Infusion reactions1

  • OCREVUS (ocrelizumab) can cause infusion reactions that can be serious and require hospitalization 
    • Management recommendations for infusion reactions depend on the type and severity of the reaction
    • Permanently discontinue OCREVUS if a life-threatening or disabling infusion reaction occurs
  • In clinical studies, all patients received premedications for infusion reactions before treatment with OCREVUS. In these studies, the rate of infusion reactions was 34%-40%
  • Infusion reactions were highest with the first infusion
Controlled period

Infusion reaction rates in ORATORIO (PPMS) were similar to those in the OPERA I and II (RMS) clinical trials

See relapsing multiple sclerosis infusion reaction data.


Observed rates of infection1,3,46

Controlled period

Patients who experienced 1 or more infections 

Patients who experienced one or more infections during ORATORIO clinical trial, OCREVUS® (ocrelizumab) 70% versus placebo 68%
Controlled and OLE periods
  • Upper respiratory tract infections occurred in 49% of OCREVUS-treated patients and 43% of patients on placebo
  • Lower respiratory tract infections occurred in 10% of OCREVUS-treated patients and 9% of patients on placebo
  • Herpes infections occurred in 5% of OCREVUS-treated patients and 4% of patients on placebo
  • These infections were mainly mild to moderate
  • OCREVUS did not increase the risk of serious infections vs placebo, although serious infections have occurred
SERIOUS INFECTION RATES VS PLACEBO: PHASE III TRIAL AND OLE 
Serious infection rates versus Placebo: Phase III Trials and OLE. OCREVUS® (ocrelizumab) did not increase the risk of serious infections versus placebo, though serious infections have occurred
  • OCREVUS all-exposure population: the rate per 100 PY of serious infections as of January 2020 (2.01 [95% CI: 1.81, 2.23]) was similar to the rate observed at the primary analysis cutoff date
  • The most common serious infections were UTIs and pneumonia 

See relapsing multiple sclerosis infection rate data.


Reported malignancies: additional important safety information1,3,46,47

An increased risk of malignancy, including breast cancer, may exist in OCREVUS-treated patients.

Controlled and OLE periods
AGE-STANDARDIZED INCIDENCE RATE OF FEMALE BREAST CANCER OVER OCREVUS STUDIED POPULATIONS AND SEER POPULATION (PER 100 PY)
Age standardized incidence rate of female breast cancer over OCREVUS studied populations and seer populations (per 100 PY) graph. Breast cancer was found in 6 of 781 females on OCREVUS versus 0 of 668 females on Rebif or placebo in the OPERA and ORATORIO clinical trials. Breast cancer was found in 21 of 3550 females on OCREVUS® (ocrelizumab) in the all-exposure population of the clinical trials

*Includes patients who received any dose of OCREVUS during the controlled treatment and associated OLE periods of the Phase II and Phase III studies.
Includes patients who received any dose of OCREVUS during the controlled treatment and associated OLE periods of the Phase II and Phase III studies, plus VELOCE, CHORDS, CASTING, and OBOE.
Includes patients who received any dose of OCREVUS during the controlled treatment and associated OLE periods of the Phase II and Phase III studies, plus VELOCE, CHORDS, CASTING (and associated LTE), OBOE, and ENSEMBLE.
§Includes patients who received any dose of OCREVUS during the controlled treatment and associated OLE periods of the Phase II and Phase III studies, plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO, and CONSONANCE.
SEER incidence calculated from 2000-2012 data.
The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) is an authoritative source of information reporting data on cancer incidence in ≈28% of the general US (non-MS specific) population. No comparisons should be made due to limitations which have not been fully accounted for, such as variations in patient populations, as well as differences in sample size, temporal changes, and other potential confounding factors.

Breast cancer screening recommendation1,48,49

The FDA recommends that OCREVUS patients follow standard breast cancer screening guidelines
Women with disabilities are less likely to have received a mammogram. 39% of women with disabilities did not receive a mammogram versus 25% of women without disabilities during the past 2 years. This is according to a CDC survey in 2010 of women 50-74 years of age.
American Cancer Society Recommendations: Preventative Screening Guidelines for Women chart. Women under 40 with risk factors for breast cancer (genetic or environmental) should ask their HCP whether mammograms are advisable and how often to have them. Women aged 40 to 44 should have the choice to start annual breast cancer screening with mammograms (x-rays of the breast) if it is the patient's desire. Women aged 45 to 54 should get mammograms every year.  Women aged 55+ can switch to mammograms every 2 years, or can continue annual screening

