Ocrelizumab

Screen for hepatitis B virus in all patients (HBsAg and anti-HBc measurements) prior to treatment initiation. Although there were no reports of hepatitis B reactivation in MS patients treated with ocrelizumab, fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with other anti-CD20 monoclonal antibodies. Perform HBV screening in all patients prior to treatment initiation. Do not administer ocrelizumab to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. Consult liver disease specialist prior to starting and during treatment in patients who are negative for surface antigen (HBsAg) and positive for HB core antibody (HBcAb+) or are carriers of HBV (HBsAg+).

In clinical studies, herpes infections (herpes zoster, herpes simplex, oral herpes, genital herpes, and herpes virus infection) were reported more frequently in patients who received ocrelizumab compared to patients who received comparator drug and oral herpes was reported more frequently with ocrelizumab than with placebo. Infections were predominantly mild to moderate in severity. There were no reports of disseminated herpes.

Assess for infections prior to treatment initiation and delay treatment in patients with an active infection until the infection is resolved. In clinical studies, a slightly higher incidence of infections was reported in patients receiving ocrelizumab, compared to patients receiving the comparator drug or placebo. Over half of patients who received ocrelizumab experienced one or more infections. In multiple sclerosis patients, ocrelizumab is associated with an increased risk for respiratory tract infections (upper and lower), skin infections, and herpes-related infections, although was not associated with an increased risk of serious infections. Respiratory tract infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.

Ocrelizumab may cause infusion reactions; symptoms include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, and tachycardia. The incidence of infusion reactions in patients who received methylprednisolone (or an equivalent steroid) and potentially other pre-medication to reduce the risk of infusion reactions prior to each infusion was 34% to 40% in multiple sclerosis studies; the highest incidence was with the first infusion. There were no fatal infusion reactions, although serious infusion reactions occurred (rarely), some reactions required hospitalization. Monitor for infusion reactions during the infusion and for at least one hour after the end of the infusion. Infusion reactions can occur up to 24 hours after the infusion. Administer premedications (methylprednisolone [or equivalent] and an antihistamine, with or without acetaminophen) to reduce the frequency and severity of infusion reactions. Depending on the severity of the reaction, infusion reaction may require infusion interruption, decreased infusion rate, or discontinuation; may also require symptomatic supportive management.

Ocrelizumab may be associated with an increased risk of malignancy. Malignancies (including breast cancer) occurred more frequently in ocrelizumab-treated patients in clinical studies. Breast cancer occurred in 0.8% of females who received ocrelizumab and none of the females who received the comparator drug or placebo. Patients should follow standard breast cancer screening guidelines.

Although no cases of progressive multifocal leukoencephalopathy (PML) were identified in ocrelizumab studies, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies and has been associated with some risk factors such as patients who are immunocompromised or use polytherapy with immunosuppressants. PML is an opportunistic viral infection of the brain caused by the JC virus and usually leads to death or severe disability; PML typically only occurs in patients who are immunocompromised. Symptoms associated with PML are diverse and progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, vision disturbance, and changes in thinking, memory, and/or orientation leading to confusion and personality changes. Withhold treatment and perform appropriate diagnostic evaluation at the first sign or symptom suggestive of PML (MRI findings may be apparent prior to clinical signs/symptoms). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Administer all necessary immunizations at least 6 weeks prior to treatment initiation. Immunization with live-attenuated or live vaccines is not recommended during treatment or after discontinuation until B-cell repletion. Other warnings/precautions:

Ocrelizumab has not been studied in combination with other MS therapies. When initiating ocrelizumab after an immunosuppressive therapy or initiating an immunosuppressive following ocrelizumab therapy, consider the potential for increased immunosuppressive effects.