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Transplantation Proceedings Jun 2000
Comparative Study
Topics: Acyclovir; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Cyclosporine; Cytomegalovirus Infections; Daclizumab; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Retrospective Studies
PubMed: 10856587
DOI: 10.1016/s0041-1345(00)00984-2 -
Neurology(R) Neuroimmunology &... Mar 2019
Topics: Adult; Antibodies, Monoclonal, Humanized; Daclizumab; Female; Hepatic Insufficiency; Humans; Immunosuppressive Agents; Leukemic Infiltration; Leukocytes; Liver Failure; Multiple Sclerosis
PubMed: 30800722
DOI: 10.1212/NXI.0000000000000539 -
Best Practice & Research. Clinical... Apr 2016Uveitis may exist as a clinical manifestation of an underlying systemic disease or may represent an idiopathic entity, sometimes with a very characteristic pattern.... (Review)
Review
Uveitis may exist as a clinical manifestation of an underlying systemic disease or may represent an idiopathic entity, sometimes with a very characteristic pattern. Different forms of uveitis have been defined on the basis of three important variables: chronicity, anatomic location, and underlying etiology. The evolving understanding of the immune system has resulted in a more targeted approach to manage patients with different forms of uveitis, although clearly this approach is at a very early stage. Altered patterns of cellular processing and different cytokine expression, including TNF, IL-1, IL-2, IL-6, and IL17, have been defined in uveitis, and this has laid the pathway for targeted therapy. Furthermore, approved biologic therapies for some of the more common autoimmune illnesses have now been tested in uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as the first line of treatment for ocular manifestations of Behçet's disease and the second line of treatment for other forms of uveitis. Adalimumab has been recently approved for intermediate uveitis, posterior uveitis, and panuveitis. Other biologic agents have been tested, including daclizumab, a monoclonal antibody directed against IL-2, anti-IL1, and anti-IL-6 receptor agents and therapies that block antigen-presenting cell and T-cell interaction, such as abatacept. In small case series, other biologics such as interferon and rituximab have also been evaluated. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a disease, but a manifestation of many potential systemic diseases that may have specific individual therapeutic targets. Identification and characterization of these underlying diseases are not always possible and, more importantly, the most effective therapies for each entity have not been defined. In this study, an approach to manage patients with uveitis is presented and current therapy is reviewed.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Daclizumab; Humans; Immunoglobulin G; Infliximab; Uveitis
PubMed: 27886802
DOI: 10.1016/j.berh.2016.07.005 -
Proceedings of the National Academy of... Oct 2015Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We...
Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with (90)Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.
Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Daclizumab; Female; Hodgkin Disease; Humans; Immunoglobulin G; Interleukin-2 Receptor alpha Subunit; Male; Middle Aged; Phosphorylation; Recurrence; Young Adult; Yttrium Radioisotopes
PubMed: 26438866
DOI: 10.1073/pnas.1516107112 -
Journal of Neurology Oct 2020SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the... (Clinical Trial)
Clinical Trial
OBJECTIVE
SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED.
METHODS
Eligible participants who completed 1-2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION.
RESULTS
Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0-24 was 0.21 (0.16-0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time.
CONCLUSIONS
The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED.
TRIAL REGISTRATION
Clinicaltrials.gov NCT01051349; first registered on January 15, 2010.
Topics: Adult; Antibodies, Monoclonal, Humanized; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Male; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
PubMed: 32451615
DOI: 10.1007/s00415-020-09835-y -
Transplantation Proceedings 2010Allograft rejection in intestinal transplantation occurs frequently, and bacterial, fungal, and viral infections related to strong immunosuppression regimens remain an...
Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceral transplantation: rejection and infection rates in 40 recipients during the early postoperative period.
BACKGROUND
Allograft rejection in intestinal transplantation occurs frequently, and bacterial, fungal, and viral infections related to strong immunosuppression regimens remain an important complication posttransplantation. Induction therapy has enabled improvement in graft and patient survival rates.
OBJECTIVES
In analyze the effects of daclizumab and alemtuzumab as induction therapies on inflections complications and incidence of acute cellular rejection (ACR) during the early posttransplantation period.
