Opgehaald van Efficacy and Safety of BIIB019 (Daclizumab High Yield Process)
Versus Interferon ? 1a in
Participants With Relapsing-Remitting Multiple Sclerosis ((DECIDE)):
Jiwon Oh, S. S.
(2014, March 14). Neurology . Opgehaald van Daclizumab-induced adverse
events in multiple organ systems in multiple sclerosis:
Ludwig Kappos, H. W. (2015, October 8). The New England
Journal of Medicine . Opgehaald van Daclizumab HYP versus Interferon
Beta-1a in Relapsing Multiple Sclerosis:
MS Centrum Amsterdam . (2017). Opgehaald van Behandelingen :
Zorginstituut Nederland . (2017, November 27). Opgehaald van Daclizumab :
All the patients provided written informed consent and
a consent to continue participation was obtained from patients who had a
confirmed relapse or progression of disability. The study was approved by the
local ethics committees and was conducted in accordance with the International
Conference on Harmonisation guidelines for Good Clinical Practice and the
principles of the Declaration of Helsinki (Ludwig Kappos, 2015).
Daclizumab is a
second-line medication for MS patients; it can cause an increase in liver enzymes.
For this reason a blood sample will be taken every month during treatment and
four months after treatment. If a patient has an active infection, the
treatment should be postponed or interrupted till the infection disappears. A
group of patients using daclizumab will be forced to stop the treatment if the
side effects get too severe (MS Centrum Amsterdam , 2017) (Zorginstituut Nederland , 2017).
Since February 2017,
daclizumab (Zinbryta) became available for patients with RRMS; it is given to
patients that still have a lot of relapses or have worsening attacks even
though they take the available first-line medications like interferon
Consequences and Implications
The enhanced efficacy was accompanied by an increased
frequency of adverse events, such that the net clinical benefit will need to be
carefully considered by patients and their providers (Ludwig
Daclizumab HYP demonstrated superior efficacy
regarding ARR and brain lesions versus intramuscular interferon ?-1a in relapsing-remitting
multiple sclerosis; but was not associated with a significantly lower risk of
disability progression at 12 weeks.
Elevations in liver aminotransferase levels, more than
5 times the upper limit of the normal range, was present in 6% of patients
treated with daclizumab and in 3% in the group treated with interferon
Cutaneous events such as eczema or rash were more
common in patients treated with daclizumab (37%) than with interferon
Infections were more common in the daclizumab HYP group
(65%) than in the interferon beta-1a group (57%) .
died during the study; four in the interferon ?-1a group and one in the daclizumab HYP group.
Serious adverse events were reported in 15% of the
patients treated with daclizumab HYP while 10% was reported in the interferon ?-1a group. Some of them are listed:
The number of new or newly enlarged hyperintense
lesions on T2-weighted MRI was lower with daclizumab HYP (4.3) than with
interferon ?-1a (9.4) with a 54% lower number of lesions with
daclizumab HYP; P<0.001. Secondary endpoints Ø The ARR was lower after treatment with daclizumab HYP (0.22) than with interferon ?-1a (0.39) with a 45% lower rate using daclizumab HYP; P<0.001 Primary endpoint The following data represent the results that were statistically significant (P<0.05) comparing the results of daclizumab HYP with interferon ?-1a: Results This was a multicenter study with 230 study locations in America, Europe, Asia (excluding Japan) and Australia. Medical centers To keep the study double blinded, the group receiving daclizumab SC also received a placebo IM every week. The group receiving interferon ?-1a IM also received a placebo SC every four weeks. 150 mg of daclizumab was given subcutaneously (SC) every four weeks, whereas 30 µg of the reference drug interferon ?-1a was injected intramuscularly (IM) once weekly. Dosage and route of administration Duration of the study and measuring clinical endpoints It is a 96 to 144 week study, the clinical end points were measured every 12 weeks. o The subject has not stabilized from a previous relapse prior to randomization o History of human immunodeficiency virus or hepatitis C or B virus o Known hypersensitivity to study drugs o History of treatment with Daclizumab o Known history of non-compliance with Avonex® 30 µg Some exclusion criteria o Male and female subjects of childbearing potential must be willing to practice effective contraception during the study and for four months after their last dose o EDSS between 0.0 and 5.0 o A confirmed diagnosis of RRMS and a magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with MS o Age between 18 and 55 years old Inclusion criteria A total of 1842 patients participated in this study, who were almost equally distributed between those who received daclizumab and those who received the reference drug; it involved both male and female subjects. Human subjects This was a double-blind trial; data were collected by the investigators, were analyzed by the sponsors and remained confidential during the study. Blinding or technicians who were not involved with the patients. Block randomization was used for this study. It was conducted using a centralized interactive voice response system. The efficacy assessments were performed by neurologists Randomization This was a parallel-group phase 3 study for RRMS. Study design 4. Percentage of participants With a ? 7.5 point worsening from baseline in the Multiple Sclerosis Impact Scale (MSIS-29). It is a 29-item disease-specific patient-reported outcome measure to examine the psychological and physical impact of MS (ClinicalTrials.org, 2015) (Ludwig Kappos, 2015). 3. Proportion of participants Relapse-free. EDSS is a mean to quantify disability in MS; the scale ranges from 0 to 10, a higher score indicates more disability. 2. Sustained Disability Progression; it is defined as when there is an increase in at least one point on the Expanded Disability Status Scale (EDSS) scale from Baseline that is sustained for 12 weeks. 1. Mean number of new or newly enlarging T2 hyperintense lesions. Secondary endpoints v The annualized relapse rate (ARR); it is the number of confirmed relapses during a 12-month period. Primary endpoint Clinical endpoints Daclizumab is a monoclonal antibody that binds to the CD25 which is a ? subunit of the interleukin 2 (IL-2) receptor located on (activated) T-cells. It blocks the IL-2 receptors and thus modulates IL-2 signaling. The exact mechanism of action is still unknown but the overall effect is reduction of T-cell responses and proliferation of CD56bright natural killer cells which lead to a decrease in MS related inflammation (Jiwon Oh, 2014). Mechanism of action of daclizumab The aim was to test the superiority of Daclizumab High Yield Process (DAC HYP) in efficacy and safety compared with the reference drug Avonex® ,interferon ?-1a, in patients with relapsing-remitting multiple sclerosis (RRMS) (Ludwig Kappos, 2015). Aim Article review of a Phase III study - Cherien Ghandour