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received interferon beta-1a placebo injections 3 times a
week, and patients in the interferon beta-1a group received
ocrelizumab placebo infusions every 24 weeks.
Results
Primary End Point(s)
** Protocol-defined annualized relapse rate (ARR) at 96
weeks: Protocol-defined ARR and ARR for all clinical relapses were reduced with ocrelizumab. In
OPERA I, there was a 46% reduction in protocoldefined ARR (P < .001) and a 42% reduction in ARR
for all clinical relapses (P < .001). In OPERA II, protocol-defined ARR was reduced by 47% (P < .001),
and ARR for all clinical relapses was reduced by 43%
(P < .001).
Secondary End Point(s)
** Confirmed disability progression: Pooled analysis of
OPERA I and OPERA II showed that ocrelizumab
reduced the risk of 12-week confirmed disability progression by 40% (P < .001) and the risk of 24-week
confirmed disability progression by 40% (P = .003).
** Confirmed disability improvement: Pooled analysis
of OPERA I and OPERA II showed that a greater proportion of patients treated with ocrelizumab achieved
confirmed disability improvement at week 12, with a
33% higher rate of improvement with ocrelizumab
than interferon beta-1a (P = .02).
** The difference in the adjusted mean change in the
Multiple Sclerosis Functional Composite (MSFC)
score from baseline to week 96 between ocrelizumab
and interferon beta-1a was 0.04 (95% CI, −0.04 to
0.12) for OPERA I (P = .33) and 0.11 (95% CI, 0.03
to 0.18) for OPERA II (P = .004).
** Total number of T1 Gd+-enhancing lesions by week 96
was reduced with ocrelizumab (OPERA I: 94% [P <
.001]; OPERA II: 95% [P < .001]). The number of new
or enlarging T2 lesions by week 96 was also reduced
with ocrelizumab (OPERA I: 77% [P < .001]; OPERA
II: 83% [P < .001]). The mean number of new T1
hypointense lesions by week 96 was reduced with ocrelizumab (OPERA I: 57% [P < .001]; OPERA II: 64% [P
< .001]). The rate of brain volume change from week 24
to 96 was lower for patients on ocrelizumab. The difference in brain volume loss was 22.8% for OPERA I (P =
.004) and 14.9% for OPERA II (P = .09).
** Proportion of patients with no evidence of disease
activity from baseline to week 96 was higher for
patients treated with ocrelizumab (OPERA I: 47.9%
vs 29.2% with interferon beta-1a [P < .001]; OPERA
II: 47.5% of patients receiving ocrelizumab vs 25.1%
with interferon beta-1a [P < .001]).
Hospital Pharmacy 52(9)
** Difference in mean change in SF-36 PCS score from
baseline to week 96 between ocrelizumab and interferon beta-1a was 0.69 (95% CI, −0.41 to 1.8) for
OPERA I and 1.16 (95% CI, 0.05 to 2.27) for
OPERA II.
Comments: The OPERA I and OPERA II trials used the
same study design, with 89 trial sites across more than 30
countries; the majority of study sites were in the United
States. The estimated sample size for each trial was 400
patients per treatment arm, to achieve 84% power to
detect a 50% lower ARR with ocrelizumab compared
with interferon beta-1a. An additional assumption for the
sample size was an estimated ARR of 0.165 in the ocrelizumab group and of 0.33 in the interferon beta-1a group.
There were 10 hierarchically ordered secondary end
points, with subsequent end points evaluated only if the
primary end point, and each preceding end point in the
ordered hierarchy, achieved statistical significance. After
the first P value greater than .05, all subsequent P values
were deemed nonconfirmatory and only nominally significant. Over the 96-week treatment period, ocrelizumab
reduced incidence of clinical relapses and disease
progression.
Adverse effects of the study medication included infusion-related reactions, infections, and herpes-associated
infections. The incidence of adverse events was similar for
ocrelizumab and interferon beta-1a. Infusion-related reactions that occurred with ocrelizumab were generally mild to
moderate in severity and were manageable with premedication (IV methylprednisolone), infusion adjustments, or
symptomatic treatment (analgesics, antipyretics).3,15 The
incidence of adverse events leading to treatment discontinuation was generally lower for patients receiving ocrelizumab, for both OPERA I and II. Ocrelizumab had no effect
on preexisting humoral immunity to common viral and bacterial antigens.16 Estimated primary completion dates are
November 2019 for OPERA I and January 2020 for OPERA
II. Patients who complete the 96-week trial have the option
to continue treatment in an open-label trial extension phase
if they (continue to) meet eligibility criteria. The findings
reported thus far align with results of a phase 2 study in
which ocrelizumab showed reduced disease progression as
well as lower ARRs in patients with RRMS after 24 weeks
of therapy.12
Limitations: Some secondary efficacy end points were
reported only as pooled analysis; however, given the identical trial designs, pooled analysis was considered valid if
between-group treatment differences for ARR through
week 96 and 12-week confirmed disability progression
were consistent between trials.3 The difference in the
adjusted mean change in the MSFC score between the
ocrelizumab group and the interferon beta-1a group was
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
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