-
Multiple Sclerosis (Houndmills,... Oct 2019Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe...
BACKGROUND
Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018.
OBJECTIVE AND METHODS
This retrospective cohort study summarizes clinical, laboratory, radiological, and histological findings of seven patients who developed meningo-/encephalitis after daclizumab therapy.
RESULTS
Patients presented with encephalitis and/or meningitis and suffered from systemic symptoms such as fever (5/7), exanthema (5/7), or gastrointestinal symptoms (4/7). Secondary autoimmune diseases developed. Blood analysis revealed an increase in eosinophils (5/7). Six patients fulfilled the diagnostic criteria for a drug reaction with eosinophilia and systemic symptoms (DRESS). Magnetic resonance imaging (MRI) showed multiple contrast-enhancing lesions, and enhancement of the ependyma (6/7), meninges (5/7), cranial or spinal nerves (2/7), and a vasculitic pattern (3/7). Histology revealed a pronounced inflammatory infiltrate consisting of lymphocytes, plasma cells and eosinophils, and densely infiltrated vessels. Most patients showed an insufficient therapeutic response and a high disability at last follow-up (median Expanded Disability Status Scale (EDSS) 8). Two patients died.
CONCLUSION
Meningoencephalitis and DRESS may occur with daclizumab therapy. This potential lethal side effect is characterized by a dysregulated immune response. Our findings underline the importance of postmarketing drug surveillance.
Topics: Adult; Antibodies, Monoclonal; Autoimmune Diseases; Brain; Daclizumab; Encephalitis; Female; Humans; Immunosuppressive Agents; Lymphocytes; Male; Middle Aged; Multiple Sclerosis; Retrospective Studies
PubMed: 30657420
DOI: 10.1177/1352458518819098 -
International MS Journal Sep 2008Monoclonal antibodies are a promising new class of therapeutic agents that can be employed to target specific molecules of the immune system or any tissue. They are... (Review)
Review
Monoclonal antibodies are a promising new class of therapeutic agents that can be employed to target specific molecules of the immune system or any tissue. They are currently being tested in a number of clinical trials in autoimmune diseases such as multiple sclerosis (MS). One of these, the humanized monoclonal anti-CD25 antibody daclizumab (Zenapax), is directed against the interleukin-2 (IL-2) receptor alpha chain (CD25) that is involved in clonal expansion of autoreactive T-cells by binding of its ligand IL- 2. Several years ago daclizumab was approved for the prevention of renal allograft rejection. Following promising observations in uveitis, daclizumab has since been tested in a number of small clinical trials in MS based on the rationale that blocking CD25 would prevent the expansion of autoreactive T-lymphocytes. Safety and efficacy data from the preliminary clinical exploration as well as findings about the mechanism of action of anti-CD25 treatment are reviewed here.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Daclizumab; Humans; Immunoglobulin G; Immunosuppressive Agents; Interleukin-2 Receptor alpha Subunit; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting
PubMed: 18808743
DOI: No ID Found -
Archives of Neurology Jan 2012Daclizumab, a humanized monoclonal antibody specific for the interleukin 2 receptor α chain, reduces clinical and magnetic resonance imaging disease activity in... (Clinical Trial)
Clinical Trial
BACKGROUND
Daclizumab, a humanized monoclonal antibody specific for the interleukin 2 receptor α chain, reduces clinical and magnetic resonance imaging disease activity in patients with adult-onset multiple sclerosis (MS) as monotherapy or add-on therapy with interferon.
OBJECTIVE
To report the use of daclizumab in pediatric-onset MS.
DESIGN
Case series.
SETTING
Two comprehensive pediatric MS centers.
PATIENTS
Seven patients with pediatric-onset MS with clinical and magnetic resonance imaging disease activity despite first-line disease-modifying therapy.
INTERVENTION
Intravenous daclizumab, 1 mg/kg monthly.
