Efficacy and safety of abatacept for systemic juvenile idiopathic arthritis: a systematic review.

OBJECTIVES: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan. RESULTS: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases. CONCLUSIONS: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.

Efficacy and safety of tumor necrosis factor inhibitors for systemic juvenile idiopathic arthritis: a systematic review.

OBJECTIVES: This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies. RESULTS: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%. CONCLUSIONS: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA.

High plasma mycophenolate acid concentration in the early phase of induction therapy predicts good renal outcome in lupus nephritis.

Objectives: To identify the prognostic predictive factor of complete renal response (CR) at week 12 by focusing on the plasma mycophenolic acid (MPA) concentration in induction therapy in lupus nephritis.Methods: We prospectively enrolled patients with biopsy-proven LN class III/IV who were hospitalized between 2016 and 2017. As an induction therapy, mycophenolate mofetil was continuously introduced at 2000 mg/day. We measured the MPA plasma concentration at two time points depending on the induction therapy phase, early (week 4) or middle (week 12). The association between these concentrations and CR rate at week 12 was evaluated.Results: Ten patients were enrolled. A significantly higher AUC0-12 between 0 and 12 h of MPA at the early phase was observed in the patients with CR at week 12 than in those without (p = .03). All the patients with high MPA-AUC0-12 (> 40 mg h/L) at the early phase achieved CR at week 12, but no such association was found at the middle phase. The multivariate analysis revealed that MPA-AUC0-12 was selected as an independent predictive factor of CR at week 12 (odds ratio: 1.12; 95% confidence interval: 1.01-1.45, p = .02).Conclusion: The high AUC0-12 of MPA at the early phase of induction therapy may predict good renal response.

Adult-onset Still's disease-associated interstitial lung disease represents severe phenotype of the disease with higher rate of haemophagocytic syndrome and relapse.

OBJECTIVES: Adult-onset Still's disease (AOSD) is an inflammatory disorder characterised by sustained fevers, arthritis, and skin involvement. Interstitial lung disease (ILD) is a rare manifestation, and its clinical characteristics have yet to be determined. METHODS: We sought to examine the clinical characteristics of AOSD-associated ILD. We retrospectively investigated 78 patients diagnosed as AOSD. ILD was diagnosed based on chest high-resolution computed tomography (HRCT). Clinical characteristics were compared between patients with and without ILD. Relapse was defined as sustained fevers, re-emergence of arthritis, and skin involvement after remission. We further investigated the pathological features of ILD on available samples. RESULTS: Patients with ILD, found in 9 of 78 (11.5 %), had older age of onset (mean age 62.6) than those without ILD (mean age 38.8) (p<0.01). The 3-year survival rates were comparable between patients with ILD (92.5%) and those without ILD (88.9%) (p=0.23). Patients with ILD had a higher cumulative rate of haemophagocytic syndrome (HPS) and relapse than those without (p<0.0001 and p=0.009, respectively). Chest HRCT showed marked thickening of the interlobular septa, the bronchovascular bundles, or the visceral pleura in all cases. There was no honeycomb or volume loss. Pulmonary pathological findings revealed marked thickening of the visceral pleura and the interlobular septa. CONCLUSIONS: Patients with ILD might have higher risks for HPS and relapse. Careful observation and appropriate therapeutic intervention might be needed.

Clinical subsets associated with different anti-aminoacyl transfer RNA synthetase antibodies and their association with coexisting anti-Ro52.

