Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: Lessons learned from the midpoint analysis

Manwani, Deepa; Xu, Chengfu; Lee, Sung Kyun; Amatuni, George S.; Cohen, Hillel W.; Carullo, Veronica; Morrone, Kerry; Davila, Jennifer; Shi, Patricia A.; Ireland, Karen; Keenan, Janine; Frenette, Paul S.

doi:10.1016/j.ctim.2020.102481

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…Based on the laboratory results showing the ability of IVIg to reverse acute VOC in SCD mice [ 66 , 67 ], a Phase 1/2 study was performed with a fixed dose of IVIg at 800 mg/kg. Unfortunately, the laboratory successes could not be reproduced in the clinic [ 68 ]. It may be worthwhile exploring a higher dose of IVIg, although it will have to be administered carefully due to the high sodium load on the renal functions.…”

Section: Introductionmentioning

confidence: 99%

Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events

et al. 2021

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Painful vaso-occlusive crisis (VOC) remains the most common reason for presenting to the Emergency Department and hospitalization in patients with sickle cell disease (SCD). Although two new agents have been approved by the Food and Drug Administration for treating SCD, they both target to reduce the frequency of VOC. Results from studies investigating various approaches to treat and shorten VOC have so far been generally disappointing. In this paper, we will summarize the complex pathophysiology and downstream events of VOC and discuss the likely reasons for the disappointing results using monotherapy. We will put forward the rationale for exploring some of the currently available agents to either protect erythrocytes un-involved in the hemoglobin polymerization process from sickling induced by the secondary events, or a multipronged combination approach that targets the complex downstream pathways of VOC.

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Section: Introductionmentioning

confidence: 99%

Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events

et al. 2021

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“…In the younger age group (<14 years old), the median length of VOC was 59.65 h, compared to 78.30 h for the control group. No significant changes were reported in the older age group [63].…”

Section: Intravenous Gamma Globulin (Ivig)mentioning

confidence: 75%

Current and Future Therapeutics for Treating Patients with Sickle Cell Disease

Barak,

Hu,

Matthews

et al. 2024

Cells

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Sickle cell disease (SCD) is the most common genetic blood disorder in the United States, with over 100,000 people suffering from this debilitating disease. SCD is caused by abnormal hemoglobin (Hb) variants that interfere with normal red blood cell (RBC) function. Research on SCD has led to the development and approval of several new SCD therapies in recent years. The recent FDA-approved novel gene therapies are potentially curative, giving patients an additional option besides a hematopoietic bone marrow transplant. Despite the promise of existing therapies, questions remain regarding their long-term pharmacological effects on adults and children. These questions, along with the exorbitant cost of the new gene therapies, justify additional research into more effective therapeutic options. Continual research in this field focuses on not only developing cheaper, more effective cures/treatments but also investigating the physiological effects of the current therapies on SCD patients, particularly on the brain and kidneys. In this article, we undertake a comprehensive review of ongoing clinical trials with completion dates in 2024 or later. Our exploration provides insights into the landscape of current therapeutics and emerging novel therapies designed to combat and potentially eradicate SCD, including the latest FDA-approved gene therapies.

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“…Forty records were excluded after full-text appraisal (a complete list of excluded studies is available in Supplemental Material 2), remaining 21 records for data extraction and analyses referring to 18 RCTs (see flowchart in Supplemental Material 3). 44,45,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] No additional study was found through manual searches. It is important to disclosure that results from the BABYHUG trial (NCT00006400) were published in three different articles, 44,50,51 while data from the NCT02961218 is available in two publications.…”

Section: Resultsmentioning

confidence: 99%

“…82,83 These big molecules were assessed as potential therapies for pediatric SCD, as they act on the inflammatory path of the disease and decrease neutrophil adhesion to endothelium and red blood cell-neutrophil interactions. 45,61 In our analyses, these treatments ranked among the most effective therapies, alongside with HU, which should be further evaluated in head-to-head, welldesign and long-term RCTs for this population. Conversely, placebo and L-arginine (100-200 mg/kg) were more prone to therapeutic failure and should probably be avoided as mainstay approaches.…”

Section: Discussionmentioning

confidence: 98%

Efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: Systematic review with network meta‐analysis

Tonin

Ginete

Ferreira

et al. 2023

Pediatric Blood & Cancer

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This study aimed to synthesize the evidence on the effects of disease‐modifying agents for managing sickle cell disease (SCD) in children and adolescents by means of a systematic review with network meta‐analyses, surface under the cumulative ranking curve (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) (CRD42022328471). Eightteen randomized controlled trials (hydroxyurea [n = 7], l‐arginine [n = 3], antiplatelets [n = 2], immunotherapy/monoclonal antibodies [n = 2], sulfates [n = 2], docosahexaenoic acid [n = 1], niprisan [n = 1]) were analyzed. SUCRA and SMAA demonstrated that hydroxyurea at higher doses (30 mg/kg/day) or at fixed doses (20 mg/kg/day) and immunotherapy/monoclonal antibodies are more effective for preventing vaso‐occlusive crisis (i.e., lower probabilities of incidence of this event; 14, 25, and 30%, respectively), acute chest syndrome (probabilities ranging from 8 to 30%), and needing of transfusions (11–31%), while l‐arginine (100–200 mg/kg) and placebo were more prone to these events. Therapies were overall considered safe; however, antiplatelets and sulfates may lead to more severe adverse events. Although the evidence was graded as insufficient and weak, hydroxyurea remains the standard of care for this population, especially if a maximum tolerated dose schedule is considered.

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Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: Lessons learned from the midpoint analysis

Cited by 6 publications

References 25 publications

Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events

Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events

Current and Future Therapeutics for Treating Patients with Sickle Cell Disease

Efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: Systematic review with network meta‐analysis

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