Nationwide epidemiological survey of juvenile idiopathic arthritis during transition to young adulthood in Japan using the National Database of Designated Incurable Diseases of Japan.

Objectives We aimed to assess the unmet medical needs of young adult patients with juvenile idiopathic arthritis by evaluating real-world treatment data. Methods We analyzed data on juvenile idiopathic arthritis in the 20-29 age group from the National Database of Designated Incurable Diseases of Japan, which records severe cases or those requiring high-cost medical care registered between April 2018 and March 2020. Results Overall, 322 patients with juvenile idiopathic arthritis transitioning to adulthood were included. A high frequency of methotrexate use was observed among all juvenile idiopathic arthritis subtypes. The frequency of methotrexate use at registration was significantly higher in patients with rheumatoid factor-positive polyarthritis and those with oligoarthritis or polyarthritis than in those with systemic arthritis. The historical use percentage of any biological disease-modifying antirheumatic drug was ≥85% for all juvenile idiopathic arthritis subtypes. The proportion of patients with ≥2 biological disease-modifying antirheumatic drug prescriptions was significantly higher in patients with rheumatoid factor-positive polyarthritis than in those with systemic arthritis. Conclusions High-cost drugs were necessary for many patients with juvenile idiopathic arthritis transitioning to young adulthood and registered in the database. Further studies on the medical interventions and support for these patients are needed.

Pregnancy and childbirth in Takayasu arteritis in Japan: A nationwide retrospective study.

OBJECTIVES: This study aimed to understand the status quo of medical treatments of the primary disease and pregnancy outcomes in patients with Takayasu arteritis (TAK) and children's birth outcomes. METHODS: This study retrospectively enrolled patients with TAK who conceived after the disease onset and were managed at medical facilities participating in the Japan Research Committee of the Ministry of Health, Labor, and Welfare for Intractable Vasculitis. RESULTS: This study enrolled 51 cases and 68 pregnancies 2019-2021. Of these, 48 cases and 65 pregnancies (95.6%) resulted in delivery and live-born babies. The median age of diagnosis and delivery was 22 and 31, respectively. Preconception therapy included prednisolone (PSL) in 51 (78.5%, median 7.5 mg/day), immunosuppressants in 18 (27.7%), and biologics in 12 (18.5%) pregnancies. Six cases underwent surgical treatment before pregnancy. Medications during pregnancy included PSL in 48 (73.8%, median: 9 mg/day), immunosuppressants in 13 (20.0%), and biologics in 9 (13.8%) pregnancies. Enlargement of an aneurysm was reported in one pregnancy, which might be associated with increased circulating plasma volume. TAK relapsed in 4 (6.2%) and 8 (12.3%) pregnancies during pregnancy and after delivery, respectively. Additionally, 13/62 (20.9%) preterm infants and 17/59 (28.8%) low birth weight infants were observed, and none had serious postnatal abnormalities. Of the 51 confirmed infants, 42 (82.4%) were exclusively breastfed or mixed with formula. CONCLUSION: Most pregnancies in TAK were manageable with PSL at ≤10 mg/day. Relapse during pregnancy and postpartum occurred in <20% of pregnancies.

Low-Dose Glucocorticoids in Older Patients with Rheumatoid Arthritis: What Does the Evidence Say?

The short-term use of glucocorticoids (GCs) in combination with methotrexate was recommended for the initial treatment of rheumatoid arthritis by the European League Against Rheumatism. A randomized controlled trial (GLORIA) showed that treatment of older patients with low-dose GCs in combination with disease-modifying anti-rheumatic drugs was more efficacious than disease-modifying anti-rheumatic drugs plus placebo in terms of disease activity control and prevention of joint destruction. Glucocorticoid-related adverse events were likely to increase relative to placebo, with no increase in serious adverse events and fractures over 2 years. Observational studies showed an increased risk of serious infections, cardiovascular events, and fractures associated with long-term continuation of GCs in older patients, but the adverse events may be associated not only with GC toxicity but also with poor disease control of rheumatoid arthritis. In the GLORIA study, low-dose GCs during 2 years could be tapered off safely, but many patients had a flare of disease activity after discontinuation of GCs. In the two representative large Japanese registries (IORRA and NinJa), the proportion of patients using GCs and non-tumor necrosis factor inhibitors increased with increasing age at disease onset, with a decreasing trend in methotrexate use. The proportion of patients in remission with GC treatment also increased with increasing age at onset. These suggested that it is not easy to discontinue GCs in older patients. If GCs cannot be terminated in the short term, it may be acceptable to use GCs to control disease activity for up to 2 years.

