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The Cochrane Database of Systematic... Apr 2012The anti-CD25 treatment of daclizumab appears to be effective in patients with relapsing remitting multiple sclerosis (RRMS) as regards clinical and MRI outcomes.... (Review)
Review
BACKGROUND
The anti-CD25 treatment of daclizumab appears to be effective in patients with relapsing remitting multiple sclerosis (RRMS) as regards clinical and MRI outcomes. Moreover, there are no severe safety concerns arising from clinical testing so far.
OBJECTIVES
To assess the efficacy and safety of daclizumab for the clinical progression of patients with relapsing remitting multiple sclerosis.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's Trials Register (February 2012), MEDLINE (January 1966 to February 2012), EMBASE (January 1985 to February 2012). At the same time, we handsearched the references quoted in the identified trials reports (February 2012) from the most important neurological associations and MS Societies. Contacts with researchers participating in trials on daclizumab have been established.
SELECTION CRITERIA
All randomized controlled clinical trials (RCTs) evaluating daclizumab, alone or combined with other treatments versus placebo, or any other treatment for patients with RRMS.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed references retrieved for possible inclusion. Disagreements regarding inclusion were resolved by consensus. We contacted study authors for additional information. We collected adverse effects information from the trials.
MAIN RESULTS
We identified 470 references from all electronic databases searched excluding duplicate. After screening of titles and abstracts, full papers of 10 studies were obtained and assessed for eligibility. An additional ongoing trial was found. Only one trial (230 participants) evaluating the efficacy of daclizumab versus placebo in interferon beta treated patients was included. It was judged as of high quality study. No significant difference was found in the expanded disability score changes and the annualised relapse rate comparing treated versus placebo groups. No significant difference of common adverse events was found across all the groups at the endpoint. The mean number of new or enlarged gadolinium contrast-enhancing lesions was significantly decreased in the interferon beta and high-dose daclizumab group, compared with that in the interferon beta and placebo group.
AUTHORS' CONCLUSIONS
Daclizumab is well tolerated in combination with interferon beta treated multiple sclerosis population. Comparing with placebo, high-dose daclizumab can significantly decreased the number of new or enlarged gadolinium contrast-enhancing lesions. However, the evidence of recommendation is insufficient. More well-designed RCTs or crossover controlled trials are required to evaluate the efficacy and safety of daclizumab.
Topics: Antibodies, Monoclonal, Humanized; Daclizumab; Humans; Immunoglobulin G; Immunosuppressive Agents; Interferon-beta; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 22513956
DOI: 10.1002/14651858.CD008127.pub3 -
Drugs of Today (Barcelona, Spain : 1998) Jan 2017Daclizumab is a humanized monoclonal antibody that binds to the a-subunit (CD25) of the interleukin-2 receptor (IL-2R), thus blocking the formation of the high-affinity... (Review)
Review
Daclizumab is a humanized monoclonal antibody that binds to the a-subunit (CD25) of the interleukin-2 receptor (IL-2R), thus blocking the formation of the high-affinity IL-2R which is expressed mainly on activated and regulatory T cells. IL-2R modulation by daclizumab results primarily in the expansion of regulatory CD56(bright) natural killer cells that are capable of killing activated T cells, rather than direct suppression of activated T cells. The pharmacokinetic profile of its currently available form, daclizumab high-yield process (DAC-HYP, Zinbryta), suggests high subcutaneous bioavailability, linear pharmacokinetics and an effective half-life suitable for monthly administration. A comprehensive clinical program in relapsing-remitting multiple sclerosis demonstrated an impressive effect of DAC-HYP on inflammatory and clinical disease activity compared with placebo or interferon beta, which led to its recent approval for the treatment of relapsing forms of multiple sclerosis. Several serious adverse events and risks call for the implementation of a risk management program in multiple sclerosis patients treated with DAC-HYP.
Topics: Animals; Antibodies, Monoclonal, Humanized; Daclizumab; Drug Interactions; Humans; Immunoglobulin G; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Patient Safety; Risk Factors; T-Lymphocytes; Treatment Outcome
PubMed: 28387383
DOI: 10.1358/dot.2017.53.1.2570979 -
The Cochrane Database of Systematic... Dec 2013Monoclonal antibodies such as daclizumab could be a possible alternative immunotherapy to interferon beta treatment in people with multiple sclerosis (MS). It blocks the... (Review)
Review
BACKGROUND
Monoclonal antibodies such as daclizumab could be a possible alternative immunotherapy to interferon beta treatment in people with multiple sclerosis (MS). It blocks the interleukin-2 receptor alpha subunit (CD25), and seems to be beneficial to patients with relapsing remitting multiple sclerosis (RRMS) in clinical and magnetic resonance imaging (MRI) measures of outcomes.This is an update of a Cochrane review first published in 2010, and previously updated in 2012.
