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We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis ( n  = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs.

Plasma exchange (PE) outcomes in patients with trigger-associated thrombotic microangiopathy (TMA) have not been comprehensively reviewed. Embase and MEDLINE® were searched on 03/14/2022 for English language articles published after 2007, alongside a congress materials search (2019-2022; PROSPERO: CRD42022325170). Studies with patients with trigger-associated TMA (excluding thrombotic thrombocytopenic purpura, 'typical' hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli, post-partum TMA, and TMAs with known genetic cause) who received PE or plasma infusion (PI) and reported treatment response (including measures), safety, patient-/caregiver-reported outcomes, or economic burden data were examined. The NICE quality appraisal checklist assessed bias risk. After screening 695 articles, 49 PE or PI studies were identified, of which 42 reported PE exclusively; most were retrospective observational studies (n = 37). The most common TMA trigger was transplantation (n = 12). The median number of PE sessions was 3.5-25.0. Outcomes following PE varied by trigger type. Treatment response rates and definitions varied (0-100 %; 24 studies); in studies of > 25 patients, response rates were 5-63 %. TMA relapse rates were 0-67 % (7 studies). Mortality was 10-91 % (23 studies). Progression to chronic kidney disease (CKD; 5 studies) and end-stage renal disease (ESRD; 6 studies) occurred in 0-93 % and 17-100 % of patients, respectively. Two serious adverse events were identified (transfusion-related injury, acute lung injury; 10 studies; 231 patients). Patients with trigger-associated TMA may experience a substantial burden in terms of mortality, relapse, and progression to CKD and ESRD following PE, leading to increased healthcare resource utilization. Additional interventions may be required., Competing Interests: Declaration of Competing Interest Shinya Kaname has received advisory fees and speaker fees from Alexion Pharmaceutical Co., Ltd. Moh-Lim Ong is an employee and shareholder of Alexion, AstraZeneca Rare Disease, Boston, Massachusetts. Jonathan Mathias is an employee and shareholder of Alexion, AstraZeneca Rare Disease, Boston, Massachusetts. Francesca Gatta is an employee and shareholder of Alexion Pharma GmbH, AstraZeneca Rare Disease, Zurich, Switzerland. Lisa Law was an employee of Oxford PharmaGenesis Ltd, Oxford, UK at the time of the study, which was contracted by Alexion, AstraZeneca Rare Disease to support the design and conduct of the systematic literature review. Yan Wang is an employee and shareholder of Alexion, AstraZeneca Rare Disease, Boston, Massachusetts., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Eculizumab has been approved for atypical haemolytic-uraemic syndrome (aHUS) in Japan since 2013. Post-marketing surveillance enrolled patients with aHUS who received ≥ 1 dose of eculizumab to assess eculizumab safety and effectiveness., Methods: We evaluated serious adverse events and effectiveness endpoints, i.e., haematologic normalization, a decrease of ≥ 25% in serum creatinine (sCr) levels, and complete thrombotic microangiopathy (TMA) response in adult patients with aHUS without other underlying diseases. In addition, the difference of baseline characteristics between patients who did and did not meet effectiveness endpoints was examined., Results: In this safety and effectiveness analysis, 79 adult patients were included; median age was 54.0 years, median treatment duration was 30 weeks. Total exposure time of eculizumab was 75.51 patient-years, and 94 serious adverse events were reported in 39 patients. No unexpected safety signals were identified in this population. Mean platelet count, lactate dehydrogenase and estimated glomerular filtration rate significantly improved after 7 days of treatment. Complete TMA response, haematologic normalization and the improvement of sCr levels were met by 35.3%, 40.4% and 51.3% of patients, respectively. Median treatment duration was shorter in patients who did not achieve complete TMA response (6 weeks) than in patients who did (114 weeks). Multivariate analysis suggested that the time from the most recent TMA episode to start of eculizumab treatment was negatively associated with kidney function improvement., Conclusions: No unexpected safety signals of eculizumab were identified in Japanese patients with aHUS in a real-world setting. Renal outcomes were negatively associated with the time from the most recent TMA episode to the initiation of eculizumab treatment., Competing Interests: Declarations. Conflict of interest: S. Maruyama received honoraria for lectures and participation on advisory board from Alexion Pharma GK. S. Kaname received honoraria for lectures and participation on advisory board from Alexion Pharma GK. M. Matsumoto received honoraria for lectures