PATIENTS AND METHODS
Between December 2000 and August 2009, we performed 43 intestinal transplantation procedures in 42 adult recipients (median [SD] age, 34.8 [9.5] years; male-female ratio, 22:20; isolated or multivisceral graft, 32/11), and compared findings during the first 30 days posttransplantation in 40 recipients. Patients were divided into 2 groups: 12 treated with daclizumab (Zenapax; Hoffman-La Roche Ltd, Basel, Switzerland): 8 isolated intestinal grafts and 4 multivisceral grafts) and 28 treated with alemtuzumab (Campath-1H: 22 isolated intestinal grafts and 6 multivisceral grafts). Maintenance immunosuppression was based on tacrolimus and steroids in the first group and low-dose tacrolimus in the second group.
RESULTS
During the first month posttransplantation, 8 daclizumab recipients (66.6%) experienced 9 episodes of mild ACR, which were successfully treated with steroid therapy, and 8 patients (66.6%) developed a bacterial infection requiring treatment. Fourteen episodes of ACR occurred in 12 alemtuzumab recipients (42.8%): 11 mild, 1 mild to moderate, and 2 moderate; 16 patients (57.1%) required treatment for infections. Five-year patient cumulative survival was 66% in daclizumab recipients and 43% in alemtuzumab recipients. Five-year graft survivals was 66% in daclizumab recipients and 41% in alemtuzumab recipients. In both groups, P was not statistically significative.
CONCLUSIONS
The infection rate is considerably high with both protocols. Alemtuzumab seems to offer better immunosuppression against ACRs during the first month posttransplantation.
Topics: Adolescent; Adult; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Daclizumab; Female; Follow-Up Studies; Gardner Syndrome; Graft Survival; Humans; Immunoglobulin G; Immunosuppressive Agents; Intestines; Male; Middle Aged; Postoperative Complications; Postoperative Period; Short Bowel Syndrome; Survival Rate; Viscera
PubMed: 20172276
DOI: 10.1016/j.transproceed.2009.12.019 -
Ugeskrift For Laeger Oct 2000Basiliximab and daclizumab are analogous immunosuppressive agents approved for clinical renal transplantation. Both drugs are gene manipulated chimeric human/murine... (Review)
Review
Basiliximab and daclizumab are analogous immunosuppressive agents approved for clinical renal transplantation. Both drugs are gene manipulated chimeric human/murine monoclonal antibodies with specificity against the alpha-chain of the interleukin-2 receptor (IL-2R) on activated T lymphocytes. By combining the drugs with calcineurin inhibitor based immunosuppression, an inhibition of the interleukin-2 (IL-2) synthesis as well as the IL-2/IL-2R reception is obtained. Consequently, the allogeneic immune response is suppressed and the risk of acute rejection of the transplant is reduced. By treatment with basiliximab or daclizumab in the recommended doses, a blockade of the IL-2R is obtained for up to 12 weeks. The incidence of acute rejection episodes is reduced by approx. 33%. The incorporation of human amino acid sequences has almost eliminated the immunogenicity of the drugs and reduced their rates of elimination. The side effects of prophylactic treatment with basiliximab/daclizumab do not differ from those of placebo.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Basiliximab; Daclizumab; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Receptors, Interleukin-2; Recombinant Fusion Proteins
PubMed: 11059309
DOI: No ID Found -
Pediatric Transplantation Jun 2009DCZ, an IL-2 receptor antagonist, has been widely used for induction therapy in pediatric and adult solid organ transplantation. Originally, it was recommended as a...
DCZ, an IL-2 receptor antagonist, has been widely used for induction therapy in pediatric and adult solid organ transplantation. Originally, it was recommended as a five-dose regimen; however, fewer doses may be efficacious and less costly for prevention of rejection. There is limited experience with the use of fewer doses in pediatric renal transplantation. We retrospectively reviewed the outcomes of 26 primary pediatric renal transplants performed at a single center between June 2004 and May 2007 receiving induction therapy with two-dose DCZ (1.5 mg/kg preoperatively and day seven post-transplant). Maintenance immunosuppression included tacrolimus, MMF, and prednisone in all patients. Forty-six percent were African American and 92% were deceased-donor transplants. After a mean follow-up of 17.8 +/- 7.5 months, acute rejection was noted in 11.5% and graft survival was 92.3%. CMV infection occurred in 11.5%, but no case of BK nephropathy or post-transplant lymphoproliferative disorder was observed. Our preliminary results suggest that induction therapy with two-dose DCZ was convenient, economical, and effective in preventing rejection episodes without an increase in adverse events or hospital stay. Larger randomized clinical trials with longer duration of follow-up are needed to more fully validate the use of this regimen in pediatric renal transplantation.
