Browsing by Subject "Rituximab"

Now showing 1 - 6 of 6
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    Depletion of the Chimeric Drug Rituximab from Biological Samples
    (Elsevier, 2017) Book, Benita K.; Pescovitz, Mark D.; Guo, Lili; Wiebke, Eric A.; Department of Surgery, IU School of Medicine
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    Diffuse Alveolar Hemorrhage
    (Springer Nature, 2019-07-24) Desai, Hem; Smith, Joshua; Williams, Mark Daren; Department of Medicine, Indiana University School of Medicine
    Diffuse alveolar hemorrhage[DAH] is a serious condition that can be life threatening. It can be caused by a constellation of disorders which presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Respiratory failure from DAH can be so severe that it has been called an ARDS mimic/imitator. Early recognition is crucial because prompt diagnosis and treatment are required for survival. DAH should be distinguished from other causes of pulmonary hemorrhage caused by localized pulmonary abnormalities and the bronchial circulation. Early bronchoscopy with bronchoalveolar lavage (BAL) is generally required to confirm the diagnosis of DAH and rule out infection. Progressively bloody bronchoalveolar lavage samples can distinguish DAH. Systemic vasculitis is one of the most common causes of DAH and can be pathologically defined by the presence of cellular inflammation, vessel destruction, tissue necrosis, and eventually, organ dysfunction. Corticosteroids and immunosuppressive agents remain the gold standard for the treatment. The following case illustrates a patient who was dependent on dialysis, then presented with hemoptysis. Bronchoscopy demonstrated progressively bloody bronchoalveolar lavage samples consistent with diffuse alveolar hemorrhage. Serologic testing was consistent with microscopic polyangiitis. The patient experienced a clinical remission with cyclophosphamide and corticosteroids.
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    Dysthyroid optic neuropathy: update on pathogenesis, diagnosis, and management
    (Taylor & Francis, 2017) Blandford, Alexander D.; Zhang, Dalia; Chundury, Rao V.; Perry, Julian D.; Ophthalmology, School of Medicine
    INTRODUCTION: Dysthyroid optic neuropathy (DON) is a severe manifestation of thyroid eye disease (TED) that can result in permanent vision loss. Management is complex, multidisciplinary, and involves medical and/or surgical therapies. This review describes current concepts in the epidemiology, pathophysiology, diagnosis, and treatment of DON. AREAS COVERED: An extensive review of the literature was performed to detail current concepts on the diagnosis and management of DON. This includes utilization of various medical and surgical modalities for disease management. EXPERT COMMENTARY: DON can result in permanent blindness and often requires the use of corticosteroids and surgical decompression. We favor the use of intravenous corticosteroids and a transcaruncular approach when surgical decompression is indicated. The use of orbital radiation for DON is often reserved for patients that are poor surgical candidates and/or patients with refractory disease.
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    Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.
    (Wiley, 2018-07) Grace, Rachael F.; Despotovic, Jenny M.; Bennett, Carolyn M.; Bussel, James B.; Neier, Michelle; Neunert, Cindy; Crary, Shelley E.; Pastore, Yves D.; Klaassen, Robert J.; Rothman, Jennifer A.; Hege, Kerry; Breakey, Vicky R.; Rose, Melissa J.; Shimano, Kristin A.; Buchanan, George R.; Geddis, Amy; Haley, Kristina M.; Lorenzana, Adonis; Thompson, Alexis; Jeng, Michael; Neufeld, Ellis J.; Brown, Travis; Forbes, Peter W.; Lambert, Michele P.; Pediatrics, School of Medicine
    Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians.