and participation on advisory board from Alexion Pharma GK. Y. Miyakawa received research grant, clinical trials, and honoraria for participation on advisory board from Alexion Pharma GK. Y. Ishikawa. and A. Shimono are employees of Alexion Pharma GK and shareholders of Alexion Pharmaceutical Inc. All other authors have nothing to disclose. Ethical approval: Post-marketing surveillance was mandated by the Japanese government as part of the regulatory approval of eculizumab for aHUS in Japan. Post-marketing surveillance was conducted in accordance with Good Post-Marketing Study Practice (Ministry of Health, Labour and Welfare, Ministerial Ordinance No. 171 of 2004) to evaluate the safety and effectiveness of eculizumab in clinical practice. Ethical approval by an institutional review board is not mandatory for post-marketing surveillance. Human and animal rights: All procedures followed were in accordance with the Helsinki Declaration of 1964 and later versions. This article does not contain any studies with animal subjects performed by any of the authors. Infomed consent: Informed consent from individual patients is not mandatory for post-marketing surveillance., (© 2024. The Author(s).)

Background: Esophageal cancer is one of the most common types of cancer in Japan. Herein, we report the efficacy and safety of E7389-LF plus the immune checkpoint inhibitor, nivolumab, from the esophageal cancer cohort of the phase 2 part of Study 120., Methods: Eligible patients received E7389-LF 2.1 mg/m 2 plus nivolumab 360 mg intravenously Q3W. The primary objective was to evaluate the objective response rate (ORR); other objectives included safety, progression-free survival (PFS), and overall survival (OS)., Results: Of the 35 Japanese patients enrolled, 7 (20.0%) had a partial response as their best overall response, and 14 (40.0%) had stable disease. The ORR was 20.0% (95% CI 8.4-36.9). The duration of response was 5.6 months (95% CI 1.7-not estimable [NE]). The median PFS was 2.81 months (95% CI 1.31-4.17). The median OS was not reached (95% CI 6.54 months-NE). The most common treatment-emergent adverse events were neutropenia (65.7%), pyrexia (60.0%), and leukopenia (57.1%). Select plasma endothelial cell markers levels increased from day 1 of cycle 1 and changes were pronounced between days 8-15 of each cycle., Conclusions: E7389-LF plus nivolumab showed antitumor activity in patients with unresectable and pretreated esophageal cancer and should be evaluated further in a broader population., Clinical Trial Registration: NCT04078295., (© 2024. The Author(s).)

Purpose: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin and has shown preliminary efficacy in the treatment of gastric cancer. Study 120, a phase Ib/II open-label study, assessed efficacy and safety of E7389-LF in combination with nivolumab, a programmed cell death (PD)-1 inhibitor. This report focuses on the gastric cancer cohort within the expansion phase., Patients and Methods: Eligible patients had unresectable, measurable gastric cancer, progression following a platinum drug plus fluoropyrimidine (1L), and a taxane-containing regimen (2L). The primary objective of the expansion phase was objective response rate, secondary objectives included safety and PFS, and exploratory objectives included overall survival and biomarker evaluation. Patients received E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks, both as intravenous infusions. Tumor responses were assessed every 6 weeks by the investigators per RECIST v1.1. Plasma and tumor biomarkers were assessed., Results: In the 31 patients who received E7389-LF in combination with nivolumab, the objective response rate was 25.8% [confidence interval (CI), 11.9-44.6]. The median progression-free survival was 2.69 months (95% CI, 1.91-2.99) and median overall survival was 7.85 months (95% CI, 4.47-not estimable). The most common treatment-related TEAE of any grade were neutropenia (77.4%), leukopenia (74.2%), and decreased appetite (51.6%). E7389-LF in combination with nivolumab significantly increased CD8-positive cells at C2D1 (P = 0.039), and six of seven vascular markers and four IFNγ-related markers showed increases from C1D1., Conclusions: Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with gastric cancer, and no new safety signals were observed, compared with either monotherapy., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: This study aimed to evaluate the Ministry of Health, Labour and Welfare (MHLW) diagnostic criteria for antineutrophil cytoplasmic antibody-associated vasculitis compared to the new American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria., Methods: Two nationwide cohort studies were used, and participants were categorised as having eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 and MHLW criteria., Results: Of the entire patient population, only 10 (2.1%) were unclassifiable according to the MHLW probable criteria, while a significant number