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Respiratory Medicine Mar 2019Several drugs have been associated with druginduced sarcoidosis-like reactions (DISRs) that are clinically indistinguishable from sarcoidosis. Daclizumab is a humanized... (Comparative Study)
Comparative Study
INTRODUCTION
Several drugs have been associated with druginduced sarcoidosis-like reactions (DISRs) that are clinically indistinguishable from sarcoidosis. Daclizumab is a humanized monoclonal IgG1 antibody that binds to CD25 that has been studied for the treatment of multiple sclerosis (MS). During MS clinical trials of daclizumab, 12 subjects developed clinical conditions potentially consistent with sarcoidosis. Therefore, an independent adjudication committee of individuals with expertise in sarcoidosis was organized to determine the likelihood of these cases representing sarcoidosis.
METHODS
The adjudication committee consisted of a pulmonologist, pathologist, and radiologist with clinical experience in sarcoidosis. The committee had access to the subjects' laboratory data, narratives of all suspect adverse reaction reports, radiographic imaging and histology from biopsies. A priori, a grading system was developed to determine criteria to establish the likelihood that the patient had developed sarcoidosis.
RESULTS
The adjudication confirmed sarcoidosis in 11/12 subjects. The committee's decisions were unanimous in all cases. Biopsies were available in 7/11 of these. In the 4 subjects who did not have a biopsy, they all had presentations, clinical findings, and/or laboratory findings that were highly specific for sarcoidosis. Alternative causes for these clinical findings were reasonably excluded in all cases. The lung (8/11) and skin (6/11) were the most common organs involved. The mean daclizumab dose given when signs or symptoms of sarcoidosis occurred was 5413 ± 2704 mg and the median time from first daclizumab dose was 996 days. The incidence rate of developing sarcoidosis in those participating in these daclizumab trials was 154/100,000 patient-years compared with incidence rates of sarcoidosis in the United States of 3.2-17.8/100,000/year. These data suggest that these sarcoidosis cases may have represented DISRs related to daclizumab therapy.
CONCLUSIONS
Given the clinical presentation and subsequent evaluation of these 11 subjects, we suspect that they had DISRs from daclizumab.
Topics: Adult; Daclizumab; Female; Humans; Immunosuppressive Agents; Incidence; Lung Diseases; Male; Middle Aged; Multiple Sclerosis; Pharmacovigilance; Sarcoidosis; Skin Diseases
PubMed: 30885425
DOI: 10.1016/j.rmed.2019.01.015 -
Journal of Neurology Dec 2017Discontinuation of natalizumab can lead to severe rebound of disease activity in patients with relapsing-remitting multiple sclerosis (RRMS); nevertheless, the treatment... (Observational Study)
Observational Study
Discontinuation of natalizumab can lead to severe rebound of disease activity in patients with relapsing-remitting multiple sclerosis (RRMS); nevertheless, the treatment regimen in this clinical situation remains controversial. We report the case of a 25-year-old male patient with RRMS who was clinically stable under 3 years of natalizumab before treatment was stopped due to progressive multifocal leucencephalopathy (PML) safety concerns. After initiation of daclizumab, the patient suffered from disease reactivation, which was ultimately controlled by intravenous methylprednisolone and alemtuzumab treatment. Therefore, in some patients, daclizumab might not be sufficient to control disease activity after discontinuing natalizumab treatment.
Topics: Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Daclizumab; Drug Substitution; Humans; Immunoglobulin G; Immunologic Factors; Magnetic Resonance Imaging; Male; Methylprednisolone; Multiple Sclerosis, Relapsing-Remitting; Natalizumab
PubMed: 28975400
DOI: 10.1007/s00415-017-8622-9 -
Acta Dermato-venereologica 2005
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Middle Aged; Pemphigoid, Bullous
PubMed: 15848995
DOI: 10.1080/00015550410022221 -
Transplantation Jun 2003A new class of monoclonal antibodies (non-T-cell depleting) has gained favor for induction therapy after transplantation. This study evaluated the non-T-cell depleting... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
A new class of monoclonal antibodies (non-T-cell depleting) has gained favor for induction therapy after transplantation. This study evaluated the non-T-cell depleting antibody to the CD25 cell, daclizumab, as a single-dose induction agent immediately after pediatric liver transplantation to spare the use of the calcineurin inhibitor, tacrolimus, for 7 days in respect to both efficacy and renal function.
