Predictors of damage accrual in patients with antineutrophil cytoplasmic antibody-associated vasculitis: A nationwide prospective study.

OBJECTIVES: This study elucidated the prognosis and risk factors associated with damage accrual during long-term remission maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We obtained data from 120 patients registered in a nationwide prospective cohort study on remission induction therapy in Japanese patients with AAV and rapidly progressive glomerulonephritis (RemIT-JAV-RPGN), who achieved remission at 24 months after treatment initiation and were followed up for additional 24 months. The primary outcome was the vasculitis damage index (VDI) score at Month 48, and the secondary outcome included risk factors associated with increased total VDI at Month 48. RESULTS: The understudied patients comprised 52 men and 68 women aged 68 ± 13 years. Between Months 25 and 48, the patients' survival rate was 95% (114/120). End-stage renal disease developed in seven patients by Month 48, and 64 cases had increased VDI. The multivariable analysis results revealed that oral prednisolone (PSL) doses at Month 24 were associated with damage accrual between Months 24 and 48. CONCLUSIONS: VDI accrual was observed in more than half of patients with AAV during maintenance therapy, and increased VDI scores were associated with oral PSL doses 24 months after initiating remission induction therapy in Japan.

Evaluation of Ministry of Health, Labour and Welfare diagnostic criteria for antineutrophil cytoplasmic antibody-associated vasculitis compared to ACR/EULAR 2022 classification criteria.

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.

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

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

Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of microscopic polyangiitis and granulomatosis with polyangiitis: The 2023 update - secondary publication.

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.

Ixekizumab Efficacy in Patients with Severe Peripheral Psoriatic Arthritis: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (SPIRIT-P1).

INTRODUCTION: The efficacy and safety of ixekizumab, an anti-interleukin-17A antibody, in patients with severe symptoms of psoriatic arthritis are largely unexplored. We report the efficacy and safety of ixekizumab in a post hoc analysis of the SPIRIT-P1 trial. METHODS: Patients were treated with placebo, ixekizumab 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), or adalimumab 40 mg Q2W for 24 weeks. In this subgroup analysis of SPIRIT-P1, the population with severe psoriatic arthritis was defined using the modified composite psoriatic activity index total score > 7 and peripheral arthritis score = 3 (> 4 tender or swollen joint count and ≥ 0.5 Health Assessment Questionnaire-Disability Index). Efficacy was measured by joint and skin endpoints including disease progression. RESULTS: In the severe population, significantly more patients (p ≤ 0.001) treated with ixekizumab than placebo achieved 20% improvement according to the American College of Rheumatology criteria (ACR 20): 63.3% for ixekizumab Q4W, 60.4% for ixekizumab Q2W, and 24.5% for placebo. Statistically greater responses compared with placebo were observed in the severe population for ACR 50, ACR 70, ACR core set, disease activity index for psoriatic arthritis (DAPSA) low disease activity and DAPSA remission, and 28-joint disease activity score using C-reactive protein, as well as Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 (p ≤ 0.001). Efficacy findings and the safety profile of ixekizumab in the severe population were consistent with those of the overall population, with no new safety concerns identified. CONCLUSIONS: In patients with severe psoriatic arthritis, 24 weeks of treatment with ixekizumab resulted in improvements in both joint and skin symptoms. The safety profile in the severe population was consistent with the established safety profile of ixekizumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01695239.

Immunological disease activity parameters at conception are risk factors for preterm birth and low birth weight in patients with systemic lupus erythematosus.

