For Patients and Caregivers
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DECADE OF DATA

10+ years of safety experience in RMS and PPMS1

The most clinical trial data and real-world MS experience in the aCD20 class and 400,000+ patients treated globally2-4

MS expert perspective on OCREVUS safety

MS specialist Dr Gabriel Pardo shares his thoughts on the long-term safety data of OCREVUS

  • SEE why 10+ years of longitudinal data with OCREVUS is an important consideration when making treatment decisions
  • LEARN what to tell your patients when asked about OCREVUS

COMMON ADVERSE EVENTS

For complete safety information, please see the full Prescribing Information.

Well-established safety profile with 10+ years of clinical trial data1

As of November 2023, 6155 patients have received OCREVUS in the all-exposure trial population, resulting in 30,396 patient-years (PY) of exposure5

In Phase III trials, the most common adverse events (AEs) were infusion reactions and infections (mainly mild to moderate)2

  • Other common AE rates were similar with Rebif® (interferon beta-1a) and placebo2
  • In the OCREVUS all-exposure population, reported rates of AEs continue to be consistent with those seen during the controlled RMS and PPMS trials5

AEs per 100 PY in OCREVUS trial population

RMS PPMS OCREVUS all-exposure population

AEs were classified according to Medical Dictionary for Regulatory Activities (MedDRA) versions 18.0, 18.1, 22.1, and 24.1. Multiple occurrences of the same AE in one patient are counted multiple times, except for malignancies. *Data as of April–July 2015.5 †Includes patients with RMS who received any dose of OCREVUS during the controlled period and associated OLE periods of the Phase II and Phase III studies plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO, CHIMES, and OLERO (data as of November 2023).5 ‡Serious infections are defined using AEs falling into the MedDRA system organ class “Infections and infestations” and using “Is the event nonserious or serious?” from the AE case report form.5 §Malignancies are identified using AEs falling into the standard MedDRA query “Malignant tumors (narrow)."5 ║For malignancies, incidence rates are reported and exposure in PY was calculated from first treatment to onset of first malignancy.5 OPERA I and II (RMS): Two randomized, double-blind, double-dummy, active comparator–controlled clinical trials of identical design vs Rebif in 1656 patients (OCREVUS: OPERA I [n=410], OPERA II [n=417]; Rebif: OPERA I [n=411], OPERA II [n=418]) with RMS treated for 96 weeks. Both studies included patients who had experienced ≥1 relapse within the prior year, or ≥2 relapses within the prior 2 years, and had an EDSS score between 0 and 5.5.1,3

AEs were classified according to Medical Dictionary for Regulatory Activities (MedDRA) versions 18.0, 18.1, 22.1, and 24.1. Multiple occurrences of the same AE in one patient are counted multiple times, except for malignancies. *Data as of April–July 2015.5 †Includes patients with PPMS who received any dose of OCREVUS during the controlled period and associated OLE periods of OBOE, CONSONANCE, and OLERO (data as of November 2023).5 ‡Serious infections are defined using AEs falling into the MedDRA system organ class “Infections and infestations” and using “Is the event nonserious or serious?” from the AE case report form.5 §Malignancies are identified using AEs falling into the standard MedDRA query “Malignant tumors (narrow)."5 ║For malignancies, incidence rates are reported and exposure in PY was calculated from first treatment to onset of first malignancy.5 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 functional systems score due to lower extremity findings. Patients also had no history of RMS, SPMS (secondary progressive multiple sclerosis), or PRMS (progressive relapsing multiple sclerosis).2,6

  • Potential serious opportunistic infections in the OCREVUS all-exposure population: 0.03 per 100 PY (95% CI: 0.01, 0.06) as of November 20237

