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Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
N Engl J Med. 2015 Oct 08; 373(15):1418-28.NEJM

Abstract

BACKGROUND

Daclizumab high-yield process (HYP) is a humanized monoclonal antibody that binds to CD25 (alpha subunit of the interleukin-2 receptor) and modulates interleukin-2 signaling. Abnormalities in interleukin-2 signaling have been implicated in the pathogenesis of multiple sclerosis and other autoimmune disorders.

METHODS

We conducted a randomized, double-blind, active-controlled, phase 3 study involving 1841 patients with relapsing-remitting multiple sclerosis to compare daclizumab HYP, administered subcutaneously at a dose of 150 mg every 4 weeks, with interferon beta-1a, administered intramuscularly at a dose of 30 μg once weekly, for up to 144 weeks. The primary end point was the annualized relapse rate.

RESULTS

The annualized relapse rate was lower with daclizumab HYP than with interferon beta-1a (0.22 vs. 0.39; 45% lower rate with daclizumab HYP; P<0.001). The number of new or newly enlarged hyperintense lesions on T2-weighted magnetic resonance imaging (MRI) over a period of 96 weeks was lower with daclizumab HYP than with interferon beta-1a (4.3 vs. 9.4; 54% lower number of lesions with daclizumab HYP; P<0.001). At week 144, the estimated incidence of disability progression confirmed at 12 weeks was 16% with daclizumab HYP and 20% with interferon beta-1a (P=0.16). Serious adverse events, excluding relapse of multiple sclerosis, were reported in 15% of the patients in the daclizumab HYP group and in 10% of those in the interferon beta-1a group. Infections were more common in the daclizumab HYP group than in the interferon beta-1a group (in 65% vs. 57% of the patients, including serious infection in 4% vs. 2%), as were cutaneous events such as rash or eczema (in 37% vs. 19%, including serious events in 2% vs. <1%) and elevations in liver aminotransferase levels that were more than 5 times the upper limit of the normal range (in 6% vs. 3%).

CONCLUSIONS

Among patients with relapsing-remitting multiple sclerosis, daclizumab HYP showed efficacy superior to that of interferon beta-1a with regard to the annualized relapse rate and lesions, as assessed by means of MRI, but was not associated with a significantly lower risk of disability progression confirmed at 12 weeks. The rates of infection, rash, and abnormalities on liver-function testing were higher with daclizumab HYP than with interferon beta-1a. (Funded by Biogen and AbbVie Biotherapeutics; DECIDE ClinicalTrials.gov number, NCT01064401.).

Authors+Show Affiliations

From the Neurologic Clinic and Policlinic, the Departments of Medicine, Clinical Research, and Biomedicine and Biomedical Engineering, University Hospital, Basel, Switzerland (L.K.); the Department of Neurology, University of Münster, Münster, Germany (H.W.); the Department of Neurology, Medical University of Lodz, Lodz, Poland (K.S.); NeuroRx Research and Montreal Neurological Institute, McGill University - both in Montreal (D.L.A.); the Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic (E.H.); the Department of Neurology and Neurosurgery, Russian National Research Medical University, and Moscow Multiple Sclerosis Center - both in Moscow (A.B.); Cole Neurological Institute, University of Tennessee, Knoxville (M.K.); the Department of Neurology and the Neurovirology Research Laboratory, University of Utah, and the Veterans Affairs Salt Lake City Health Care System - both in Salt Lake City (J.R.); AbbVie Biotherapeutics, Redwood City, CA (S.G.); and Biogen, Cambridge, MA (M.S., K.R., G.O., J.E.).No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26444729

Citation

Kappos, Ludwig, et al. "Daclizumab HYP Versus Interferon Beta-1a in Relapsing Multiple Sclerosis." The New England Journal of Medicine, vol. 373, no. 15, 2015, pp. 1418-28.
Kappos L, Wiendl H, Selmaj K, et al. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2015;373(15):1418-28.
Kappos, L., Wiendl, H., Selmaj, K., Arnold, D. L., Havrdova, E., Boyko, A., Kaufman, M., Rose, J., Greenberg, S., Sweetser, M., Riester, K., O'Neill, G., & Elkins, J. (2015). Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. The New England Journal of Medicine, 373(15), 1418-28. https://doi.org/10.1056/NEJMoa1501481
Kappos L, et al. Daclizumab HYP Versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2015 Oct 8;373(15):1418-28. PubMed PMID: 26444729.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. AU - Kappos,Ludwig, AU - Wiendl,Heinz, AU - Selmaj,Krzysztof, AU - Arnold,Douglas L, AU - Havrdova,Eva, AU - Boyko,Alexey, AU - Kaufman,Michael, AU - Rose,John, AU - Greenberg,Steven, AU - Sweetser,Marianne, AU - Riester,Katherine, AU - O'Neill,Gilmore, AU - Elkins,Jacob, PY - 2015/10/8/entrez PY - 2015/10/9/pubmed PY - 2015/10/16/medline SP - 1418 EP - 28 JF - The New England journal of medicine JO - N Engl J Med VL - 373 IS - 15 N2 - BACKGROUND: Daclizumab high-yield process (HYP) is a humanized monoclonal antibody that binds to CD25 (alpha subunit of the interleukin-2 receptor) and modulates interleukin-2 signaling. Abnormalities in interleukin-2 signaling have been implicated in the pathogenesis of multiple sclerosis and other autoimmune disorders. METHODS: We conducted a randomized, double-blind, active-controlled, phase 3 study involving 1841 patients with relapsing-remitting multiple sclerosis to compare daclizumab HYP, administered subcutaneously at a dose of 150 mg every 4 weeks, with interferon beta-1a, administered intramuscularly at a dose of 30 μg once weekly, for up to 144 weeks. The primary end point was the annualized relapse rate. RESULTS: The annualized relapse rate was lower with daclizumab HYP than with interferon beta-1a (0.22 vs. 0.39; 45% lower rate with daclizumab HYP; P<0.001). The number of new or newly enlarged hyperintense lesions on T2-weighted magnetic resonance imaging (MRI) over a period of 96 weeks was lower with daclizumab HYP than with interferon beta-1a (4.3 vs. 9.4; 54% lower number of lesions with daclizumab HYP; P<0.001). At week 144, the estimated incidence of disability progression confirmed at 12 weeks was 16% with daclizumab HYP and 20% with interferon beta-1a (P=0.16). Serious adverse events, excluding relapse of multiple sclerosis, were reported in 15% of the patients in the daclizumab HYP group and in 10% of those in the interferon beta-1a group. Infections were more common in the daclizumab HYP group than in the interferon beta-1a group (in 65% vs. 57% of the patients, including serious infection in 4% vs. 2%), as were cutaneous events such as rash or eczema (in 37% vs. 19%, including serious events in 2% vs. <1%) and elevations in liver aminotransferase levels that were more than 5 times the upper limit of the normal range (in 6% vs. 3%). CONCLUSIONS: Among patients with relapsing-remitting multiple sclerosis, daclizumab HYP showed efficacy superior to that of interferon beta-1a with regard to the annualized relapse rate and lesions, as assessed by means of MRI, but was not associated with a significantly lower risk of disability progression confirmed at 12 weeks. The rates of infection, rash, and abnormalities on liver-function testing were higher with daclizumab HYP than with interferon beta-1a. (Funded by Biogen and AbbVie Biotherapeutics; DECIDE ClinicalTrials.gov number, NCT01064401.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/26444729/Daclizumab_HYP_versus_Interferon_Beta_1a_in_Relapsing_Multiple_Sclerosis_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa1501481?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -