Rituximab VS Obinutuzumab (Rituxan Vs Gazyva) Comparison

Rituximab VS Obinutuzumab is a comparison of the two monoclonal antibodies that target the CD-20 B-lymphocytes. Obinutuzumab is a newer generation anti-CD 20 monoclonal antibody with greater efficacy and immune suppression.

Obinutuzumab is believed to be twice as effective as Rituximab

Drug Description:

Mechanism of Action of Rituximab (Rituxan):

Rituximab:

• Rituximab is a monoclonal antibody against the CD20 antigen on the B cell’s surface.
• It induces complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity after binding to the CD 20 surface antigen.
• It invokes structural changes, apoptosis, and sensitization of cancer cells to chemotherapy.

Obinutuzumab:

• Monoclonal type II CD20 antibody modified by glycoengineering
• Pre-B- and mature B-lymphocytes express surface CD20 antigen.
• It binds to the antigen and activates complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and anti-body-dependent cellular phagocytosis, resulting in cellular death.

Pharmacokinetics of Rituximab VS Obinutuzumab (Rituxan Vs Gazyva):

Indications of Rituximab VS Obinutuzumab (Rituxan Vs Gazyva):

Rituximab:

• Non-Hodgkin’s Lymphoma (NHL)
• Chronic Lymphocytic Leukemia (CLL)
• Rheumatoid Arthritis (RA) in combination with methotrexate in adult
• Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis)
• Microscopic Polyangiitis (MPA) in adult patients in combination with glucocorticoids

Obinutuzumab:

• Chronic lymphocytic leukemia: Used for treatment of previously untreated chronic lymphocytic leukemia (CLL) in combination with chlorambucil.
• Treatment of previously untreated stage II bulky, stage III, or stage IV follicular lymphoma in combination with chemotherapy and (in patients achieving at least a partial remission) followed by Obinutuzumab monotherapy.
• Treatment of follicular lymphoma (in combination with bendamustine followed by Obinutuzumab monotherapy) in patients who relapsed after, or are refractory to, a rituximab-containing regimen.

Side effects and Precautions/ Warnings:

Rituximab:

It should be used with caution in the following conditions:

• Bowel obstruction or perforation
• Ventricular fibrillation
• Myocardial infarction
• Cardiogenic shock.
• Patients should be screened for Hepatitis B before therapy. Screening should include HBsAg (hepatitis B surface antigen) and Hepatitis B core antibody (anti-HBc). All patients who develop viral hepatitis should be treated with appropriate antiviral therapy.

Obinutuzumab:

• Bacterial, fungal, and new or reactivated viral infections may occur during and/or the following therapy.
• In patients who have received Obinutuzumab hypersensitivity reactions have been reported.
• Hepatitis B virus (HBV) reactivation may occur with the use of CD20-directed cytolytic antibodies (including Obinutuzumab) and may result in fulminant hepatitis, hepatic failure, and death.

Rituximab Vs Obinutuzumab use in Pregnancy:

Rituximab:

• Based on the studies conducted on pregnant female animals. It causes B-cell Lymphocytopenia in infants exposed to the drug in-utero.
• Thus, this drug is contraindicated in a pregnant patient

Obinutuzumab:

• It is contraindicated in pregnant women as it may cause fetal B-cell depletion
• It is recommended for females of reproductive age to use effective contraception during the treatment and for 6 months after the last dose.

Both Rituximab and Obinutuzumab are contraindicated during pregnancy

Rituximab VS Obinutuzumab in Rheumatoid Arthritis:

• A  standard dose of Rituximab (500 mg/50 mL) when given in patients with RA showed a poor clinical response. Therefore, the patients required higher doses of the drug to show efficient B cell Deletion. But increasing the risk of toxicity. Thus a standard dose of RTX is ineffective in these patients.
• The recent studies show that Obinutuzumab is 2-times more efficient than rituximab at inducing B Cell Cytotoxicity.
• However, rituximab showed more potent complement-dependent cellular cytotoxicity.
• Obinutuzumab showed great interaction with Fc gamma Receptors than Rituximab. It includes the proper activation of NK cells and neutrophils. It is due to the intrinsic ability of the Obinutuzumab to remain attached to the cell surface following CD20 engagement.
• Furthermore, Obinutuzumab is more potent in inducing cell death directly. It includes cells such as CD19 + B cells (IgD + CD27 – ) and memory B cells (IgD – CD27 + )
• Rituximab becomes internalized and is associated with poor clinical response in the patients taking this drug.

Obinutuzumab is more potent in inducing cell death directly

Rituximab VS Obinutuzumab in Lymphoma:

• Obinutuzumab is a type II anti-CD20 monoclonal antibody that has lower complement-dependent cytotoxicity than rituximab.
• However, Obinutuzumab has greater antibody-dependent cellular cytotoxicity and phagocytosis ultimately potent B-cell killing effects than Rituximab.
• Obinutuzumab-based chemotherapy and maintenance therapy resulted in a lower risk of progression, relapse, and mortality in patients than those who were taking rituximab-based chemotherapy.
• The major drawback of Obinutuzumab noticed during GALLIUM Clinical Trials are adverse effects of grade greater than 3. The most common side effects include neutropenia and nausea. Thus making the patient more susceptible to infections and low compliance to the drug [Ref].

Obinutuzumab-based chemotherapy resulted in a lower risk of progression, relapse, and mortality than rituximab-based chemotherapy

Rituximab VS Obinutuzumab in Vasculitis:

• Rituximab activates NK cells given that B cells are not depleted in the patient with the vasculitis. NK cell degranulation activates CD69 Marker while decreasing the expression of CD. It is accompanied by a reduction of B cells that results in the remission phase.
• The next-generation anti-CD20 antibody Obinutuzumab showed marked activation of NK cells and reduction of B cells as compared to patients taking Rituximab [Ref].

Obinutuzumab is better than Rituximab in reducing B cells

Rituximab VS Obinutuzumab in Transplant Rejection:

• Rituximab, a type I Chimeric IgG1 anti-CD20 antibody is an essential drug to prevent and treat alloantibody mediated graft injury. However, there is a certain limitation to its use. More than often it results in incomplete B-Cell depletion thus failing to prevent Transplant Rejection.
• Obinutuzumab used in the treatment of Donor-specific antibodies (DSA) and antibody-mediated allograft rejection (ABMR) appears to have early DSA reduction and stabilization of serum creatinine.
• Both the drugs have some adverse effects spectrum but Obinutuzumab has better B-cell reduction properties [Ref].

Obinutuzumab has better B-cell reduction properties

Conclusion:

Over the last two decades, Rituximab has drastically improved the outcome of patients with autoimmune disorders and CD20+ malignancies. However, resistance is developing against this drug. On the other hand, Obinutuzumab has shown better results in comparison.

Whether to switch to Obinutuzumab has yet to be figured out given its increased toxicity and cost as compared to Rituximab. A recent phase III clinical trial results have been mixed regarding the superiority of one drug over the other.