These results suggest that the clinical/laboratory features in the course of MAS appear to be similar among patients regardless of whether TCZ is administered. Similarities in the pathophysiological background of MAS and EB-VAHS were also suggested.

Background/Purpose: Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA). Changes in therapies, including biologics, may trigger MAS. Interleukin‐6 (IL‐6) plays a major pathogenic role in sJIA; data in animals suggest that high IL‐6 levels contribute to the triggering of MAS. Treatment with the IL‐6 receptor inhibitor tocilizumab (TCZ) is very effective in patients with sJIA. In this study, we investigated the rates and features of MAS occurring during TCZ treatment in patients with sJIA. Methods: Data were collected from patients with sJIA treated with TCZ in the international phase 3 trial (TENDER), 4 clinical trials in Japan, and the Japanese postmarketing surveillance (JPMS) program. Reported MAS events or disease flares associated with alanine aminotransferase/aspartate aminotransferase (ALT/AST) elevations were collected. Worksheets with event information were assessed by an independent panel (2 pediatric rheumatologists, 1 pediatric hematologist with MAS expertise) overseen by the TENDER lead investigator. Cases were adjudicated as definite MAS, potential MAS, not MAS, or insufficient data. Results: The data set included 112 patients from TENDER (403.0 patient‐years' [PY] exposure to TCZ), 149 patients from the Japanese trials (326 PY), and 366 patients from the JPMS program (523.9 PY). Of 31 cases reviewed, 22 events were adjudicated as definite or potential MAS: 5 from TENDER (3 definite, 2 potential), 6 from the Japanese trials (3 definite, 3 potential), and 11 from the JPMS program (5 definite, 6 potential). The rates/100 PY of definite/potential MAS were 1.24 (95% CI, 0.4–2.90) in TENDER, 1.84 (95% CI, 0.68–4.00) in the Japanese trials, and 2.10 (95% CI, 1.05–3.76) in the JPMS program. Features contributing to the adjudication of definite MAS are listed in the . All 11 events adjudicated as definite MAS met the preliminary MAS diagnostic guidelines. All definite and potential MAS resolved with the exception of MAS in a patient from the Japanese phase 3 study who died after respiratory/cardiac arrest. Criteria for Adjudication of Cases as Definite MAS (n = 11) Features of MAS Patients for Whom These Features Led to Adjudication of Definite MAS n (%)mg Clinical signsFever6 (55)Rash3 (27)Hemorrhage with purpura, hematuria2 (18)Hepatomegaly0 (0)Laboratory featuresElevated ALT/AST11 (100)Thrombocytopenia9 (82)Elevated ferritin8 (73)Leukopenia7 (64)Neutropenia6 (55)Elevated lactate dehydrogenase4 (36)Low fibrinogen4 (36)Increased triglycerides4 (36)Elevated D‐dimers3 (27)Low hemoglobin4 (36)Elevated C‐reactive protein2 (18)Low erythrocyte sedimentation rate2 (18)aThresholds for abnormal values were determined according to age and local guidelines. Conclusion: The use of TCZ does not appear to be associated with increased risk for MAS in sJIA. There were no unusual clinical or laboratory features in these MAS cases.

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The effect of hypercholesterolemia on diabetic nephropathy was studied in rats fed with or without

Abstract:The effect of hypertriglyceridemia was examined on streptozotocin (STZ)-induced diabetic nephropathy in rats.