OBJECTIVE:We investigated the factors associated with treatment discontinuation and safety of abatacept treatment up to 5 years as the first-line biologic in Japanese patients with rheumatoid arthritis (RA) of moderate disease activity (MDA). METHODS:We analyzed 5-year data from the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study (UMIN000021263). We examined the factors associated with treatment discontinuation, overall and age-stratified safety, and effectiveness. RESULTS:Among 279 analyzed patients, the cumulative incidence (95% CI) of discontinuation was 0.210 (0.158-0.262) for insufficient effectiveness and 0.266 (0.208-0.323) for adverse events (AEs). Older age (subdistribution hazard ratio [95% CI] 0.970 [0.946-0.995]; P = .018) and anti-citrullinated peptide antibody-positive status (0.284 [0.140-0.575]; P < .001) were associated with lower risk of discontinuation due to insufficient effectiveness. Presence of comorbidities was associated with greater risk of discontinuation due to AEs. The frequencies of AEs and adverse drug reactions remained stable or decreased over time. The safety was consistent with prior analyses of ORIGAMI and comparable among three age groups (<65, ≥65 to <75, and ≥75 years). CONCLUSIONS:Five-year results of the ORIGAMI study provide further evidence supporting the factors associated with long-term treatment continuation and safety of subcutaneous abatacept in patients with RA of MDA.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.This article has been retracted at the request of the author. This study was conducted under the supervision of author Takako Miyamae as the principal investigator and was approved by the central ethics review board of Tokyo Women's Medical University. However, at the final stage of the peer-review process, it became apparent that one of the participating institutions had continued involvement in the study without securing approval from its own institutional review board.As a result, the data from 12 patients at that institution cannot be included in the analysis. Following internal review, Tokyo Women's Medical University determined that action needed to be taken and the authors and Editor-in-Chief agreed with this conclusion.

Objective:Rheumatoid arthritis (RA) is classified into seropositive (SP-RA) and seronegative (SN-RA) types, reflecting distinct immunological profiles. This study aimed to identify the T cell phenotypes associated with each type, thereby enhancing our understanding of their unique pathophysiological mechanisms. Methods:We analyzed peripheral blood T cells from 50 participants, including 16 patients with untreated SP-RA, 17 patients with SN-RA, and 17 healthy controls, utilizing 25 T cell markers. For initial analysis, a dataset was established through manual T cell subset gating analysis. For advanced analysis, two distinct datasets derived from a self-organizing map algorithm, FlowSOM, were used: one encompassing all CD3+ T cells and another focusing on activated T cell subsets. Subsequently, these datasets were rigorously analyzed using adaptive least absolute shrinkage and selection operator in conjunction with leave-one-out cross-validation. This approach enhanced analysis robustness, identifying T cell clusters consistently discriminative between SP-RA and SN-RA. Results:Our analysis revealed significant differences in T cell subsets between RA patients and healthy controls, including elevated levels of activated T cells (CD3+, CD4+, CD8+) and helper subsets (Th1, Th17, Th17.1, and Tph cells). The Tph/Treg ratio was markedly higher in SP-RA, underscoring an effector-dominant immune imbalance. FlowSOM-based clustering identified 44 unique T cell clusters, six of which were selected as discriminative T cell clusters (D-TCLs) for distinguishing SP-RA from SN-RA. TCL21, an activated Th1-type Tph-like cell, was strongly associated with SP-RA's aggressive profile, while TCL02, a central memory CD4+ T cell subset, displayed ICOS+, CTLA-4low+, PD-1low+, and CXCR3+, providing insights into immune memory mechanisms. Additionally, TCL31 and TCL35, both CD4-CD8- T cells, exhibited unique phenotypes: CD161+ for TCL31 and HLA-DR+CD38+TIM-3+ for TCL35, suggesting distinct pro-inflammatory roles. Support vector machine analysis (bootstrap n = 1000) validated the D-TCLs' discriminative power, achieving an accuracy of 86.2%, sensitivity of 85.7%, and specificity of 80.9%. Conclusions:This study advances our understanding of immunological distinctions between SP-RA and SN-RA, identifying key T cell phenotypes as potential targets for SP-RA disease progression. These findings provide a basis for studies on targeted therapeutic strategies tailored to modulate the markers and improve treatment for SP-RA.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis primarily affecting the respiratory tract and kidneys, with external genital and urethral lesions (EGUL) being exceedingly rare. We present a case of a middle-aged man with relapsing proteinase 3-antineutrophil antibody-positive GPA who developed isolated granulomatous, ulcerative balanitis, and urethritis. His condition abruptly worsened after a prolonged indolent course, requiring treatment with glucocorticoids and rituximab, leading to successful remission. To better characterize EGUL in GPA, a systematic literature search was performed in PubMed, Scopus, and the NPO Japanese Society of Medical Abstracts databases using keywords related to GPA and EGUL. Cases meeting the American College of Rheumatology or Japanese Ministry of Health, Labor, and Welfare criteria for GPA and the 2012 Chapel Hill Consensus Conference definitions were included for analysis. Our review identified that EGUL often presents as an initial symptom and can be classified by the presence or absence of preceding urethritis. Cases with preceding urethritis had a higher risk of severe complications with extensive penile or urethral involvement. In contrast, penile lesions without preceding urethritis typically presented as characteristic mucosal lesions localized around the glans. In females, GPA-associated urethritis frequently led to periurethral mass formation, vaginal involvement, and significant sequelae. Given the potential for delayed diagnosis and serious complications, clinicians should be vigilant for EGUL in patients with suspected or diagnosed GPA. Future prospective studies with larger cohorts are needed to elucidate the prevalence, clinical spectrum, and optimal management of these rare but significant manifestations of GPA.

