Ocrevus (Ocrelizumab) is a humanized monoclonal antibody that targets the CD-20 positive B-lymphocytes. It acts as an immunosuppressant like rituximab.

Ocrelizumab (Ocrevus) Uses:

Multiple sclerosis (relapsing or primary progressive):

• Used for treatment of primary progressive multiple sclerosis (MS) and relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Ocrevus Dose in Adults:

Note:

• Premedicate with methylprednisolone (100 mg IV) 30 minutes prior to each infusion, and an antihistamine (eg, diphenhydramine) 30 to 60 minutes prior to each infusion.
• May also consider premedication with acetaminophen.
• Assess for infection; delay administration for active infection.

Ocrevus (Ocrelizumab) dose in the treatment of Primary progressive or relapsing Multiple sclerosis:

Intravenous:

• 300 mg on day 1, followed by 300 mg 2 weeks later.
• Subsequent doses of 600 mg are administered once every 6 months (beginning 6 months after the first 300 mg dose) (Hauser 2017; Montalban 2017).

Missed doses:

• Administer as soon as possible if a dose is missed, (do not wait until the next scheduled dose).
• Then adjust the dosing schedule to administer the next sequential dose 6 months after the missed dose was administered.
• Doses must be separated by at least 5 months.

Use in children:

The safety and efficacy of the drug in children have not been approved.

Ocrelizumab (Ocrevus) FDA Pregnancy Risk Category: N (Not assigned)

• Ocrelizumab (IgG) is a humanized monoclonal anti-bodies.
• The potential placental transfer human IgG depends on the IgG subclass and gestational age. This generally increases as pregnancy progresses.
• The lowest possible exposure is expected during the period of organogenesis.
• Limited information is available on the pregnancy use of ocrelizumab.
• Infants born to mothers who received similar drugs have experienced lymphocytopenia and peripheral B-cell depletion.
• Infants who are exposed to ocrelizumab may have a decreased immune response to live and live-attenuated vaccinations.
• Before administering live or live-attenuated vaccinations, measure the immune response of exposed infants by measuring CD19 B cells.
• Pregnancy-modifying therapies for multiple sclerosis (DMTs) should be stopped before a planned pregnancy. This is except for females with high MS risk.
• For females who are at high risk of developing a disease reactivation and who are pregnant, consider other agents.
• It is recommended that pregnant women with high levels of disease activity delay their pregnancy.
• Other agents are preferred when disease-modifying treatment is required in these patients.
• Effective contraception should be used by females with reproductive potential during therapy, and for six months following the last ocrelizumab injection.

Use of Ocrelizumab while breastfeeding

• It is unknown if breast milk contains ocrelizumab.
• It is unknown if breastfeeding infants could experience B-cell depletion after maternal use of ocrelizumab.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.
• Other sources don't recommend breastfeeding during therapy.

Ocrevus Dose in Kidney Disease:

• In the manufacturer's labeling, there are no dosage adjustments provided
• In patients with renal impairment however, no significant change in pharmacokinetics was observed

Ocrevus (Ocrelizumab) Dose in Liver Disease:

• In the manufacturer's labeling, there are no dosage adjustments provided
• However, in patients with hepatic impairment, no significant change in pharmacokinetics was observed.

Common Side Effects of Ocrelizumab (Ocrevus):

• Dermatologic:

  • Skin infection

• Hematologic & oncologic:

  • Decreased serum immunoglobulins
  • Decreased neutrophils

• Respiratory:

  • Upper respiratory tract infection

• Miscellaneous:

  • Infusion-related reaction

Less Common Side Effects of Ocrevus Ocrelizumab):

• Cardiovascular:

  • Peripheral edema

• Central nervous system:

  • Depression

• Gastrointestinal:

  • Diarrhea

• Infection:

  • Herpes virus infection

• Neuromuscular & skeletal:

  • Back pain
  • limb pain

• Respiratory:

  • Lower respiratory tract infection
  • Cough

Contraindications to Ocrevus (Ocrelizumab):

• History of life-threatening infusion reactions to ocrelizumab.
• Hepatitis B virus (HBV), active hepatitis B virus infection

• Canadian labelingAdditional contraindications not listed in the US labeling:

  • Hypersensitivity to any component of the formulation or ocrelizumab has been reported.
  • Active, severe infections
  • Current or past history of progressive multifocal encephalopathy (PML)
  • Active malignancies
  • Severely immunocompromised States

Warnings and precautions

• Hepatitis B reactivation

  • Screening for Hepatitis B virus (HBsAg, anti-HBc) in all patients prior to starting treatment
  • There were no cases of hepatitis B activation in MS patients who received ocrelizumab.
  • However, patients receiving anti-CD20 monoclonal antibody treatment have reported hepatitis B reactivation and hepatic failure.
  • Before starting treatment, screen for HBV in all patients
  • Patients with active HBV who have had positive results for HBsAg or anti-HB tests should not be given ocrelizumab.
  • Before starting or continuing treatment for patients with HBV (HBsAg+), who are positive for surface antigen (HBsAg), and/or are carriers of HBsAg+, consult a liver disease specialist.

• Herpes infection

  • Clinical studies showed that herpes infections, including herpes simplex and herpes zoster were more common in patients who received ocrelizumab, than in those who received the comparator drug.
  • Oral herpes was also reported more often with ocrelizumab, than with placebo.
  • Most infections were mild to moderately severe.
  • No reports were made of disseminated herpes.