AEs were classified according to Medical Dictionary for Regulatory Activities (MedDRA) versions 18.0, 18.1, 22.1, and 24.1. Multiple occurrences of the same AE in one patient are counted multiple times, except for malignancies. *Includes patients who received any dose of OCREVUS during the controlled period and associated OLE periods of the Phase II and Phase III studies, plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO, and CONSONANCE, including patients originally randomized to comparator (IFN β-1a or placebo) who switched to open-label OCR treatment (data as of November 2023).5 †Includes patients with RMS who received any dose of OCREVUS during the controlled period and associated OLE periods of the Phase II and Phase III studies plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO, CHIMES and OLERO (data as of November 2023).5 ‡Includes patients with PPMS who received any dose of OCREVUS during the controlled period and associated OLE periods of OBOE, CONSONANCE, and OLERO (data as of November 2023).5 §Serious infections are defined using AEs falling into the MedDRA system organ class “Infections and infestations” and using “Is the event nonserious or serious?” from the AE case report form.5 ║Malignancies are identified using AEs falling into the standard MedDRA query “Malignant tumors (narrow)."5 For malignancies, incidence rates are reported and exposure in PY was calculated from first treatment to onset of first malignancy.5

Patients in the OLE period successfully completed the controlled period and are subject to continued dropout; they may represent an enriched population. Measured endpoints only convey numerical trends and were not or powered to conclude statistical significance. Conclusions regarding the treatment effect of OCREVUS cannot be drawn on the basis of OLE data

Infusion reactions2

  • OCREVUS 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 risk of infusion reactions was 34% to 40%
  • Infusion reactions were highest with the first infusion

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

OBSERVED RATES OF INFECTION

Patients who experienced ≥1 infection in the controlled period

Infections in the controlled period were mainly mild to moderate in severity2

OPERA I and II2
58%
OCREVUS		 vs 52%
Rebif
ORATORIO2
70%
OCREVUS		 vs 68%
Rebif
  • In the controlled period, infections were mainly mild to moderate2
  • In the controlled period, OCREVUS did not increase the risk of serious infections vs Rebif or placebo, though serious infections have occurred2,7
  • In the post-marketing period, serious, including life-threatening or fatal, bacterial, viral, parasitic, and fungal infections have been reported in patients receiving OCREVUS. An increased risk of infections has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies2

Rate of serious infections observed for 10+ years (Phase III trials and OLE)*

All-exposure population7†

  • Serious infections in the OCREVUS all-exposure population: 2.2 per 100 PY (95% CI: 2.0, 2.4) as of November 20235,9
  • The most common serious infections were urinary tract infections, pneumonia, and cellulitis5,9

Serious infections and IgG levels based on 10+ years of clinical trial data (as of November 2022)*

Most patients taking OCREVUS remained at or above the lower limit of normal for IgG (LLN; 5.65 g/L)

TOTAL PATIENTS TREATED WITH OCREVUS IN OPERA, ORATORIO, AND OLE10
N=2092

Photo of an African American woman talking into a loudspeaker while driving a school bus

Out of 2092 patients treated with OCREVUS, 62 serious infections were observed in 46 patients during episodes of IgG<LLN (OPERA, ORATORIO, and OLE).10,11

Rate of serious infections (data as of November 2023)5

2.2

/100 PY

All-exposure population

1.7

/100 PY

All-RMS population

3.7

/100 PY

All-PPMS population

  • Serious infections during episodes of IgG<LLN were consistent with overall serious infections observed in patients treated with OCREVUS in terms of type, severity, latency, duration, and outcome2

*The COVID-19 pandemic resulted in an increased number of cases of infections related to SARS-CoV-2 during the reporting interval. For both RMS and PPMS, serious infections data are presented for the full OCREVUS all-exposure population and a subset of this population without COVID-19 infections (Ex-COVID-19). In the Ex-COVID-19 analysis, patients continued to contribute to the incidence of all other AEs.7
†Includes patients who received any dose of OCREVUS during the controlled period and associated OLE periods of the Phase II and Phase III studies plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO, CONSONANCE, CHIMES, and OLERO, including patients originally randomized to comparator (IFN β-1a or placebo) who switched to open-label OCREVUS treatment (data as of November 2022).7
‡The exposure in PY during Years 9 and 10 is limited for meaningful interpretation.7

REPORTED MALIGNANCIES

An increased risk of malignancy, including breast cancer, may exist in patients treated with OCREVUS2

Age-standardized incidence rate of female breast cancer over populations studied with OCREVUS and the SEER population (per 100 PY)7,12-14

CONTROLLED AND OLE PERIODS

Breast cancer was found in:

  • 6/781 females treated with OCREVUS and 0/668 females treated with Rebif or placebo in the controlled period2
  • 35/3857 females on OCREVUS (18,207 PY) in the all-exposure population as of November 202312

The FDA recommends that OCREVUS patients follow standard breast cancer screening guidelines.2

The American Cancer Society recommends that patients <40 years of age with risk factors for breast cancer should ask their healthcare provider whether mammograms are advisable and how often to have them. Patients age 45 to 54 should get mammograms every year.15,16

“Age-at-enrollment” methodology only captures how old a patient was at the trial baseline and not when the event occurred. However, as study follow-up continues and patients become older, the “age-at-event onset” methodology based on the age of the patient at the onset of malignancy is a more precise method of calculating the standardized incidence rate.13
*Nonmelanoma skin cancer (NMSC) is not reported in the Surveillance, Epidemiology, and End Results (SEER) program.13
†Includes patients who received any dose of OCREVUS during the controlled period, extended-controlled period, and associated OLE periods of the Phase II and Phase III studies, including patients originally randomized to comparator (Rebif or placebo) who switched to open-label OCREVUS treatment.13
‡Includes patients described in footnote † plus VELOCE, CHORDS, CASTING, and OBOE.13
§Includes patients described in footnote ‡ plus ENSEMBLE.13
║Includes patients described in footnote § plus LIBERTO.13
Includes patients described in footnote ║ plus CONSONANCE.13
#Includes patients who received any dose of OCREVUS during the controlled period, and associated OLE periods of the Phase II and Phase III studies, plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO, and CONSONANCE, including patients originally randomized to comparator (Rebif or placebo) who switched to open-label OCREVUS treatment.13
††Includes patients who received any dose of OCREVUS during the controlled period and associated OLE periods of the Phase II and Phase III studies plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO, CHIMES, CONSONANCE, and OLERO, including patients originally randomized to comparator (Rebif or placebo) who switched to open-label OCREVUS treatment.
The SEER Program of the National Cancer Institute (NCI) is an authoritative source of information reporting data on cancer incidence in 48% of the general US (non-MS specific) population. No comparisons should be made due to limitations that 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.17
aCD20=anti-CD20; AE=adverse event; COVID-19=coronavirus disease 2019; EDSS=Expanded Disability Status Scale; IFN β-1a=interferon beta-1a; IgG=immunoglobulin G; IV=intravenous; LLN=lower limit of normal; MedDRA=Medical Dictionary for Regulatory Activities; MS=multiple sclerosis; NCI=National Cancer Institute; NMSC=nonmelanoma skin cancer; 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.

NEXT: OCREVUS Pregnancy & Lactation Data

 

Important Safety Information & Indications

Indications

OCREVUS and OCREVUS ZUNOVO are 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

Treatment with ocrelizumab is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening administration reactions to ocrelizumab. OCREVUS ZUNOVO is also contraindicated in patients with a history of hypersensitivity to ocrelizumab, hyaluronidase, or any component of OCREVUS ZUNOVO.

Warnings and Precautions
Injection Reactions (OCREVUS ZUNOVO) OR Infusion Reactions (OCREVUS)

OCREVUS ZUNOVO can cause injection reactions, which can be local or systemic. Common symptoms of local injection reactions reported by patients treated with OCREVUS ZUNOVO in multiple sclerosis (MS) clinical trials included erythema, pain, swelling, and pruritus. Common symptoms of systemic injection reactions reported by patients included headache and nausea. In an open-label, active-controlled trial, injection reactions were more frequently reported with the first injection; 49% of patients experienced an injection reaction with the first injection.

In OCREVUS MS clinical trials, the incidence of infusion reactions in patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to infusion] was 34% to 40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of intravenous ocrelizumab-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization. Symptoms of infusion reactions 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.

Monitor OCREVUS ZUNOVO patients during and after injections. 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 administration reactions can occur during or within 24 hours of treatment.

Reducing the Risk and Managing Injection or Infusion Reactions

For OCREVUS ZUNOVO, administer oral pre-medication (e.g., dexamethasone or an equivalent corticosteroid, and an antihistamine) at least 30 minutes prior to each OCREVUS ZUNOVO injection to reduce the risk of injection reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered.