of patients (71.3%) met at least two criteria. The MHLW probable criteria for MPA had some challenges in differentiating between MPA and eosinophilic granulomatosis with polyangiitis, and the same was true for MHLW probable criteria for GPA in differentiating MPA from GPA. Nevertheless, improved classification results were obtained when the MHLW probable criteria were applied in the order of eosinophilic granulomatosis with polyangiitis, MPA, and GPA., Conclusions: The application of MHLW criteria could categorise a substantial number of patients with antineutrophil cytoplasmic antibody-associated vasculitis into one of the three antineutrophil cytoplasmic antibody-associated vasculitis diseases. The classification was in accordance with the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria when considering the order of application., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field., Methods: Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added., Results: We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy., Conclusions: The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase II part of this phase Ib/II study assessed the efficacy/safety of E7389-LF in combination with nivolumab in several disease cohorts; herein, we report results from the small cell lung cancer (SCLC) cohort., Experimental Design: Patients with unresectable/measurable SCLC and disease progression with first-line platinum-based chemotherapy with/without an immune checkpoint inhibitor (ICI) were enrolled to receive E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously every 3 weeks. The primary objective of this part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory assessments included overall survival (OS) and biomarkers., Results: Thirty-four patients were enrolled. By the data cut-off date (May 31, 2022), 29 (85.3%) had discontinued. Efficacy/biomarker analyses included 33 patients (1 had their diagnosis changed postenrollment); the ORR of E7389-LF plus nivolumab was 24.2% [95% confidence interval (CI): 11.1-42.3], the median PFS was 3.98 months (95% CI: 2.63-4.40), and, at a median follow-up of 10.6 months, the median OS was not reached (95% CI: not estimable). Notably, 27 of 33 patients (81.8%) had received an ICI as their prior first-line therapy. Treatment-related, treatment-emergent adverse events occurred in 97.1% (any grade) and 82.4% (grade ≥3) of enrolled patients; the most common event was neutropenia. Changes in vascular and immune-related plasma markers were observed., Conclusions: E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks showed notable antitumor activity as second-line therapy for SCLC; no new safety signals were observed compared with either agent as monotherapy., Significance: This phase II part of a phase Ib/II study assessed liposomal eribulin (E7389-LF) plus nivolumab in 34 patients with pretreated SCLC; 8 of 33 evaluable patients (including 6/27 pretreated with ICIs) had objective responses. The combination was tolerable; increases in vasculature-related biomarkers tended to correlate with responses., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Objective: The objective of this study was to compare the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria with the previous classification algorithm for anti-neutrophil cytoplasmic antibody-associated vasculitis., Methods: We used data from two nationwide, prospective, inception cohort studies. The enrolled patients were classified as having eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the new criteria; these criteria were compared with Watts' algorithm., Results: Among 477 patients, 10.7%, 9.9%, and 75.6% were classified as having EGPA, GPA, and MPA, respectively; 6.1% were unclassifiable. Three patients met both the EGPA and MPA criteria, and eight patients met both the GPA and MPA criteria. Of 78 patients with GPA classified using Watts' algorithm, 27 (34.6%) patients were reclassified as having MPA. Ear, nose, and throat involvement was significantly less frequent in patients reclassified as having MPA than in those reclassified as having GPA. Of 73 patients unclassifiable using Watts' algorithm, 62 were reclassified as having MPA. All patients reclassified as having MPA were myeloperoxidase-anti-neutrophil cytoplasmic antibody positive, and 46 had interstitial lung disease., Conclusion: Although the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria cause overlapping multiple criteria fulfilments in some patients, those items contribute to classifying unclassifiable patients using Watts' algorithm into MPA., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objectives: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan., Methods: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome., Results: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months., Conclusions: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Background: Multidisciplinary team-based integrated care (MDC) has been recommended for patients with chronic kidney disease (CKD). However, team-based specific structured care systems are not yet established. Therefore, we investigated the efficacy of MDC system and the optimal number of professionals that make up the team for maintaining kidney function and improving prognosis., Methods: This nationwide, multicenter, observational study included 2,957 Japanese patients with CKD who received MDC from 2015 to 2019. The patients were divided into four groups according to the number of professionals in the MDC team. Groups A, B, C, and D included nephrologists and one, two, three, and four or more other professionals, respectively. Changes in the annual decline in estimated glomerular filtration rate before and after MDC were evaluated. Cox regression was utilized to estimate the correlation between each group and all-cause mortality and the start of renal replacement therapy (RRT) for 7 years., Results: The change in eGFR significantly improved between before and at 6, 12, and 24 months after MDC in all groups (all p < 0.0001). Comparing group D to group A (reference), the hazard ratio (HR) for all-cause mortality and the start of the RRT was 0.60 (95% confidence interval, 0.48-0.73; p < 0.0001) after adjustment for multiple confounders. Lower HR in group D was confirmed in both diabetes and nondiabetes subgroups., Conclusion: An MDC team comprised of five or more professionals might be associated with improvements in mortality and kidney prognosis. Furthermore, MDC might be effective for treating CKD other than diabetes.

Objectives: We conducted a descriptive study of the physicians' evidence-practice gap for adults covered by the 2017 clinical practice guidelines for the management of antineutrophil cytoplasmic antibody-associated vasculitis in Japan., Methods: This web-based survey, conducted between January and February 2021, involved physicians who had treated at least five patients in the preceding year at a regional core hospital. The outcome was the physicians' experience in treating patients with microscopic polyangiitis or granulomatosis with polyangiitis [prevalence with 95% confidence intervals (CIs)], defined as treating at least 60% of their patients with the recommended therapy during the year. A modified Poisson regression analysis was performed to explore the factors associated with concordance., Results: The 202 participants included 49 pulmonologists, 65 nephrologists, 61 rheumatologists, and other physicians. The concordance was 31.5% (95% CI, 25.1-38.5) of physicians who used cyclophosphamide or rituximab for the induction of remission. Rheumatology showed the highest concordance with published evidence (risk ratio = 2.4; 95% CI, 1.10-5.22, p = .03)., Conclusions: These results suggest an evidence-practice gap, which varies substantially among subspecialties. Further studies and a new promotional initiative are necessary to close this gap in clinical practice., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

Background: Multidisciplinary care is necessary to prevent worsening renal function and all-cause mortality in patients with chronic kidney disease (CKD) but has mostly been investigated in the outpatient setting. In this study, we evaluated the outcome of multidisciplinary care for CKD according to whether it was provided in an outpatient or inpatient setting., Methods: This nationwide, multicenter, retrospective, observational study included 2954 Japanese patients with CKD stage 3-5 who received multidisciplinary care in 2015-2019. Patients were divided into two groups: an inpatient group and an outpatient group, according to the delivery of multidisciplinary care. The primary composite endpoint was the initiation of renal replacement therapy (RRT) and all-cause mortality, and the secondary endpoints were the annual decline in the estimated glomerular filtration rate (ΔeGFR) and the changes in proteinuria between the two groups., Results: Multidisciplinary care was provided on an inpatient basis in 59.7% and on an outpatient basis in 40.3%. The mean number of health care professionals involved in multidisciplinary care was 4.5 in the inpatient group and 2.6 in the outpatient group (P < 0.0001). After adjustment for confounders, the hazard ratio of the primary composite endpoint was significantly lower in the inpatient group than in the outpatient group (0.71, 95% confidence interval 0.60-0.85, P = 0.0001). In both groups, the mean annual ΔeGFR was significantly improved, and proteinuria significantly decreased 24 months after the initiation of multidisciplinary care., Conclusion: Multidisciplinary care may significantly slow deterioration of eGFR and reduce proteinuria in patients with CKD and be more effective in terms of reducing initiation of RRT and all-cause mortality when provided on an inpatient basis., Competing Interests: The 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 Abe, Hatta, Imamura, Sakurada and Kaname.)