• Infection

  • Before starting treatment, check for infection and defer treatment until the infection is gone.
  • Clinical studies showed that patients who received ocrelizumab had a slightly higher rate of infection than patients who received the placebo or comparator drug.
  • More than half of patients who received ocrelizumab had one or more infections.
  • Multiple sclerosis patients are at greater risk for skin infections, respiratory tract infections (upper or lower), and herpes-related infection. However, it is not associated with an increase in serious infections.
  • Most respiratory tract infections were mild to moderate in nature and included bronchitis and upper respiratory tract infections.

• Infusion reactions

  • Infusion reactions may occur with Ocrelizumab
  • Pruritus, rash and urticaria are some of the symptoms.
  • Multiple sclerosis research showed that infusion reactions were more common in patients who had received methylprednisolone or an equivalent steroid prior to each infusion. The highest incidence occurred with the first infusion.
  • Although there were no infusion-related deaths, some serious reactions did occur (rarely), and required hospitalization.
  • Monitor infusion reactions throughout the infusion, and at least for one hour after it is completed.
  • Infusion reactions may occur up to 24 hours following the infusion.
  • Premedications are administered (methylprednisolone [or an equivalent]) and an antihistamine with or without Acetaminophen to reduce the severity and frequency of infusion reactions.
  • Infusion reactions can be severe or mild and may need to be stopped, reduced, or discontinued depending on how severe they are.

• Malignancy

  • Ocrelizumab could increase the risk of malignancy.
  • In clinical trials, ocrelizumab patients who were treated for cancer had more cases of breast cancer.
  • Breast cancer was found in 0.8% of women who received ocrelizumab, and none of those who received placebo or the comparator drug.
  • Breast cancer screening guidelines should be followed by patients.

• Progressive multifocal Leukoencephalopathy

  • Ocrelizumab did not identify any cases of progressive multifocal Leukoencephalopathy (PML), but JC virus infection resulting from PML was observed in patients receiving anti-CD20 antibody therapies. It has also been linked to patients who have been immunocompromised, or are using immunosuppressants in combination.
  • PML, an opportunistic virus infection of the brain that is caused by the JCvirus, can lead to severe disability or death.
  • PML is most common in immunocompromised patients.
  • PML symptoms can be varied and vary in severity. They include progressive weakness or clumsiness on one side of your body, vision disturbance and changes to thinking, memory and/or orientation that lead to confusion and personality shifts.
  • Do not proceed with treatment. Perform a proper diagnostic evaluation at any sign or symptom that suggests PML. (MRI findings might be more evident than clinical signs/symptoms).

Ocrelizumab: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters for Ocrevus:

• Before therapy is initiated, all patients must be screened for the hepatitis B viruses (HBsAg or anti-HBc)

Screening recommendations for anti-CD20 monoclonal antibody monoclonal antibodies (American Society of Clinical Oncology provisional Clinical Opinion Update [Hwang 2015]).

• Hepatitis A virus (HBV),HBV infection can be detected by hepatitis B antigen (HBsAg), and hepatitis B core antibodies (anti-HBc), before treatment initiation. A total anti-HBc test (with immunoglobulin IgG [IgG] or immunoglobulin [IgM]) should be performed to confirm chronic or unresolved HBV infections. Anti-HBc IgG tests cannot be used as they may only confirm acute HBV infection.
• Patients with HBsAg-negative/anti HBc-positive status should be tested for HBV reactivation by HBV DNA and ALT testing every three months.
• Monitor infusion reactions throughout the infusion and for at least one hour after the infusion has ended.
• Be aware of signs and symptoms such as infection, malignancy, or progressive multifocal encephalopathy.

How to administer Ocrelizumab (Ocrevus)?

Intravenous

• Use a 0.22-micron or 0.22-micron intravenous line to administer the medication.
• Premedicate with methylprednisolone (100mg IV) 30 minutes before each infusion and an antihistamine, eg, diphenhydramine, 30-60 minutes before each infusion.
• You may also want to consider premedication with Acetaminophen.

Initial 2 infusions (300mg dose)

• Infusions should be started at 30 mL/hour
• To reach a maximum of 180 mL/hour, increase by 30 mL/hour for every 30 minutes.
• Infusions last for 2.5 hours or more.

Infusions subsequent to that (600 mg):

• Infusions should be started at 40 mL/hour
• To reach a maximum of 200 mL/hour, increase by 40 mL/hour for every 30 minutes.
• Infusions last for 3.5 hours or more.
• Observe for any infusion reactions throughout the infusion, and for at least an hour after it is completed.
• Infusion reactions can be stopped, discontinued, or decreased depending on the severity.

Mechanism of action of Ocrelizumab (Ocrevus):

• Ocrelizumab, a monoclonal recombinant humanized IgG monoclonal anti-B-cells that express CD20 on their cell surfaces; CD20 can be found on both pre-B and mature lymphocytes.
• Multiple sclerosis is thought to be influenced by B-cells through antigen presentation, cytokine regulation and formation of ectopiclyid aggregates within the meninges.
• Ocrelizumab targets and binds selectively to the cell surface with high affinity. This is done to reduce CD20-expressing B-cells via antibody-dependent cell-mediated cell-mediated cell-mediated death and cytotoxicity as well as complement-mediated cell-mediated cytolysis.

The onset of action:

• Serum CD-19+ B-cell counts (used as a marker for B-cell counts) are reduced within 14 days after infusion.

Duration of action:

• The median time for B-cell recovery (to baseline or the lower limit of normal): 72 weeks (range: 27 to 175 weeks).

Metabolism:

• Antibodies are primarily cleared by catabolism.

Half-life elimination:

• 26 days

Excretion:

• Constant clearance (estimated): 0.17 L per day;
• Initial time-dependent clearance: 0.05 L per day.

International Brands of Ocrelizumab:

• Ocrevus

Ocrelizumab Brand Names in Pakistan:

• Ocrevus
• One injection in Pakistan costs Rs. 510,000/-