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CNS Drugs Sep 2022Autoimmune encephalitis represents a potentially treatable immune-mediated condition that is being more frequently recognized. Prompt immunotherapy is a key factor for... (Review)
Review
Autoimmune encephalitis represents a potentially treatable immune-mediated condition that is being more frequently recognized. Prompt immunotherapy is a key factor for the management of autoimmune encephalitis. First-line treatments include intravenous steroids, plasma exchange, and intravenous immunoglobulins, which can be combined in most severe cases. Rituximab and cyclophosphamide are administered as second-line agents in unresponsive cases. A minority of patients may still remain refractory, thus representing a major clinical challenge. In these cases, treatment strategies are controversial, and no guidelines exist. Treatments proposed for refractory autoimmune encephalitis include (1) cytokine-based drugs (such as tocilizumab, interleukin-2/basiliximab, anakinra, and tofacitinib); (2) plasma cell-depleting agents (such as bortezomib and daratumumab); and (3) treatments targeting intrathecal immune cells or their trafficking through the blood-brain barrier (such as intrathecal methotrexate and natalizumab). The efficacy evidence of these drugs is mostly based on case reports or small case series, with few reported controlled studies or systematic reviews. The aim of the present review is to summarize the current evidence and related methodological issues in the use of these drugs for the treatment of refractory autoimmune encephalitis.
Topics: Basiliximab; Bortezomib; Cyclophosphamide; Encephalitis; Hashimoto Disease; Humans; Immunoglobulins, Intravenous; Interleukin 1 Receptor Antagonist Protein; Interleukin-2; Methotrexate; Natalizumab; Rituximab; Steroids
PubMed: 35917105
DOI: 10.1007/s40263-022-00943-z -
American Journal of Transplantation :... Nov 2017Despite the abundance of information on cutaneous malignancies associated with solid organ transplantation in the transplant literature, there is limited information... (Review)
Review
Despite the abundance of information on cutaneous malignancies associated with solid organ transplantation in the transplant literature, there is limited information regarding nonmalignant skin changes after transplantation. There are numerous skin toxicities secondary to immunosuppressive and other transplant-related medications that can vary in presentation, severity, and prognosis. To limit associated morbidity and mortality, solid organ transplant recipient care providers should effectively identify and manage cutaneous manifestations secondary to drug toxicity. Toxicities from the following transplant-related medications will be discussed: antithymocyte globulins, systemic steroids, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mammalian target of rapamycin inhibitors sirolimus and everolimus, basiliximab and daclizumab, belatacept, and voriconazole.
Topics: Humans; Immunosuppressive Agents; Organ Transplantation; Skin Diseases
PubMed: 28452165
DOI: 10.1111/ajt.14337 -
Indian Journal of Thoracic and... Jul 2022Immunosuppression for lung transplant recipients is a critical part of post-transplant care, to prevent acute and chronic rejection. Treatment protocols consist of... (Review)
Review
Immunosuppression for lung transplant recipients is a critical part of post-transplant care, to prevent acute and chronic rejection. Treatment protocols consist of induction and maintenance immunotherapy. Induction agents provide an immediate state of immunosuppression following transplantation and over time, and their use has become more commonplace. Several agents are available for clinical use, including anti-thymocyte globulin, alemtuzumab, and basiliximab, the latter being most commonly employed. Each induction agent has unique side effects and caveats to their use, of which we must be aware. Maintenance immunosuppression is initiated following transplant but requires multiple doses prior to reaching therapeutic levels. A calcineurin inhibitor, an anti-metabolite, and a corticosteroid are traditionally used, most commonly tacrolimus, mycophenolate mofetil, and prednisone. Dosing regimens and goal trough levels vary and are tailored to a patient's clinical status and duration post-transplant. Future clinical studies may be able to assist in determining the optimal induction and maintenance immunosuppression regimens. In the interim, we use cohort and registry data to guide our therapies.
PubMed: 35756950
DOI: 10.1007/s12055-021-01225-x -
Journal of Clinical and Experimental... 2022Liver transplantation (LT) is the standard of care for end-stage liver failure and hepatocellular carcinoma. Over the years, immunosuppression regimens have improved,... (Review)
Review
Liver transplantation (LT) is the standard of care for end-stage liver failure and hepatocellular carcinoma. Over the years, immunosuppression regimens have improved, resulting in enhanced graft and patient survival. At present, the side effects of immunosuppressive agents are a significant threat to post-LT quality of life and long-term outcome. The role of personalized immunosuppression is to reach a delicate balance between optimal immunosuppression and minimal side effects. Today, immunosuppression in LT is more of an art than a science. There are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring and immunosuppression regimens vary from center to center. The immunosuppressive agents are broadly classified into biological agents and pharmacological agents. Most regimens use multiple agents with different modes of action to reduce the dosage and minimize the toxicities. The calcineurin inhibitor (CNI)-related toxicities are reduced by antibody induction or using mTOR inhibitor/antimetabolites as CNI sparing or CNI minimization strategies. Post-liver transplant immunosuppression has an intensive phase in the first three months when alloreactivity is high, followed by a maintenance phase when immunosuppression minimization protocols are implemented. Over time some patients achieve "tolerance," defined as the successful stopping of immunosuppression with good graft function and no indication of rejection. Cell-based therapy using immune cells with tolerogenic potential is the future and may permit complete withdrawal of immunosuppressive agents.