Background: Multidisciplinary care is well established in clinical practice, but its effectiveness in patients with chronic kidney disease (CKD) remains unclear. The aim of this study was to determine whether multidisciplinary care could help to avoid worsening kidney function in patients with CKD., Methods: This nationwide study had a multicenter retrospective observational design and included 3015 Japanese patients with CKD stage 3-5 who received multidisciplinary care. We assessed the annual decrease in estimated glomerular filtration rate (ΔeGFR) and urinary protein in the 12 months before and 24 months after the start of multidisciplinary care. All-cause mortality and initiation of renal replacement therapy were investigated according to baseline characteristics., Results: Most of the patients had CKD stage 3b or higher and a median eGFR of 23.5 mL/min/1.73 m 2 . The multidisciplinary care teams consisted of health care professionals from an average of four disciplines. ΔeGFR was significantly smaller at 6, 12, and 24 months after initiation of multidisciplinary care (all P < 0.0001), regardless of the primary cause of CKD and its stage when multidisciplinary intervention was started. Urinary protein level also decreased after initiation of multidisciplinary care. After a median follow-up of 2.9 years, 149 patients had died and 727 had started renal replacement therapy., Conclusion: Multidisciplinary care may significantly slow the decline in eGFR in patients with CKD and might be effective regardless of the primary disease, including in its earlier stages. Multidisciplinary care is recommended for patients with CKD stage 3-5., Trial Registration: UMIN00004999., (© 2023. The Author(s).)

Objectives: This subgroup analysis of the randomized, double-blind, Phase 3 ADVOCATE study evaluated the efficacy and safety of avacopan compared with tapered prednisone in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis., Methods: Patients with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) received either avacopan 30 mg twice daily for 52 weeks plus prednisone-matching placebo or tapered prednisone over 20 weeks plus avacopan-matching placebo for 52 weeks. The two primary efficacy endpoints were clinical remission at Week 26 and sustained remission at Week 52., Results: Compared with the overall population (N = 330), Japanese patients (N = 21) were older and had worse renal function, and a higher proportion were female and had MPA. The proportion of Japanese patients with clinical remission at Week 26 was 9/11 (81.8%) with avacopan vs. 7/10 (70.0%) with prednisone (overall population: 72.3% vs. 70.1%) and with sustained remission at Week 52 was 8/11 (72.7%) vs. 4/10 (40.0%), respectively (overall population: 65.7% vs. 54.9%). The safety profile of avacopan was similar in Japanese patients and the overall study population., Conclusions: The efficacy and safety of avacopan in Japanese patients with MPA or GPA were comparable to that observed in the overall ADVOCATE study population., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Introduction: Atopic dermatitis is one of the most prevalent chronic skin diseases. Topical therapies continue to be the mainstay of treatment but are limited by noncompliance and side-effects from inappropriate or long-term use. Systemic therapies including cyclosporine and dupilumab have been the treatments of choice for refractory cases. However, outcomes may remain less than satisfactory, and cyclosporine use is further limited by nephrotoxicity.Upadacitinib, an oral Janus kinase inhibitor, is widely used for treating rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and has recently received approval for atopic dermatitis in the United States, Europe, Japan, and other countries. These approvals were based on results from several randomized controlled trials in which upadacitinib demonstrated better and faster response versus placebo or dupilumab., Area Covered: Therapies for atopic dermatitis are reviewed, with emphasis on drug profile, efficacy, and safety profile of upadacitinib for atopic dermatitis. In the review of the clinical trials, special focus is placed on efficacy in the Japanese population., Expert Opinion: Currently, there are several treatment options for atopic dermatitis refractory to topical therapies. However, appropriate utilization of Janus kinase inhibitors in clinical practice remains challenging, especially with regard to proper case selection, optimal timing, and appropriateness of use.