OBJECTIVE: To characterize clinical features of polymyositis/dermatomyositis (PM/DM) patients with different anti-aminoacyl transfer RNA synthetase (ARS) antibodies and their association with anti-Ro52. METHODS: Autoantibodies in sera from 97 Japanese patients (36 PM, 56 DM, and 5 clinically amyopathic DM), who satisfied Bohan and Peter or modified Sontheimer's criteria, were characterized by immunoprecipitation and enzyme-linked immunosorbent assay. Clinical information was from medical records. Features associated with different anti-ARS and anti-Ro52 antibodies were analyzed. RESULTS: The prevalence of anti-ARS was similar to other studies (Jo-1, 22%; EJ, 4%; OJ, 1%; PL-12, 1%), except for a high prevalence of anti-PL-7 (12%), which allowed us to characterize patients carrying this specificity. Serum creatine kinase >3000 IU/l was less common in anti-PL-7-positive patients (57%) than anti-Jo-1-positive patients (18%) (p = 0.0328) and was not found in anti-EJ-positive individuals. Interstitial lung disease was common in anti-ARS-positive patients (97%) (p < 0.0001 vs. 48% in anti-ARS-negative). Anti-Ro52 antibodies were frequently detected with anti-ARS (59%) (57% in anti-Jo-1, 67% in anti-PL-7) (vs. 21% in anti-ARS-negative, p < 0.0002). Anti-Ro52 was associated with overlap syndrome (26%) (vs. 7% in anti-Ro52-negative, p = 0.0119). CONCLUSIONS: Patients with different anti-ARS in combination with anti-Ro52 appear to be associated with distinctive clinical subsets.

Protein profiles of peripheral blood mononuclear cells as a candidate biomarker for Behçet's disease.

OBJECTIVES: To investigate the pathophysiology of Behçet's disease (BD) and find biomarkers for the disease, we analysed protein profiles of peripheral blood mononuclear cells (PBMCs). METHODS: Proteins, extracted from PBMCs, were comprehensively analysed in 16 patients with BD, 16 patients with rheumatoid arthritis (RA), 12 patients with Crohn's disease (CD), and 16 healthy control subjects (HC) by 2-dimensional differential gel electrophoResis (2D-DIGE). Differently expressed proteins were identified by mass spectrometry. RESULTS: 563 protein spots were detected. We completely discriminated between the BD and HC groups, between the BD and RA groups, and between the BD and CD groups by multivariate analysis of intensity of 23, 35, and 1 spots, respectively. The spots contributing to the differences included proteins related to cytoskeleton, transcription/translation, T cell activation, bone turnover, regulating apoptosis, and microbial infection. Intensity of 3 spots (tyrosine-protein phosphatase non-receptor type 4, threonine synthase-like 2, and ß-actin) provided area under the receiver operating characteristic curves (AUROC) of 0.889 for discrimination between the BD group and the non-BD groups. Informatively, intensity of the above 1 spot completely discriminated the CD group from the other groups (AUROC 1.000). This spot, identified as ß-actin, had different pI from the above ß-actin-spot probably due to different post-translational modification. CONCLUSIONS: PBMC protein profiles, especially the profile of the 3 spots, would be candidate biomarkers for BD. The latter ß-actin subtype would be useful for discriminating inflammatory bowel diseases from BD and other diseases. The identified proteins may play important roles in the pathophysiology of BD.

Long-term survival, causes of death, and prognostic factors for mortality in patients with microscopic polyangiitis and those with anti-neutrophil cytoplasmic antibody-positive interstitial lung disease: A single-center retrospective study.

AIM: To elucidate the clinical features, long-term survival, and prognostic factors for mortality among patients with microscopic polyangiitis (MPA), including those with anti-neutrophil cytoplasmic antibody-positive interstitial lung disease (ILD) (ANCA-ILD), which could be a subset of its variant phenotype. METHODS: We retrospectively included 76 consecutive patients between 2006 and 2014, diagnosed with MPA according to the European Medicines Agency algorithm using the Chapel Hill Consensus Conference definitions or ANCA-ILD. ILD was classified as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia pattern using chest computed tomography. RESULTS: The mean (standard deviation) age of the patients (female, 68%) was 69 (12) years. The median (interquartile range) follow-up period was 68 (33-95) months. Comorbid ILD and glomerulonephritis were observed in 44 (58%) (68% UIP) and 54 (71%) patients, respectively. Comorbid ILD was associated with low survival (P = .0563). There were 17 (39%) and 5 (16%) deaths in the ILD and non-ILD groups, respectively (P = .0404). In the ILD group, 6 and 5 of the deaths were attributed to infection and ILD progression, respectively. In the non-ILD group, 1 and 2 patients expired from subsequently developed ILD and aspiration pneumonia, respectively. Age ≥ 70 years (hazard ratio = 2.78; 95% confidential interval 1.15-6.70) and UIP (3.95; 1.60-9.77) were independent risk factors for mortality. CONCLUSION: Age ≥ 70 years and ILD with a UIP pattern were associated with high mortality, owing to susceptibility to infection and ILD progression. A more effective and less toxic treatment is required for progressive ILD.