A preliminary survey of rheumatologists on the management of late-onset rheumatoid arthritis in Japan.

Objectives We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice. Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses. Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation. Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA.

Challenges Nurses Face in Providing Care for Patients with Juvenile Idiopathic Arthritis.

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 with caring for JIA patients. Data was analyzed using qualitative content analysis. RESULTS: Responses were collected from 89 participants. 58 issues were identified from 40 participants with experience caring for JIA patients. Sixteen categories emerged, 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, grouped into two challenges: expertise and opportunity. Issues included in expertise between both groups were similar. Even with no experience caring for JIA patients, nurses recognized the importance of acquiring knowledge. CONCLUSION: 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, is crucial to improve treatment outcome and overall patient quality of life.

The real-world clinical decisions of physicians in the management of Takayasu arteritis and giant cell arteritis in Japan: A cross-sectional web-questionnaire survey.

OBJECTIVES: To access the real-world clinical management of physicians who treat Takayasu arteritis (TAK) and giant cell arteritis (GCA) after the publication of the Japanese Circulation Society (JCS) 2017 Guidelines for the Management of Vasculitis Syndrome. METHODS: This descriptive, cross-sectional study utilized self-administered electronic questionnaires, which were answered in February 2022 by physicians treating TAK or GCA and registered with Macromill Inc. RESULTS: The 329 survey respondents comprised 110 cardiologists, 110 rheumatologists, 34 cardiovascular surgeons, 24 surgeons, 35 internal medicine physicians, 13 nephrologists, and 7 pediatricians. The 2017 JCS Guidelines were the most commonly referenced information source for resolving clinical questions, accessed by 70% of respondents. Ophthalmoscopy was performed in only 50% of patients with TAK, and in 70% for GCA. The median percentages of patients who underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomography for TAK and GCA patients were 23% and 20% at diagnosis, respectively, and 10% each at follow-up within 12 months. Tocilizumab was the most frequently used medication in combination with glucocorticoids for both TAK and GCA, especially in remission induction therapy for relapsed patients. CONCLUSIONS: The majority of physician treating TAK and GCA referred to the 2017 JCS guidelines. This report clarified the current clinical practice for large vessel vasculitis in Japan, providing information for the next revision of the guidelines.

Long-term effects of abatacept on atherosclerosis and arthritis in older vs. younger patients with rheumatoid arthritis: 3-year results of a prospective, multicenter, observational study.

BACKGROUND: We aimed to reveal the effect of abatacept (ABT) on atherosclerosis in rheumatoid arthritis (RA) patients, 3-year efficacy for arthritis, and safety in a population of older vs. younger patients. METHODS: In this open-label, prospective, observational study, patients were stratified into four groups: younger (20-64 years old) and older (≥ 65 years) patients taking ABT (AY and AO) and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (CY and CO). Primary endpoints were change from baseline in mean intima-media thickness (IMT) of the common carotid artery, IMT max (bulbus, bifurcation, and internal and common carotid artery), and plaque score at Week 156. Disease activity, retention rate, and adverse effects were also evaluated. RESULTS: The ABT group (AY + AO) tended to have smaller increases in mean IMT, max IMT, and plaque score than the csDMARD group (CY + CO) at Week 156, although the differences between groups were not statistically significant. Multivariate analysis showed significantly lower increases in plaque score with ABT than with csDMARDs, only when considering disease activity at 156 weeks (p = 0.0303). Proportions of patients with good or good/moderate European League Against Rheumatism response were higher in the ABT group, without significant difference between older and younger patients. No significant differences were observed in ABT retention rates between older and younger patients. Serious adverse effects, especially infection, tended to be more frequent with ABT than with csDMARDs, although no significant differences were found. CONCLUSIONS: ABT may decelerate atherosclerosis progression and may be useful for patients with high risk of cardiovascular disease, such as older patients. TRIAL REGISTRATION NUMBER: UMIN000014913.

Consensus statement on the management of late-onset rheumatoid arthritis.

OBJECTIVES: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. METHODS: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. RESULTS: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. CONCLUSIONS: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases.

Effectiveness and safety of treat-to-target strategy for methotrexate-naïve rheumatoid arthritis patients >75 years of age.

Objectives: To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients (LORA) ≥75 or <75 years of age. Methods: Treatment was adjusted to target low disease activity with conventional synthetic DMARDs followed by biologic DMARDs (bDMARDs) in LORA ≥75 years (n = 98, mean age 80.0 years) and LORA <75 years (n = 99) with moderate-high disease activity. Achievement of Simplified Disease Activity Index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome. Results: LORA ≥75 years had more comorbidities than LORA <75 years, but SDAI and ACPA positivity were similar at baseline. Of the LORA ≥75 years, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA <75 years). Glucocorticoid use was more frequent in the LORA ≥75 years than in the LORA <75 years. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥75 than in the LORA <75. At week 156, 32.7% of the LORA ≥75 and 66.7% of the LORA <75 achieved SDAI remission (P < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥75 and 22.1% in the LORA <75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥75 [odds ratio 2.82 (95% CI 1.29. 6.14)] after adjusting for comorbidities at baseline, non-adherence to T2T and SAEs. Conclusions: It was more difficult to achieve remission in the LORA ≥75 patients than in the LORA <75 patients due to both poor treatment response and safety issues.

Systematic review for the treatment of older rheumatoid arthritis patients informing the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

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.

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.

Establishing clinical remission criteria for giant cell arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis.

OBJECTIVE: To develop a proposal for giant cell arteritis remission criteria in order to implement a treat-to-target algorithm. METHODS: A task force consisting of 10 rheumatologists, 3 cardiologists, 1 nephrologist, and 1 cardiac surgeon was established in the Large-vessel Vasculitis Group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis to conduct a Delphi survey of remission criteria for giant cell arteritis. The survey was circulated among the members over four reiterations with four face-to-face meetings. Items with a mean score of ≥4 were extracted as items for defining remission criteria. RESULTS: An initial literature review yielded a total of 117 candidate items for disease activity domains and treatment/comorbidity domains of remission criteria, of which 35 were extracted as disease activity domains (systematic symptoms, signs and symptoms of cranial and large-vessel area, inflammatory markers, and imaging findings). For the treatment/comorbidity domain, ≤5 mg/day of prednisolone 1 year after starting glucocorticoids was extracted. The definition of achievement of remission was the disappearance of active disease in the disease activity domain, normalization of inflammatory markers, and ≤5 mg/day of prednisolone. CONCLUSION: We developed proposals for remission criteria to guide the implementation of a treat-to-target algorithm for giant cell arteritis.

Organ Damage and Quality of Life in Takayasu Arteritis　- Evidence From a National Registry Analysis.

BACKGROUND: Takayasu arteritis, affecting primarily young women, damages large arteries and organs. We examined the impact of disease duration and sex on organ damage and quality of life using Japan's Intractable Disease Registry. METHODS AND RESULTS: After refining data, 2,013 of 2,795 patients were included in the study. Longer disease duration was related to a lower prevalence of disease activity symptoms, a higher prevalence of organ damage, and a higher proportion of patients requiring nursing care. Compared with men, women tended to have an earlier onset age, exhibiting longer disease duration. A higher proportion of women had aortic regurgitation and required nursing care. The proportion of female patients in employment was lower than that of the general female population, whereas no difference was observed between male patients and the general male population. Logistic regression analysis revealed that age at surveillance, brain ischemia, visual impairment/loss, and ischemic heart disease were significant factors associated with high nursing care needs (Level ≥2, with daily activity limitations). CONCLUSIONS: Early diagnosis and effective treatment, particularly to prevent brain ischemia, visual impairment, and ischemic heart disease, may improve the quality of life of patients with Takayasu arteritis, especially women.