Topics: Adolescent; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Daclizumab; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Retrospective Studies
PubMed: 18992052
DOI: 10.1111/j.1399-3046.2008.01033.x -
Multiple Sclerosis (Houndmills,... Dec 2018Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments.
BACKGROUND
Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments.
OBJECTIVE
Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE.
METHODS
Twenty-four-week confirmed disability progression (CDP), 24-week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the overall population and subgroups defined by baseline demographic/disease characteristics.
RESULTS
Daclizumab beta significantly reduced risk of 24-week CDP (hazard ratio (HR), 0.73; 95% confidence interval (95% CI), 0.55-0.98), risk of 24-week sustained MSFCS progression (HR, 0.80; 95% CI, 0.67-0.95), and odds of clinically meaningful worsening in MSIS-29 PHYS (odds ratio, 0.76; 95% CI, 0.60-0.95) versus IM interferon beta-1a. Point estimates showed trends favoring daclizumab beta over IM interferon beta-1a across several patient subgroups for all three outcome measures.
CONCLUSION
Daclizumab beta showed consistent benefit versus IM interferon beta-1a across measures assessing patient disability/function and across a range of clinical baseline characteristics in patients with relapsing-remitting MS.
Topics: Adult; Antibodies, Monoclonal, Humanized; Daclizumab; Disease Progression; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Interferon beta-1a; Male; Middle Aged; Multiple Sclerosis; Treatment Outcome
PubMed: 28984179
DOI: 10.1177/1352458517735190 -
Multiple Sclerosis and Related Disorders Oct 2017Daclizumab beta is a humanized monoclonal antibody specific for the human interleukin-2 receptor alpha chain (CD25). In two pivotal studies in relapsing multiple...
BACKGROUND
Daclizumab beta is a humanized monoclonal antibody specific for the human interleukin-2 receptor alpha chain (CD25). In two pivotal studies in relapsing multiple sclerosis (MS), patients treated with daclizumab beta exhibited lower annualized relapse rates (ARR) when compared with placebo or with intramuscular (IM) interferon beta-1a.
OBJECTIVES
To determine if the efficacy of daclizumab beta demonstrated in the phase 2 SELECT study and the phase 3 DECIDE study was consistent in patient subgroups.
METHODS
In the SELECT study, patients received daclizumab beta 150 or 300mg administered subcutaneously every 4 weeks for 52 weeks, and were compared with patients who received placebo. In the DECIDE study, patients received daclizumab beta 150mg administered subcutaneously every 4 weeks for 96-144 weeks, and were compared with patients who received IM interferon beta-1a 30µg. Subgroups were defined by sex, age, the number of relapses in the year before the study, disease duration, baseline disability measured by EDSS, presence of Gd-enhancing lesions, T2 hyperintense lesion volume at baseline, and previous interferon beta-1a use.
RESULTS
Treatment with daclizumab beta was associated with relative lower ARR, with 95% confidence intervals (CIs) below 1 in 13 of 15 subgroups (SELECT study) compared with placebo and in all 17 subgroups compared with interferon beta-1a (DECIDE study). In 2 subgroups in the SELECT study (patients who were older than 35 years of age or who had a disease duration of 10 or more years), the rate ratio point estimate for the ARR was in favor of daclizumab beta but the 95% CI overlapped with 1. The clinical benefits in ARR achieved with daclizumab beta treatment compared with placebo or interferon beta-1a across subgroups were similarly supported by reductions in lesion activity on magnetic resonance images (MRIs).
CONCLUSIONS
These findings suggest that treatment with daclizumab beta is consistently effective among clinically important patient subgroups and support its potential as a viable therapeutic option across the spectrum of relapsing MS.
Topics: Adult; Antibodies, Monoclonal, Humanized; Daclizumab; Female; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Male; Multiple Sclerosis, Relapsing-Remitting
PubMed: 29055471
DOI: 10.1016/j.msard.2017.06.006