FDA label 7075d975-19b9-497b-9657-3a99a527ffd4

5 WARNINGS AND PRECAUTIONS Injection Reactions: Management recommendations for injection reactions depend on the type and severity of the reaction. Permanently discontinue OCREVUS ZUNOVO if a life-threatening injection reaction occurs ( 4 , 5.1 ) Infections: Serious, including life-threatening and fatal, infections have occurred in patients treated with ocrelizumab. Delay OCREVUS ZUNOVO administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with OCREVUS ZUNOVO and after discontinuation, until B-cell repletion ( 5.2 ) Progressive Multifocal Leukoencephalopathy (PML): Withhold OCREVUS ZUNOVO at the first sign or symptom suggestive of PML ( 5.3 ) Reduction in Immunoglobulins: Monitor the level of immunoglobulins at the beginning of treatment. Monitor during and after discontinuation of treatment with OCREVUS ZUNOVO, until B-cell repletion, and especially when recurrent serious infections are suspected. Consider discontinuing OCREVUS ZUNOVO in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins ( 2.1 , 5.4 ) Malignancies: An increased risk of malignancy, including breast cancer, may exist with OCREVUS ZUNOVO ( 5.5 ) Immune-Mediated Colitis: Immune-mediated colitis has been reported in the postmarketing setting. Monitor patients for new or persistent diarrhea or other gastrointestinal symptoms, and evaluate promptly if colitis is suspected ( 5.6 ) Liver Injury: Clinically significant liver injury has occurred. Obtain serum aminotransferases, alkaline phosphatase, and bilirubin levels before initiating OCREVUS ZUNOVO, and during treatment as clinically indicated. Discontinue OCREVUS ZUNOVO in patients with evidence of liver injury in the absence of an alternative etiology ( 5.7 ) 5.1 Injection Reactions 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 [see Adverse Reactions (6.1) ] . In MS clinical trials where ocrelizumab was administered intravenously, the incidence of infusion reactions in patients [who received methylprednisolone (or an equivalent steroid) and possibly other premedication 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 patients during and after injections [see Dosage and Administration (2.4) ] . Inform patients that injection reactions can occur during or within 24 hours of the injection. Reducing the Risk of Injection Reactions and Managing Injection Reactions Administer oral premedication (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 [see Dosage and Administration (2.3) ]. Management recommendations for injection reactions depend on the type and severity of the reaction. For life-threatening injection reactions, immediately and permanently stop OCREVUS ZUNOVO and administer appropriate supportive treatment. For less severe 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. 5.2 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 intravenous ocrelizumab-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of intravenous ocrelizumab-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of intravenous ocrelizumab-treated patients experienced one or more infections compared to 68% of patients on placebo. Intravenous ocrelizumab 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 [see Adverse Reactions (6.1) ]. Delay OCREVUS ZUNOVO administration in patients with an active infection until the infection is resolved. Respiratory Tract Infections A higher proportion of intravenous ocrelizumab-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of patients treated with intravenous ocrelizumab experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of patients treated with intravenous ocrelizumab experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of patients treated with intravenous ocrelizumab experienced upper respiratory tract infections compared to 43% of patients on placebo, and 10% of patients treated with intravenous ocrelizumab 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 patients treated with intravenous ocrelizumab 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 patients treated with intravenous ocrelizumab 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. Some cases were life-threatening. Serious herpes virus infections may occur at any time during treatment with OCREVUS ZUNOVO. If serious herpes infections occur, OCREVUS ZUNOVO should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered [see Patient Counseling Information (17) ]. 