MAIN OUTCOME MEASURES
Annualized relapse rates, Expanded Disability Status Scale scores, contrast-enhancing lesions, and adverse effects.
RESULTS
Treatment with daclizumab, primarily combined with interferon, was associated with reductions in annualized relapse rates and contrast-enhancing lesions and with reduction or stabilization of Expanded Disability Status Scale scores in each patient. However, 4 patients had relapses and new contrast-enhancing lesions during daclizumab treatment. No significant adverse effects occurred.
CONCLUSION
Daclizumab may be a safe and at least partially effective treatment option for patients with pediatric-onset MS with disease activity despite first-line disease-modifying therapy.
Topics: Adolescent; Antibodies, Monoclonal, Humanized; Child; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Interleukin-2; Interleukin-2 Receptor alpha Subunit; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Retrospective Studies
PubMed: 22232346
DOI: 10.1001/archneurol.2011.581 -
Expert Opinion on Drug Safety Jul 2015Daclizumab (DAC) is a mAb that binds to CD25, a receptor on the surface of lymphocytes for IL-2, a chemical messenger in the immune system. This prevents activation and... (Review)
Review
INTRODUCTION
Daclizumab (DAC) is a mAb that binds to CD25, a receptor on the surface of lymphocytes for IL-2, a chemical messenger in the immune system. This prevents activation and proliferation of lymphocytes, which are involved in the immune attack in multiple sclerosis (MS).
AREAS COVERED
In this review, we will focus on newly emerging DAC-high-yield process (HYP) therapy for MS. Based on published original articles and citable meeting abstracts, we will discuss its mode of action as well as data on efficacy and safety.
EXPERT OPINION
DAC has been observed to have multiple (biological) effects, which may contribute to beneficial effects in immune-related disease and particularly in relapsing-remitting MS. The positive results in the clinical studies represent achievement of an important milestone in the development of DAC-HYP as a potential new treatment option for MS patients. The benefit/risk ratios of this new biological agent in MS therapy are still being evaluated. Soon, DAC-HYP might qualify as MS therapy. A safety monitoring program is recommended in the clinical practice.
Topics: Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Daclizumab; Drug Monitoring; Humans; Immunoglobulin G; Immunosuppressive Agents; Interleukin-2 Receptor alpha Subunit; Multiple Sclerosis, Relapsing-Remitting; Treatment Outcome
PubMed: 25826609
DOI: 10.1517/14740338.2015.1032937 -
Pediatric Transplantation May 2009MAbs such as daclizumab have shown promising results in the treatment of corticosteroid-resistant aGVHD. Data describing the efficacy of MAbs in children are limited. We...
MAbs such as daclizumab have shown promising results in the treatment of corticosteroid-resistant aGVHD. Data describing the efficacy of MAbs in children are limited. We describe the efficacy of daclizumab in children with corticosteroid-resistant aGVHD. Seventeen children (0.4-16.2 yr) received daclizumab for aGVHD. Safety was evaluated in all 17. Response was evaluated in the 15 children who received a full course of daclizumab. A PR was defined as improvement of aGVHD symptoms in at least one organ without worsening in other organs. We observed an overall response rate (CR plus PR) of 40% (6/15). Four children had a CR and two had a PR. aGVHD involving the gut had the highest response rate (five of 10; 50%). Adverse effects attributed to daclizumab were limited to an episode of reactive arthritis. Mortality was high (47%; eight of 17) though five of the six responders to daclizumab survived. The mean length of follow-up in the surviving nine patients was 32 months (range seven to 48). We conclude that daclizumab is effective in the treatment of children with corticosteroid-resistant aGVHD, especially in patients with gut involvement.
Topics: Acute Disease; Adolescent; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Daclizumab; Female; Glucocorticoids; Graft vs Host Disease; Humans; Immunoglobulin G; Immunosuppressive Agents; Infant; Male
PubMed: 18482218
DOI: 10.1111/j.1399-3046.2008.00959.x -
Nederlands Tijdschrift Voor Geneeskunde Dec 2000Four major double-blind randomized trials in kidney transplant patients have shown that the interleukin-2 receptor (IL-2R alpha) antagonists declizumab or basiliximab,... (Review)
Review
Four major double-blind randomized trials in kidney transplant patients have shown that the interleukin-2 receptor (IL-2R alpha) antagonists declizumab or basiliximab, when added to an immunosuppressive regimen consisting of cyclosporin and prednisone, reduce the incidence of acute rejections after kidney transplantation by 30-40%, during the first 6 months. Daclizumab and basiliximab are monoclonal antibodies of which the variable parts are of mouse origin and the other components of human origin. The addition of the interleukin-2 receptor antagonists was not accompanied by extra side effects. Ongoing clinical trials aim at answering the question whether the addition of daclizumab and basiliximab will allow to avoid or decrease the use of more toxic immunosuppressive drugs.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Basiliximab; Daclizumab; Graft Rejection; Humans; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Treatment Outcome
PubMed: 11145094
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2023Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects mainly young adults (two to three times more frequently in women than in men) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects mainly young adults (two to three times more frequently in women than in men) and causes significant disability after onset. Although it is accepted that immunotherapies for people with MS decrease disease activity, uncertainty regarding their relative safety remains.
OBJECTIVES
To compare adverse effects of immunotherapies for people with MS or clinically isolated syndrome (CIS), and to rank these treatments according to their relative risks of adverse effects through network meta-analyses (NMAs).
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, two other databases and trials registers up to March 2022, together with reference checking and citation searching to identify additional studies.
SELECTION CRITERIA
We included participants 18 years of age or older with a diagnosis of MS or CIS, according to any accepted diagnostic criteria, who were included in randomized controlled trials (RCTs) that examined one or more of the agents used in MS or CIS, and compared them versus placebo or another active agent. We excluded RCTs in which a drug regimen was compared with a different regimen of the same drug without another active agent or placebo as a control arm.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods for data extraction and pairwise meta-analyses. For NMAs, we used the netmeta suite of commands in R to fit random-effects NMAs assuming a common between-study variance. We used the CINeMA platform to GRADE the certainty of the body of evidence in NMAs. We considered a relative risk (RR) of 1.5 as a non-inferiority safety threshold compared to placebo. We assessed the certainty of evidence for primary outcomes within the NMA according to GRADE, as very low, low, moderate or high.
MAIN RESULTS
This NMA included 123 trials with 57,682 participants Serious adverse events (SAEs) Reporting of SAEs was available from 84 studies including 5696 (11%) events in 51,833 (89.9%) participants out of 57,682 participants in all studies. Based on the absolute frequency of SAEs, our non-inferiority threshold (up to a 50% increased risk) meant that no more than 1 in 18 additional people would have a SAE compared to placebo. Low-certainty evidence suggested that three drugs may decrease SAEs compared to placebo (relative risk [RR], 95% confidence interval [CI]): interferon beta-1a (Avonex) (0.78, 0.66 to 0.94); dimethyl fumarate (0.79, 0.67 to 0.93), and