This study evaluates the long-term effectiveness and safety of methotrexate-tacrolimus combination therapy compared to methotrexate monotherapy in maintaining successful tumor necrosis factor (TNF) inhibitor discontinuation in rheumatoid arthritis (RA) patients. We retrospectively analyzed consecutive RA patients who discontinued TNF inhibitors after achieving disease control by October 2022 and received either methotrexate monotherapy or methotrexate-tacrolimus combination therapy for up to 10 years. Per-observation time-to-event analyses assessed treatment failure, treatment intensification, first disease flare, and irreversible functional deterioration. Mixed-effects Cox models, time-dependent Cox models without random effects, and Kaplan-Meier estimates with inverse probability weighting were applied. Safety assessment included treatment-limiting adverse events and renal function trends. A total of 147 treatment lines (96 methotrexate monotherapy and 51 combination therapy) in 116 patients were analyzed. The combination therapy significantly reduced treatment failure (hazard ratio [HR], 0.42; 95

We report a fatal case of hepatic portal venous gas (HPVG) following percutaneous endoscopic gastrostomy (PEG) and initiation of enteral nutrition in a 57-year-old Japanese woman with systemic sclerosis-myositis overlap syndrome complicated by pneumatosis cystoides intestinalis (PCI). She had interstitial lung disease with right heart strain, congestive heart failure, and respiratory muscle fatigue, requiring mechanical ventilation. After improvement in ventilatory failure, PEG was performed, and enteral feeding was initiated. Transient abdominal pain and recurrent vomiting developed, and computed tomography (CT) revealed intramural gastric gas and extensive HPVG. Based on the clinical course, absence of peritoneal irritation, and postmortem CT findings, gastrointestinal ischaemia or necrosis was considered unlikely. The abdominal pain was attributed to gastric overdistension with intramural dissection from luminal gas entry, while HPVG was thought to result from gas tracking from the PEG site into the portal system. The presumed mechanism involved delayed wound healing at the PEG site due to systemic sclerosis-related gastric involvement, long-term glucocorticoid therapy, and malnutrition, combined with elevated intragastric pressure from routine feeding advancement and peristalsis, enabling luminal gas to dissect into the wall. The marked reduction of PCI findings when HPVG was detected suggested that gas from PCI may have contributed to its formation. Although the exact cause of death could not be determined, gas embolism was suspected. This case underscores the need for extreme caution when initiating enteral nutrition in similar patients.

Background: This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. Methods and Results: A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at <= 10mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. Conclusions: We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

