|OPERA I OPERA II (Pooled)a
Incidence Rate per 100 Patient-Years (95% CI)
Incidence Rate per 100 Patient-Years (95% CI)
|Phase III 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 III, 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 III, 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 programme.
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), pneumonia (n=2), acute coronary insufficiency (n=1), adenocarcinoma of oesophagus (n=1), aspiration pneumonia (n=1), bladder cancer (n=1), epileptic seizure (n=1), injury (n=1), MS disease progression (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|
|APR 2017–DEC 2019
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 in patients treated with ocrelizumab within the designated post-marketing period.
The causes of the post-marketing fatalities are as follows: Unknown cause (n=247), myocardial infarction (n=15), completed suicide (n=13), pneumonia (n=10), sepsis (n=10), pulmonary embolism (n=6), pancreatic cancer (n=4), fall (n=4), lung cancer (n=3), infection (n=3), MS (n=3), sudden death (n=3), urosepsis (n=3), aspiration pneumonia (n=3), cardiac arrest (n=3), cardiac disorder (n=2), urinary tract infection (n=2), subdural hematoma (n=2), victim of homicide (n=2), renal failure (n=2), colon cancer (n=2), metastatic renal cell carcinoma (n=2), urinary tract infection with sepsis (n=2), head injury (n=2), septic shock (n=2), symptoms reported as a cause of death (pyrexia, chest pain, and decreased appetite) (n=1), tumefactive MS (n=1), MS relapse (n=1), MS relapse with infection (n=1), MS relapse with influenza-like illness (n=1), cerebral hemorrhage (n=1), cerebral hemorrhage and subdural hemorrhage (n=1), opioid overdose (n=1), bacterial pneumonia with lactic acidosis and sepsis (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), metastatic lung cancer (n=1), acute respiratory failure with urosepsis (n=1), acute respiratory failure with pneumonia (n=1), dyspnea (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 (n=1), lung infection with osteomyelitis (n=1), choking (n=1), stroke (n=1), cardiac failure congestive (n=1), cardiac failure with nephropathy (n=1), respiratory failure (n=1), encephalopathy, seizure, and respiratory failure (n=1), cardiorespiratory arrest (n=1), adenocarcinoma (n=1), aspiration and septic shock (n=1), cardiac failure (n=1), lung disorder (n=1), fracture (n=1), peritonitis (n=1), aortic aneurysm (n=1), myocardial infarction with 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), liver cancer (n=1), breast cancer (n=1), sudden death and metastatic neoplasm (n=1), respiratory disorder (n=1), respiratory distress (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), acute promyelocytic leukemia (n=1), adult failure to thrive (n=1), cardiac failure, MS, and hypotension (n=1), acute kidney injury, hepatic cirrhosis, ascites, and hepatorenal syndrome (n=1), amyotrophic lateral sclerosis (n=1), anaphylactic shock (n=1) arteriovenous fistula site hemorrhage (n=1), cerebrovascular accident (n=1), circulatory collapse (n=1), glioblastoma (n=1), glioblastoma multiforme (n=1), intestinal dilatation with sepsis (n=1), lip and/or oral cavity cancer and throat cancer (n=1), malignant melanoma (n=1), multiple organ dysfunction syndrome with sepsis (n=1), myelodysplastic syndrome (n=1), metastatic non-small cell lung cancer (n=1), pancreatic cancer with cardiopulmonary arrest and pleural effusion (n=1), post-procedural pulmonary embolism (n=1), procedural complication (n=1), pulmonary mass (n=1), pulmonary edema and pulmonary hemorrhage (n=1), road traffic accident (n=1), ruptured cerebral aneurysm (n=1), seizure (n=1), septic shock with atrial fibrillation and brain injury (n=1), accident (n=1), and sleep apnea syndrome (n=1).
Indications vary in different countries. The local prescribing information from your country is the primary source of information on the known and potential risks associated with ocrelizumab.
*There are well-recognised limitations that should be considered when interpreting spontaneous post-marketing safety reports, including events may not be causally related to drug exposure; in the real-world setting, events are frequently confounded by factors such as multiple drug use and the presence of pre-existing comorbidities; reporting bias may exist for more significant outcomes, which may result in an overrepresentation of the more serious outcomes; and reporting rates can be stimulated by external factors such as press reports.
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.
CI, confidence interval; IFN, interferon; MS, multiple sclerosis; PY, patient-years.