OBJECTIVE: This study aimed to identify which disease activity parameters may be risk factors for preterm birth (PB) and low birth weight (LBW) in patients with systemic lupus erythematosus (SLE). We also analyzed the extent to which these parameters affected PB and LBW. METHODS: We collected the SLE Disease Activity Index (SLEDAI), the rate of lupus low disease activity state (LLDAS) attainment, complement levels, and the titer of anti-double stranded DNA (dsDNA) antibody as disease activity parameters. We retrospectively analyzed the associations of these parameters with PB and LBW. RESULTS: Sixty pregnancies were included in this study. C3 levels and anti-dsDNA antibody titers at conception were strongly associated with PB (p = 0.03 and p = 0.01, respectively), whereas C3 and CH50 levels were associated with LBW (p = 0.02 and p = 0.03, respectively). A logistic regression analysis showed that the cutoff values of C3 and anti-dsDNA antibody for PB were 62.0 mg/dl and 5.4 IU/ml, respectively. The cutoff values of C3 and CH50 for LBW were 87.0 mg/dl and 41.8 U/ml, respectively. The risk of PB or LBW was increased when divided by the cutoff value, and the combination of these cutoff values showed a significantly higher risk of PB and LBW (p = 0.01 and p < 0.01, respectively). CONCLUSIONS: PB and LBW are strongly associated with disease activity parameters in patients with SLE. Therefore, strictly monitoring and controlling these disease activity parameters, with or without clinical manifestation, is important for women who want to become mothers.

Colchicine-responsive chronic recurrent multifocal osteomyelitis associated with familial Mediterranean fever in the presence of MEFV mutation: A case report.

A 38-year-old female was referred with a history of fever, polyarthralgia, and bone pain. She was diagnosed with chronic recurrent multifocal osteomyelitis based on imaging and biopsy findings. Non-steroidal anti-inflammatory drugs and bisphosphonate caused no improvement. Then, she developed recurrent diarrhoea and abdominal pain. Genetic testing revealed MEFV mutation. Based on the symptoms and genetic mutation results that emerged during the course of these events, she was diagnosed with familial Mediterranean fever. All symptoms, including bone pain, improved with daily colchicine administration. This case was considered familial Mediterranean fever complicated with a clinical diagnosis of chronic recurrent multifocal osteomyelitis, which is included in the spectrum of pyrine autoinflammatory diseases. Considering this case, patients with chronic recurrent multifocal osteomyelitis with MEFV gene variants may respond to colchicine.

Pregnancy course and outcomes of patients with polymyositis and dermatomyositis (PM/DM) managed in a single center.

We aimed to determine the association between disease activity during pregnancy and pregnancy outcomes of women with polymyositis and dermatomyositis (PM/DM). Patients with PM/DM who were managed from pregnancy to delivery at Kagawa University Hospital from March 2006 to May 2021 were enrolled. Clinical data were retrospectively analyzed to evaluate the association between disease activity during pregnancy and pregnancy outcomes. Eight pregnancies in 5 women with PM/DM were analyzed. The mean age at conception was 28.3 ± 3.8 years, and mean disease duration was 6.3 ± 3.2 years. Four patients required an increased glucocorticoid dosage because of worsening disease activity (sustained elevation of creatine phosphokinase [CPK] concentration). Two patients who continuously received immunosuppressive drugs from conception to delivery showed no increase in disease activity and did not need increased glucocorticoid dosages. The pregnancy outcomes were 1 spontaneous abortion and 7 live births. The mean gestation length was 35.3 ± 5.2 weeks, and mean birthweight was 2297.7 ± 1041.4 g. Five adverse pregnancy outcomes (APOs) occurred (2 preterm births and 4 low birthweights); most of these cases had sustained elevation of CPK concentration and increased glucocorticoid dosages. No APOs occurred in the 2 patients who received continuous immunosuppressive medication. Continued use of pregnancy-compatible medications and control of disease activity with lower glucocorticoid dosages in pregnancies with PM/DM may be important to achieve good pregnancy outcomes.

The management of women of childbearing age with rheumatoid arthritis: an expert report.