International Journal of Rheumatic DiseasesVolume 27, Issue 2 e15056 LETTER TO THE EDITOR Case report: Additional use of hydroxychloroquine in treatment-resistant recurrent cerebral infarctions with antiphospholipid antibody syndrome Shuntaro Isogai, Shuntaro Isogai Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Aichi, Japan Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorMasayuki Mizuno, Masayuki Mizuno Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorKoji Uehara, Koji Uehara Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Aichi, Japan Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorKenji Okita, Kenji Okita Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorTaio Naniwa, Corresponding Author Taio Naniwa [email protected] orcid.org/0000-0002-0489-2611 Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Aichi, Japan Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan Correspondence Taio Naniwa, Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, and Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-ku, Nagoya-city, Aichi 467-8601, Japan. Email: [email protected]Search for more papers by this author Shuntaro Isogai, Shuntaro Isogai Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Aichi, Japan Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorMasayuki Mizuno, Masayuki Mizuno Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorKoji Uehara, Koji Uehara Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Aichi, Japan Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorKenji Okita, Kenji Okita Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanSearch for more papers by this authorTaio Naniwa, Corresponding Author Taio Naniwa [email protected] orcid.org/0000-0002-0489-2611 Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Aichi, Japan Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan Correspondence Taio Naniwa, Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, and Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-ku, Nagoya-city, Aichi 467-8601, Japan. Email: [email protected]Search for more papers by this author First published: 09 February 2024 https://doi.org/10.1111/1756-185X.15056Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat CONFLICT OF INTEREST STATEMENT TN has received grants and honoraria from Asahi Kasei Pharma. The other authors declare no conflict of interest. Open Research DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. 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ABSTRACT Objectives We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. Methods The Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as a historical, weighted control group. The primary end point for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. Results Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% [95% confidence interval (CI) 34.7–46.2%] and 28.9% (95% CI 9.9–47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. Conclusions This study confirmed the 3-year effectiveness and safety and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

There have been no reports of the coexistence of allergic bronchopulmonary aspergillosis (ABPA) and granulomatosis with polyangiitis (GPA). The first case of ABPA with comorbid GPA that developed exophthalmos is reported. A 69-year-old man was referred to our hospital for exophthalmos, fever, anorexia and weight loss. The patient had been diagnosed with ABPA six years earlier, which had been repeatedly treated but recurred with oral corticosteroids with or without antifungal therapy. The laboratory data on referral showed elevations of the white blood cell count, C-reactive protein and specific immunoglobulin E against Aspergillus fumigatus, but antineutrophil cytoplasmic antibody was not positive. Urinalysis showed proteinuria. Paranasal sinus and chest computed tomography showed sinusitis with osteochondral destruction, bronchiectasis, mucus plugging, and a pulmonary nodule. Orbital magnetic resonance imaging showed swelling of the medial rectus muscle and peripheral mass. The intraorbital tissue biopsy showed a necrotic granuloma and necrotizing vasculitis. The patient was diagnosed with GPA, on the basis of the Ministry of Health, Labour and Welfare's criteria of Japan. The patient was treated with induction therapy consisting of glucocorticoids and rituximab, and his symptoms improved. Though the pathogenesis common to ABPA and GPA remains unknown, neutrophilic inflammation induced by airway Aspergillus persistent infection might be involved. Study of further cases is needed.

ABSTRACT Objectives This study aimed to understand the status quo of medical treatments 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, Labour, and Welfare for Intractable Vasculitis. Results This study enrolled 51 cases and 68 pregnancies during 2019–21. Of these, 48 cases and 65 pregnancies resulted in delivery and live-born babies. The median age of diagnosis and delivery was 22 and 31 years, 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. TAK relapsed in four (6.2%) and eight (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. Conclusions Most pregnancies in TAK were manageable with PSL at ≤10 mg/day. Relapse during pregnancy and postpartum occurred in <20% of pregnancies.

Mycobacterium chelonae, a rapidly growing mycobacterium found in the natural environment, is known to cause localized lesions in the skin, soft tissue, and bone through traumatic inoculation, but widespread lesions are uncommon. We herein report an immunocompromised 79-year-old man suspected of having polyangiitis granulomatosis due to weight loss, epistaxis, and nasal crusts with impending septal perforation who was subsequently diagnosed with mucocutaneous and bone disease caused by widespread M. chelonae infection. Given these findings, clinicians should be aware of the tendency to develop unusual widespread lesions in immunocompromised patients, which can present a clinical picture similar to systemic vasculitides, such as granulomatosis with polyangiitis.

Objectives We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naive patients with rheumatoid arthritis. Methods Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. Results At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. Conclusion The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