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    Rituximab, B-lymphocyte depletion, and preservation of beta-cell function
    (Massachusetts Medical Society, 2009-11-26) Pescovitz, Mark D.; Greenbaum, Carla J.; Krause-Steinrauf, Heidi; Becker, Dorothy J.; Gitelman, Stephen E.; Goland, Robin; Gottlieb, Peter A.; Marks, Jennifer B.; McGee, Paula F.; Moran, Antoinette M.; Raskin, Philip; Rodriguez, Henry; Schatz, Desmond A.; Wherrett, Diane; Wilson, Darrell M.; Lachin, John M.; Skyler, Jay S.; Type 1 Diabetes TrialNet Anti-CD20 Study Group; Medicine, School of Medicine
    BACKGROUND: The immunopathogenesis of type 1 diabetes mellitus is associated with T-lymphocyte autoimmunity. However, there is growing evidence that B lymphocytes play a role in many T-lymphocyte-mediated diseases. It is possible to achieve selective depletion of B lymphocytes with rituximab, an anti-CD20 monoclonal antibody. This phase 2 study evaluated the role of B-lymphocyte depletion in patients with type 1 diabetes. METHODS: We conducted a randomized, double-blind study in which 87 patients between 8 and 40 years of age who had newly diagnosed type 1 diabetes were assigned to receive infusions of rituximab or placebo on days 1, 8, 15, and 22 of the study. The primary outcome, assessed 1 year after the first infusion, was the geometric mean area under the curve (AUC) for the serum C-peptide level during the first 2 hours of a mixed-meal tolerance test. Secondary outcomes included safety and changes in the glycated hemoglobin level and insulin dose. RESULTS: At 1 year, the mean AUC for the level of C peptide was significantly higher in the rituximab group than in the placebo group. The rituximab group also had significantly lower levels of glycated hemoglobin and required less insulin. Between 3 months and 12 months, the rate of decline in C-peptide levels in the rituximab group was significantly less than that in the placebo group. CD19+ B lymphocytes were depleted in patients in the rituximab group, but levels increased to 69% of baseline values at 12 months. More patients in the rituximab group than in the placebo group had adverse events, mostly grade 1 or grade 2, after the first infusion. The reactions appeared to be minimal with subsequent infusions. There was no increase in infections or neutropenia with rituximab. CONCLUSIONS: A four-dose course of rituximab partially preserved beta-cell function over a period of 1 year in patients with type 1 diabetes. The finding that B lymphocytes contribute to the pathogenesis of type 1 diabetes may open a new pathway for exploration in the treatment of patients with this condition.
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    Second-line treatments in children with immune thrombocytopenia: Effect on platelet count and patient-centered outcomes
    (Wiley, 2019-04-03) Grace, Rachael F.; Shimano, Kristin A.; Bhat, Rukhmi; Neunert, Cindy; Bussel, James B.; Klaassen, Robert J.; Lambert, Michele P.; Rothman, Jennifer A.; Breakey, Vicky R.; Hege, Kerry; Bennett, Carolyn M.; Rose, Melissa J.; Haley, Kristina M.; Buchanan, George R.; Geddis, Amy; Lorenzana, Adonis; Jeng, Michael; Pastore, Yves D.; Crary, Shelley E.; Neier, Michelle; Neufeld, Ellis J.; Neu, Nolan; Forbes, Peter W.; Despotovic, Jenny M.; Pediatrics, School of Medicine
    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and hemorrhagic risk. While many children with ITP can be safely observed, treatments are often needed for various reasons, including to decrease bleeding or improve health related quality of life (HRQoL). There are a number of available second-line treatments, including rituximab, thrombopoietin-receptor agonists, oral immunosuppressive agents, and splenectomy, but data comparing treatment outcomes are lacking. ICON1 is a prospective, multi-center, observational study of 120 children starting second-line treatments for ITP designed to compare treatment outcomes including platelet count, bleeding, and HRQoL utilizing the Kids ITP Tool (KIT). While all treatments resulted in increased platelet counts, romiplostim had the most pronounced effect at 6 months (p=0.04). Only patients on romiplostim and rituximab had a significant reduction in both skin-related (84% to 48%, p=0.01 and 81% to 43%, p=0.004) and non-skin-related bleeding symptoms (58% to 14%, p=0.0001 and 54% to 17%, p=0.0006) after 1 month of treatment. HRQoL significantly improved on all treatments. However, only patients treated with eltrombopag had a median improvement in KIT scores at 1 month that met the minimal important difference (MID). Bleeding, platelet count, and HRQoL improved in each treatment group, but the extent and timing of the effect varied among treatments. These results are hypothesis generating and help to improve our understanding of the effect of each treatment on specific patient outcomes. Combined with future randomized trials, these findings will help clinicians select the optimal second-line treatment for an individual child with ITP.