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Objectives To elucidate the serum cytokine profile and address the pathomechanism of interstitial lung disease (ILD) complicated with PM/DM. Methods Forty patients with PM/DM-ILD were enrolled, and principal components analysis and cluster analysis were performed to classify patients into subgroups. Additionally, we compared cytokine profiles between the survivors and dead patients and between anti-melanoma differentiation-associated gene 5 antibody- and anti-aminoacyl tRNA synthetase antibody-positive ILD patients. We also examined the association of various cytokines with disease activity indicators and prognosis of ILD. Results The principal components analysis data allowed classification of the cytokine profile into three groups: group 1, neutrophilic and M1-macrophage-driven cytokines; group 2, type 1 Th cell-driven and M2-macrophage-induced cytokines; and group 3, M2-macrophage-driven cytokines. Cluster analysis showed the presence of PM/DM-ILD patient groups with high or low levels of total cytokines. Ninety percent of patients who died of ILD were included in clusters with high cytokine levels. Serum cytokine levels of all groups were significantly higher in the anti-melanoma differentiation-associated gene 5 antibody-positive patients than in the anti-aminoacyl tRNA synthetase antibody-positive patients. Groups 1 and 2 significantly correlated with known factors for poor prognosis, such as serum ferritin levels and alveolar-arterial oxygen difference. Serum cytokine levels of patients in group 1 were significantly higher initially and at 2 and 4 weeks in those who died. Conclusion These findings suggested that the activation of monocytes, macrophages and type 1 Th cells, and neutrophils play roles in the pathomechanism of PM/DM-ILD, and group 1 cytokines could be useful biomarkers for predicting prognosis of PM/DM-ILD. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling. [ABSTRACT FROM AUTHOR]

The efficacy and safety of liposomal amphotericin B (L-AMB) in the treatment of invasive fungal infections (IFIs) were retrospectively evaluated for patients with connective tissue diseases (CTDs) during treatment with immunosuppressive therapy. Subjects were 13 patients with CTDs complicated by IFI, on the basis of clinical symptoms, imaging findings, and microbiological and histological examinations. All patients were treated with L-AMB. Efficacy and safety were evaluated before and after administration of L-AMB. Underlying diseases were systemic lupus erythematosus for 4 patients, rheumatoid arthritis for 3, microscopic polyangiitis for 2, adult-onset Still disease for 1, dermatomyositis for 1, and mixed connective tissue disease for 1. Eight patients were resistant to other antifungal drugs. Prednisolone was given to 11 patients and the median dose was 10 mg/day. Immunosuppressants were used for 8 patients. The median duration of administration of L-AMB was 8.5 days (range 4-38 days). In proven and probable diagnosis patients ( n = 5), the treatment was effective for 3 patients and ineffective for 2 (efficacy rate 60 %). Serum 1,3-β- d-glucan antigenemia (BG) levels decreased after treatment in the 2 patients who were positive for BG. Serum Aspergillus galactomannan antigen levels decreased in 3 of 4 patients with Aspergillus infection. No patient died of IFI. Regarding potential adverse reactions, there were no significant changes in serum creatinine and potassium levels. L-AMB is effective and well-tolerated for treatment of IFI in patients with CTDs. [ABSTRACT FROM AUTHOR]

We retrospectively examined the effect of combination therapy with prednisolone and cyclosporin-A (CSA) on the findings of pulmonary function tests (PFTs) and chest high-resolution computed tomography (HRCTs) scans in patients with dermatomyositis (DM) and acute/subacute interstitial pneumonia (A/SIP). We also examined whether CSA therapy improved PFT and chest HRCT findings. DM patients ( n = 14) with A/SIP were treated with 1 mg/kg/day prednisolone and 4 mg/kg/day CSA within 4.4 days (range, 1-12 days) from diagnosis. The trough level (C0) and 2-h post-dose blood concentration (C2) of CSA were measured. PFTs and HRCT scans were performed before and 1 year after treatment. The total ground-glass opacity area was calculated with the HRCT findings and used as the CT score. Combination prednisolone and CSA therapy improved the TLC%, VC%, FVC%, EFV1.0%, and CT score ( P = 0.027, 0.003, 0.002, 0.001, and 0.001, respectively). The C0 level was 178.8 ng/ml (range, 71-456 ng/ml), and the C2 level was 1,336.6 ng/ml (range, 814-2,873 ng/ml). Therapeutic changes in FVC%, FEV1.0%, and DLCO% were correlated with the C2 CSA level ( P = 0.047, 0.025, and 0.035, respectively). However, the PFT results and CT scan scores did not correlate with the daily dose or C0 level of CSA. Improvements in the CT score were correlated with time from IP diagnosis to CSA initiation ( P = 0.014). Early intervention with prednisolone and CSA combination therapy and tight control of the daily CSA dose by monitoring the C2 level improved PFT and chest HRCT findings in DM-A/SIP. [ABSTRACT FROM AUTHOR]