Hospital Pharmacy - October 2017 - 601
601
Ali and Baker
** Change from baseline in T2 lesion volume was
−3.4% with ocrelizumab compared with +7.4% with
placebo (P < .001). In addition, there was a 17.5%
relative reduction in rate of whole brain volume loss
from week 24 to week 120 in the ocrelizumab group
(P = .02).
** Patient-reported outcomes were evaluated via Short
Form-36 (SF-36), which assessed patient perception of
functional health and was used to provide a Physical
Component Summary (PCS) and Mental Component
Summary (MCS). There was no significant difference
between ocrelizumab and placebo for the change in
SF-36 PCS scores (adjusted mean, −0.7 vs −1.1; P = .6).
Comments: This multicenter study enrolled patients from
Europe, the United Kingdom, Australia, New Zealand,
and North and South America. Patients were randomized
using an interactive web-response system, and concealed
allocation and blinding were maintained for the 120-week
study duration. Patients who completed the blinded treatment were eligible to enter the open-label extension
phase. The estimated sample size was 630 patients, randomized 2:1 to receive ocrelizumab or placebo, to achieve
80% power for 253 expected disease progression events,
with a type I error rate of 0.01. Efficacy end points were
analyzed in the intention-to-treat population; patients
with missing EDSS score data at baseline were excluded
from the analysis, and patients with an initial disability
progression during the blinded trial period who discontinued ocrelizumab or placebo early and did not have a subsequent visit with confirmatory measurement of the EDSS
score were considered to have confirmed disease progression (ie, worst case scenario). Missing data for the 25-foot
walk and the volume of lesions on T2-weighted images
were imputed using the last-observation-carried-forward
method. Ocrelizumab reduced clinical and MRI disease
activity compared with placebo. The most common
adverse events included infusion-related reactions and
infections. Infusion-related reactions were more common
in patients receiving ocrelizumab but were mostly mild to
moderate in severity and were managed with premedication (ie, methylprednisolone) or symptomatic treatment
(ie, analgesics or antipyretics).4,14 Neoplasms, including
breast cancer, basal cell carcinoma, endometrial adenocarcinoma, anaplastic large-cell lymphoma, malignant
fibrous histiocytoma, and pancreatic carcinoma, were
reported in 2.3% of patients receiving ocrelizumab compared with 0.8% in the placebo group. No progressive
multifocal leukoencephalopathy (PML), a treatment-limiting factor in MS, was reported.
Limitations: The study included patients in the earlier
stages of PPMS, with fewer disabilities (per EDSS scores)
than in later stages. A hierarchical analysis of end points
was used, and the authors did not report data for any of the
exploratory end points.
Indication: Relapsing Multiple Sclerosis
Studies
Drug: Ocrelizumab vs Interferon Beta-1a
Reference: Hauser SL, et al, 2017 (OPERA I and OPERA
II trials)3
Study Design: Two identical randomized, double-blind,
double-dummy, active-controlled, international, multicenter phase 3 studies
Study Funding: F. Hoffmann-La Roche Ltd.
Patients: 1656 patients (821 in OPERA I and 835 in
OPERA II) 18 to 55 years of age with relapsing MS diagnosed via 2010 McDonald criteria. Patients were required
to have at least 2 documented clinical attacks/relapses
within the last 2 years or at least 1 clinical attack/relapse
within 1 year prior to screening, neurologic stability for
at least 30 days prior to both screening and baseline, and
EDSS score of 0 to 5.5. Patients were excluded if they
had PPMS; disease duration of more than 10 years if
EDSS score was 2 or less at screening; other neurological disorder; immunodeficiency or infection; severe
allergic or anaphylactic reaction to humanized or murine
monoclonal antibodies; contraindication to study drugs;
or a history of PML. Other exclusion criteria included
previous treatment with B-cell-targeted therapies (ie,
rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab), alemtuzumab, anti-CD4 agents, cladribine,
mitoxantrone, daclizumab, teriflunomide, total body irradiation, or bone marrow transplantation; cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine,
methotrexate (within 24 months of screening); natalizumab (duration of treatment was required to be less than
1 year); any investigational agent, fingolimod, or
dimethyl fumarate (within 6 months prior to screening);
and IV immune globulin (within 12 weeks prior to baseline). Patient demographic and disease characteristics at
baseline (eg, age, gender, time since MS onset, time since
MS diagnosis, EDSS score) were well balanced between
studies and treatment groups.
