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Renal transplantation and renovascular hypertension
Published in J Kellogg Parsons, E James Wright, The Brady Urology Manual, 2019
Given at the time of surgery: Daclizumab and basiliximabBlock IL-2 receptorMinimal side-effect profile.12,13
Paraneoplastic pemphigus
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
High-dose systemic glucocorticoids are often the first-line therapy in patients with PNP. The cutaneous manifestations are more likely to respond to systemic glucocorticoids than the oral mucosa [18]. Other immunosuppressives such as cyclophosphamide, mycophenolate mofetil, azathioprine, and cyclosporine are often combined with systemic steroids for their glucocorticoid-sparing effects [19]. The response to rituximab therapy is highly variable [20]. The limited efficacy of rituximab may reflect the effect of the drug on humoral immunity and the lesser effect on cell-mediated immunity. Plasmapheresis [21], cyclophosphamide, IV immunoglobulin (IVIG), alemtuzumab, and daclizumab have been reported to be effective in combination with other therapies (Table 10.4).
Treatment
Published in Raymond Downing, Suffering and Healing in America, 2018
A neighbor with long-standing diabetes has finally developed renal failure, and is being prepared for a kidney transplant. He has heard that with standard treatment to prevent rejection of the kidney graft, a third to a half of people will show symptoms of acute rejection by six months post-transplant. Graft survival at a year, though, is near 90%. One of two new expensive drugs (Daclizumab for $5855 or Basiliximab for $2448) can be added to the standard antirejection drugs, decreasing the acute rejection symptoms at six months to about one-fourth of people. Graft survival at a year is only a few percentage points higher. State funds do not cover these new drugs, and he is trying to raise money for them by a neighborhood campaign. Should you contribute?
Assessing the risk of multiple sclerosis disease-modifying therapies
Published in Expert Review of Neurotherapeutics, 2019
Xavier Ayrignac, Philippe-Antoine Bilodeau, Alexandre Prat, Marc Girard, Pierre Labauge, Jacques Le Lorier, Catherine Larochelle, Pierre Duquette
A dramatic shift in MS therapy occurred in 2005 when the first cases of progressive multifocal encephalopathy (PML) associated with natalizumab were described [4]. Since then, hundreds of natalizumab-associated PML cases have been reported (804) cases, as of December 2018), with a 24% mortality rate and a significant worsening of the disability in ±35% of the survivors. Thereafter, PML was also reported in association with other DMTs used in monotherapy, including 5 cases on dimethyl fumarate, and 19 cases on fingolimod. Opportunistic infections, including CNS infections, hematopoietic anomalies, liver disorders and autoimmune diseases were reported with almost all recent DMTs [3,5]. Recently, daclizumab was withdrawn, following several cases of fatal inflammatory liver and brain disorders. These events underline the limitations of phase III randomized control trials (RCTs) in fully assessing the real-world safety profile of drugs.
Modulating acute neuroinflammation in intracerebral hemorrhage: the potential promise of currently approved medications for multiple sclerosis
Published in Immunopharmacology and Immunotoxicology, 2019
Jarred Napier, Lucas Rose, Opeolu Adeoye, Edmond Hooker, Kyle B. Walsh
Daclizumab is a monoclonal antibody that specifically targets the CD25 cell surface marker, which is the alpha subunit of the IL-2 receptor, and whose inhibition blocks T cell maturation and proliferation. The anti-inflammatory effects of Daclizumab are multifold. Wuest et al. found that when daclizumab blocked CD25 on monocytes, lymphocytic proliferation was reduced, plateauing at an average reduction of 78–88% by day 7 of treatment (p < .001), with consistent findings regardless of the antigen used for stimulation [29]. In patients with MS, treatment with daclizumab normalized the abnormal CSF WBC counts. Specifically, a decrease in CSF monocytes seen in these patients was reversed (p < .001), and this was theorized to improve the clinical outcome because monocytes phagocytose debris generated by damaged myelin sheaths and promote repair [30]. Furthermore, daclizumab treatment normalized the disease-associated elevation in CSF CD4+ T cells and B cells [30].
Meta-analysis of the association of IL2RA polymorphisms rs2104286 and rs12722489 with multiple sclerosis risk
Published in Immunological Investigations, 2018
The IL-2 receptor is an integral membrane complex composed of three different proteins, termed α (CD25), β (CD122), and γc (CD132). The IL-2 receptor signaling is crucial for the activation of CD4 + T helper and CD8+ effector T cells. As a consequence, it is believed that blockade of the IL-2 signaling would inhibit T-cell effector functions (Chistiakov et al., 2008). Daclizumab is a humanized monoclonal antibody of IgG1 subtype that binds to IL-2RA. Phase II and III clinical trials have shown that monthly subcutaneous injections of daclizumab in patients with relapsing MS result in decreased number of contrast-enhanced lesions on brain MRI and a significant reduction of the annualized relapse rate (Rose et al., 2017). Daclizumab causes expansion and enhanced function of regulatory CD56bright natural killer cells, which are capable of killing activated T cells (Rose et al., 2017). In addition, Daclizumab blocks trans-presentation of IL-2 by mature dendritic cells to primed T cells, leading to profound inhibition of antigen-specific T cells (Wuest et al., 2011). Daclizumab also impedes the maintenance of meningeal lymphoid aggregates and associated immune memory responses by inhibiting lymphoid tissue inducer (LTi) cells (Howell et al., 2011). The beneficial effects of Daclizumab on MS suggest a critical contribution of IL-2RA to T-cell immunity and MS immunopathogenesis.