding from Nippon Shinyaku. RY received a speaker’s fee from GlaxoSmithKline PLC, AstraZeneca PLC, and Sanofi S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hidekawa, Yoshimi, Saigusa, Tamura, Kojitani, Suzuki, Sakurai, Yoshioka, Sugiyama-Kawahara, Kunishita, Kishimoto, Higashitani, Sato, Komiya, Nagai, Hamada, Maeda, Tsuchida, Hirahara, Soejima, Takase-Minegishi, Kirino, Yajima, Sada, Miyawaki, Ichinose, Ohno, Kajiyama, Sato, Shimojima, Fujiwara and Nakajima.)

Objective: To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)., Methods: We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season., Results: A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season ( P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA ( P < 0.001), but not in those with PR3-ANCA ( P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis., Conclusion: The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency., (Copyright © 2023 by the Journal of Rheumatology.)

Objectives: The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis., Methods: PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach., Results: For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively., Conclusions: This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objective: Poor medication adherence among patients with SLE is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one's physician and goal-oriented thinking, hope and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians., Methods: This cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centres. Patients with SLE who were prescribed oral medications were included. The main exposures were trust in one's physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. Medication adherence was measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects and concerns regarding lupus medications., Results: Altogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years; among them, 329 (88.2%) were women. Both trust in one's physician (per 10-point increase: 0.86, 95% CI 0.49, 1.22) and the Health-related Hope score (per 10-point increase: 0.66, 95% CI 0.35, 0.97) were associated with better medication adherence., Conclusions: This study demonstrated that patients' health-related hope and trust in their rheumatologist were both associated with better medication adherence in SLE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE., Methods: This cross-sectional study was conducted at five referral hospitals. The main exposure was 'consistency of interest' and 'perseverance of effort' of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians' grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders., Results: The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9-3.6), 3.3 (2.8-3.8) and 3.3 (3.0-3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question 'I often set a goal but later choose to pursue a different one' was significantly higher in patients achieving LLDAS., Conclusions: Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE)., Methods: This was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one's physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit., Results: A total of 362 patients with SLE were included. Trust in one's physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference -6.88, 95% CI -11.72 to -2.04, respectively). Longer internet use was associated with both higher communicative and critical HL., Conclusion: The findings suggest that rheumatologists need to improve their communication to match each patient's HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Fatigue is one of the most common complaints and is a potentially modifiable issue in systemic lupus erythematosus (SLE). Studies suggest that alcohol consumption has a protective effect against the development of SLE; however, an association between alcohol consumption and fatigue in patients with SLE has not been studied. Here, we assessed whether alcohol consumption was associated with fatigue using lupus patient-reported outcomes (LupusPRO)., Methods: This cross-sectional study, conducted between 2018 and 2019, included 534 patients (median age, 45 years; 87.3% female) from 10 institutions in Japan. The main exposure was alcohol consumption, which was defined as the frequency of drinking [<1 day/month (none group), ≤1 day/week (moderate group), and ≥2 days/week (frequent group)]. The outcome measure was the Pain Vitality domain score in LupusPRO. Multiple regression analysis was performed as the primary analysis after adjusting for confounding factors, such as age, sex, and damage. Subsequently, the same analysis was performed as a sensitivity analysis after multiple imputations (MIs) for missing data ( n = 580)., Results: In total, 326 (61.0%) patients were categorized into the none group, 121 (22.7%) into the moderate group, and 87 (16.3%) into the frequent group. The frequent group was independently associated with less fatigue compared with none group [β = 5.98 (95% CI 0.19-11.76), p = 0.04], and the results did not substantially deviate after MI., Conclusions: Frequent drinking was associated with less fatigue, which highlights the need for further longitudinal studies focusing on drinking habits in patients with SLE.