OBJECTIVES
To assess the safety of daclizumab and its efficacy to prevent clinical worsening in patients with RRMS.
SEARCH METHODS
The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (17 May 2013). We handsearched the references quoted in the identified trials and reports (May 2013) from the most important neurological associations and MS societies. We contacted researchers participating in trials on daclizumab.
SELECTION CRITERIA
All randomised controlled clinical trials (RCTs) evaluating daclizumab, alone or combined with other treatments versus placebo, or any other treatment for patients with RRMS.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed references retrieved for possible inclusion, extracted eligible data, cross-checked the data for accuracy and assessed the methodological quality. We resolved any disagreements by consensus among review authors.
MAIN RESULTS
We included two trials with 851 patients that evaluated the efficacy and safety of daclizumab versus placebo for RRMS. We judged them to be at low risk of bias. Due to different time point evaluations and available data on primary studies, we were unable to undertake a meta-analysis. At 24 weeks, the median change was 0 (range -2 to 3) in the interferon beta and placebo group, 0 (-2 to 4) in the interferon beta and low-dose daclizumab group and 0 (-2 to 2) in the interferon beta and high-dose daclizumab group in 230 participants. The proportion of patients who had new clinical relapses were the following: 16 patients (21%) in the interferon beta and high-dose daclizumab group, 19 (24%) in the interferon beta and low-dose daclizumab group and 19 (25%) in the interferon beta and placebo group had relapses (P value = 0.87). At 52 weeks, the changes in Expanded Disability Status Scale (EDSS) from baseline was 0.09 ± 0.71 in placebo group, -0.08 ± 0.52 in low-dose daclizumab group and 0.05 ± 0.61 in high-dose daclizumab group in 621 participants. There was a significant difference between placebo and low-dose daclizumab groups (P value = 0.01), but no significant difference between placebo and high-dose daclizumab groups (P value = 0.49). The proportion of patients with new relapsing MS was significantly reduced in both daclizumab groups (19% in low-dose daclizumab group, 20% in high-dose daclizumab group) compared with placebo group (36%) (P value < 0.0001 and P value = 0.00032, respectively). There was no increased number of patients in any adverse events (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07) or serious adverse events in daclizumab groups compared with placebo (RR 1.15, 95% CI 0.29 to 4.54). Infections were the most frequent adverse events in treated participants and were resolved with standard therapies. One trial was still ongoing.
AUTHORS' CONCLUSIONS
There was insufficient evidence to determine whether daclizumab was more effective than placebo in patients affected by RRMS in terms of clinical and MRI measures of outcomes. Daclizumab appeared to be relatively well tolerated. Infections were the most frequent adverse events, and were resolved with standard therapies.
Topics: Antibodies, Monoclonal, Humanized; Daclizumab; Humans; Immunoglobulin G; Immunosuppressive Agents; Interferon-beta; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 24363032
DOI: 10.1002/14651858.CD008127.pub4 -
The Cochrane Database of Systematic... Jun 2010The anti-CD25 treatment of daclizumab appears to be effective in patients with relapsing remitting multiple sclerosis (RRMS) as regards clinical and MRI outcomes.... (Review)
Review
BACKGROUND
The anti-CD25 treatment of daclizumab appears to be effective in patients with relapsing remitting multiple sclerosis (RRMS) as regards clinical and MRI outcomes. Moreover, there are no severe safety concerns arising from clinical testing so far.
OBJECTIVES
To assess the efficacy and safety of daclizumab for patients with relapsing remitting multiple sclerosis.
SEARCH STRATEGY
We searched the Cochrane Multiple Sclerosis Group trials register (September 2009), MEDLINE (January 1966 to September 2009), EMBASE (January 1985 to September 2009). At the same time, we handsearched the references quoted in the identified trials, reports (September 2009) from the most important neurological associations and MS Societies in Europe and America, contacted researchers who were participating in trials on daclizumab.
SELECTION CRITERIA
All randomized controlled clinical trials (RCTs) evaluating daclizumab, alone or combined with other treatments versus placebo, or any other treatment for patients with RRMS. Both parallel group and cross-over designs were included.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed references retrieved for possible inclusion. All disagreements were resolved by an independent party. Study authors were contacted for additional information. Adverse effects information was collected from the trials.
MAIN RESULTS
We found no study meeting our inclusion criteria.
