Efficacy of denosumab on bisphosphonate-treated osteoporosis and osteopenia in systemic rheumatic disease patients receiving glucocorticoids.

INTRODUCTION: Evidence on second-line agents for osteoporosis and osteopenia associated with glucocorticoid use after first-line bisphosphonate therapy is limited. We, therefore, examine the efficacy of denosumab on bisphosphonate-treated osteoporosis and osteopenia in Japanese systemic rheumatic disease (SRD) patients receiving glucocorticoids. MATERIALS AND METHODS: Glucocorticoid-treated SRD patients with a pre-existing fragility fracture, either lumbar spine (LS) or femoral neck (FN) bone mineral density (BMD) T-score of ≤ -2.5 or of ≤ -1.5 without a significant increase in BMD in the past year despite oral bisphosphonate therapy were enrolled in this study. They were randomized to switch to 60 mg subcutaneous denosumab every six months (switching group) or to continue the bisphosphonate (continuing group). The primary endpoint was the percent change from baseline in BMD at the LS and FN at week 52. RESULTS: Of the 39 subjects, 19 were assigned to the switching group and 20 to the continuing group. The switching group showed significant increases in LS BMD (5.7% vs. 1.1%, p = 0.002) and FN BMD (4.2% vs. -0.3%, p = 0.008) at week 52 than the continuing group, with a significant decrease in serum tartrate-resistant acid phosphatase 5b (-28.1% vs. 7.0%, p < 0.001) and improved patient satisfaction. CONCLUSION: Switching to denosumab demonstrated greater efficacy than continuing bisphosphonates in increasing BMD, inhibiting osteoclast activation, and enhancing patient satisfaction in Japanese bisphosphonate-treated osteoporosis and osteopenia patients with concomitant SRD receiving glucocorticoids.

Macrophage activation syndrome in patients with adult-onset Still's disease under tocilizumab treatment: A single-center observational study.

OBJECTIVES: Macrophage activation syndrome (MAS) developed under tocilizumab treatment poses a diagnostic challenge. This study aims to demonstrate the frequency and the clinical features of MAS developed in patients with adult-onset Still's disease (AOSD) receiving tocilizumab. METHODS: The consecutive AOSD patients treated with tocilizumab in our institution from April 2008 to March 2020 were studied. The frequency of clinically diagnosed MAS during tocilizumab treatment, their conformity to the several criteria relevant for MAS, and laboratory characteristics compared to AOSD flare were investigated. RESULTS: Of the 20 AOSD patients treated with tocilizumab, six developed clinically diagnosed MAS, four immediately after starting tocilizumab and two after long-term treatment. Some of them had already met the MAS criteria before starting tocilizumab. At MAS diagnosis, although some did not meet the MAS criteria due to lack of fever and/or the lower ferritin levels, all consistently showed sharp increases in ferritin along with marked abnormal changes in two or more different markers of organ damage, unlike the AOSD flares. CONCLUSION: MAS is not a rare complication in AOSD patients receiving tocilizumab. The clinical similarities between systemic AOSD and MAS, and substantial alterations in MAS features by inhibition of interleukin-6 signaling may limit the utility of the existing diagnostic/classification criteria in diagnosing MAS under tocilizumab treatment. The emergence of abnormalities in MAS-related organ damage markers with a rapid elevation of ferritin should be considered as MAS development in AOSD patients receiving tocilizumab even if the patients are afebrile or have relatively low ferritin levels.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim therapy for Pneumocystis jirovecii pneumonia in patients with systemic rheumatic diseases: A retrospective multicenter study.

OBJECTIVES: To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases. METHODS: In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10-15 mg/kg/day; and the high and conventional, 15-20 mg/kg/day for TMP dose. RESULTS: Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs. CONCLUSIONS: Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases.

Long-Term Dysphagia Severity in Patients With Idiopathic Inflammatory Myopathy: A Single-Center Retrospective Study.