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 OCREVUS ZUNOVO 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 ZUNOVO after an immunosuppressive therapy or initiating an immunosuppressive therapy after OCREVUS ZUNOVO, consider the potential for increased immunosuppressive effects [see Drug Interactions (7.1) and Clinical Pharmacology (12.1 , 12.2) ]. OCREVUS ZUNOVO 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 for non-live vaccines. OCREVUS ZUNOVO may interfere with the effectiveness of non-live vaccines [see Drug Interactions (7.2) ]. The safety of immunization with live or live-attenuated vaccines following OCREVUS ZUNOVO therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion [see Clinical Pharmacology (12.2) ] . Vaccination of Infants Born to Mothers Treated with OCREVUS ZUNOVO During Pregnancy In infants of mothers exposed to OCREVUS ZUNOVO 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 [see Use in Specific Populations (8.1) ]. 5.3 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 only occurs 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 the 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 OCREVUS ZUNOVO 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. MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be 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. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients. If PML is confirmed, treatment with OCREVUS ZUNOVO should be discontinued. 5.4 Reduction in Immunoglobulins As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with ocrelizumab treatment. The pooled data of intravenous ocrelizumab 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 ZUNOVO treatment and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing OCREVUS ZUNOVO therapy in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins [see Adverse Reactions (6.1) ] . 5.5 Malignancies An increased risk of malignancy with OCREVUS ZUNOVO may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in patients treated with intravenous ocrelizumab. Breast cancer occurred in 6 of 781 females treated with intravenous ocrelizumab and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines. 5.6 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 OCREVUS ZUNOVO 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. 5.7 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 OCREVUS ZUNOVO found to have an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3× the upper limit of normal (ULN) with serum total bilirubin greater than 2× ULN are potentially at risk for severe drug-induced liver injury. Obtain liver function tests prior to initiating treatment with OCREVUS ZUNOVO [see Dosage and Administration (2.2) ] , 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 OCREVUS ZUNOVO.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Injection Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.3) ] Reduction in Immunoglobulins [see Warnings and Precautions (5.4) ] Malignancies [see Warnings and Precautions (5.5) ] Immune-Mediated Colitis [see Warnings and Precautions (5.6) ] Liver Injury [see Warnings and Precautions (5.7) ] The most common adverse reactions in patients treated with intravenous ocrelizumab were: RMS (incidence ≥10% and > REBIF ® ): upper respiratory tract infections and infusion reactions ( 6.1 ) PPMS (incidence ≥10% and > placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections ( 6.1 ) The most common adverse reaction observed with OCREVUS ZUNOVO in patients with RMS and PPMS was injection reactions (incidence of 49%) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of ocrelizumab has been evaluated in active-controlled clinical trials of ocrelizumab administered intravenously in patients with relapsing forms of MS (RMS) (Study 1 and Study 2) [see Clinical Studies (14.1) ] and primary progressive MS (PPMS) (Study 3) [see Clinical Studies (14.2) ] , and in an open-label, active-controlled trial of OCREVUS ZUNOVO administered subcutaneously in patients with RMS and PPMS (Study 4) [see Clinical Studies (14.3) ] . Adverse Reactions With Ocrelizumab Intravenous in Patients With RMS and PPMS The safety of intravenous ocrelizumab has been evaluated in 1311 patients across the MS clinical studies, which included 825 patients in active-controlled clinical trials in patients with RMS and 486 patients in a placebo-controlled study in patients with PPMS. RMS In active-controlled intravenous ocrelizumab clinical trials (Study 1 and Study 2), 825 patients with RMS received ocrelizumab 600 mg intravenously every 24 weeks (initial treatment was given as two separate 300 mg infusions at Weeks 0 and 2) [see Clinical Studies (14.1) ]. The overall exposure in the 96-week controlled treatment periods was 1448 patient-years. The most common adverse reactions in RMS trials (incidence ≥ 10%) were upper respiratory tract infections and infusion reactions. Table 1 summarizes the adverse reactions that occurred in active-controlled intravenous ocrelizumab RMS trials (Study 1 and Study 2). Table 1 Adverse Reactions in Adult Patients