AUTHORS' CONCLUSIONS
Although studies examining daclizumab for relapsing remitting multiple sclerosis were located, methodologic limitations resulted in the exclusion of all studies. Some of the studies were labelled as crossover trials, however they only compared the effect of different interventions for the same individual. The true randomized crossover trial should compare the effect of different groups, which receive the same intervention, only with the difference in sequence. In other words, the crossover comparison should be between the different groups, rather than on the individual between pretreatment and post treatment. At the same time, all the individuals should be randomly allocated to different groups. There was also a rigorous randomized controlled trial, but the follow-up was shorter than one year (only 44 weeks). In general, daclizumab is safe and well tolerated in combination of interferon treated multiple sclerosis population. Improvements in methodology in future studies are required for meaningful synthesis of data.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Humans; Immunoglobulin G; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting
PubMed: 20556791
DOI: 10.1002/14651858.CD008127.pub2 -
Multiple Sclerosis (Houndmills,... Oct 2019
Topics: Daclizumab; Encephalitis; Humans; Immunosuppressive Agents; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
PubMed: 31549941
DOI: 10.1177/1352458519845079 -
BioDrugs : Clinical Immunotherapeutics,... 2001The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in solid organ transplantation. It is specific for the alpha... (Review)
Review
UNLABELLED
The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in solid organ transplantation. It is specific for the alpha subunit (Tac/CD25) of the interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. When added to standard triple immunosuppression regimens, daclizumab significantly reduces the rate of acute rejection at 1 year in renal transplantation by 36% and there are indications that it may be effective in other solid organ transplantations. Three-year outcomes of two phase III clinical trials in renal transplantation indicate similar values for graft and patient survival between daclizumab and placebo when given in addition to triple immunosuppression; however, these pivotal trials were not designed with sufficient power to demonstrate any statistical significance. The addition of daclizumab induction shows potential in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without increasing the rate of acute graft rejection or adverse effects in renal and liver transplantation. Preliminary reports indicate that daclizumab may also be a useful agent in delayed graft function and graft versus host disease (GVHD). Further investigation of its efficacy in these groups and in children is needed. Data from clinical trials show daclizumab to be well tolerated in solid organ transplantation. It does not increase the incidence of infection, including cytomegalovirus infection, when compared with placebo or no induction groups. Preliminary comparative data with muromonab CD3 indicate that daclizumab may be associated with a lower rate of infectious complications and similar or better efficacy.
CONCLUSIONS
In conclusion, daclizumab has been proven to reduce acute rejection in renal transplant recipients when given in addition to traditional baseline immunosuppression. It has shown potential to reduce acute rejection in other solid organ transplants; however, well designed, randomised studies are required to confirm this. Clinical experience from trials to date indicate that daclizumab has a tolerability profile similar to placebo with no significant effect on the incidence of infection. The relative efficacy and tolerability of daclizumab compared with other induction agents has yet to be defined. Available data suggest that daclizumab may allow the use of calcineurin inhibitor-sparing and corticosteroid-sparing regimens and may have potential in the treatment of GVHD.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents
PubMed: 11707149
DOI: 10.2165/00063030-200115110-00005 -
Expert Opinion on Drug Metabolism &... Mar 2018Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Despite the availability of several disease-modifying therapies... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Despite the availability of several disease-modifying therapies for relapsing MS, there is a need for highly efficacious targeted therapy with a favorable benefit-risk profile and a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Areas covered: Daclizumab blocks the activation and expansion of autoreactive T cells that plays a role in the immune pathogenesis of MS. As its modulatory effects on the immune system, daclizumab's potential for use in MS was tested extensively showing a high efficacy in reducing relapse rate, disability progression and the number and volume of gadolinium-enhancing lesions on brain magnetic resonance imaging. Moreover, phase II and III trials showed a favorable pharmacokinetic (PK) profile with slow clearance, linear pharmacokinetics at doses above 100 mg and high subcutaneous bioavailability, not influenced by age, sex or other clinical parameters. Expert opinion: Among the new emerging drugs for MS, daclizumab also, thanks to a favorable PK profile, may represent an interesting and promising therapeutic option in the wide MS therapies armamentarium.