glatiramer acetate (0.84, 0.72 to 0.98). Several drugs met our non-inferiority criterion versus placebo: moderate-certainty evidence for teriflunomide (1.08, 0.88 to 1.31); low-certainty evidence for ocrelizumab (0.85, 0.67 to 1.07), ozanimod (0.88, 0.59 to 1.33), interferon beta-1b (0.94, 0.78 to 1.12), interferon beta-1a (Rebif) (0.96, 0.80 to 1.15), natalizumab (0.97, 0.79 to 1.19), fingolimod (1.05, 0.92 to 1.20) and laquinimod (1.06, 0.83 to 1.34); very low-certainty evidence for daclizumab (0.83, 0.68 to 1.02). Non-inferiority with placebo was not met due to imprecision for the other drugs: low-certainty evidence for cladribine (1.10, 0.79 to 1.52), siponimod (1.20, 0.95 to 1.51), ofatumumab (1.26, 0.88 to 1.79) and rituximab (1.01, 0.67 to 1.52); very low-certainty evidence for immunoglobulins (1.05, 0.33 to 3.32), diroximel fumarate (1.05, 0.23 to 4.69), peg-interferon beta-1a (1.07, 0.66 to 1.74), alemtuzumab (1.16, 0.85 to 1.60), interferons (1.62, 0.21 to 12.72) and azathioprine (3.62, 0.76 to 17.19). Withdrawals due to adverse events Reporting of withdrawals due to AEs was available from 105 studies (85.4%) including 3537 (6.39%) events in 55,320 (95.9%) patients out of 57,682 patients in all studies. Based on the absolute frequency of withdrawals, our non-inferiority threshold (up to a 50% increased risk) meant that no more than 1 in 31 additional people would withdraw compared to placebo. No drug reduced withdrawals due to adverse events when compared with placebo. There was very low-certainty evidence (meaning that estimates are not reliable) that two drugs met our non-inferiority criterion versus placebo, assuming an upper 95% CI RR limit of 1.5: diroximel fumarate (0.38, 0.11 to 1.27) and alemtuzumab (0.63, 0.33 to 1.19). Non-inferiority with placebo was not met due to imprecision for the following drugs: low-certainty evidence for ofatumumab (1.50, 0.87 to 2.59); very low-certainty evidence for methotrexate (0.94, 0.02 to 46.70), corticosteroids (1.05, 0.16 to 7.14), ozanimod (1.06, 0.58 to 1.93), natalizumab (1.20, 0.77 to 1.85), ocrelizumab (1.32, 0.81 to 2.14), dimethyl fumarate (1.34, 0.96 to 1.86), siponimod (1.63, 0.96 to 2.79), rituximab (1.63, 0.53 to 5.00), cladribine (1.80, 0.89 to 3.62), mitoxantrone (2.11, 0.50 to 8.87), interferons (3.47, 0.95 to 12.72), and cyclophosphamide (3.86, 0.45 to 33.50). Eleven drugs may have increased withdrawals due to adverse events compared with placebo: low-certainty evidence for teriflunomide (1.37, 1.01 to 1.85), glatiramer acetate (1.76, 1.36 to 2.26), fingolimod (1.79, 1.40 to 2.28), interferon beta-1a (Rebif) (2.15, 1.58 to 2.93), daclizumab (2.19, 1.31 to 3.65) and interferon beta-1b (2.59, 1.87 to 3.77); very low-certainty evidence for laquinimod (1.42, 1.01 to 2.00), interferon beta-1a (Avonex) (1.54, 1.13 to 2.10), immunoglobulins (1.87, 1.01 to 3.45), peg-interferon beta-1a (3.46, 1.44 to 8.33) and azathioprine (6.95, 2.57 to 18.78); however, very low-certainty evidence is unreliable. Sensitivity analyses including only studies with low attrition bias, drug dose above the group median, or only patients with relapsing remitting MS or CIS, and subgroup analyses by prior disease-modifying treatments did not change these figures. Rankings No drug yielded consistent P scores in the upper quartile of the probability of being better than others for primary and secondary outcomes.
AUTHORS' CONCLUSIONS
We found mostly low and very low-certainty evidence that drugs used to treat MS may not increase SAEs, but may increase withdrawals compared with placebo. The results suggest that there is no important difference in the occurrence of SAEs between first- and second-line drugs and between oral, injectable, or infused drugs, compared with placebo. Our review, along with other work in the literature, confirms poor-quality reporting of adverse events from RCTs of interventions. At the least, future studies should follow the CONSORT recommendations about reporting harm-related issues. To address adverse effects, future systematic reviews should also include non-randomized studies.
