|OPERA I and OPERA II (Pooled)a
Incidence Rate per 100 Patient-Years (95% CI)
Incidence Rate per 100 Patient-Years (95% CI)
|Phase 3 Controlled Treatment Period||0.14 (0.02-0.52)||0.07 (0-0.38)||0.41 (0.08-1.20)||0.25 (0.07-0.64)|
a Two identical phase 3, global, randomised, double-blind, double-dummy studies with a 96-week controlled period during which 1656 patients with relapsing forms of MS received either intravenous ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly.5
b A phase 3, global, randomised, double-blind study with a ≥120-week controlled period during which 732 patients with primary progressive MS received either intravenous ocrelizumab (600 mg) or placebo every 24 weeks.6
|Data Cutoff Datea||Patients on Ocrelizumab (n)||Patient-Years||Fatalities (n)||Incidence Rate per 100 Patient-Years||95% CIs|
a Data cuts are cumulative; each data cut includes the previous cut and fatalities are included from both the controlled treatment period and open-label extension.
b Includes all patients exposed to ocrelizumab in the global and US MS clinical trials; excludes patients in compassionate use program.
The causes of the fatalities in the all-exposure population are as follows: suicide (n=5), cardiac arrest (n=2), metastatic pancreatic cancer (n=2), acute coronary insufficiency (n=1), adenocarcinoma of esophagus (n=1), aspiration pneumonia (n=1), bladder cancer (n=1), epileptic seizure (n=1), injury (n=1), MS disease progression (n=1), pneumonia (n=1), pulmonary embolism (n=1), systemic inflammatory response syndrome of undetermined origin (n=1), unknown (n=1), urinary infection/urosepsis (n=1), and fall (n=1)
|Market Perioda||Patients on Ocrelizumabb||Patient-Years||Fatalities (n)c||Incidence Rate per 100 Patient-Years|
|Ocrelizumab Post-Marketing||APR 2017–DEC 2017
|APR 2017–MAR 2018
|APR 2017–MAY 2018
|APR 2017–JULY 2018
|APR 2017–SEP 2018
|APR 2017–DEC 2018
|APR 2017–MAY 2019
|APR 2017–JULY 2019||~114,943||~111,166||293||0.26|
a Numbers reported for the marketing period are inclusive of the whole month stated
b The number of post-marketing patients exposed to ocrelizumab is based on estimated total number of vials sold, as well as US claims data.
c Based on reported fatalities in the Roche safety database with patients suffering from relapsing or progressive MS treated with ocrelizumab reported within the designated post-marketing period
The causes of the post-marketing fatalities are as follows: unknown cause (n=155), myocardial infarction (n=13), completed suicide (n=9), pneumonia (n=9), pulmonary embolism (n=8), sepsis (n=7), pancreatic carcinoma (n=4), fall (n=3), infection (n=3), multiple sclerosis (n=3), sudden death (n=3), cerebral hemorrhage (n=2), urosepsis (n=2), cardiac disorder (n=2), cardiac arrest (n=2), urinary tract infection (n=2), subdural hematoma (n=2), victim of homicide (n=2), symptoms reported as a cause of death (asthenia, chest pain, pyrexia and decreased appetite) (n=1), multiple sclerosis relapse with infection (n=1), tumefactive multiple sclerosis (n=1), opioid overdose (n=1), aspiration pneumonia (n=1), acute kidney injury (n=1), influenza (n=1), influenza-like illness (n=1), brain herniation with toxic leukoencephalopathy (n=1), cardiogenic shock with circulatory collapse and urinary tract infection (n=1), epilepsy with status epilepticus (n=1), cellulitis with pneumonia, sepsis and urinary tract infection (n=1), aspiration pneumonia with respiratory failure (n=1), lung cancer with metastases to bone and CNS (n=1), metastatic lung adenocarcinoma (n=1), acute respiratory failure with urosepsis (n=1), dyspnea, hyperhidrosis, and circulatory collapse (n=1), cardiopulmonary arrest with pulmonary embolism and deep vein thrombosis (n=1), sepsis with aspiration pneumonia, intestinal sepsis, cardiac arrest, and intestinal obstruction (n=1), lung infection with osteomyelitis (n=1), urinary tract infection with sepsis (n=1), choking (n=1), stroke (n=1), cardiac failure congestive (n=1), respiratory failure (n=1), encephalopathy, asthenia, seizure, and respiratory failure (n=1), cardiorespiratory arrest (n=1), adenocarcinoma (n=1), renal failure (n=1), aspiration and septic shock (n=1), lung infection (n=1), cardiac failure (n=1), lung disorder (n=1), fracture (n=1), peritonitis (n=1), aortic aneurysm (n=1), acute myocardial infarction with nasopharyngitis, cardiac failure, and cardiac disorder (n=1), cardiac arrest with pulmonary embolism (n=1), hemorrhage (n=1), hepatic and renal failure (n=1), kidney infection (n=1), metastatic neoplasm (n=1), colon cancer (n=1), metastatic liver cancer (n=1), metastatic renal cell carcinoma (n=1), breast cancer with metastasis to lung (n=1), malignant lung neoplasm (n=1), sudden death and metastatic neoplasm (n=1), respiratory disorder (n=1), respiratory failure, multiple organ dysfunction syndrome, and circulatory collapse (n=1), generalized edema (n=1), thrombosis (n=1), sarcoma (n=1), angiosarcoma (n=1), septic shock (n=1), intentional product use issue, off label use (n=1), acute promyelocytic leukaemia (n=1), dyspnea (n=1), adult failure to thrive (n=1), cardiac failure, multiple sclerosis and hypotension (n=1), metastatic colon cancer (n=1), and multiple sclerosis with influenza-like illness (n=1).
Information current as of 31 July 2019.
Existence of a safety report does not establish causation. By regulation, all cases where causality is unknown or not captured are reported as related to ocrelizumab. The causes of fatalities are recorded as reported to the company; while the company follows up on all reports to identify the cause, an exact diagnosis is not always possible. Some of the investigations remain ongoing and, therefore, the information may be subject to change.
Date of preparation: August 2019