Topics: Animals; Antibodies, Monoclonal, Humanized; Biological Availability; Daclizumab; Dose-Response Relationship, Drug; Humans; Immunoglobulin G; Immunosuppressive Agents; Interleukin-2 Receptor alpha Subunit; Magnetic Resonance Imaging; Medication Adherence; Multiple Sclerosis, Relapsing-Remitting
PubMed: 29363337
DOI: 10.1080/17425255.2018.1432594 -
Recent Patents on Inflammation &... Nov 2010Airways inflammation in asthma is triggered and maintained by CD4+ (Th2) cells which are activated by IL-2 and stimulate the eosinophilic inflammation, IgE secretion and... (Review)
Review
Airways inflammation in asthma is triggered and maintained by CD4+ (Th2) cells which are activated by IL-2 and stimulate the eosinophilic inflammation, IgE secretion and mucus hyperproduction. Current anti-inflammatory therapies include inhaled corticosteroids, and leukotriene modifiers but they are not universally effective. IL-2 pathway inhibition might represent a potent anti-inflammatory therapy in asthma given the cytokine early role in the asthma complex inflammatory cascade and daclizumab which is a IL-2R blocker currently used as an immunsupressor in organ transplantation might be a potential asthma therapy. This is review on the pathogenic role of IL-2, on the therapeutic potential of daclizumab and on its related patents.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Daclizumab; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Interleukin-2; Organ Transplantation; Patents as Topic; Receptors, Interleukin-2; Signal Transduction
PubMed: 20804450
DOI: 10.2174/187221310793564254 -
Daclizumab: a review of its use in the prevention of acute rejection in renal transplant recipients.Drugs Dec 1999The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in renal transplant recipients. It is specific for the alpha... (Review)
Review
UNLABELLED
The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in renal transplant recipients. It is specific for the alpha subunit (Tac/CD25) of the interleukin-2 (IL-2) receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. Daclizumab has advantages over murine antibodies to the IL-2 receptor, including improved effector function, a low potential for immunogenicity and long elimination half-life. When added to standard cyclosporin-based immunosuppressive therapy with or without azathioprine, daclizumab (1 mg/kg prior to surgery and once every 2 weeks thereafter for a total of 5 doses) significantly reduced the 6-month rate of acute rejection compared with placebo in 2 phase III studies. The mean number of rejection episodes was significantly reduced and the time to first acute rejection significantly increased in daclizumab versus placebo recipients. Patient survival at 1 year after transplantation was significantly higher with daclizumab than placebo in 1 study and showed a trend in favour of the drug in the other study. The 1-year graft survival rate tended to be greater in daclizumab than in placebo recipients in both studies, In a phase II study, acute rejection rates in patients treated with both daclizumab and mycophenolate mofetil (plus standard cyclosporin-based immunosuppression) were lower than those achieved with mycophenolate mofetil alone. Preliminary results indicate that daclizumab is also a useful agent in paediatric renal transplant recipients. Further investigation of the efficacy and tolerability of the drug in this patient group is clearly warranted. Daclizumab does not increase the incidence of adverse events when added to standard cyclosporin-based therapy. The incidence of opportunistic infections, lymphoproliferative disorders and malignancies was not increased above that seen with placebo.
CONCLUSIONS
Although the effects of daclizumab on long term graft and patient survival require further investigation, available data indicate that daclizumab is an important advance in renal transplant immunosuppression, reducing acute graft rejection without affecting the tolerability of standard cyclosporin-based immunosuppression.
Topics: Acute Disease; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation
PubMed: 10651389
DOI: 10.2165/00003495-199958060-00006 -
Nature Reviews. Neurology Jul 2013Multiple sclerosis (MS) is a debilitating neurological disorder involving autoimmune destruction of myelin. Although the pathogenic mechanisms underlying MS are not... (Review)
Review
Multiple sclerosis (MS) is a debilitating neurological disorder involving autoimmune destruction of myelin. Although the pathogenic mechanisms underlying MS are not fully understood, T cells are thought to have a key role in orchestrating the aberrant CNS-directed adaptive immune response in the early and relapsing-remitting phase of disease. New therapeutic interventions with improved efficacy over existing drugs and good tolerability are needed. A promising therapy under investigation is daclizumab--a humanized monoclonal antibody directed against the IL-2 receptor α chain (CD25). Clinical trials have shown that daclizumab strongly inhibits disease activity and slows disease progression in MS. Novel and intriguing mechanisms of action of daclizumab have been identified that might explain its clinical efficacy--namely, expansion and enhancement of the immune regulatory function of CD56bright natural killer cells, reduction of early T-cell activation through blockade of IL-2 cross-presentation by dendritic cells, and reduction of lymphoid tissue inducer cells--thereby enhancing endogenous mechanisms of immune tolerance. This Review discusses the efficacy and safety of daclizumab in patients with MS and provides a detailed insight into the multifunctional mechanisms of action of this drug.
Topics: Antibodies, Monoclonal, Humanized; Daclizumab; Humans; Immunoglobulin G; Interleukin-2 Receptor alpha Subunit; Lymphocytes; Multiple Sclerosis
PubMed: 23732529
DOI: 10.1038/nrneurol.2013.95