Objective To investigate long-term dysphagia severity and survival outcomes in patients with idiopathic inflammatory myopathy (IIM). Methods We retrospectively included consecutive Japanese patients with IIM between April 2000 and March 2022. The primary endpoint was the complete oral intake rate according to the Food Intake LEVEL Scale (FILS) within one year after the onset of dysphagia in patients with IIM.The secondary outcome was the overall mortality rate in IIM patients with dysphagia.  Results Of the 108 patients with IIM, 18 (16.7%) developed dysphagia during the observation period. The baseline median dysphagia severity in IIM patients with dysphagia using the FILS was 7.0 and improved to 10.0 at the final observation. Almost all IIM patients recovered from dysphagia severity, and the complete oral intake rate within one year in IIM patients with dysphagia was 72.2%. The overall mortality rate of patients with IIM patients with dysphagia was 44.4%, which is significantly lower than that of those without dysphagia (P < 0.05). Cox regression analysis demonstrated that malignancy-associated myositis was a poor prognostic factor in patients with IIM and survival outcomes in IIM patients with dysphagia were poor compared with those in patients without dysphagia when with malignancies. Conclusions The dysphagia severity in patients with IIM improved; however, their survival rate was lower than that of those without dysphagia when malignancy occurred.

New-onset of giant cell arteritis with ischemic optic neuropathy following the seventh-dose of COVID-19 mRNA vaccination: A case report and literature review.

Coronavirus disease (COVID-19) vaccines have demonstrated excellent efficacy in reducing the morbidity and severity of the disease. However, some patients have been reported to develop systemic rheumatic diseases, such as rheumatoid arthritis, myocarditis, Guillain-Barre syndrome, and giant cell arteritis (GCA) following COVID-19 vaccination. We present a case of GCA with ischemic optic neuropathy following COVID-19 mRNA vaccination. A 73-year-old woman developed headache, myalgia, scalp tenderness, and jaw claudication 4 days after her seventh dose of the vaccination; she also developed severe visual disturbances 1 month after the vaccination. The blood examination tests showed an increased serum C-reactive protein level and erythrocyte sedimentation rate. The echogram for the temporal artery showed a halo sign. Ophthalmic examination revealed ischemic optic neuropathy in both eyes. The patient was treated with a high-dose glucocorticoid and tocilizumab under the diagnosis of GCA with ischemic optic neuropathy, obtaining mild improvement of the symptoms. This report underscores the need for clinical vigilance and further data collection regarding GCA cases after COVID-19 vaccination.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in patients with systemic rheumatic diseases receiving moderate-to high-dose glucocorticoids.

OBJECTIVES: To compare the effectiveness and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with systemic rheumatic disease (SRD) who were receiving glucocorticoids. METHODS: We retrospectively analyzed data obtained from Japanese patients with SRD who received glucocorticoids between January 2006 and April 2024. Patients were divided into two groups based on the initial dose of SMX/TMP: low-dose (one tablet twice weekly on non-consecutive days); conventional-dose (one tablet per day). The primary endpoint was the incidence of PCP after 1 year since the initiation of SMX/TMP. Secondary endpoints were discontinuation rates of SMX/TMP therapy and severe adverse drug reactions (ADRs) after 1 year since the initiation of SMX/TMP in both groups, before and after adjusting for patient characteristics. RESULTS: A total of 186 patients were included in this study: 60 in the low-dose group and 126 in the conventional-dose group. No patients developed PCP within one year after starting SMX/TMP; however, two patients in the low-dose group required escalation of the SMX/TMP dose to the conventional dose due to subclinical PCP. In the adjusted analysis, the low-dose group had a significantly lower discontinuation rate and a lower incidence rate of severe ADRs than the conventional-dose group. CONCLUSIONS: Lower-dose SMX/TMP therapy was as effective as conventional therapy for PCP prophylaxis and was associated with lower discontinuation rates in patients with SRD receiving glucocorticoids.

Possible usefulness of fluorodeoxyglucose positron emission tomography in diagnosing polyarteritis nodosa: A case report and literature review.

Polyarteritis nodosa (PAN) is a systemic rheumatic disease that affects medium-sized arteries. PAN is typically not associated with anti-neutrophil cytoplasmic antibodies and has no serological surrogate markers. Therefore, its diagnosis requires pathological findings. However, the positive rate of biopsy in diagnosing PAN is not high, and the biopsy area is often limited. Several investigators have reported the usefulness of imaging findings in diagnosing PAN, independent of pathological findings. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET)/CT has recently been approved for the diagnosis of large-vessel vasculitis in Japan. Several studies have also demonstrated the usefulness of FDG-PET/CT in diagnosing medium-vessel vasculitis. However, no studies have evaluated the usefulness of FDG-PET/CT for diagnosing PAN compared to other modalities, and it is not clear whether FDG-PET/CT is superior to other modalities for diagnosing PAN. Herein, we report a case of PAN and compare the usefulness of FDG-PET/CT with other modalities in diagnosing PAN.

Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. RESEARCH QUESTION: What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? STUDY DESIGN AND METHODS: In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP < 12.5 mg/kg/d) and conventional-dose (TMP 12.5-20 mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. RESULTS: Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71 mg/kg/d in the low-dose group and 17.78 mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7% vs 18.4%, respectively; P = .080) or 180-day mortality (14.6% vs 26.1%, respectively; P = .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8% vs 59.0%, respectively; P = .005). The initial treatment completion rates were 43.3% and 29.6% in the low-dose and conventional-dose groups (P = .158), respectively. INTERPRETATION: Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.

Possible Case of Elderly-onset Intestinal Behcet's Disease with Trisomy 8 Following COVID-19 Vaccination Exacerbated by COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) vaccines are effective in reducing the prevalence of this disease. However, some patients develop autoimmune diseases after vaccination. We herein report a case of elderly onset intestinal Behçet's disease (BD) with trisomy 8 following COVID-19 vaccination in which the disease was exacerbated by COVID-19 infection. The patient developed refractory stomatitis and genital ulcers two weeks after receiving the second vaccination and presented with bloody stool two years later. Intestinal BD with trisomy 8, exacerbated by COVID-19, was treated with high-dose glucocorticoids and infliximab; however, surgical intervention was required. The findings of this case suggest that the COVID-19 vaccination may induce BD.

Comparison of the outcomes of Pneumocystis jirovecii pneumonia in rheumatoid arthritis patients treated with and without biologics.

BACKGROUND: To investigate the outcomes of Pneumocystis jirovecii pneumonia (PCP) between patients with rheumatoid arthritis (RA) treated with and without biologics before PCP onset. PATIENTS AND METHODS: We retrospectively included rheumatoid arthritis (RA) patients with PCP treated with and without biologics before PCP onset. The primary endpoints were 30-day and 180-day survival rates, and the secondary endpoint was severe PCP, including in-hospital death, intensive care unit admission, and requirement of respiratory support during hospitalization. RESULTS: Eighty-two patients were enrolled in this study, including the Biologics group (n = 39) and Non-Biologics group (n = 43). There were no significantly differences in the 30-day and 180-day survival rates and severe PCP rate in the Biologics group and the Non-Biologics group before and after adjusting the patient characteristics. Kaplan-Meier survival curves for death showed no significantly differences between the Biologics and Non-Biologics groups. Cox regression hazard analysis revealed that the average daily prednisolone dose within 90 days before PCP onset was weakly associated with mortality after PCP. CONCLUSIONS: Biologic use before PCP onset did not increase the severity and mortality of PCP compared to non-biologics use in patients with RA.

Possible case of polyarteritis nodosa with epididymitis following COVID-19 vaccination: A case report and review of the literature.

The global outbreak of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 has prompted the rapid spread and development of vaccines to prevent the spread of the disease. COVID-19 vaccine has demonstrated excellent efficacy in reducing morbidity and severity of the disease, and most adverse reactions are very minor. However, some patients have been reported to develop autoimmune diseases, such as rheumatoid arthritis, myocarditis, Guillain-Barre syndrome, and vasculitis, following COVID-19 vaccination. Herein, we present a case of polyarteritis nodosa with epididymitis, following COVID-19 mRNA vaccination. The patient's initial symptoms were fever and testicular pain, and magnetic resonance imaging showed epididymitis. He was diagnosed as having polyarteritis nodosa with epididymitis and was treated with high-dose prednisolone, with a good clinical outcome.

Successful switching treatment of adalimumab for refractory pyoderma gangrenosum in a patient with rheumatoid arthritis with prior use of tumour necrosis factor inhibitors: A case report and review of the literature.

Pyoderma gangrenosum (PG) is a rare chronic skin disease characterised by painful skin ulcers. There are no treatment guidelines for PG, but systemic treatments including biologics are often used. Recently, adalimumab (ADA), a fully human monoclonal antibody against tumour necrosis factor, was approved for refractory PG treatment in Japan. Herein, we report a case of rheumatoid arthritis with refractory PG 2 months after orthopaedic surgery of the foot during treatment with low-dose etanercept and methotrexate. Although adding a moderate dose of glucocorticoid did not improve her PG, the patient showed a remarkable response after switching from etanercept to ADA in a higher dose than that used to treat rheumatoid arthritis. This higher dose of ADA may be effective for the treatment of refractory PG after the failure of other tumour necrosis factor inhibitors.

New-onset of eosinophilic granulomatosis with polyangiitis without eosinophilia and eosinophilic infiltration under benralizumab treatment: A case report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small- to medium-vessel necrotising vasculitis and eosinophilic inflammation. Mepolizumab, an anti-interleukin-5 (IL-5) monoclonal antibody has been approved in Japan since 2018 for refractory EGPA treatment. Benralizumab, an anti-IL-5 receptor monoclonal antibody, also has been reported to reduce the glucocorticoid dose in patients with refractory EGPA. On the other hand, several investigators have demonstrated new-onset EGPA under biologics, and it is unclear whether this treatment for severe allergic diseases can prevent the development of EGPA. Herein, we report a case of new-onset EGPA under benralizumab treatment. The patient had fever, weight loss, muscle pain, and paraesthesia, the serum eosinophil count was 0/µL, and the biopsy showed necrotizing vasculitis without eosinophilic infiltration. She was diagnosed as having EGPA and treated with high-dose glucocorticoid and intravenous cyclophosphamide, with a good response. Our case report indicates that anti-IL-5 agents may mask the development of EGPA and clinicians should be aware of the development of EGPA during anti-IL-5 agents.

Transient Pneumonitis as a Possible Adverse Reaction to the BNT162b2 COVID-19 mRNA Vaccine in a Patient with Rheumatoid Arthritis: A Case Report and Review of the Literature.

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to rapid progress in vaccine development to prevent the spread of the disease. Although COVID-19 vaccines have excellent effectiveness in reducing morbidity and disease severity with minor adverse reactions, some patients develop late hypersensitivity events as autoimmune reactions such as rheumatoid arthritis, lupus nephritis, and vasculitis following COVID-19 vaccination. Herein, we describe a case of pneumonitis following COVID-19 mRNA vaccination in a patient with rheumatoid arthritis, which resolved spontaneously.

New-onset Seropositive Rheumatoid Arthritis Following COVID-19 Vaccination in a Patient with Seronegative Status.

Coronavirus disease 2019 (COVID-19) has spread worldwide since 2019, and mRNA vaccines for the disease have been rapidly delivered to limit the severity of infection. However, while these vaccines are effective in reducing the morbidity and severity of the disease, some patients develop severe adverse drug reactions and new-onset autoimmune phenomena, such as myocarditis, thrombosis with thrombocytopenia, and vasculitis. In addition, some patients develop arthritis following vaccination, including rheumatoid arthritis (RA). We herein report a case of new-onset seropositive RA following COVID-19 mRNA vaccination. Although tests for rheumatoid factor and anti-cyclic citrullinated peptide antibody had been negative three years before vaccination, the patient developed seropositive RA following COVID-19 mRNA vaccination.

Successful Use of Certolizumab Pegol for Refractory Psoriatic Arthritis Triggered by COVID-19 Infection.

Recently, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread worldwide. Although nearly all patients incur mild-to-moderate disease from this viral infection, some develop severe manifestations with a poor prognosis. COVID-19 can also induce autoimmune disease; several cases of arthritis following COVID-19 have been documented in the literature, such as reactive arthritis and chronic arthritis. We herein report a case of psoriatic arthritis triggered by COVID-19. Although the arthritis had been refractory to glucocorticoids and methotrexate, certolizumab pegol subsequently led to remission.

Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthritis Receiving Methotrexate: A Single-center Retrospective Study.

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.

Medium-vessel Vasculitis Presenting with Myalgia Following COVID-19 Moderna Vaccination.

Coronavirus disease 2019 (COVID-19) vaccines have been delivered worldwide to prevent the spread of the disease, and almost all Japanese have received the mRNA vaccines "BNT162b2" (Pfizer-BioNTech) or "mRNA-1273" (Moderna). These vaccines have shown efficacy and safety with only minor adverse drug reactions. However, some patients develop severe adverse drug reactions, including autoimmune reactions. In addition, systemic vasculitis, mainly small-vessel vasculitis, following COVID-19 vaccination, has been reported. However, only a few investigators have reported medium-vessel vasculitis following vaccination. We herein report a case of medium-vessel vasculitis presenting with myalgia as the initial clinical manifestation following COVID-19 Moderna vaccination.

Impact of dysphagia and its severity on long-term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathies other than inclusion body myositis.

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.

Baseline clinical features predicting macrophage activation syndrome in patients with systemic adult-onset Still's disease receiving interleukin-6 inhibitor treatment.

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.