For OCREVUS, 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.

Management recommendations depend on the type and severity of the reaction. For life-threatening reactions, immediately and permanently stop OCREVUS ZUNOVO or OCREVUS and administer appropriate supportive treatment. For less severe OCREVUS ZUNOVO injection reactions, the injection should be interrupted immediately, and the patient should receive symptomatic treatment. The injection should be completed at the healthcare provider’s discretion and only after all symptoms have resolved. For less severe OCREVUS infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

Serious, including life-threatening or fatal, bacterial, viral, parasitic and fungal infections have been reported in patients receiving ocrelizumab. An increased risk of infections (including serious and fatal bacterial, fungal, and new or reactivated viral infections) has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies.

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 was not associated with an increased risk of serious infections in MS patients in controlled trials.

Ocrelizumab increases the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. Delay administration of ocrelizumab in patients with an active infection until the infection has 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 ocrelizumab. Serious herpes virus infections may occur at any time during treatment with ocrelizumab. Some cases were life-threatening.

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

Hepatitis B Virus Reactivation

Hepatitis B virus (HBV) reactivation has been reported in MS patients treated with ocrelizumab 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 ocrelizumab. Do not administer ocrelizumab 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 treatment with ocrelizumab after an immunosuppressive therapy or initiating an immunosuppressive therapy after ocrelizumab-containing products, consider the potential for increased immunosuppressive effect. Treatment with ocrelizumab 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 ocrelizumab treatment for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ocrelizumab treatment for non-live vaccines. Ocrelizumab may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following treatment with ocrelizumab 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 Ocrelizumab Products During Pregnancy

In infants of mothers exposed to ocrelizumab 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 you should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Progressive Multifocal Leukoencephalopathy

Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients with MS treated with ocrelizumab in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically occurs only in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in ocrelizumab-treated patients who had not been treated previously with natalizumab, (which has a known association with PML), were not taking any immunosuppressive or immunomodulatory medications associated with risk of PML prior to or concomitantly with ocrelizumab and did not have any known ongoing systemic medical conditions resulting in compromised immune system function.

JCV infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

At the first sign or symptom suggestive of PML, withhold treatment with ocrelizumab-containing products and perform an appropriate diagnostic evaluation. 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. 

Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms of PML. Monitoring with MRI for signs consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. If PML is confirmed, treatment with ocrelizumab should be discontinued.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with ocrelizumab 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 treatment with ocrelizumab and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing treatment with ocrelizumab 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 ocrelizumab 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.

Immune-Mediated Colitis

Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving ocrelizumab in the postmarketing setting. Some cases of colitis were serious, requiring hospitalization, with a few patients requiring surgical intervention. Systemic corticosteroids were required in many of these patients. The time from treatment initiation to onset of symptoms in these cases ranged from a few weeks to years. Monitor patients for immune-mediated colitis during ocrelizumab treatment and evaluate promptly if signs and symptoms that may indicate immune-mediated colitis, such as new or persistent diarrhea or other gastrointestinal signs and symptoms, occur.

Liver Injury

Clinically significant liver injury, without findings of viral hepatitis, has been reported in the postmarketing setting in patients treated with anti-CD20 B-cell depleting therapies approved for the treatment of MS, including ocrelizumab. Signs of liver injury, including markedly elevated serum hepatic enzymes with elevated total bilirubin, have occurred from weeks to months after administration.

Patients treated with ocrelizumab found to have an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3x the upper limit of normal (ULN) with serum total bilirubin greater than 2x ULN are potentially at risk for severe drug-induced liver injury.

Obtain liver function tests prior to initiating treatment with ocrelizumab, and monitor for signs and symptoms of any hepatic injury during treatment. Measure serum aminotransferases, alkaline phosphatase, and bilirubin levels promptly in patients who report symptoms that may indicate liver injury, including new or worsening fatigue, anorexia, nausea, vomiting, right upper abdominal discomfort, dark urine, or jaundice. If liver injury is present and an alternative etiology is not identified, discontinue ocrelizumab.

