Daclizumab in treatment of multiple sclerosis patients

Ali, EN; Healy, BC; Stazzone, LA; Ba, Brown; Weiner, H L; Khoury, Samia J.

doi:10.1177/1352458508097468

Cited by 32 publications

(14 citation statements)

References 7 publications

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“…One form of this antibody, intravenous daclizumab has been used off-label in adult MS patients [84][85][86], and another subcutaneous form is being tested in clinical trials in adult MS [87,88]. Adverse effects have been reportedly associated with intravenous daclizumab therapy, including elevated liver function tests, infections, psoriasis, and oral ulcers [84][85][86].…”

Section: Daclizumabmentioning

confidence: 99%

Disease-Modifying Therapy of Pediatric Multiple Sclerosis

Chitnis

2013

Neurotherapeutics

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Multiple sclerosis (MS) is increasingly recognized in children and adolescents. Improved awareness, access to care, and subspecialty training in pediatric MS has allowed for better access to treatment. Children with MS present with an overwhelmingly relapsing form of the disease and have more frequent relapses than their adult counterparts during the early phases of disease. Cognitive deficits are prominent in pediatric MS, as opposed to locomotor disability. Beta interferons and glatiramer acetate are frequently used off-label drugs. Additional second-line therapies have occasionally been used in treatment failures. No randomized clinical trials have been performed to date in pediatric MS; however, recent legislation necessitates pediatric studies for new agents, which will allow for better defined pharmacokinetic, dosing, and efficacy data to guide the treating neurologist.

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Section: Daclizumabmentioning

confidence: 99%

Disease-Modifying Therapy of Pediatric Multiple Sclerosis

Chitnis

2013

Neurotherapeutics

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“…No deaths or SAEs were reported [Bielekova et al 2004[Bielekova et al , 2009Rose et al 2004Rose et al , 2007. The safety and tolerability of monthly IV daclizumab 1 mg/ kg have also been evaluated in 55 MS patients who received the drug offlabel in a single center [Ali et al 2009]. Among 36 patients who reported any AEs, the most common were fatigue (8), gastrointestinal upset (4), rash (3) and generalized weakness (3).…”

Section: Safetymentioning

confidence: 99%

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis

Milo

2013

Ther Adv Neurol Disord

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Daclizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) isotype that binds to the α-subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor expressed on activated T cells and CD4+CD25+FoxP3+ regulatory T cells. Based on the assumption that it would block the activation and expansion of autoreactive T cells that are central to the immune pathogenesis of multiple sclerosis (MS), daclizumab was tested in several small open-label clinical trials in MS and demonstrated a profound inhibition of inflammatory disease activity. Surprisingly, accompanying mechanistic studies revealed that the most important biological effect of daclizumab was rather a dramatic expansion and activation of immunoregulatory CD56 bright natural-killer (NK) cells that correlated with treatment response, while there was no or only minor effect on peripheral T-cell activation and function. These CD56 bright NK cells were able to gain access to the central nervous system in MS and kill autologous activated T cells. Additional and relatively large phase IIb clinical trials showed that daclizumab, as add-on or monotherapy in relapsing-remitting (RR) MS, was highly effective in reducing relapse rate, disability progression, and the number and volume of gadolinium-enhancing, T1 and T2 lesions on brain magnetic resonance imaging (MRI), and reproduced the expansion of CD56 bright NK cells as a biomarker for daclizumab activity. Daclizumab is generally very well tolerated and has shown a favorable adverse event (AE) profile in transplant recipients. However, several potentially serious and newly emerging AEs (mainly infections, skin reactions, elevated liver function tests and autoimmune phenomena in several body organs) may require strict safety monitoring programs in future clinical practice and place daclizumab together with other new and highly effective MS drugs as a second-line therapy. Ongoing phase III clinical trials in RRMS are expected to provide definite information on the efficacy and safety of daclizumab and to determine its place in the fast-growing armamentarium of MS therapies.

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“…The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the placebo group, 1.32 in the high-dose daclizumab group, and 3.58 in the low-dose daclizumab group. Adverse events reported for daclizumab in clinical trials [90][91][92][93] include rash, infections and infestations, lymphadenopathy, elevation in liver enzymes, fever, and fatigue. In the CHOICE study, NAbs to daclizumab were observed in 8% of patients.…”

Section: Daclizumabmentioning

confidence: 97%

Treatment of multiple sclerosis: current concepts and future perspectives

Buck

Hemmer

2011

J Neurol

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Currently, several disease-modifying therapies for the treatment of multiple sclerosis are established and more are likely to be introduced. These treatment options differ with respect to their application profile, mechanism of action, efficacy, safety, and tolerance. Here, we review current concepts of MS therapies, report recent results of clinical trials, and discuss emerging treatment options.

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Daclizumab in treatment of multiple sclerosis patients

Abstract: At the Partners MS center, we have been using Daclizumab in an open-label fashion in patients who fail first line therapy or non-standard immunosuppressive treatment. Our aim was to assess its safety and tolerability in our patient population.

Cited by 32 publications

References 7 publications

Disease-Modifying Therapy of Pediatric Multiple Sclerosis

Disease-Modifying Therapy of Pediatric Multiple Sclerosis

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis

Treatment of multiple sclerosis: current concepts and future perspectives

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