METHODS
From January 1998 to November 2001, 81 pediatric orthotopic liver transplant recipients receiving 89 liver grafts were evaluated. The treatment arm (n=61) received daclizumab 1 mg/kg immediately after liver transplantation along with mycophenolate, steroids, and, on postoperative day 7, tacrolimus. The control group did not receive induction therapy, whereas tacrolimus, mycophenolate, and steroids were started immediately after surgery.
RESULTS
The induction group had fewer patients with rejection within the first 30 days after liver transplantation (9 [14.8%] vs. 10 [50%]; P=0.003). The mean time to first rejection was similar between groups (12.1 [+/-7.8] days vs. 18.5 [+/-8.1] days; P=not significant). There was a 3.39 increase in relative risk to develop rejection within the first 30 days after orthotopic liver transplantation if the patient did not receive induction therapy (relative risk=3.39; 95% confidence interval [1.61, 7.14]). Two-year actuarial survival for the induction group was 93.2% compared with 85% in the control; graft survival was also similar between groups (87.8% vs. 72.7%) at 2 years.
CONCLUSION
Daclizumab 1 mg/kg given immediately after pediatric liver transplantation and withholding tacrolimus, is safe, efficacious, and reduces rejections within the first 30 days after surgery.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Blood Urea Nitrogen; Child; Child, Preschool; Creatinine; Daclizumab; Drug Administration Schedule; Female; Follow-Up Studies; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Liver Transplantation; Male; Reoperation; Survival Analysis; Tacrolimus; Time Factors
PubMed: 12829908
DOI: 10.1097/01.TP.0000065740.69296.DA -
Transplantation Proceedings Oct 2015Interleukin-2 receptor antagonists (IL-2RAs) have been extensively used in kidney transplant patients to prevent the occurrence of acute rejection. The efficacy and... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Interleukin-2 receptor antagonists (IL-2RAs) have been extensively used in kidney transplant patients to prevent the occurrence of acute rejection. The efficacy and safety of basiliximab and daclizumab, the 2 most commonly used IL-2RAs in clinics, have been compared in a number of randomized controlled trials, but no definite conclusions have been drawn.
OBJECTIVE
This meta-analysis aimed to compare the efficacy and safety of basiliximab and daclizumab in kidney transplant patients.
METHODS
We performed keyword searches in Pubmed, Embase, and the Cochrane library. In total, 6 randomized controlled trials with 509 patients were included in this meta-analysis. Data collected included patient survival, graft survival, acute rejection, infection, and cytomegalovirus infection. The outcome measure was the relative risk of basiliximab versus daclizumab.
RESULTS
Therapy with basiliximab and daclizumab resulted in similar outcomes regarding acute rejection (6-month 95% confidence interval [CI], 0.09-1.14; 12-month 95% CI, 0.53-1.91), patient survival (95% CI, 0.97-1.04), graft survival (95% CI, 0.98-1.08), infection (95% CI, 0.66-1.01), and cytomegalovirus infection (95% CI, 0.45-1.14) within the follow-up period. There were no significant differences in safety and efficacy between the 2 drugs.