Background: The burden of COVID-19 on healthcare workers (HCWs) is reported to be increasing, yet the psychometric scales now in use evaluate only single aspects; few measure the pandemic-specific burden on HCWs comprehensively., Objective: To develop a scale to quantify the physical, mental, and socioeconomic burden of the COVID-19 pandemic on HCWs., Design: Scale development and cross-sectional survey., Participants: Consenting HCWs aged ≥20., Main Measures: Development of an item-list based on literature reviews and HCW panel input, evaluation of content validity and item selection using the Delphi method, psychometric testing conducted on HCWs, validity assessment by factor analyses and hypothesis verification, internal consistency evaluation by Cronbach's alpha, test-retest analysis, and interpretability assessment., Key Results: Through the Delphi process, a 29-item pilot scale was generated. In psychometric testing, data from 863 HCWs contributed to the development of the final version of this scale, called Pandemic Burden Index twenty for HCWs (PBI-20), a 20-item scale to measure six domains: fatigue, fear of infection, inadequacy as a medical professional, mental health concerns, prejudice or discrimination, and anxiety about one's livelihood and daily life. Factor analysis showed each factor corresponded to the six domains of this scale. Hypothesis verification showed the PBI-20 total score to be moderately to highly correlated with the Short Form 36 vitality score and mental health score and with intention of turnover. The PBI-20 had good internal consistency (Cronbach's alpha 0.92). Test-retest analysis showed the intraclass correlation coefficient to be 0.70 and the minimal important change to be -7.0., Conclusions: The psychometrically sound questionnaire we developed to measure pandemic-specific burdens for HCWs provides an understanding of comprehensive burdens on HCWs and may serve to evaluate interventions to reduce the burdens., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Introduction: Patients with systemic lupus erythematosus (SLE) frequently change attending physicians. The number of changes in attending physicians is related to the accumulated organ damage in patients with diabetes mellitus and inflammatory bowel disease, although similar results are not known for patients with SLE. This study investigated whether the number of attending physicians after the onset of SLE is associated with organ damage., Methods: Patients with SLE were enrolled in a multicenter registry of 14 institutions (the Lupus Registry of Nationwide Institutions). Patients with a disease duration of 6 months to 10 years were included. Exposure was defined as the number of attending physicians. The primary outcome was the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The secondary outcomes were corticosteroid- and non-corticosteroid-related damage. Multiple logistic regression analysis was used to estimate the association between the number of attending physicians and SDI, adjusting for potential confounders, including age, sex, disease duration, number of hospitalizations due to SLE, disease activity at diagnosis, and emotional health., Results: Of the 702 patients, 86.5% were women (median age 46 years, interquartile range 35-58). The disease duration was 7.3 years (4.3-11.3), the number of hospitalizations due to SLE was 1 (1-3), the number of attending physicians was 3 (2-4), and SDI was 0 points (0-1). The number of attending physicians was significantly associated with SDI [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.03-1.26]. In the secondary outcome, the number of attending physicians was significantly associated with corticosteroid-related damage (OR 1.22, 95% CI 1.09-1.38). The number of attending physicians was not significantly associated with non-corticosteroid-related damage (OR 1.08, 95% CI 0.99-1.19)., Conclusions: This study showed that SDI could increase as the number of attending physicians increases. The impact of changing attending physicians warrants greater attention for SLE and other diseases., (© 2023. The Author(s).)

Granulomatosis with polyangiitis (GPA) is a systemic disease that causes vasculitis in various organs. Although the mechanism of pathogenesis remains unclear, infection has been reported to be a causative factor. We herein report a case of GPA that developed following coronavirus disease 2019 (COVID-19) in an adolescent girl. One month after contracting mild COVID-19, the patient had facial allodynia, a fever, and weight loss and was admitted for multiple nodular shadows on a chest roentgenogram. GPA was diagnosed based on pathological findings of the lung and nasal mucosal biopsies. She received methylprednisolone and rituximab, and her symptoms and radiological findings improved.

Background: Assessing medication adherence in rheumatoid arthritis (RA) is clinically significant as low adherence is associated with high disease activity. Self-reported medication adherence surveys have been shown to have problems with overestimation of adherence due to social desirability bias. However, no MTX adherence studies adjusted for social desirability have been conducted to date. This study aimed to evaluate adherence to MTX and perform an investigatory search for factors associated with MTX adherence including social desirability., Methods: This cross-sectional multicenter study was conducted among adult RA patients consuming oral MTX for ≥ 3 months. We examined the distribution of MTX adherence, according to the eight-item Morisky Medication Adherence Scale (MMAS-8). Social desirability was using the Social Desirability Scale (SDS). Furthermore, an exploratory factor analysis involving social desirability was examined to identify factors associated with MTX adherence using linear regression analysis. To deal with missing values, we used multiple imputations with chained equations methods., Results: A total of 165 RA patients were enrolled. The median age was 64 years, and 86.1% were women. Based on the MMAS-8, low, medium, and high adherences were noted in 12.1%, 60.0%, and 27.9% of participants, respectively. High social desirability (coefficient, 0.14; 95% confidence interval [CI], 0.05-0.23; p < 0.05) and high age (coefficient per 10 years, 0.16; 95% CI, 0.01-0.03; p < 0.05) were associated with high MTX adherence, whereas full-time work was negatively associated with high MTX adherence (coefficient, -0.50; 95% CI, -0.95--0.05; p < 0.05)., Conclusions: A large proportion of patients with RA do not take MTX as prescribed. High social desirability, high educational level, and non-full-time work may be associated with high MTX adherence. Physicians should confirm MTX adherence before switching or adding disease-modifying anti-rheumatic drugs in cases of uncontrolled disease activity., (© 2022. The Author(s).)