Altered posttranslational modification on U1 small nuclear ribonucleoprotein 68k in systemic autoimmune diseases detected by 2D Western blot.

Anti-ribonucleoprotein (anti-RNP) antibodies are one of the representative autoantibodies detectable in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Generally, posttranslational modifications (PTMs) on autoantigens are proposed to be involved in the production of autoantibodies. In this study, we tried to detect the alteration in PTMs on a U1 small nuclear RNP 68k subunit (U1-68k), a major antigen of anti-RNP antibodies. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with MCTD, SLE, and rheumatoid arthritis (RA), and from healthy donors. U1-68ks in the PBMCs were detected by 2D Western blot (WB), where extracted nuclear proteins were separated by 2DE, followed by the detection of U1-68k using WB. More than 20 PTM isoforms were detected with different molecular weights of 65.0 , 66.5, and 68.0kDa, and different pIs between 6.0 and 8.5. Importantly, the relative intensity of the spot with 66.5 kDa and pI 7.5 was significantly increased in the MCTD and SLE groups compared to the RA and healthy groups. Further, this U1-68k isoform, in particular, in its RS domain, was found to have significantly decreased phosphorylation compared to the other isoforms. The PTM alternation may be one of the steps to generate the anti-RNP antibodies.

AC13, a C-terminal fragment of apolipoprotein A-I, is a candidate biomarker for microscopic polyangiitis.

OBJECTIVE: Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease. METHODS: Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg-Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme-linked immunosorbent assay and real-time polymerase chain reaction. RESULTS: A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C-terminal amino acid residues of apolipoprotein A-I (Apo A-I) and was designated "AC13." Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A-I and high-density lipoprotein cholesterol were down-regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up-regulated secretion of interleukin-6 (IL-6) (P < 0.05) and IL-8 (P < 0.01). CONCLUSION: AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up-regulation of proinflammatory cytokines.

Cutaneous polyarteritis nodosa associated with HLA-B39-positive undifferentiated spondyloarthritis in a Japanese patient.

We present the case of a 43-year-old man diagnosed with HLA-B39-positive spondyloarthritis who developed cutaneous lesions consistent with cutaneous polyarteritis nodosa (CPN). Previous studies indicated an elevated incidence of HLA-B39 in HLA-B27-negative Japanese patients with spondyloarthritis. This case suggested that CPN may also occur in association with forms of HLA-B39-positive spondyloarthritis. The rarity of this association is emphasized. Therapy with corticosteroid and methotrexate improved both the cutaneous lesions and the clinical symptoms of spondyloarthritis.

Usefulness of 123I-BMIPP and 201TlCl nuclide scintigraphy in evaluation of myocarditis in patients with polymyositis or dermatomyositis.

ABSTRACT: To investigate the usefulness of 123I-BMIPP/201TlCl scintigraphy for evaluating the presence of myocarditis in patients with polymyositis (PM) or dermatomyositis (DM).We performed a retrospective study of 26 patients diagnosed with new-onset active PM/DM who underwent 123I-BMIPP/201TlCl scintigraphy between 01 April 2010 and 20 March 2015. We determined the 123I-BMIPP/201TlCl ratio and grouped the patients according to presence or absence of a mismatch. We evaluated the relationship between mismatch and the laboratory and echocardiographic findings.Mismatch was found in 13 (50%) patients. There was no statistically significant difference in age, cardiac troponin T, myoglobin, myosin light chain, aldolase levels, E wave/A wave ratio, right ventricular systolic pressure between the mismatch and non-mismatch groups. Left ventricular end-diastolic and end-systolic dimensions were significantly greater in the mismatch group (45.0 vs 42.5 mm, P =  < .01 and 29.5 mm vs 25.0 mm, P < .01). Left ventricular ejection fraction was significantly lower in the mismatch group (63.5% vs 71.5%, P = .04). Significant inverse correlation (r = -0.44, P = .03) was observed between left ventricular ejection fraction and mismatch ratio.The use of 123I-BMIPP/ 201TlCl scintigraphy may be considered for evaluating myocarditis in patients with PM/DM.