Use in Specific Populations
Pregnancy

There are no adequate data on the developmental risk associated with use of ocrelizumab in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to ocrelizumab-containing products. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. Ocrelizumab 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 or hyaluronidase 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 ocrelizumab and any potential adverse effects on the breastfed infant from ocrelizumab or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving ocrelizumab and for 6 months after the last dose of ocrelizumab. Instruct patients that if they are pregnant or plan to become pregnant while taking OCREVUS or OCREVUS ZUNOVO, they should inform their healthcare provider.

Most Common Adverse Reactions

In patients treated with OCREVUS:

  • RMS: The most common adverse reactions (≥10% and >REBIF): upper respiratory tract infections and infusion reactions
  • PPMS: The most common adverse reactions (≥10% and >placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections

The most common adverse reaction observed with OCREVUS ZUNOVO in patients with RMS and PPMS was injection reactions (incidence of 49%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see additional Important Safety Information throughout and click here for full OCREVUS Prescribing Information and Medication Guide. For OCREVUS ZUNOVO, click here for full Prescribing Information and Medication Guide.

    • Weber MS, Kappos L, Hauser SL, et al. The patient impact of 10 years of ocrelizumab treatment in multiple sclerosis: long-term data from the phase III OPERA and ORATORIO studies. Poster presented at: 9th Joint ECTRIMS-ACTRIMS Meeting; October 11-13, 2023; Milan, Italy. Poster P302.

      Weber MS, Kappos L, Hauser SL, et al. The patient impact of 10 years of ocrelizumab treatment in multiple sclerosis: long-term data from the phase III OPERA and ORATORIO studies. Poster presented at: 9th Joint ECTRIMS-ACTRIMS Meeting; October 11-13, 2023; Milan, Italy. Poster P302.

    • OCREVUS [prescribing information]. South San Francisco, CA: Genentech, Inc. 2025.

      OCREVUS [prescribing information]. South San Francisco, CA: Genentech, Inc. 2025.

    • Hauser SL, Bar-Or A, Comi G, et al; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221-234. doi:10.1056/NEJMoa1601277

      Hauser SL, Bar-Or A, Comi G, et al; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221-234. doi:10.1056/NEJMoa1601277

    • Data on file. Genentech, Inc. November 2024.

      Data on file. Genentech, Inc. November 2024.

    • Hauser SL, Kappos L, Montalban X, et al. Safety of ocrelizumab in multiple sclerosis: up to 11 years of updated analysis in patients with relapsing and progressive multiple sclerosis. Poster presented at: 5th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 27-29, 2020; West Palm Beach, FL, USA. Poster P115.

      Hauser SL, Kappos L, Montalban X, et al. Safety of ocrelizumab in multiple sclerosis: up to 11 years of updated analysis in patients with relapsing and progressive multiple sclerosis. Poster presented at: 5th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 27-29, 2020; West Palm Beach, FL, USA. Poster P115.

    • Montalban X, Hauser SL, Kappos L, et al; ORATORIO Clinical Investigators. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220. doi:10.1056/NEJMoa1606468

      Montalban X, Hauser SL, Kappos L, et al; ORATORIO Clinical Investigators. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220. doi:10.1056/NEJMoa1606468

    • Hauser SL, Kappos L, Montalban X, et al. Safety of ocrelizumab in multiple sclerosis: updated analysis in patients with relapsing and primary progressive multiple sclerosis. Poster presented at: 9th Joint ECTRIMS-ACTRIMS Meeting; October 11-13, 2023; Milan, Italy. Poster P304.

      Hauser SL, Kappos L, Montalban X, et al. Safety of ocrelizumab in multiple sclerosis: updated analysis in patients with relapsing and primary progressive multiple sclerosis. Poster presented at: 9th Joint ECTRIMS-ACTRIMS Meeting; October 11-13, 2023; Milan, Italy. Poster P304.

    • De Seze J, Arnold DL, Bar-Or A, et al; OPERA I, OPERA II and ORATORIO clinical investigators. Infusion-related reactions with ocrelizumab in relapsing multiple sclerosis and primary progressive multiple sclerosis. Poster presented at: 32nd Congress of the European Committee for Treatment and Research of Multiple Sclerosis; September 14-17, 2016; London, United Kingdom. Poster P720.

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