Intervention: Patients were randomized 1:1 (stratified by
baseline EDSS score [less than 4 or greater than or equal
to 4] and region [United States or other]) to receive ocrelizumab 600 mg via IV infusion every 24 weeks or interferon beta-1a 44 µg via subcutaneous injection 3 times a
week for 96 weeks. Patients received 4 cycles of ocrelizumab, which was given as two 300 mg infusions on days
1 and 15 of the first 24-week treatment cycle, and then as
a single 600 mg infusion for the remaining 24-week
cycles. Interferon beta-1a was initiated at 8.8 µg for weeks
1 and 2, then 22 µg for weeks 3 and 4, and then 44 µg for
the remainder of the 96-week treatment period. All
patients received IV methylprednisolone 100 mg prior to
each infusion; prophylaxis with an analgesic or antipyretic and an antihistamine was also recommended. To
ensure blinding, patients in the ocrelizumab group
Table of Contents for the Digital Edition of Hospital Pharmacy - October 2017
Pharmacists and Medical Missions
Current FDA-Related Drug Information
Summaries of Safety Labeling Changes Approved By FDA- Boxed Warnings Highlights April-June 2017
Pharmaceutical Pipeline Update
Cholesterol Ester Transfer Protein Inhibitor Review
Formulary Drug Review
Ocrelizumab
Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review
Development of a Pharmacy Technician–Driven Program to Improve Vaccination Rates at an Academic Medical Center
Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin for Venous Thromboembolism Prophylaxis in Hemodialysis Patients
Multilayer Model of Pharmacy Participation in the Antimicrobial Stewardship Program at a Large Academic Medical Center
Impact of Inpatient Automatic Therapeutic Substitutions on Postdischarge Medication Prescribing
Impact of Respiratory Viral Panel Polymerase Chain Reaction Assay Turnaround Time on Length of Stay and Antibiotic Use in Patients With Respiratory Viral Illnesses
Administration of Injectable Vitamin K Orally
Hospital Pharmacy - October 2017 - 577
Hospital Pharmacy - October 2017 - 578
Hospital Pharmacy - October 2017 - 579
Hospital Pharmacy - October 2017 - 580
Hospital Pharmacy - October 2017 - 581
Hospital Pharmacy - October 2017 - 582
Hospital Pharmacy - October 2017 - 583
Hospital Pharmacy - October 2017 - 584
Hospital Pharmacy - October 2017 - 585
Hospital Pharmacy - October 2017 - 586
Hospital Pharmacy - October 2017 - 587
Hospital Pharmacy - October 2017 - 588
Hospital Pharmacy - October 2017 - Pharmacists and Medical Missions
Hospital Pharmacy - October 2017 - Current FDA-Related Drug Information
Hospital Pharmacy - October 2017 - Summaries of Safety Labeling Changes Approved By FDA- Boxed Warnings Highlights April-June 2017
Hospital Pharmacy - October 2017 - 592
Hospital Pharmacy - October 2017 - Pharmaceutical Pipeline Update
Hospital Pharmacy - October 2017 - Cholesterol Ester Transfer Protein Inhibitor Review
Hospital Pharmacy - October 2017 - 595
Hospital Pharmacy - October 2017 - Formulary Drug Review
Hospital Pharmacy - October 2017 - Ocrelizumab
Hospital Pharmacy - October 2017 - 598
Hospital Pharmacy - October 2017 - 599
Hospital Pharmacy - October 2017 - 600
Hospital Pharmacy - October 2017 - 601
Hospital Pharmacy - October 2017 - 602
Hospital Pharmacy - October 2017 - 603
Hospital Pharmacy - October 2017 - 604
Hospital Pharmacy - October 2017 - Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review
Hospital Pharmacy - October 2017 - 606
Hospital Pharmacy - October 2017 - 607
Hospital Pharmacy - October 2017 - 608
Hospital Pharmacy - October 2017 - 609
Hospital Pharmacy - October 2017 - 610
Hospital Pharmacy - October 2017 - 611
Hospital Pharmacy - October 2017 - 612
Hospital Pharmacy - October 2017 - 613
Hospital Pharmacy - October 2017 - 614
Hospital Pharmacy - October 2017 - Development of a Pharmacy Technician–Driven Program to Improve Vaccination Rates at an Academic Medical Center
Hospital Pharmacy - October 2017 - 616
Hospital Pharmacy - October 2017 - 617
Hospital Pharmacy - October 2017 - 618
Hospital Pharmacy - October 2017 - 619
Hospital Pharmacy - October 2017 - 620
Hospital Pharmacy - October 2017 - Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin for Venous Thromboembolism Prophylaxis in Hemodialysis Patients
Hospital Pharmacy - October 2017 - 622
Hospital Pharmacy - October 2017 - 623
Hospital Pharmacy - October 2017 - 624
Hospital Pharmacy - October 2017 - 625
Hospital Pharmacy - October 2017 - Multilayer Model of Pharmacy Participation in the Antimicrobial Stewardship Program at a Large Academic Medical Center
Hospital Pharmacy - October 2017 - 627
Hospital Pharmacy - October 2017 - 628
Hospital Pharmacy - October 2017 - 629
Hospital Pharmacy - October 2017 - 630
Hospital Pharmacy - October 2017 - 631
Hospital Pharmacy - October 2017 - 632
Hospital Pharmacy - October 2017 - Impact of Inpatient Automatic Therapeutic Substitutions on Postdischarge Medication Prescribing
Hospital Pharmacy - October 2017 - 634
Hospital Pharmacy - October 2017 - 635
Hospital Pharmacy - October 2017 - 636
Hospital Pharmacy - October 2017 - 637
Hospital Pharmacy - October 2017 - Impact of Respiratory Viral Panel Polymerase Chain Reaction Assay Turnaround Time on Length of Stay and Antibiotic Use in Patients With Respiratory Viral Illnesses
Hospital Pharmacy - October 2017 - 639
Hospital Pharmacy - October 2017 - 640
Hospital Pharmacy - October 2017 - 641
Hospital Pharmacy - October 2017 - 642
Hospital Pharmacy - October 2017 - Administration of Injectable Vitamin K Orally
Hospital Pharmacy - October 2017 - 644
Hospital Pharmacy - October 2017 - 645
Hospital Pharmacy - October 2017 - 646
Hospital Pharmacy - October 2017 - 647
Hospital Pharmacy - October 2017 - 648
Hospital Pharmacy - October 2017 - 649
Hospital Pharmacy - October 2017 - 650
Hospital Pharmacy - October 2017 - 651
Hospital Pharmacy - October 2017 - 652
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2020
https://www.nxtbook.com/nxtbooks/sage/psychologicalscience_demo
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2020
https://www.nxtbook.com/nxtbooks/sage/fai_202009
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_august2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2019
https://www.nxtbook.com/nxtbooks/sage/fai_201909
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_july2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2019
https://www.nxtbook.com/nxtbooks/sage/canadianpharmacistsjournal_05062019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2019
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201903
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2018
https://www.nxtbook.com/nxtbooks/sage/tec_20180810
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2018
https://www.nxtbook.com/nxtbooks/sage/fai_201807
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2018
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201803
https://www.nxtbook.com/nxtbooks/sage/slas_discovery_201712
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_november2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_september2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2017
https://www.nxtbook.com/nxtbooks/sage/fai_supplement_201709
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_may2017
https://www.nxtbook.com/nxtbooks/sage/fai_201706
https://www.nxtbook.com/nxtbooks/sage/fai_201607
https://www.nxtbookmedia.com