Comparison between rheumatoid arthritis with malignant lymphoma and other malignancies: Analysis of a National Database of Rheumatic Disease in Japan.

BACKGROUND: The background status and the current treatment options of patients with rheumatoid arthritis (RA) who develop malignant lymphoma (ML) and other malignancies are unclear. This study investigated the differences in background factors between ML and other malignancies that occur in RA patients and post-malignancy treatment. METHODS: We identified 935 RA patients with new-onset malignancies among 110,571 person-years registered in the National Database of Rheumatic Disease in Japan from 2012 to 2018. Analysis cohorts 1 and 2 included 597 and 490 patients with available data for 1 year before and after the development of malignancies, respectively. Factors associated with the development of ML were longitudinally evaluated by multiple logistic regression analyses. RESULTS: Of the 935 patients (mean age 70.5, standard deviation 9.9), 15.5% had ML; this was comparable to the rate of lung cancer (14.3%). In cohort 1, methotrexate (MTX), biological disease-modifying anti-rheumatic drugs (bDMARDs), and non-steroidal anti-inflammatory drugs (NSAIDs) were used in 74.4%, 23.4%, and 56.7% of ML and in 56.8%, 25.4%, and 35.3% of other malignancies 1 year before the occurrence of malignancies. Clinical disease activity index (CDAI) and C-reactive protein were similar between the two groups. Multivariable analysis showed that MTX use (odds ratio [OR]: 2.22, 95% CI [confidence interval]: 1.32-3.73, p=0.003) and NSAID use (OR: 2.51, 95% CI: 1.58-3.98, p <0.001) were significantly associated with the development of ML versus other malignancies. However, this association was not observed with bDMARDs. In cohort 2, one year after the development of malignancies, MTX was used in none of ML and 41.8% of patients who developed other malignancies. In both malignancy groups, approximately 15% of patients received bDMARDs and 50% received glucocorticoids. IL-6 inhibitors were preferentially prescribed in patients with ML versus those with other malignancies. At year 1, CDAI remission was achieved in 37.3% and 31.1% of patients in the ML and other malignancy groups, respectively. CONCLUSION: Patients receiving long-term treatment with MTX and NSAIDs may be at a relatively high risk of developing ML. The treatment landscape after developing malignancies differed considerably between patients with ML and other malignancies, and different treatment strategies should be established.

Challenges faced by nurses engaged in rheumatology care in Japan.

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-centered 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.

Granulomatosis with Polyangiitis Complicated by Severe Exudative Retinal Detachment and Orbital Granuloma Successfully Controlled with Rituximab: A Case Report.

We report a rare case of severe exudative retinal detachment with orbital granuloma associated with granulomatosis with polyangiitis (GPA). A 42-year-old man developed bilateral conjunctival hyperemia and eye pain 15 months before presenting to us. Because vitreous cells and retinal detachment were detected in his left eye, he was referred to us for further evaluation. The left eye showed scleral edema, cells in the anterior chamber and anterior vitreous, exudative retinal detachment, and elevated white subretinal lesions from the nasal to the inferior parts of the eye fundus. Orbital contrast-enhanced magnetic resonance imaging revealed a granulomatous lesion, retinal detachment, and fluid retention in the left eyeball. Comprehensive rheumatological evaluation revealed proteinase 3 anti-neutrophil cytoplasmic antibody positivity and a history of otitis media, leading to a GPA diagnosis. Methylprednisolone 1,000 mg/day was administered intravenously for 3 days, followed by oral prednisolone and intravenous cyclophosphamide. Although the retinal detachment decreased, scleritis and choroidal detachment relapse were observed in the left eye after the fifth cyclophosphamide administration. After switching from cyclophosphamide to rituximab, the scleritis and choroidal detachment resolved. Remission was successfully maintained with biannual rituximab administration. In this case, we conclude that rituximab was important to re-induce and maintain remission after recurrence. Collaboration with a rheumatologist is essential for proper treatment in related cases. This is the first report of ultra-widefield and multimodal imaging for retinal detachment associated with GPA.