With RMS With an Incidence of at least 5% for Intravenous Ocrelizumab and Higher than REBIF Adverse Reactions Studies 1 and 2 Ocrelizumab 600 mg IV Every 24 Weeks The first dose was given as two separate 300 mg infusions at Weeks 0 and 2. (n=825) % REBIF 44 mcg SQ 3 Times per Week (n=826) % Upper respiratory tract infections 40 33 Infusion reactions 34 10 Depression 8 7 Lower respiratory tract infections 8 5 Back pain 6 5 Herpes virus- associated infections 6 4 Pain in extremity 5 4 PPMS In a placebo-controlled intravenous ocrelizumab clinical trial (Study 3), a total of 486 patients with PPMS received one course of ocrelizumab (600 mg of ocrelizumab administered as two 300 mg infusions two weeks apart) given intravenously every 24 weeks and 239 patients received placebo intravenously [see Clinical Studies (14.2) ]. The overall exposure in the controlled treatment period was 1416 patient-years, with median treatment duration of 3 years. The most common adverse reactions in the PPMS trial (incidence ≥ 10%) were upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections. Table 2 summarizes the adverse reactions that occurred in the placebo-controlled intravenous ocrelizumab PPMS trial (Study 3). Table 2 Adverse Reactions in Adult Patients With PPMS With an Incidence of at Least 5% for Intravenous Ocrelizumab and Higher Than Placebo Adverse Reactions Study 3 Ocrelizumab 600 mg IV Every 24 Weeks One dose of intravenous ocrelizumab (600 mg administered as two 300 mg infusions two weeks apart) Placebo (n=486) % (n=239) % Upper respiratory tract infections 49 43 Infusion reactions 40 26 Skin infections 14 11 Lower respiratory tract infections 10 9 Cough 7 3 Diarrhea 6 5 Edema peripheral 6 5 Herpes virus associated infections 5 4 Laboratory Abnormalities Decreased Immunoglobulins Ocrelizumab decreased total immunoglobulins, with the greatest decline seen in IgM levels; however, a decrease in IgG levels was associated with an increased rate of serious infections . In the active-controlled (RMS) trials (Study 1 and Study 2), the proportion of patients at baseline reporting IgG, IgA, and IgM below the lower limit of normal (LLN) in patients treated with intravenous ocrelizumab was 0.5%, 1.5%, and 0.1%, respectively. Following treatment, the proportion of patients treated with intravenous ocrelizumab reporting IgG, IgA, and IgM below the LLN at 96 weeks was 1.5%, 2.4%, and 16.5%, respectively. In the placebo-controlled (PPMS) trial (Study 3), the proportion of patients at baseline reporting IgG, IgA, and IgM below the LLN in patients treated with intravenous ocrelizumab was 0.0%, 0.2%, and 0.2%, respectively. Following treatment, the proportion of patients treated with intravenous ocrelizumab reporting IgG, IgA, and IgM below the LLN at 120 weeks was 1.1%, 0.5%, and 15.5%, respectively. The pooled data of intravenous ocrelizumab 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 IgG and increased rates of serious infections. The type, severity, latency, duration, and outcome of serious infections observed during episodes of immunoglobulins below LLN were consistent with the overall serious infections observed in patients treated with intravenous ocrelizumab. Decreased Neutrophil Levels In the PPMS clinical trial (Study 3), decreased neutrophil counts occurred in 13% of patients treated with intravenous ocrelizumab compared to 10% in placebo patients. The majority of the decreased neutrophil counts were only observed once for a given patient treated with intravenous ocrelizumab and were between the LLN and 1.0 × 10 9 /L. Overall, 1% of the patients in the intravenous ocrelizumab group had neutrophil counts less than 1.0 × 10 9 /L and these were not associated with an infection. Adverse Reactions With OCREVUS ZUNOVO in Patients With RMS and PPMS The safety of OCREVUS ZUNOVO was evaluated in Study 4, an active-controlled, open-label, randomized study in ocrelizumab-naïve patients with RMS or PPMS [see Clinical Studies (14.3) ] . One hundred eighteen patients received OCREVUS ZUNOVO as their first dose and 118 patients received intravenous ocrelizumab for their first dose (two separate 300 mg infusions at Weeks 0 and 2). The most common adverse reactions (reported in at least 10% of OCREVUS ZUNOVO-treated patients) were injection reactions. In Study 4, injection reactions occurred in 49% (58/118) of patients after the first injection of OCREVUS ZUNOVO. Of these 118 patients, 47% and 11% experienced at least one local injection reaction and one systemic injection reaction, respectively. The most common symptoms reported by patients with local and systemic injection reactions included: injection site erythema, injection site pain, injection site swelling, injection site pruritus, headache, and