Concurrent onset of acute lupus myocarditis, pulmonary arterial hypertension and digital gangrene in a lupus patient: a possible role of vasculitis to the rare disorders.

Acute lupus myocarditis and pulmonary arterial hypertension (PAH) are rare complications associated with systemic lupus erythematosus (SLE). No previous reports have shown the coexistence of these disorders. Here we present a 41-year-old patient with SLE who concurrently developed severe acute lupus myocarditis and PAH with digital gangrene as an initial manifestation. Acute lupus myocarditis and PAH were successfully treated with prednisolone and intravenous cyclophosphamide pulse therapy (600-700 mg × 6) along with anticoagulant therapy. Catheter-directed thrombolysis was required for digital gangrene caused by vasculitis. Concurrent development of these rare disorders may represent a common mechanism such vasculitis as an underlining cause of SLE.

Mycophenolate mofetil treatment with or without a calcineurin inhibitor in resistant inflammatory myopathy.

To evaluate the efficacy and tolerability of mycophenolate mofetil (MMF) with or without calcineurin inhibitors (CNIs) in patients with inflammatory myopathy taking prednisolone, but refractory to conventional immunosuppressive therapy. The records of patients with inflammatory myopathy who had previously failed treatment with at least one immunosuppressant were retrospectively evaluated. We selected patients treated with MMF and divided them into two groups depending on whether or not there was concomitant use of CNIs. We investigated the efficacy by changes in creatine kinase (CK) levels, forced vital capacity (%FVC), prednisolone dose, and high-resolution computed tomography (HRCT) findings. Interstitial lung disease (ILD) progression was defined by more than 10% decline of %FVC from baseline. We identified 19 patients on MMF treatment. There were seven (36.8%) patients on MMF and CNIs, including five on cyclosporine and two on tacrolimus. At baseline, no significant difference was seen in the prevalence of ILD between patients taking or not taking CNIs (85.7% vs. 75.0%, P = 0.68). Improvement in CK was seen in patients treated with CNIs (P = 0.04) but not in those without (P = 0.39). No significant improvement in %FVC and HRCT findings were found in patients with ILD in either group, and there were no differences in death or ILD progression. The combination of CNIs and MMF might be more effective for decreasing CK levels than MMF alone. Neither treatment arm had a beneficial effect on ILD over a variable observation period.

Low additive effect of hydroxychloroquine on Japanese patients with systemic lupus erythematosus taking calcineurin inhibitor.

AIM: To assess for any additive value of hydroxychloroquine (HCQ) in Japanese patients with systemic lupus erythematosus (SLE) depending on calcineurin inhibitors (CNIs). METHODS: We retrospectively evaluated patients with SLE who visited our hospital from 2015 to 2016 and were taking prednisolone (PSL) at <20 mg/d and one immunosuppressant (IS). Patients were divided into two groups depending on HCQ use and the groups were compared for changes in SLE Disease Activity Index (SLEDAI), prednisolone (PSL) dose, and cumulative flare rate between patients who were treated and not treated with CNI. RESULTS: Among the 103 patients evaluated, 19 (18.4%) were treated with HCQ. On analysis of all patients, SLEDAI, PSL doses, and cumulative flare rate were significantly reduced in patients who received HCQ compared to those who did not (P = 0.04, P = 0.01, and P = 0.03, respectively). Regarding IS use, we found less additive therapeutic effect in CNI users than in users of other ISs in terms of reduction in SLEDAI and PSL dose (P = 0.05 and P < 0.01, respectively). CONCLUSIONS: The addition of HCQ reduced disease activity, PSL dose, and flares in Japanese SLE patients but conferred less additive clinical efficacy when added to CNIs.