INTRODUCTION: The introduction of biologic therapies and a treat-to-target approach has transformed the management of rheumatoid arthritis (RA), which has led to improved outcomes for women with RA who wish to become pregnant. However, guidelines for the management of reproductive health in female patients with RA are still lacking. AREAS COVERED: A task force (Women of Childbearing Age [WoCBA]-Rheumatoid Arthritis in Japan) comprising 10 experts in the fields of rheumatology, obstetrics and orthopedic surgery developed 10 clinical questions (CQ) related to the management of WoCBA with RA. For each CQ, a systematic literature review was conducted to identify relevant evidence. Based on this evidence, a set of recommendations for each CQ were drafted and evaluated using the modified Delphi method. This article describes the agreed recommendations along with the supporting evidence. EXPERT OPINION: There are many ongoing challenges associated with the provision of reproductive healthcare in WoCBA with RA. It is hoped that the consensus-based recommendations provided here can be implemented in clinical practice in order to increase collaboration between rheumatologists and obstetricians/gynecologists and to improve reproductive health outcomes for WoCBA with RA.

Feasibility of whole-body 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography angiography using continuous bed motion in patients with vascular disease: a pilot study.

OBJECTIVE: Positron emission tomography (PET) angiography is a promising PET imaging method for vessel evaluation. With advances in PET technologies, PET angiography of the whole body is now possible using continuous bed motion (CBM) mode. This study aimed to evaluate the image quality for depicting the aorta and main branches and the diagnostic performance of whole-body PET angiography in patients with vascular disease. METHODS: We retrospectively identified 12 consecutive patients who underwent whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET angiography in CBM mode. Whole-body PET angiography was performed between 20 and 45 s after administering [18F]FDG using CBM from the neck to the pelvis. The visibility of whole-body PET angiography was assessed for the 24 segments in three regions per patient using a 4-point grading scale (1, unacceptable; 2, poor; 3, good; 4, excellent), and grades 3 and 4 were considered diagnostic. The diagnostic accuracy of whole-body PET angiography for detecting vascular abnormalities was calculated using contrast-enhanced CT as a reference standard. RESULTS: We evaluated 285 segments from 12 patients, and overall, 170/285 segments (60%) were considered diagnostic throughout the whole body, including 96/117 (82%), 22/72 (31%), and 52/96 (54%) segments in the neck-to-chest region, abdominal region, and pelvic region, respectively. The sensitivity, specificity, and accuracy of whole-body PET angiography for detecting vascular abnormalities were 75.9%, 98.8%, and 96.5%, respectively. CONCLUSIONS: Whole-body PET angiography showed a better image quality for the neck-to-chest and pelvic regions in this setting, although it provided limited information on the vessels in the abdominal region.

[18F] FDG uptake in patients with spondyloarthritis: correlation with serum inflammatory biomarker levels.

BACKGROUND: We aimed to evaluate the correlation between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake and disease activity assessed by serum inflammatory biomarker levels in patients with spondyloarthritis (SpA). METHODS: A total of 36 SpA patients (24 untreated and 12 treated) were examined using FDG positron emission tomography (PET)/computed tomography and classified into axial SpA (axSpA) and peripheral SpA (pSpA). FDG uptake was evaluated in 23 regions of the body and scored as follows: 0 = less than liver uptake; 1 = more than or equal to liver uptake; and 2 = more than or equal to twice liver uptake. A score of 1 or 2 was considered positive. The number of positive regions and the total score were counted in each patient. The maximum standardized uptake value (SUVmax) was calculated for each region, and maximum SUVmax (MaxSUVmax) was used as a representative value. Correlation of PET findings with serum inflammatory biomarker levels, including C-reactive protein (CRP), erythrocyte sedimentation rate, and matrix metalloproteinase 3 (MMP-3), was analyzed. RESULTS: All but two patients had at least one positive lesion. PET indices correlated significantly with most of the serum inflammatory biomarker levels in untreated SpA, but not in treated SpA. Further, MaxSUVmax, number of positive regions, and total score correlated significantly with CRP (all P values < 0.001), and the number of positive regions (P = 0.012) and total score (P = 0.007) correlated significantly with MMP-3 in untreated pSpA. PET indices did not correlate with any serum inflammatory biomarker level in untreated axSpA. CONCLUSION: FDG uptake in untreated pSpA correlated significantly with serum inflammatory biomarker levels.