nausea. Among the patients experiencing an injection reaction, the majority of patients (83%) had injection reactions occur within 24 hours after the end of the injection, as opposed to during the injection (19%). All injection reactions were of mild (73%) or moderate (27%) severity. The median duration of symptoms was 3 days for systemic injection reactions and 3.5 days for local injection reactions. All patients recovered from injection reactions, of which 26% required symptomatic treatment. For subsequent injections, among the 118 patients who received OCREVUS ZUNOVO only throughout the study, the frequency of local injection reactions ranged from 31% to 43% and the frequency of systemic injection reactions ranged from 3% to 7% from Injection 2 to Injection 4. All injection reactions were of mild or moderate severity. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ocrelizumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: Immune-mediated colitis [see Warnings and Precautions (5.6) ] Hepatobiliary Disorders: Liver injury [see Warnings and Precautions (5.7) ] Infections and Infestations: Serious herpes infections [see Warnings and Precautions (5.2) ] , progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.3) ] , and babesiosis Skin: Pyoderma gangrenosum

<table ID="table1" width="85%"><caption>Table 1 Adverse Reactions in Adult Patients With RMS With an Incidence of at least 5% for Intravenous Ocrelizumab and Higher than REBIF</caption><col width="50%" align="left" valign="middle"/><col width="25%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr><th rowspan="2" styleCode="Lrule Rrule" align="center">Adverse Reactions</th><th colspan="2" styleCode="Botrule Rrule">Studies 1 and 2</th></tr><tr><th align="center" styleCode="Rrule">Ocrelizumab 600 mg IV Every 24 Weeks<footnote>The first dose was given as two separate 300 mg infusions at Weeks 0 and 2.</footnote> (n=825) %</th><th styleCode="Rrule">REBIF 44 mcg SQ 3 Times per Week (n=826) %</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Upper respiratory tract infections</td><td styleCode="Rrule">40</td><td styleCode="Rrule">33</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Infusion reactions</td><td styleCode="Rrule">34</td><td styleCode="Rrule">10</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Depression</td><td styleCode="Rrule">8</td><td styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Lower respiratory tract infections</td><td styleCode="Rrule">8</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Back pain</td><td styleCode="Rrule">6</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Herpes virus- associated infections</td><td styleCode="Rrule">6</td><td styleCode="Rrule">4</td></tr><tr><td styleCode="Lrule Rrule">Pain in extremity</td><td styleCode="Rrule">5</td><td styleCode="Rrule">4</td></tr></tbody></table>

<table ID="table2" width="65%"><caption>Table 2 Adverse Reactions in Adult Patients With PPMS With an Incidence of at Least 5% for Intravenous Ocrelizumab and Higher Than Placebo</caption><col width="50%" align="left" valign="middle"/><col width="23%" align="center" valign="top"/><col width="27%" align="center" valign="middle"/><thead><tr><th align="center" rowspan="3" styleCode="Lrule Rrule">Adverse Reactions</th><th colspan="2" styleCode="Rrule Botrule">Study 3</th></tr><tr><th styleCode="Lrule Rrule" valign="top" align="center">Ocrelizumab 600 mg IV Every 24 Weeks<footnote>One dose of intravenous ocrelizumab (600 mg administered as two 300 mg infusions two weeks apart)</footnote></th><th styleCode="Rrule" valign="top">Placebo</th></tr><tr><th align="center" styleCode="Lrule Rrule" valign="bottom">(n=486) %</th><th styleCode="Rrule" valign="bottom">(n=239) %</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Upper respiratory tract infections</td><td styleCode="Rrule">49</td><td styleCode="Rrule">43</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Infusion reactions</td><td styleCode="Rrule">40</td><td styleCode="Rrule">26</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Skin infections</td><td styleCode="Rrule">14</td><td styleCode="Rrule">11</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Lower respiratory tract infections</td><td styleCode="Rrule">10</td><td styleCode="Rrule">9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Cough</td><td styleCode="Rrule">7</td><td styleCode="Rrule">3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Diarrhea</td><td styleCode="Rrule">6</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Edema peripheral</td><td styleCode="Rrule">6</td><td styleCode="Rrule">5</td></tr><tr><td styleCode="Lrule Rrule">Herpes virus associated infections</td><td styleCode="Rrule">5</td><td styleCode="Rrule">4</td></tr></tbody></table>