Topics: Male; Female; Young Adult; Humans; Adolescent; Adult; Interferon beta-1a; Immunosuppressive Agents; Glatiramer Acetate; Network Meta-Analysis; Cladribine; Natalizumab; Interferon beta-1b; Alemtuzumab; Dimethyl Fumarate; Daclizumab; Azathioprine; Rituximab; Fingolimod Hydrochloride; Multiple Sclerosis; Immunotherapy
PubMed: 38032059
DOI: 10.1002/14651858.CD012186.pub2 -
The New England Journal of Medicine Jun 2005Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients.
METHODS
We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months.
RESULTS
By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy.
CONCLUSIONS
Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cyclosporine; Daclizumab; Double-Blind Method; Drug Therapy, Combination; Female; Graft Rejection; Heart Transplantation; Humans; Immunoglobulin G; Immunosuppressive Agents; Logistic Models; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Survival Analysis
PubMed: 15987919
DOI: 10.1056/NEJMoa032953 -
The Medical Letter on Drugs and... Sep 2016
Topics: Antibodies, Monoclonal, Humanized; Daclizumab; Drug Administration Schedule; Humans; Immunoglobulin G; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Treatment Outcome
PubMed: 27603962
DOI: No ID Found -
Lancet (London, England) Jun 2013Daclizumab, a humanised monoclonal antibody, modulates interleukin-2 signalling by blocking the α subunit (CD25) of the interleukin-2 receptor. We assessed whether... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Daclizumab, a humanised monoclonal antibody, modulates interleukin-2 signalling by blocking the α subunit (CD25) of the interleukin-2 receptor. We assessed whether daclizumab high-yield process (HYP) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis.
METHODS
We did a randomised, double-blind, placebo-controlled trial at 76 centres in the Czech Republic, Germany, Hungary, India, Poland, Russia, Ukraine, Turkey, and the UK between Feb 15, 2008, and May 14, 2010. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1), via a central interactive voice response system, to subcutaneous injections of daclizumab HYP 150 mg or 300 mg, or placebo, every 4 weeks for 52 weeks. Patients and study personnel were masked to treatment assignment, except for the site pharmacist who prepared the study drug for injection, but had no interaction with the patient. The primary endpoint was annualised relapse rate. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00390221.
FINDINGS
204 patients were assigned to receive placebo, 208 to daclizumab HYP 150 mg, and 209 to daclizumab HYP 300 mg, of whom 188 (92%), 192 (92%), and 197 (94%), respectively, completed follow-up to week 52. The annualised relapse rate was lower for patients given daclizumab HYP 150 mg (0·21, 95% CI 0·16-0·29; 54% reduction, 95% CI 33-68%; p<0·0001) or 300 mg (0·23, 0·17-0·31, 50% reduction, 28-65%; p=0·00015) than for those given placebo (0·46, 0·37-0·57). More patients were relapse free in the daclizumab HYP 150 mg (81%) and 300 mg (80%) groups than in the placebo group (64%; p<0·0001 in the 150 mg group and p=0·0003 in the 300 mg group). 12 (6%) patients in the placebo group, 15 (7%) of those in the daclizumab 150 mg group, and 19 (9%) in the 300 mg group had serious adverse events excluding multiple sclerosis relapse. One patient given daclizumab HYP 150 mg who was recovering from a serious rash died because of local complication of a psoas abscess.
INTERPRETATION
Subcutaneous daclizumab HYP administered every 4 weeks led to clinically important effects on multiple sclerosis disease activity during 1 year of treatment. Our findings support the potential for daclizumab HYP to offer an additional treatment option for relapsing-remitting disease.
FUNDING
Biogen Idec and AbbVie Biotherapeutics Inc.
Topics: Adolescent; Adult; Antibodies, Monoclonal, Humanized; Daclizumab; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Europe; Female; Follow-Up Studies; Humans; Immunoglobulin G; Injections, Subcutaneous; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Quality of Life; Reference Values; Risk Assessment; Time Factors; Treatment Outcome; Young Adult
PubMed: 23562009
DOI: 10.1016/S0140-6736(12)62190-4