CONCLUSIONS
The safety and efficacy of daclizumab and basiliximab are similar in kidney transplant recipients.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Basiliximab; Daclizumab; Graft Rejection; Graft Survival; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Receptors, Interleukin-2; Recombinant Fusion Proteins
PubMed: 26518947
DOI: 10.1016/j.transproceed.2015.08.009 -
The New England Journal of Medicine Jun 2005
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Graft Rejection; Heart Transplantation; Humans; Immunoglobulin G; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Research Design
PubMed: 15987926
DOI: 10.1056/NEJMe058087 -
Bone Marrow Transplantation Feb 2008
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin G; Immunosuppressive Agents; Male; Medical Audit; Methylprednisolone; Middle Aged; Retrospective Studies; Salvage Therapy; Transplantation, Homologous; Treatment Failure
PubMed: 18026147
DOI: 10.1038/sj.bmt.1705927 -
Liver Transplantation : Official... Mar 2001The addition of daclizumab (a human immunoglobulin G1 monoclonal antibody that blocks interleukin-2 receptors on T lymphocytes) to mycophenolate mofetil (MMF) and...
The addition of daclizumab (a human immunoglobulin G1 monoclonal antibody that blocks interleukin-2 receptors on T lymphocytes) to mycophenolate mofetil (MMF) and steroids is a new option for initial immunosuppression in patients undergoing liver transplantation (LT) with impaired renal function. We evaluated the efficacy and safety of daclizumab in preventing rejection in 25 patients with impaired kidney function undergoing LT. Patients with serum creatinine (Cr) levels greater than 2 mg/dL immediately before LT were administered initial immunosuppression with daclizumab, 1 mg/kg, in addition to MMF, 2 g/d, and methylprednisolone. Tacrolimus was added after kidney function improved (when Cr levels improved by >25% of initial value). Daclizumab-treated patients were compared retrospectively with 2 other groups of patients who underwent LT with kidney impairment (Cr > 2 mg/dL): 56 patients were administered OKT3 induction, and 48 patients were administered low-dose tacrolimus. The incidence of rejection and infection (bacterial, fungal, and viral), need for preoperative and postoperative dialysis, Cr level immediately post-LT and at 3 months, and graft and patient survival were analyzed. There was no difference among the groups in 3-month Cr levels or the incidence of rejection or fungal or viral infection. The daclizumab group had fewer bacterial infections (n = 13) than the tacrolimus group (n = 28) and significantly fewer than the OKT3 group (n = 58; P =.006). Only 1 patient (4%) in the daclizumab group required dialysis post-LT versus 13 patients in each of the other groups (OKT3, 23.21%; P <.05; tacrolimus, 27%). In the daclizumab group, 2-year patient and graft survival rates were statistically significant compared with the low-dose tacrolimus group (89% and 81% v 73% and 69%, respectively; P =.06). There were no side effects related to daclizumab use, and all patients tolerated the drug well. In patients with impaired renal function before LT, daclizumab-based initial immunosuppression can be used safely to reduce the risk for infection and need for dialysis post-LT, with improved long-term graft and patient survival.
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Creatinine; Daclizumab; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Function Tests; Liver Diseases; Liver Transplantation; Male; Middle Aged; Muromonab-CD3
PubMed: 11244163
DOI: 10.1053/jlts.2001.22455 -
Clinical Pharmacokinetics Aug 2016Daclizumab high-yield process (HYP) is a humanized IgG1 monoclonal antibody that binds to the α-subunit (CD25) of the interleukin-2 receptor. The present work... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Daclizumab high-yield process (HYP) is a humanized IgG1 monoclonal antibody that binds to the α-subunit (CD25) of the interleukin-2 receptor. The present work characterized the population pharmacokinetics of daclizumab HYP in healthy volunteers (HVs) and subjects with relapsing-remitting multiple sclerosis (RRMS) and evaluated the effects of covariates on daclizumab HYP exposure.
METHODS
Measurable serum concentrations (n = 17,139) from 1670 subjects in seven clinical studies (three phase I, one immunogenicity, one phase II with extension, and one phase III) were included in this pharmacokinetic analysis using non-linear mixed-effects modeling. The three phase I studies evaluated single or multiple doses that ranged from 50 to 400 mg with either intravenous or subcutaneous (SC) administration in HVs (n = 71). The phase II with extension studies evaluated doses of 150 or 300 mg SC every 4 weeks (n = 567), and the immunogenicity (n = 113) and the phase III (n = 919) studies evaluated 150 mg SC every 4 weeks, all in RRMS patients.
RESULTS
A two-compartment model with first-order absorption and elimination adequately described daclizumab HYP pharmacokinetics. Clearance (CL) was 0.212 L/day and the central volume of distribution was 3.92 L, scaled by [body weight (kg)/68] with exponents of 0.87 and 1.12, respectively. The peripheral volume of distribution was 2.42 L. Absorption lag time, mean absorption time, and absolute bioavailability (100-300 mg SC) were 1.61 h, 7.2 days, and 88 %, respectively. The daclizumab HYP terminal half-life was 21 days. Baseline CD25, age, and sex did not influence daclizumab HYP pharmacokinetics. Body weight explained 37 and 27 % of the inter-individual variability for CL and central volume of distribution, respectively. Neutralizing antibody (NAb)-positive status (included as a time-varying covariate) increased daclizumab HYP CL by 19 %.
CONCLUSIONS
Consistent with previous findings in HVs, this analysis including extensive data from RRMS patients demonstrates that daclizumab HYP is characterized by slow CL, linear pharmacokinetics at doses above 100 mg, and high SC bioavailability. The pharmacokinetics of daclizumab HYP were not influenced by age (range 18-66 years), the sex of adult subjects, or the baseline CD4+CD25+ T cells (target level). The impact of covariates (body weight, NAb) on daclizumab HYP pharmacokinetics is unlikely to be clinically relevant.
Topics: Administration, Intravenous; Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Biological Availability; Daclizumab; Dose-Response Relationship, Drug; Female; Healthy Volunteers; Humans; Immunoglobulin G; Immunosuppressive Agents; Interleukin-2 Receptor alpha Subunit; Male; Middle Aged; Models, Biological; Multiple Sclerosis, Relapsing-Remitting; Receptors, Interleukin-2; Young Adult
PubMed: 26873229
DOI: 10.1007/s40262-016-0366-7 -
Neurology Jul 2018To report on 2 women with multiple sclerosis (MS) who developed severe neurologic deterioration and a drug reaction with eosinophilia and systemic symptoms (DRESS) after...
OBJECTIVE
To report on 2 women with multiple sclerosis (MS) who developed severe neurologic deterioration and a drug reaction with eosinophilia and systemic symptoms (DRESS) after treatment with 2 and 4 subcutaneous injections of daclizumab, respectively.
METHODS
This report includes clinical, MRI, and histopathologic data.
RESULTS
Daclizumab is a humanized monoclonal antibody that binds the interleukin-2 receptor. It was approved for the treatment of relapsing MS. DRESS is an immunologic reaction to various medications that is characterized by eosinophilia as well as cutaneous and visceral manifestations. Following daclizumab treatment, both patients showed fulminant neurologic deterioration along with blood eosinophilia and skin changes, and both fulfilled the clinical criteria for the diagnosis of DRESS. They presented with multiple gadolinium-enhancing supra- and infratentorial lesions, with lesions in the basal ganglia, mesencephalon, and cerebellum. Brain biopsies revealed a pronounced inflammatory infiltrate including numerous eosinophils infiltrating demyelinating lesions, a feature that is atypical for MS but compatible with DRESS. In addition, numerous plasma cells and changes reminiscent of vasculitis were evident.
CONCLUSIONS
Neurologic deterioration and DRESS occurred as severe adverse drug effects of daclizumab treatment. Early diagnosis and treatment of DRESS are essential because it is associated with complications such as new autoimmune diseases and liver failure, and may even be lethal. Because of its potential serious side effects, daclizumab was recently suspended for use in the European Union.
Topics: Adult; Daclizumab; Drug Hypersensitivity Syndrome; Eosinophilia; Female; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Multiple Sclerosis
PubMed: 29934423
DOI: 10.1212/WNL.0000000000005854