Choosing an MS Treatment for the Individual Patient

This is an unparalleled time in the field of multiple sclerosis (MS). We now know that MS is a progressive disease from the start, regardless of relapses, and the field is embracing the urgency of early diagnosis and treatment with high efficacy disease-modifying therapies (DMTs) to slow disability progression. With more than 20 DMTs now approved by the U.S. Food and Drug Administration (FDA) to treat MS,¹ neurologists may face challenges in determining a treatment strategy for each patient.

Helping Patients Navigate the MS Treatment Experience

MS is an unpredictable disease, affecting each person differently. Some may only be mildly affected, while others may lose the ability to see clearly, write, speak, or walk. There are also invisible symptoms, like cognitive impairment, fatigue, and sensory issues, that can take a physical, mental, and emotional toll and significantly impact the experience of a person living with MS.²

Dr. Kalina Sanders, a board-certified neurologist at Baptist Health in Jacksonville, FL, has been treating MS patients for over 10 years. She says, “there are many factors that neurologists and their patients need to consider when selecting an MS treatment, including its benefit-risk profile and how the medicine may work with a patient’s lifestyle.”

One option she offers her patients is Ocrevus® (ocrelizumab), the first and only FDA-approved treatment for both relapsing MS (RMS) and primary progressive MS (PPMS). Ocrevus is the only MS treatment that has demonstrated a significant impact on slowing disability progression - an important goal of treating MS - in both RMS and PPMS Phase III studies (studied vs. interferon beta-1a or placebo). Ocrevus has also been shown to reduce relapses in RMS compared to interferon beta-1a. Data from our pivotal trials shows a favorable benefit-risk profile for over 8 years. Over 250,000 people with MS have been treated with Ocrevus globally. As with any therapy, Ocrevus has side effects.There is potential for serious side effects including infusion reactions, infections and malignancies. Please see below for additional important safety information and click the links provided below for the full Prescribing Information and Medication guide.

After selecting the most appropriate MS treatment, Dr. Sanders advises patients to put a reliable support system in place. She says, “support systems can make a difference for people living with MS, potentially improving their engagement with treatment and easing some of the burdens they may experience adjusting to life with a chronic disease.”

Healthcare providers can encourage people living with MS to lean on them for support by having an honest and open dialogue as well as building a network of care partners such as a spouse, parent, extended family member, or close family friend. Professional caregivers can also provide support, especially to people who may have disabilities. Free resources, many of which are culturally and linguistically-appropriate, and support groups are available by patient advocacy organizations and may also be helpful.

Recognizing Patient Diversity - Who is the MS Patient?

Dr. Sanders emphasizes the importance of recognizing diversity in the MS community from culture, to patient demographics and even clinical manifestations of the disease associated with certain races.

Recent research has debunked the myth that the MS patient is typically a young, White woman. MS can affect people of all ages, sexes, and races, with significantly higher rates in Black and Hispanic / Latinx people than previously thought. Together these populations make up 30% of the MS community, yet each has been historically underdiagnosed and undertreated.^3,4

“We’re not sure why, but disability progression may vary in different races or ethnicities,” says Dr. Sanders. “For instance, Black people with MS may have faster disability progression, including increased risk of secondary progressive MS and cane dependence. It has been observed that Black and Hispanic / Latinx people with MS may present with more vision loss or inflammation of the optic nerve, compared to their White counterparts.”

These differences in patient outcomes may be due to health disparities, such as social determinants of health, gaps in healthcare professional cultural competency, and the stigma associated with an “invisible” disease. Ongoing and inclusive research aims to better understand what contributes to these outcomes.

Genentech is proud to be making progress on advancing inclusive research by conducting the first-ever clinical trial focusing on Black and Hispanic / Latinx people living with MS. This MS trial aims to derive insights into disease progression in these populations to potentially help healthcare providers make more informed decisions with their patients.

To learn more about Ocrevus visit Ocrevus-hcp.com.

Important Safety Information & Indication
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.

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.

Progressive Multifocal Leukoencephalopathy (PML)

Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients with MS treated with OCREVUS 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 OCREVUS-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 OCREVUS, 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 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 OCREVUS should be discontinued.

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.

Immune-Mediated Colitis

Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving OCREVUS 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 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.

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%).

You may report side effects to the FDA at (800) FDA-1088 or http://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 https://www.gene.com/download/pdf/ocrevus_prescribing.pdf and https://www.gene.com/download/pdf/ocrevus_medguide.pdf.