Glucocorticoid, immunosuppressant, hydroxychloroquine monotherapy, or no therapy for maintenance treatment in systemic lupus erythematosus without major organ manifestations.

OBJECTIVE: To study maintenance therapy after achievement of the lowest possible disease activity in systemic lupus erythematosus (SLE) without major organ manifestations. METHODS: We retrospectively evaluated patients with SLE who visited our hospital from Jan 2015 to Feb 2018 and were taking prednisolone (PSL) < 10 mg/day. After excluding those with neuropsychiatric SLE or severe lupus nephritis, patients were divided into four groups according to their maintenance monotherapy treatment, namely, prednisolone (PSL), immunosuppressant (IS), hydroxychloroquine (HCQ), and no drugs. The groups were then compared with regard to cumulative flare rate and changes in SLE Disease Activity Index (SLEDAI). RESULTS: There were 47 patients on PSL, 10 on IS, 5 on HCQ, and 11 on no drugs. Flare rate was higher in the no drug group, and no patients with the IS or HCQ group experienced a flare (p = 0.003). A reduction in SLEDAI was only seen in the IS and HCQ groups (p = 0.05 and p = 0.03, respectively). There were no differences in adverse events among groups during the study period. CONCLUSIONS: Our results suggest that the cessation of all drugs is associated with disease flare for SLE patients without major organ manifestations. IS or HCQ monotherapy might be a reasonable maintenance strategy comparing with steroid monotherapy. Key Point • Immunosuppressant or hydroxychloroquine monotherapy appears to be a reasonable maintenance strategy.

Hydroxychloroquine Improves the Disease Activity and Allows the Reduction of the Corticosteroid Dose Regardless of Background Treatment in Japanese Patients with Systemic Lupus Erythematosus.

Objective Hydroxychloroquine (HCQ) was not approved in Japan until 2015, and its therapeutic potential has not been explored in depth. We evaluated the additional therapeutic effect of HCQ in Japanese patients with systemic lupus erythematosus (SLE) on maintenance therapy. Methods Patients with SLE who visited our hospital from 2015 to 2016 and were taking prednisolone (PSL) at <20 mg/day were retrospectively evaluated. All patients were divided into three groups according to their maintenance treatment regimen: PSL + immunosuppressant, PSL alone, and no treatment. We compared the changes in the SLE disease activity index (SLEDAI), PSL dose, and cumulative flare rate between patients who were and were not treated with HCQ. Results Among the 165 patients evaluated, 35 (21.2%) were treated with HCQ. The mean period of observation did not differ markedly between patients who did and did not receive HCQ (p=0.3). The SLEDAI and PSL dose were significantly reduced in patients who received HCQ, regardless of their background treatment regimen. The cumulative flare rate was lower in patients who received HCQ than in those who did not in the PSL + immunosuppressant and no maintenance treatment groups (p=0.03 and 0.05, respectively). Conclusion The addition of HCQ reduced the disease activity and allowed PSL dose reduction, regardless of background treatment, in Japanese patients with SLE.

Anti-IL-10 antibody in systemic lupus erythematosus.

PURPOSE: IL-10 is a cytokine known to inhibit inflammatory cytokines. To determine its role in the pathogenesis of systemic lupus erythematosus (SLE), the presence of anti-IL-10 antibody is required to be examined. Although antibodies against cytokines are known to be present in SLE, no studies have determined the role of IL-10, particularly in Japanese patients. We assayed anti-IL-10 antibody in SLE and examined the clinical significance. PATIENTS AND METHODS: We performed a retrospective study of 80 Japanese patients with SLE. Sixteen scleroderma patients, 19 rheumatoid arthritis (RA) patients, 23 Behcet's disease patients, and 23 healthy subjects were selected as control groups. Clinical information was abstracted from medical records. Anti-IL-10 antibody level was determined with an ELISA. RESULTS: With the cutoff established as serum absorbance +2 SDs (OD 0.729) in healthy subjects, we defined any sample above this cutoff as anti-IL-10 antibody-positive. Fourteen patients with SLE (17.5%) were found to be anti-IL-10 antibody positive. Absorbance was significantly higher in serum from patients with SLE and RA than in healthy individuals. In SLE, patients with low complement values were significantly more common in the antibody-positive group. Serum IgG levels were significantly higher in the antibody-positive group. In multivariable analysis, high level of serum IgG is associated with anti-IL-10 antibody positive. CONCLUSION: The present study found that anti-IL-10 antibody is present in SLE and related to clinical parameters. These results suggest that the presence of anti-IL-10 antibody was associated with high level of serum IgG, but is not associated with disease activity in patients with SLE.