Introduction: Lupus nephritis (LN) is more prevalent in patients with SLE of Asian ethnicity than in Caucasian patients. Belimumab became available in Japan in 2017 to treat patients with SLE, including those with LN. In the BLISS-LN trial (NCT01639339), belimumab showed a favourable effect on renal outcomes when combined with standard therapy (ST) starting at the induction treatment phase for active LN, but real-world effectiveness of belimumab in LN has not been extensively studied. Here we describe the protocol for the MOONLIGHT (post-Marketed effectiveness of belimumab cOhOrt and JapaN Lupus NatIonwide ReGistry (LUNA) coHorT) study, which will use data from a Japan postmarketing surveillance study and the Lupus Registry of Nationwide Institutions (LUNA) to evaluate the real-world effectiveness of belimumab plus ST versus ST alone in patients with a history of active LN who are not in the induction phase., Methods and Analysis: This multicentre, retrospective, observational study (GSK Study 214710) will enrol adults with SLE and a history of active LN, holding ≥3 years of complete follow-up data from the initiation of belimumab (no continuous treatment required). Data for patients with belimumab plus ST treatment (postmarketing registry data, belimumab cohort) will be compared with those for patients with ST only treatment (LUNA data, comparison cohort). Patients who discontinue/initiate belimumab after the start of the follow-up may be included in the comparison/belimumab cohort, respectively. The primary endpoint will be the occurrence of renal flares, for which belimumab's effectiveness will be estimated using a marginal structural model to consider time-dependent treatment and confounding factors. Secondary endpoints will include change in corticosteroid dose, renal disease activity, extrarenal disease activity, disease severity/activity biomarkers, LN class changes, end-stage kidney disease events and hospitalisations., Ethics and Dissemination: This study will be conducted according to the Declaration of Helsinki and the local ethical guidelines. Findings will be submitted to peer-reviewed journals and presented at scientific meetings., Competing Interests: Competing interests: KS received speaker and consulting fees from GSK K.K. and a research grant from Pfizer. NK received a consulting fee from GSK K.K. HN received a consulting fee from GSK K.K. and personal fees from Boehringer Ingelheim, Kyowa Kirin, Toyota Motor Corporation, GSK, Ono Pharmaceutical, Sony and Terumo outside the submitted work. TM, HQ, RAL, ARJL and KG are employees of GSK and hold stocks and shares in the company. NY received a speaker’s fee from Pfizer., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status., Methods: Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5-20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index., Results: GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0

Background: This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan., Methods: We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed., Results: Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03-2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59-13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51-29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24-85.03, p < 0.0001)., Conclusion: GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development., (© 2022. The Author(s).)

Background: Infection is a major cause of mortality in patients with systemic lupus erythematosus (SLE). Therefore, minimizing the risk of infection is an important clinical goal to improve the long-term prognosis of SLE patients. Treatment with ≥7.5 mg prednisolone (PSL) or equivalent has been reported to increase the risk of infections. However, it remains unclear whether <7.5 mg PSL or equivalent dose affects the risk of infection in SLE patients. This study evaluated the association between the occurrence of infection in patients with SLE and low-dose glucocorticoid (GC) usage, especially <7.5 mg PSL or equivalent, to explore the GC dose that could reduce infection occurrence., Methods: This prospective cohort study included patients from the Japanese multicenter registry of patients with SLE (defined as ≥4 American College of Rheumatology 1997 revised criteria) over 20 years of age. The PSL dose was categorized as PSL 0-2.5, 2.6-5.0, 5.1-7.5, and 7.6-15.0 mg. The primary outcome was infection requiring hospitalization. We conducted a multivariable analysis using time-dependent Cox regression analysis to assess the hazard ratio of infection occurrence compared with a dose of 0-2.5 mg PSL or equivalent in the other three PSL dose groups. Based on previous reports and clinical importance, the covariates selected were age, sex, and concurrent use of immunosuppressants with GC. In addition, two sensitivity analyses were conducted., Results: The mean age of the 509 SLE patients was 46.7 years; 89.0% were female, and 77.2% used multiple immunosuppressants concomitantly. During the observation period, 52 infections requiring hospitalization occurred. The incidence of infection with a PSL dose of 5.0-7.5 mg was significantly higher than that in the PSL 0-2.5 mg group (adjusted hazard ratio: 6.80, 95% confidence interval: 2.17-21.27). The results of the two sensitivity analyses were similar., Conclusions: Our results suggested that the use of 5.0-7.5 mg PSL or equivalent could pose an infection risk in SLE patients. This finding indicates that PSL dose should be reduced to as low as possible in SLE patients to avoid infection., (© 2022. The Author(s).)

Background: Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE., Methods: A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control., Results: Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m2, P = 0.02) than those without supplementation. Disease-related SDI (0.73 ± 1.12 vs 0.73 ± 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age ≥ 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups., Conclusions: Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed., Competing Interests: The authors have declared that no competing interests exist.