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

OBJECTIVES: Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum. METHODS: In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24. RESULTS: 254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low. CONCLUSIONS: Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

Validation of new ACR/EULAR 2022 classification criteria for anti-neutrophil cytoplasmic antibody-associated vasculitis.

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.

Association between the patterns of large-vessel lesions and treatment outcomes in patients with large-vessel giant cell arteritis.

OBJECTIVES: We aimed to identify associations between patterns of large-vessel lesions of large-vessel giant cell arteritis (LV-GCA) and treatment outcomes. METHODS: We extracted data on 68 newly diagnosed patients with LV-GCA from a retrospective, multi-centric, nationwide registry of GCA patients treated with glucocorticoids between 2007 and 2014. Patients with aortic lesions were identified based on the findings from contrast-enhanced computed tomography, magnetic resonance imaging, or positron emission tomography-computed tomography (Group 2, n = 49). Patients without aortic lesions were subdivided into LV-GCA with or without subclavian lesions defined as Group 1 (n = 9) or Group 3 (n = 10), respectively. The primary outcome evaluation was failure to achieve clinical remission by Week 24 and/or relapse within 104 weeks. RESULTS: The mean age and proportion of patients with cranial lesions and polymyalgia rheumatica in Group 2 were numerically lower than in the other two groups. Large-vessel lesions in Group 3 included carotid, pulmonary, renal, hepatic, or mesenteric lesions. The cumulative rate of poor treatment outcomes >2 years was 11.1%, 55.3%, and 88.0% in Groups 1, 2, and 3, respectively (by Kaplan-Meier analysis). The mean time to poor outcome was significantly different between the groups. CONCLUSIONS: Classification by subclavian and aortic lesions may be useful to determine treatment strategy.

Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

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.

A multicentre study of clinical features and HLA typing in Japanese patients with ankylosing spondylitis.

OBJECTIVES: Due to the low prevalence of HLA-B27 and ankylosing spondylitis (AS) in Japan, rheumatologists have little experience with AS. We conducted a multicentre study to identify the characteristics and frequency of HLA-B types. METHODS: We analysed epidemiological and clinical data, blood tests, spine radiographs, and HLA-B types in Japanese AS patients. RESULTS: We evaluated 111 AS patients, predominantly men (82.9%). The mean age, disease onset, diagnosis, and time from onset to diagnosis were 43.7, 24.2, 36.0, and 11.6 years, respectively. Inflammatory low back pain was found in 96 cases (86.5%); peripheral arthritis in 59 (53.2%), enthesitis in 35 (31.5%), and dactylitis in 6 (5.4%). Extra-articular symptoms included uveitis, psoriasis, and inflammatory bowel disease in 41 (36.9%), 1 (0.9%), and 5 (4.5%) cases, respectively. HLA-B27 was positive in 83 cases (74.8%; odds ratio, 1146.0); and HLA-B48 in 9 (8.1%; odds ratio, 3.0). HLA-B27-positive patients were younger at onset and had a shorter diagnostic delay. CONCLUSIONS: AS clinical symptoms were almost the same as other countries except for the low coexistence of psoriasis. HLA-B27 positivity in Japanese patients was 78%. HLA-B27-positive patients were younger and diagnosed earlier. In addition to HLA-B27, a relationship with HLA-B48 was suggested.

Efficacy and safety of avacopan in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: A subanalysis of a randomized Phase 3 study.

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.

Chemoprophylaxis against Pneumocystis jirovecii pneumonia in Japanese patients with ANCA-associated vasculitis: An observational study.

OBJECTIVES: This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP. RESULTS: Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of them remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and the proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53). CONCLUSIONS: The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, although the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.