Low-dose rituximab as induction therapy for ANCA-associated vasculitis.

Administration of four once-weekly doses of 375 mg/m2 rituximab (RTX) is commonly used as remission induction therapy for ANCA-associated vasculitis (AAV). Low-dose RTX has been recently shown to produce closely similar results to conventional treatments in other autoimmune diseases. However, the therapeutic potential of this approach in AAV remains largely unknown. Here, we analyzed the efficacy and tolerability of high- and low-dose regimens of RTX in patients with AAV. We retrospectively examined AAV patients who met the classification algorithm of Watts et al. from 2006 to 2016. Patients were divided into high- (HD) and low-dose (LD) RTX groups. HD-RTX was the original regimen while LD-RTX consisted of two once-weekly doses of 375 mg/m2. Cumulative complete remission (CR) rates for 1 year were compared, and serial changes in peripheral B cell counts and serious adverse events were monitored. Apart from a higher percentage of elderly patients in the LD group (p < 0.01), the 17 patients with HD-RTX and 11 patients with LD-RTX showed no significant differences in clinical characteristics, including Birmingham Vasculitis Activity Score (BVAS), Vasculitis Damage Index (VDI), and the initial dose of glucocorticoid. On 1-year observation, cumulative CR rates did not significantly differ (p = 0.20). Further, peripheral B cell counts and incidence of serious adverse events also did not differ. Cumulative CR rate did not significantly differ between LD and HD groups. Further study is warranted to confirm these results.

A low perfusion-metabolic mismatch in 99m Tl and 123 I-BMIPP scintigraphy predicts poor prognosis in systemic sclerosis patients with asymptomatic cardiac involvement.

AIM: This study investigated the prognostic factors of cardiac death or cardiac failure using cardiac scintigraphy, echocardiography (UCG), and magnetic resonance imaging (MRI) in asymptomatic systemic sclerosis (SSc) patients. METHODS: We retrospectively evaluated SSc patients who had undergone cardiac scintigraphy using 99m thallium (99m Tl) and 123 I-ß-methyl-P-iodophenyl-pentadecanoic acid (123 I-BMIPP), UCG, and cardiac MRI. We calculated the mismatch score in scintigraphy by subtracting the uptake of 123 I-BMIPP from that of 99m Tl. Patients were divided into two groups according to whether they survived with no cardiac failure or subsequently proceeded to cardiac failure or death during the study period. We identified prognostic factors by analyzing 99m Tl and 123 I-BMIPP uptake, mismatch scores, UCG findings, and cardiac delayed enhancement on MRI. We also evaluated pathological evidence of myocardial fibrosis. RESULTS: Of 33 SSc cases, 11 proceeded to cardiac failure or death. There was no significant difference in UCG or MRI findings between the two groups. Low mismatch score in cardiac scintigraphy was the only predictive factor of cardiac failure or death by multivariate analysis (odds ratio, 6.48; 95% confidence interval, 1.22-423.2; P = 0.01). When patients were grouped according to high or low mismatch scores based on a cut-off using receiver operating characteristics curve analysis, the cumulative incidence of cardiac failure or death was higher in the low mismatch group than in the high mismatch group (P = 0.02). The percentage of fibrosis was significantly higher in deceased cases compared to surviving cases. CONCLUSIONS: Low mismatch score in cardiac scintigraphy was associated with cardiac death or cardiac failure in SSc patients.