  • The risks of and the potential benefits of mammograms should be considered and discussed with the patient’s HCP
  • Breast MRI also has a role in screening for some patients (decision should be made in consultation with a breast cancer specialist)
  • Screening should continue as long as a woman is in good health and is expected to live 10 more years or longer
  • Other screening guidelines from federally recognized sources (eg, the US Preventive Services Task Force, the CDC) may be used based on HCP preference and in consultation with their patient

Common adverse events (AEs)1,50

For complete safety information, please see the full Prescribing Information

Controlled period
Chart showing common adverse events (greater than or equal to 5% and higher than placebo) in ORATORIO with OCREVUS® (ocrelizumab) vs placebo

ORATORIO (PPMS): A randomized, double-blind, placebo–controlled clinical trial in 732 patients (OCREVUS, n=488; placebo n=244) with PPMS treated for at least 120 weeks. Selection criteria included patients aged 18 to 55 and required a baseline EDSS of 3 to 6.5 and a score of 2 or greater for the EDSS pyramidal FSS due to lower extremity findings. Patients also had no history of RMS, SPMS, or PRMS. 

See relapsing multiple sclerosis common adverse events data.

Dosing and administration

Visit the OCREVUS dosing schedule for your patients.

Request information

Speak to an OCREVUS Representative to learn more about OCREVUS.

EDSS=Expanded Disability Status Scale; FSS=Functional Systems Score; LTE=long-term extension; OCR=OCREVUS; OLE=open-label extension; PPMS=primary progressive multiple sclerosis; PRMS=progressive relapsing multiple sclerosis; PY=patient-years; RMS=relapsing multiple sclerosis; SEER=Surveillance, Epidemiology, and End Results; SPMS=secondary progressive multiple sclerosis; UTI=urinary tract infection.

Indications

OCREVUS is indicated for the treatment of:

  • Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
  • Primary progressive MS, in adults.
Contraindications

OCREVUS is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reaction to OCREVUS.

Warnings and Precautions
Infusion Reactions

OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis. In multiple sclerosis (MS) clinical trials, the incidence of infusion reactions in OCREVUS-treated patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to each infusion] was 34-40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of OCREVUS-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization.

Observe patients treated with OCREVUS for infusion reactions during the infusion and for at least one hour after completion of the infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered. For life-threatening infusion reactions, immediately and permanently stop OCREVUS and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of OCREVUS-treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS increased the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. OCREVUS was not associated with an increased risk of serious infections in MS patients. Delay OCREVUS administration in patients with an active infection until the infection is resolved.

Respiratory Tract Infections

A higher proportion of OCREVUS-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 43% of patients on placebo and 10% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.

Herpes

In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in OCREVUS-treated patients than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the OCREVUS-treated patients than in the patients on placebo (2.7% vs 0.8%).

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving OCREVUS. Serious herpes virus infections may occur at any time during treatment with OCREVUS. Some cases were life-threatening.

If serious herpes infections occur, OCREVUS should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered.

Progressive Multifocal Leukoencephalopathy (PML)

PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no cases of PML were identified in OCREVUS clinical trials, 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 (e.g., immunocompromised patients, polytherapy with immunosuppressants). At the first sign or symptom suggestive of PML, withhold OCREVUS and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes (per USPI).

Hepatitis B Virus (HBV) Reactivation

Hepatitis B reactivation has been reported in MS patients treated with OCREVUS in the postmarketing setting. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with OCREVUS. Do not administer OCREVUS to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment.

Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants

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

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines. OCREVUS may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following OCREVUS therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with OCREVUS treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during OCREVUS treatment and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing OCREVUS therapy in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Malignancies

An increased risk of malignancy with OCREVUS may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in OCREVUS-treated patients. Breast cancer occurred in 6 of 781 females treated with OCREVUS and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines.

Use in Specific Populations
Pregnancy

Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to OCREVUS during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-872-4370 or visiting www.ocrevuspregnancyregistry.com.

There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to OCREVUS. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier.

Lactation

There are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OCREVUS and any potential adverse effects on the breastfed infant from OCREVUS or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving OCREVUS and for 6 months after the last infusion of OCREVUS.

Most Common Adverse Reactions

RMS: The most common adverse reactions in RMS trials (incidence ≥10% and >REBIF) were upper respiratory tract infections (40%) and infusion reactions (34%).

PPMS: The most common adverse reactions in PPMS trials (incidence ≥10% and >placebo) were upper respiratory tract infections (49%), infusion reactions (40%), skin infections (14%), and lower respiratory tract infections (10%).

For additional safety information, please see the full Prescribing Information and Medication Guide.

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