The purpose of this study was to clarify the clinical characteristics of spondyloarthritis (SpA) patients with inflammatory bowel disease (IBD) compared to those without IBD. Furthermore, among patients with SpA and IBD, we aimed to clarify what clinical characteristics lead rheumatologists to diagnose "IBD-related arthritis." Utilizing SpA and psoriatic arthritis (PsA) patients' data from an international, cross-sectional, observational study, we analyzed information on demographics and disease characteristics, dichotomizing patients by IBD status. The presence or absence of IBD was determined based on data collection of treating rheumatologists. Patients with SpA (including PsA) and IBD were also categorized based on treating rheumatologists' definitive diagnosis in regard to SpA type, and compared by whether the patients had IBD-related arthritis or not. Among 4465 SpA patients, 287 (6.4%, 95%CI 5.7-7.2%) were identified with IBD. Compared to SpA patients without IBD, patients with SpA and IBD had a longer diagnostic delay (5.1 vs. 2.9 years, p < 0.001). In patients with SpA and IBD, 111 (38.7%, 95%CI 33.0-44.6%) were diagnosed with IBD-related arthritis. Multivariable analyses showed that HLA-B27 positivity [OR = 0.35, (95%CI 0.15-0.80)], psoriasis [OR = 0.14, (95%CI 0.04-0.50)], IBD as first symptom of SpA [OR = 3.32, (95%CI 1.84-6.01)], and need for IBD-specific treatment [OR = 5.41, (95%CI 2.02-14.50)] were independently associated with the definitive diagnosis of IBD-related arthritis. Collaboration with gastroenterologists is needed to shorten the diagnostic delay in patients with SpA and IBD. The recognition of the factors for the diagnosis of "IBD-related arthritis" may lead to the elucidation of the pathogenesis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: In Japan, clinical records of patients with intractable diseases, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), are compiled into a database. This study aimed to understand the current treatment status and changes in treatment regimens from our previous survey., Methods: Using data from 2012 and 2013, patients with new-onset MPA and GPA were extracted and analysed., Results: We analysed 1278 MPA and 215 GPA patients. The average age was 71.7 and 62.7 years, respectively. Methylprednisolone pulse therapy was used in 51.2% of MPA patients and 40.5% of GPA patients; the initial prednisolone-equivalent glucocorticoid dose was 39.5 mg/day in MPA and 46.6 mg/day in GPA. Concomitant intravenous or oral cyclophosphamide (CY) was administered to 22.6% of MPA and 56.3% of GPA. Young age, bloody sputum, low serum creatinine, and high C-reactive protein levels were independently associated with CY use in MPA. Compliance with treatment protocol for Japanese patients with myeloperoxidase (MPO)-anti-neutrophilic cytoplasmic antibody-associated vasculitis study criteria or the 2011 clinical practice guidelines for rapidly progressive glomerulonephritis was 42.7% and 49.7%, respectively., Conclusions: MPA was more prevalent than GPA in the registry. Compared to patients with GPA, MPA patients were older and used CY less frequently. No apparent changes in treatment trends were observed from the previous survey., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There are particularly few reports on kidney transplantation after hematopoietic stem cell transplantation (HSCT) for malignant lymphoma, and none of the cases reported a favorable outcome in patients who received kidney transplantation from a different donor to HSCT. In this report, we describe the first case of kidney transplantation from a different donor to HSCT with a successful outcome. Furthermore, we reviewed the previously reported cases. A 59-year-old female patient received an HSCT from her younger brother after chemotherapy for malignant lymphoma. After HSCT, she did not have graft-versus-host disease (GVHD) requiring maintenance treatment. The patient developed chronic kidney disease requiring kidney replacement therapy, probably due to drug toxicity or cardio-renal syndrome. At age 65, she underwent an ABO-compatible, HLA-A, -B, -DR 5/6 mismatched kidney transplantation from her husband. Immunosuppressive therapy with tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab was administered. The patient had urinary tract infections at 7 days, 9 weeks, and 4 months after kidney transplantation, and cytomegalovirus antigenemia at 9 weeks after kidney transplantation, which improved with antibiotic and valganciclovir, respectively. When each infection occurred, we weakened immunosuppressive therapy. Four years after kidney transplantation, the patient is in good clinical condition with a serum creatinine of 1.2 mg/dL, without critical infection or malignancy. In this case, we believe that it was important to optimize the immunosuppressive therapy. In addition, from a review of previous cases, it seemed important that there was no GVHD requiring maintenance therapy in order to prevent excessive immunosuppression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10-30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)