Objective This study sought to elucidate the molecular impacts of belimumab (BEL) treatment on T-cell immune profiling in SLE.Methods We used mass cytometry with 25 marker panels for T-cell immune profiling in peripheral blood T cells (CD3+) from 22 patients with BEL-treated SLE and 20 controls with non-BEL-treated SLE. An unsupervised machine-learning clustering, FlowSOM, was used to identify 39 T-cell clusters (TCLs; TCL01–TCL39). TCLs (% of CD3+) showing significant (p<0.05) associations with BEL treatment (BEL-TCL) were selected by a linear mixed-effects model for comparing groups of time-series data. Furthermore, we analysed the association between BEL treatment and variations in regulatory T-cell (Treg) phenotypes, and the ratio of other T-cell subsets to Treg as secondary analysis.Results Clinical outcomes: BEL treatment was associated with a decrease in daily prednisolone use (coef=−0.1769, p=0.00074), and an increase in serum CH50 (coef=0.4653, p=0.003), C3 (coef=1.1047, p=0.00001) and C4 (coef=0.2990, p=0.00157) levels. Molecular effects: five distinct BEL-TCLs (TCL 04, 07, 11, 12 and 27) were identified. Among these, BEL-treated patients exhibited increased proportions in the Treg-like cluster TCL11 (coef=0.404, p=0.037) and two naïve TCLs (TCL04 and TCL07). TCL27 showed increased levels (coef=0.222, p=0.037) inversely correlating with baseline C3 levels. Secondary analyses revealed associations between BEL treatment and an increase in Tregs (coef=1.749, p=0.0044), elevated proportions of the fraction of Tregs with inhibitory function (fTregs, coef=0.7294, p=0.0178) and changes in peripheral helper T cells/fTreg (coef=−4.475, p=0.0319) and T helper 17/fTreg ratios (coef=−6.7868, p=0.0327). Additionally, BEL was linked to variations in T-cell immunoglobulin and mucin domain-containing protein-3 expression (coef=0.2422, p=0.039).Conclusions The study suggests an association between BEL treatment and variations in T cells, particularly Tregs, in SLE pathologies involving various immune cells.

ABSTRACT 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.

AIM:Macrophage activation syndrome (MAS), a severe complication of systemic adult-onset Still's disease (AOSD), has been reported to occur during interleukin-6 (IL-6) inhibitor treatment. However, predictors for MAS development are unknown. Therefore, this study investigated predictive features for MAS development after starting IL-6 inhibitor treatment in systemic AOSD patients.METHOD:In a single-center retrospective study involving systemic AOSD patients who were refractory to high-dose glucocorticoids with immunosuppressants and started IL-6 inhibitor treatment between April 2008 and March 2020, we compared the baseline clinical features between patients who developed AOSD flare with MAS features (MAS group) and those who did not (non-MAS group) during IL-6 inhibitor treatment.RESULTS:Only tocilizumab was used as an IL-6 inhibitor. Six of 14 refractory systemic AOSD patients developed AOSD flares with MAS features during tocilizumab treatment, including 4 who developed them shortly after initiation. The MAS group had significantly lower neutrophil counts, fibrinogen, and higher IL-18/C-reactive protein (CRP) ratio at starting tocilizumab (baseline) than the non-MAS group. Before starting tocilizumab, neutrophil counts were trending downward and upward in the MAS and non-MAS groups, respectively, with significant differences in changes. Receiver operating characteristic analysis showed that baseline neutrophil counts and fibrinogen and their changes before tocilizumab treatment and baseline IL-18/CRP ratio had significant discriminatory abilities for subsequent MAS development.CONCLUSION:We identified baseline laboratory features associated with MAS development after initiating an IL-6 inhibitor in refractory systemic AOSD patients. These features may reflect the suppression of IL-6 signaling, and further suppression of IL-6 signaling might trigger early-onset MAS.

OBJECTIVE:To investigate the impact of dysphagia on long-term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathy other than inclusion body myositis.METHODS:We retrospectively evaluated consecutive patients with idiopathic inflammatory myopathy other than inclusion body myositis to investigate the impact of dysphagia and its severity assessed using the Food Intake LEVEL Scale on survival and swallowing function outcomes. Time-to-event analyses were used, including Kaplan-Meier curves with log-rank (trend) test, cumulative incidence with Gray's test, and Cox proportional hazards models.RESULTS:Of the 254 patients, 26 were dysphagic, including eight severe (Food Intake LEVEL Scale [FILS] score 2, 3) and six most severe (FILS score 1) cases; 210 were non-dysphagic, and 18 were indeterminate cases. During the 5 years after myositis diagnosis, 15 (57.7%) dysphagic and 31 (14.8%) non-dysphagic patients died, and dysphagic patients had significantly shorter survival. However, multivariate analysis showed that shorter survival was significantly associated with baseline age-adjusted Charlson Comorbidity Index (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.36-1.82]), but not with dysphagia (HR 1.46, 95% CI 0.69-3.10). Dysphagia severity was significantly associated with delayed recovery of dysphagia. In 20 non-severe or severe dysphagic cases, 19 restored swallowing function within 1 year. The most severe cases had a significantly higher cumulative probability of death before recovery from dysphagia than severe cases.CONCLUSION:The poor survival of dysphagic myositis patients was largely confounded by advanced age and comorbid malignancies. However, patients with the most severe dysphagia had a significantly worse swallowing function and survival prognosis than those with milder dysphagia.