Association of HLA-class II alleles with risk of relapse in myeloperoxidase-antineutrophil cytoplasmic antibody positive vasculitis in the Japanese population.

Background: Disease relapse remains a major problem in the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In European populations, HLA-DPB1*04:01 is associated with both susceptibility and relapse risk in proteinase 3-ANCA positive AAV. In a Japanese population, we previously reported an association between HLA-DRB1*09:01 and DQB1*03:03 with susceptibility to, and DRB1*13:02 with protection from, myeloperoxidase-ANCA positive AAV (MPO-AAV). Subsequently, the association of DQA1*03:02, which is in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, with MPO-AAV susceptibility was reported in a Chinese population. However, an association between these alleles and risk of relapse has not yet been reported. Here, we examined whether HLA-class II is associated with the risk of relapse in MPO-AAV. Methods: First, the association of HLA-DQA1*03:02 with susceptibility to MPO-AAV and microscopic polyangiitis (MPA) and its relationship with previously reported DRB1*09:01 and DQB1*03:03 were examined in 440 Japanese patients and 779 healthy controls. Next, the association with risk of relapse was analyzed in 199 MPO-ANCA positive, PR3-ANCA negative patients enrolled in previously reported cohort studies on remission induction therapy. Uncorrected P values (Puncorr) were corrected for multiple comparisons in each analysis using the false discovery rate method. Results: The association of DQA1*03:02 with susceptibility to MPO-AAV and MPA was confirmed in a Japanese population (MPO-AAV: Puncorr=5.8x10-7, odds ratio [OR] 1.74, 95% confidence interval [CI] 1.40-2.16, MPA: Puncorr=1.1x10-5, OR 1.71, 95%CI 1.34-2.17). DQA1*03:02 was in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, and the causal allele could not be determined using conditional logistic regression analysis. Relapse-free survival was shorter with nominal significance in carriers of DRB1*09:01 (Puncorr=0.049, Q=0.42, hazard ratio [HR]:1.87), DQA1*03:02 (Puncorr=0.020, Q=0.22, HR:2.11) and DQB1*03:03 (Puncorr=0.043, Q=0.48, HR:1.91) than in non-carriers in the log-rank test. Conversely, serine carriers at position 13 of HLA-DRß1 (HLA-DRß1_13S), including DRB1*13:02 carriers, showed longer relapse-free survival with nominal significance (Puncorr=0.010, Q=0.42, HR:0.31). By combining DQA1*03:02 and HLA-DRß1_13S, a significant difference was detected between groups with the highest and lowest risk for relapse (Puncorr=0.0055, Q=0.033, HR:4.02). Conclusion: HLA-class II is associated not only with susceptibility to MPO-AAV but also with risk of relapse in the Japanese population.

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.

Non-drug and surgical treatment algorithm and recommendations for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

OBJECTIVES: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) and prepare an algorithm for non-drug and surgical treatments. This article is a digest version of the guidelines. METHODS: The Japanese Ministry of Health, Labour and Welfare's research group, in collaboration with the JCR, used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. The consensus was formed by CPG panel members. RESULTS: We raised 19 clinical questions regarding non-drug and surgical treatments for RA and developed recommendations. The treatments included exercise therapy; occupational therapy; joint injection of corticosteroids; and orthopaedic surgeries including cervical spine surgery, wrist and foot arthroplasty, ankle arthrodesis, and replacement arthroplasty of the shoulder, elbow, finger, hip, knee, and ankle. Recommendations regarding the risks of surgery and perioperative discontinuation of medications have also been developed. Based on these recommendations, we created an original algorithm for the non-drug and surgical treatment of RA. CONCLUSIONS: These recommendations are expected to serve rheumatologists, health care professionals, and patients with RA as tools for shared decision-making to treat residual limb joint symptoms and functional impairment.

Drug treatment algorithm and recommendations from the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

OBJECTIVE: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA; JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members. RESULTS: We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-receptor activator for nuclear factor-κB ligand antibodies, and Janus kinase inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach. CONCLUSION: The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision-making in a variety of clinical situations.