PubMed: 36340316
DOI: 10.1016/j.jceh.2022.06.007 -
Neurotherapeutics : the Journal of the... Apr 2022Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and... (Review)
Review
Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases. All forms of myositis have progressive muscle weakness in common, with each subtype characterized by different autoantibody profiles, histological findings and extramuscular manifestations. Due to better understanding of the pathogenesis of the muscle inflammation in myositis, new molecular pathways for targeted therapy have been discovered. Current therapies aim at different components of the innate or the adaptive immune response. Additionally, non-inflammatory mechanisms in myositis have come into focus as possible treatment targets. The use of therapeutical antibodies in myositis has been examined in various clinical studies, several of them randomized controlled ones: Depletion of B-cells by rituximab has been established as treatment of refractory myositis. IVIG, an antibody therapy in the wider sense, has now been licensed for DM following a recent positive clinical trial. Negative study results were reported in randomized trials with infliximab, sifalimumab and bimagrumab. Studies on basiliximab and eculizumab are currently underway, and are expected to yield results in a couple of years. Despite some promising results of clinical studies with antibody therapy in myositis, further research is crucial to optimize the treatment for this debilitating disease and to find treatment alternatives for treatment-refractory patients.
Topics: Autoantibodies; Autoimmune Diseases; Humans; Myositis; Myositis, Inclusion Body; Polymyositis
PubMed: 35394612
DOI: 10.1007/s13311-022-01220-z -
American Journal of Hematology Apr 2022Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation...
Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.
Topics: Acute Disease; Basiliximab; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Steroids
PubMed: 35064928
DOI: 10.1002/ajh.26475 -
Frontiers in Immunology 2021Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line... (Meta-Analysis)
Meta-Analysis
Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line treatment for aGVHD, but its response rate is only approximately 50%. At present, no uniformly accepted treatment for steroid-refractory aGVHD (SR-aGVHD) is available. Blocking interleukin-2 receptors (IL-2Rs) on donor T cells using pharmaceutical antagonists alleviates SR-aGVHD. This meta-analysis aimed to compare the efficacy and safety of four commercially available IL-2R antagonists (IL-2RAs) in SR-aGVHD treatment. A total of 31 studies met the following inclusion criteria (1): patients of any race, any sex, and all ages (2); those diagnosed with SR-aGVHD after HSCT; and (3) those using IL-2RA-based therapy as the treatment for SR-aGVHD. The overall response rate (ORR) at any time after treatment with basiliximab and daclizumab was 0.81 [95% confidence interval (CI): 0.74-0.87)] and 0.71 (95% CI: 0.56-0.82), respectively, which was better than that of inolimomab 0.54 (95% CI: 0.39-0.68) and denileukin diftitox 0.56 (95% CI: 0.35-0.76). The complete response rate (CRR) at any time after treatment with basiliximab and daclizumab was 0.55 (95% CI: 0.42-0.68) and 0.42 (95%CI: 0.29-0.56), respectively, which was better than that of inolimomab 0.30 (95% CI: 0.16-0.51) and denileukin diftitox 0.37 (95% CI: 0.24-0.52). The ORR and CRR were better after 1-month treatment with basiliximab and daclizumab than after treatment with inolimomab and denileukin diftitox. The incidence of the infection was higher after inolimomab treatment than after treatment with the other IL-2RAs. In conclusion, the efficacy and safety of different IL-2RAs varied. The response rate of basiliximab was the highest, followed by that of daclizumab. Prospective, randomized controlled trials are needed to compare the efficacy and safety of different IL-2RAs.
Topics: Antibodies, Monoclonal; Basiliximab; Daclizumab; Diphtheria Toxin; Drug Resistance; Graft vs Host Disease; Humans; Immunosuppressive Agents; Interleukin-2; Receptors, Interleukin-2; Recombinant Fusion Proteins; Steroids
PubMed: 34621279
DOI: 10.3389/fimmu.2021.749266 -
American Journal of Transplantation :... Oct 2005This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a... (Clinical Trial)
Clinical Trial
This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (<3 months) rejection was observed in the alemtuzumab (4.1%) versus the basiliximab (11.6%) group, but the rates for both groups were equivalent at 1 year. Patient and kidney survival and rejection rates were nearly identical between Caucasians and African Americans that received alemtuzumab. Quality of renal function and incidence of infectious complications were similar in the two groups. Alemtuzumab induction therapy was similar in efficacy to basiliximab in a prednisone-free maintenance immunosuppressive protocol for an ethnically diverse population of kidney transplant recipients.
Topics: Adolescent; Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Creatinine; Disease Progression; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Immunotherapy; Infant, Newborn; Kidney; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Prednisone; Proportional Hazards Models; Retrospective Studies; Tacrolimus; Time Factors; Treatment Outcome
PubMed: 16162205
DOI: 10.1111/j.1600-6143.2005.01067.x